Datasets:

findzebra
/

corpus

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 30.7k rows

text stringlengths 297 230k	title stringlengths 4 145	cui stringlengths 4 10	idx int64 0 30.7k	source stringclasses 6 values	source_url stringlengths 33 155	retrieved_date timestamp[s]	classification_map stringlengths 2 1.45k
Spermatogenesis arrest is known as the interruption of germinal cells of specific cellular type, which elicits an altered spermatozoa formation. Spermatogenic arrest is usually due to genetic factors resulting in irreversible azoospermia. However some cases may be consecutive to hormonal, thermic, or toxic factors and may be reversible either spontaneously or after a specific treatment. Spermatogenic arrest results in either oligospermia or azoospermia in men. It is quite a difficult condition to proactively diagnose as it tends to affect those who have normal testicular volumes; a diagnosis can be made however through a testicular biopsy.[1] ## Contents * 1 Effects * 2 Causes * 2.1 Chemotherapy * 2.2 Radiotherapy * 2.3 Nutritional Factors * 2.4 Heat * 2.5 Infections * 3 Treatment * 4 References * 5 External links ## Effects[edit] Spermatogenic arrest results in either oligospermia or azoospermia as mentioned above. Oligospermia is when extremely low concentrations of fertile sperm are found in semen or ejaculate, while azoospermia is when no fertile sperm are found in the semen or ejaculate.[2] ## Causes[edit] Spermatogenesis is controlled by androgens, namely testosterone and follicle-stimulating hormone (FSH), these are the most important androgens that control the process. FSH uses very specific G-coupled receptors that can be found only on Sertoli cells, this hormone is secreted by the pituitary gland, located in the brain. While testosterone, is produced within the testicles by Leydig cells. This hormone is the main androgenic steroid in the process of spermatogenesis and is regulated by a hormone known as luteinizing hormone. FSH plays a role in the spermatogenic capacity of the adult male as it controls the proliferation of Sertoli cells during either the perinatal or pubertal period, or both.[3] However, testosterone has been found to be the most important hormone that is responsible for both the initiation and the maintenance of spermatogenesis.[4] It is known that spermatogenesis is under the control of androgens, but germ cells (that will become gametes), do not express a functional androgen receptor, which are activated by the binding of androgenic hormones. It has been found through studies that spermatogenetic arrest tends to occur in the late spermatocyte/spermatid stage when the androgen receptor activation in Sertoli cells is interrupted or affected in some way.[3] However, other studies have found that the condition can be due to either genetic factors or a variety of secondary factors. ### Chemotherapy[edit] When using chemotherapy treatments, the possibility of azoospermia is dependent on the dose, duration, number and type of drugs used; the male's fertility status before the treatment occurred is also taken into consideration.[5] ### Radiotherapy[edit] The use of radiotherapy can cause a temporary bout of azoospermia, this however, is dependant solely on the nature of the dose that are delivered to the testes. Those who experience less than 100 rads will recover in 9–18 months, doses of 200-300 rads will recover in 30 months and doses of 400-600 rads will recover in less than or equal to five years. An irreversible sterility may occur however, for those experiencing a single dose field with 600-800 rads.[6] ### Nutritional Factors[edit] Studies have shown that Vitamin A deficiencies in rats [7] , as well as zinc deficiencies in human males may prevent the normal functioning of spermatogenesis.[8] ### Heat[edit] Heat may also be the cause of oligozoospermia which can lead to both partial and reversible spermatogenic arrest.[9] ### Infections[edit] After the occurrence of an infectious disease in humans, such as hypothermia and/or the presence of toxic or infectious factors spermatogenic arrest is likely to follow, however, the condition may be normalized once antibiotic and anti-inflammatory treatments have been put into effect.[10] ## Treatment[edit] Various treatments have been discovered in order to aid those with spermatogenesis arrest, one of these being through the use of arginine. A study done by Jungling and Bunge in 1976 had a small breakthrough in the field by orally distributing arginine, daily to a group of infertile men. Of the eighteen men in the test group only one experienced an increase in sperm count, while others saw no improvement; these men also experienced a decreased sperm motility. However, one of the patients in the group successfully impregnated his wife while taking part in the study.[11] More recently, more successful treatments have been developed, such as through the use of gonadotropin treatment. A study conducted by Selman and El-Danasouri in 2006 proved that using long-term gonadotropin therapy on infertile men can improve sperm production quantitatively and increase sperm population in some patients and can in turn provide a successful in-vitro fertilization treatment. These results were found using men that had normal hormone levels but suffered from spermatogenic arrest. These men were treated using FSH treatments and had testicular biopsy's performed on them before and after the treatment had been administered in order to track progress.[12] ## References[edit] 1. ^ Martin-du Pan, RC; Campana, A (1993). "Physiopathology of spermatogenic arrest". Fertil Steril. 60 (6): 937–46. doi:10.1016/S0015-0282(16)56388-2. PMID 8243695. 2. ^ Franchimont, P; Millet, D; Vendrely, E; Letawe, J; Legros, JJ; Netter, A (June 1972). "Relationship between spermatogenesis and serum gonadotropin levels in azoospermia and oligospermia". The Journal of Clinical Endocrinology and Metabolism. 34 (6): 1003–8. doi:10.1210/jcem-34-6-1003. PMID 5020414. 3. ^ a b Gendt, KD; Swinnen, JV; Saunders, P; Schoonjans, L; Dewerchin, M; Devos, A; Tan, K; Atanassova, N; Claessens, F; Lecureuil, C; Heyns, W; Carmeliet, P; Guilou, F; Sharpe, RM; Verhoeven, G (2004). "A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis". PNAS. 101 (5): 1327–1332. Bibcode:2004PNAS..101.1327D. doi:10.1073/pnas.0308114100. PMC 337052. PMID 14745012. 4. ^ Sharpe, RM (1994). "Physiopathology of Reproduction": 1363–2434. Cite journal requires `\|journal=` (help) 5. ^ Damewood, MD; Grochow, LB (1986). "Prospects for fertility after chemotherapy or radiation for neoplastic disease". Fertil Steril. 45 (4): 443–59. doi:10.1016/S0015-0282(16)49268-X. PMID 3082680. 6. ^ Ash, P (1966). "The influence of radiation on fertility in man". Br. J. Radiol. 39: 901–6. 7. ^ Ismail, N; Morales, C; Clermont, Y (1990). "Role of spermatogonia in the stage-synchronization of the seminiferous epithelium in vitamin-A deficient rats". Am. J. Anat. 188 (1): 57–63. doi:10.1002/aja.1001880107. PMID 2346119. 8. ^ Abbasi, AA; Prasad, AS; Rabbani, P; DuMouchelle, E (1980). "Experimental zinc deficiency in man: effect on testicular function". J. Lab. Clin. Med. 96: 544–49. 9. ^ Kandeel, FR; Swerdloff, RS (1988). "Role of temperature in regulation of and the use of heating as a method for contraception". Fertil. Steril. 49 (1): 1–23. doi:10.1016/S0015-0282(16)59640-X. PMID 3275550. 10. ^ Osegbe, DN (1991). "Testicular function after unilateral bacterial epididymo-orchitis". Eur. Urol. 19 (3): 2014–8. doi:10.1159/000473620. 11. ^ Jungling, ML; Bunge, RG (1976). "The treatment of spermatogenic arrest with arginine". Fertility and Sterility. 27 (3): 282–3. doi:10.1016/S0015-0282(16)41718-8. PMID 1254025. 12. ^ Sleman, H; El-Danasouri, I (2006). "Rescue of spermatogenesis arrest in azoospermic men after long-term gonadotropin treatment". Fertility and Sterility. 86 (2): 446–468. doi:10.1016/j.fertnstert.2005.12.055. ## External links[edit] * Online Mendelian Inheritance in Man (OMIM): 270960 * Microscopic images of spermatogenesis arrest [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spermatogenesis arrest	c0232981	29,900	wikipedia	https://en.wikipedia.org/wiki/Spermatogenesis_arrest	2021-01-18T19:08:36	{"gard": ["8530"], "mesh": ["C536875"], "umls": ["C0232981"], "wikidata": ["Q7576389"]}
Acral nevus Other namesMelanocytic nevus of acral skin,[1] and Melanocytic nevus with intraepidermal ascent of cells[1] Acral nevus SpecialtyDermatology An acral nevus is a cutaneous condition characterized by a skin lesion that is usually macular or only slightly elevated, and may display uniform brown or dark brown color, but often with linear striations.[1]:1726 They are nevi of palms and soles, which may occur in all ethnic groups but more common in dark skin people. Acral Nevus is a benign skin tumor that can occur at any age, but is generally noticed between 10–30 years of age. Both children and adults may be observed with this skin tumor. Prevalence of aural nevi increased directly with degree of skin pigmentation. In a study palmar or plantar nevi were detected in 42.0%of black (50 of 119) vs 23.0% of whites (79 0f 343). Palmar or plantar nevi of 6 mm diameter or larger were detected in 3.4% of blacks(4 of 119) vs 0.6% of whites.[2] These are brown to dark brown in color and have linear streaks of darker pigmentation. Size is 7 mm or less, oval or spindle shaped, and are well demarcated. They become stable after initial growth phase and the number of lesions also decrease, new lesion in middle age or elderly should raise suspicion of acral lentiginous melanoma.[citation needed] ## Contents * 1 Additional image * 2 See also * 3 References * 4 External links ## Additional image[edit] Melanocytic acral nevus with intraepidermal ascent cells (MANIAC) ## See also[edit] * Acral lentiginous melanoma * List of cutaneous conditions ## References[edit] 1. ^ a b c Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1726–7. ISBN 978-1-4160-2999-1. 2. ^ Palicka, G. A.; Rhodes, A. R. (2010). "Acral melanocytic nevi: prevalence and distribution of gross morphologic features in white and black adults". Archives of Dermatology. 146 (10): 1085–94. doi:10.1001/archdermatol.2010.299. PMID 20956637. ## External links[edit] Classification D * ICD-10: D22.9 * v * t * e Skin cancer of nevi and melanomas Melanoma * Mucosal melanoma * Superficial spreading melanoma * Nodular melanoma * lentigo * Lentigo maligna/Lentigo maligna melanoma * Acral lentiginous melanoma * Amelanotic melanoma * Desmoplastic melanoma * Melanoma with features of a Spitz nevus * Melanoma with small nevus-like cells * Polypoid melanoma * Nevoid melanoma * Melanocytic tumors of uncertain malignant potential Nevus/ melanocytic nevus * Nevus of Ito/Nevus of Ota * Spitz nevus * Pigmented spindle cell nevus * Halo nevus * Pseudomelanoma * Blue nevus * of Jadassohn–Tièche * Cellular * Epithelioid * Deep penetrating * Amelanotic * Malignant * Congenital melanocytic nevus (Giant * Medium-sized * Small-sized) * Balloon cell nevus * Dysplastic nevus/Dysplastic nevus syndrome * Acral nevus * Becker's nevus * Benign melanocytic nevus * Nevus spilus This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acral nevus	c1879545	29,901	wikipedia	https://en.wikipedia.org/wiki/Acral_nevus	2021-01-18T18:56:32	{"umls": ["C1879545"], "wikidata": ["Q4675040"]}
The presbylarynx is a condition in which age-related atrophy of the soft tissues of the larynx results in weak voice and restricted vocal range and stamina. In other words, it is the loss of vocal fold tone and elasticity due to aging which affects voice quality. ## Contents * 1 Symptoms * 2 Treatment * 3 See also * 4 References ## Symptoms[edit] The list of signs and symptoms mentioned in various sources for presbylarynx includes the 4 symptoms listed below:[citation needed] 1. Hoarseness 2. Breathy voice 3. Reduced voice volume 4. Unstable voice pitch Note that presbylarynx symptoms usually refers to various symptoms known to a patient, but the phrase "presbylarynx signs" may refer to those signs only noticeable by a doctor. ## Treatment[edit] The list of treatments mentioned in various sources for presbylarynx includes the following list. Always seek professional medical advice about any treatment or change in treatment plans. * Voice therapy ## See also[edit] Look up presbylarynx in Wiktionary, the free dictionary. * Acoustic phonetics * Epiglottitis * Intubation * Laryngitis * Mechanical larynx * Phonation * Phonetics * Vocology * Voice organ ## References[edit] * Speech and Hearing Science: Anatomy and Physiology, 3rd edition. Willard R. Zemlin. 1988. Prentice-Hall, Inc. Englewood Cliffs, New Jersey. ISBN 0-13-827429-0 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Presbylarynx	c4049459	29,902	wikipedia	https://en.wikipedia.org/wiki/Presbylarynx	2021-01-18T18:28:11	{"wikidata": ["Q7240713"]}
## Clinical Features Wiedemann et al. (1993) described a well-studied patient followed from infancy to age 19 years. He was born to a 34-year-old mother and an unrelated 37-year-old father. Features of the syndrome from which the patient suffered included extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pes cavus with claw toes, an abnormal face, and mental retardation. The facial features consisted of slightly antimongoloid slant of the right palpebral fissure, epicanthic folds, broad nasal root, perhaps mild hypertelorism, and somewhat everted prominent lower lip. At the age of 16, the patient developed pain, swelling, and redness of several finger joints, and he was found to have elevated serum uric acid. This elevation and the symptoms of gout responded promptly to allopurinol. Skeletal anomalies became evident after the end of his first year. The neck became very long, and the thorax became much longer and narrower over the course of the years, with a prominent manubrium. The shoulders were down-sloping and the elbow joints unusually prominent. The right hallux was abnormally placed with chronic subluxation. There was coxa valga bilaterally with subluxation of both hip joints. Height was in the normal range. Oster et al. (1994) reported data collected on the patient reported by Wiedemann et al. (1993) at age 20 after 10 days without medication. The data were interpreted as indicating that the hyperuricemia was not caused by overproduction or by a defect in either APRT (102600) or HPRT (308000). Also, overproduction of uric acid caused by phosphoribosylpyrophosphate synthetase superactivity (300661) was excluded. Oster et al. (1994) concluded that hyperuricemia was probably due to reduced renal excretion of uric acid since renal clearance of uric acid and fractional uric acid clearance were below the normal range for age and sex. Hair \- Hirsutism Skel \- Long neck \- Down-sloping shoulders \- Coxa valga Limbs \- Abnormal thumb position \- Pes cavus \- Claw-toes Thorax \- Growth long and narrow \- Prominent manubrium Neuro \- Mental retardation Facies \- Antimongoloid eye slant \- Epicanthic folds \- Broad nasal root \- Mild hypertelorism \- Everted prominent lower lip Lab \- Elevated serum uric acid \- Reduced renal excrion of uric acid Joints \- Pain, swelling, and redness of finger joints \- Prominent elbow joints \- Hip joint subluxation \- Hallux subluxation Inheritance \- Autosomal dominant Cranium \- Brachycephaly ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HIRSUTISM, SKELETAL DYSPLASIA, AND MENTAL RETARDATION	c3149452	29,903	omim	https://www.omim.org/entry/142625	2019-09-22T16:40:11	{"omim": ["142625"]}
Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is a gluconeogenesis disorder that results from impairment in the enzyme PEPCK, and comprising cytosolic (PEPCK1) and mitochondrial (PEPCK2) forms of enzyme deficiency. Onset of symptoms is neonatal or a few months after birth and includes hypoglycemia associated with acute episodes of severe lactic acidosis, progressive neurological deterioration, severe liver failure, renal tubular acidosis and Fanconi syndrome. Patients also present progressive multisystem damage with failure to thrive, muscular weakness and hypotonia, developmental delay with seizures, spasticity, lethargy, microcephaly and cardiomyopathy. To date, there is no conclusive evidence of the existence of an isolated form of this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Phosphoenolpyruvate carboxykinase deficiency	c0268194	29,904	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2880	2021-01-23T17:15:39	{"mesh": ["C536654"], "omim": ["261650", "261680"], "umls": ["C0268194"], "icd-10": ["E74.4"], "synonyms": ["PEPCK deficiency"]}
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD2A) is caused by homozygous mutation in the PEX5 gene (600414) on chromosome 12p13. Description The peroxisome biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 2 (CG2) have mutations in the PEX5 gene. For information on the history of PBD complementation groups, see 214100. Clinical Features Thomas et al. (1975) described a male patient with hyperpipecolic acidemia. Features were persistent hepatomegaly, severe mental retardation, progressive loss of developmental milestones, and diminished visual acuity associated with nystagmus, abnormal discs, and retinal changes. He died at age 2 years following a progressive loss of neurologic function. Pipecolic acid was present in the serum at a concentration of 4 to 5 mg percent and trace amounts were detected in the urine. The complementation studies of Brul et al. (1988) assigned this patient to complementation group 2 (CG2). Molecular Genetics Dodt et al. (1995) reported a homozygous mutation in the PEX5 gene in a cell line from a patient with Zellweger syndrome (600414.0002). Head \- High forehead \- Dolichoturricephaly \- Large fontanels GU \- Polycystic kidneys \- Cryptorchidism \- Clitoromegaly Facies \- Flat \- Round Inheritance \- Autosomal recessive, several forms Limbs \- Cubitus valgus \- Camptodactyly \- Transverse palmar crease \- Metatarsus adductus \- Talipes equinovarus Eyes \- Puffy lids \- Hypertelorism \- Epicanthic folds \- Brushfield spots \- Cloudy cornea \- Cataracts \- Pigmentary retinopathy \- Optic nerve dysplasia Lab \- Elevated long chain fatty acids in plasma, fibroblasts and amniocytes \- Serum iron and iron binding capacity high \- Peroxisomes abnormal \- Pipecolic aciduria \- Serum pipecolic acid elevated Skel \- Stippled chondral calcification Growth \- Prenatal growth failure \- Poor suck \- Failure to thrive \- Early death Mouth \- Cleft palate \- Mandible:Micrognathia Liver \- Intrahepatic biliary dysgenesis \- Jaundice \- Mitochondrial abnormalities \- Hepatomegaly Cardiac \- Congenital heart defect Neuro \- Hypotonia \- Areflexia \- Absent Moro response \- Mental retardation \- Seizures Resp \- Apnea Thorax \- Thymus hypoplasia Ears \- Low set \- Helix abnormal ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PEROXISOME BIOGENESIS DISORDER 2A (ZELLWEGER)	c0043459	29,905	omim	https://www.omim.org/entry/214110	2019-09-22T16:29:48	{"doid": ["0080477"], "mesh": ["D015211"], "omim": ["214110"], "orphanet": ["912"]}
A rare congenital respiratory disorder characterized by marked dilatation of the trachea and proximal bronchi that leads to impaired airway secretion clearance and recurrent lower respiratory tract infections. ## Epidemiology Mounier-Kühn syndrome is a rare underdiagnosed condition of unknown prevalence. About 300 cases have been reported to date. The condition is more frequent in men. ## Clinical description The disorder may manifest at various ages but is usually diagnosed in young adults with recurrent bronchopulmonary infections (e.g. bronchitis, pneumonia), and tracheobronchial irritation of varying degrees of severity causing chronic dry or productive cough with purulent sputum production, dyspnea (occasionally on exertion) and hemoptysis. Progressive hoarseness has also been observed. Bronchial crackles and/or wheezing and finger clubbing are common. In mild cases, patients are asymptomatic or present only with chronic cough and have normal pulmonary function. In the rare severe cases, patients may suffer from pulmonary obstructive diseases such as bronchiectasis or bullous emphysema, and airflow obstruction that can lead to chronic respiratory failure. ## Etiology Mounier-Kühn syndrome results from the atrophy of elastic fibers in the trachea and main bronchi which lead to thinning of the smooth muscle layer and subsequent tracheobroncheal flaccidity, dilatation and collapse. The etiologic mechanism remains unknown. Irritants like cigarette smoke and air pollution could act as irritating factors. The disease is sometimes associated with connective tissue diseases such as Ehlers-Danlos syndrome, Marfan syndrome and cutis laxa and might have a genetic origin; however no gene mutation has been identified to date. ## Diagnostic methods Mounier-Kühn syndrome is diagnosed when the coronal and the sagittal diameters of the trachea, measured on plain chest radiography or computed tomography (CT), are greater than 25 mm and 27 mm, respectively in males, and greater than 21 mm and 23 mm in females. Fiberoptic bronchoscopy shows dilatation of the trachea and proximal bronchi, expiratory collapse in patients with tracheomalacia, and possible presence of diverticula on the posterior wall. Biopsies of bronchial and tracheal wall tissue show loss of elastic fibers but are usually unnecessary. Pulmonary function tests can be normal or show varying degrees of airflow obstruction and increased residual volume. ## Differential diagnosis Differential diagnosis includes lower respiratory tract infections like bronchitis and chronic obstructive pulmonary disease, ankylosing spondylitis, and Williams-Campbell syndrome. ## Genetic counseling The disease is sporadic in most cases, although several familial cases have been described. ## Management and treatment Treatment is symptomatic. Chest physiotherapy can be proposed to improve mucociliary clearance and antibiotics are administered for treatment of pulmonary infections. Some patients may benefit from non-invasive positive-pressure ventilation, also needed at night in severe cases. Insertion of a tracheal or tracheobronchial stent, with or without surgical tracheobronchoplasty, was shown to reduce airway collapsibility in some highly selected cases with tracheomalacia. Double lung transplantation has been successful in one case. ## Prognosis The impact of this condition on life expectancy has not been evaluated. Complications include respiratory infections, tracheomalacia, pulmonary obstructive diseases, pneumothorax, and exceptionally lung fibrosis that can lead to chronic respiratory failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mounier-Kühn syndrome	c0040587	29,906	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3347	2021-01-23T18:15:38	{"gard": ["3793", "5234"], "mesh": ["D014137"], "omim": ["275300"], "umls": ["C0040587", "C2713583"], "icd-10": ["J98.0"], "synonyms": ["Congenital tracheobronchomegaly", "Idiopathic tracheobronchomegaly", "Tracheobronchomegaly"]}
Jackson-Weiss syndrome (JWS) is a rare genetic disorder characterized by foot malformations (tarsal and metatarsal fusions; short, broad, medially deviated great toes) and in some patients craniosynostosis with facial anomalies. Hands are normal in affected patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Jackson-Weiss syndrome	c0795998	29,907	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1540	2021-01-23T18:34:14	{"gard": ["6796"], "mesh": ["C537559"], "omim": ["123150"], "umls": ["C0795998"], "icd-10": ["Q87.8"], "synonyms": ["Craniosynostosis-midfacial hypoplasia-foot abnormalities syndrome", "JWS"]}
See also: Segmental colitis associated with diverticulosis Diverticulosis Other namesDiverticular disease of the colon Diverticulosis as seen endoscopically SpecialtyGeneral surgery Diverticulosis is the condition of having multiple pouches (diverticula) in the colon that are not inflamed. These are outpockets of the colonic mucosa and submucosa through weaknesses of muscle layers in the colon wall.[1] They typically cause no symptoms.[2] Diverticular disease occurs when diverticula become inflamed, known as diverticulitis, or bleed.[3] They typically occur in the sigmoid colon, which is a common place for increased pressure. The left side of the colon is more commonly affected in the United States while the right side is more commonly affected in Asia.[4] Diagnosis is often during routine colonoscopy or as an incidental finding during CT scan.[2] It is common in Western countries with about half of those over the age of 60 in Canada and the United States affected.[4] Diverticula are uncommon before the age of 40, and increase in incidence beyond that age.[5] Rates are lower in Africa which has been attributed to a shorter life expectancy and poor healthcare access.[4][dubious – discuss] However, earlier epidemiological studies by Burkitt suggested that the lower incidence of diverticulosis coli in Africa correlated with softer stools in native populations who consume a high-roughage diet in contrast with the refined, lower-roughage diet of Western populations.[6] ## Contents * 1 Signs and symptoms * 1.1 Bleeding * 1.2 Diverticulitis * 1.3 Segmental colitis associated with diverticulosis * 2 Causes * 2.1 Diet * 2.2 Genetics * 2.3 Intestinal motility * 2.4 Risk factors * 3 Pathophysiology * 4 Diagnosis * 4.1 Imaging * 5 Management * 5.1 Diet * 5.2 Complications * 6 Epidemiology * 7 History * 8 Society and culture * 8.1 Economics * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Diverticulosis, 70 y.o, sigmoid colon Some people with diverticulosis complain of symptoms such as cramping, bloating, flatulence, and irregular defecation. However, it is unclear if these symptoms are attributable to the underlying diverticulosis or to coexistent irritable bowel syndrome.[7] Diverticular disease was found associated with a higher risk of left sided colon cancer.[8] ### Bleeding[edit] Diverticular disease can present with painless rectal bleeding as bright red blood per rectum. Diverticular bleeding is the most common cause of acute lower gastrointestinal bleeding.[9] However, it is estimated that 80% of these cases are self-limiting and require no specific therapy.[10] ### Diverticulitis[edit] Infection of a diverticulum can result in diverticulitis. A recent study[11] found that it happens only about 4% of the time. That contradicts prevailing thinking that 10% to 25% of people with diverticulosis go on to develop diverticulitis. Tears in the colon leading to bleeding or perforations may occur; intestinal obstruction may occur (constipation or diarrhea does not rule this possibility out); and peritonitis, abscess formation, retroperitoneal fibrosis, sepsis, and fistula formation are also possible occurrences. Rarely, an enterolith may form. Infection of a diverticulum often occurs as a result of stool collecting in a diverticulum. It is defined as diverticular disease with signs and symptoms of diverticular inflammation. Clinical features of acute diverticulitis include constant abdominal pain, localized abdominal tenderness in the left lower quadrant of the abdomen, nausea, vomiting, constipation or diarrhea, fever and leukocytosis.[12] Most people with colonic diverticulosis are unaware of this structural change. When symptoms do appear in a person over 40 years of age it is important to obtain medical advice and exclude more dangerous conditions such as cancer of the colon or rectum.[13][14][15][16] ### Segmental colitis associated with diverticulosis[edit] Main article: Segmental colitis associated with diverticulosis Segmental colitis associated with diverticulosis (SCAD) is a condition characterized by localized inflammation of the colon between diverticula (interdiverticular mucosa), while sparing the diverticular orifices. SCAD may lead to abdominal pain, especially in the left lower quadrant, intermittent rectal bleeding and chronic diarrhea. ## Causes[edit] ### Diet[edit] The U.S. National Institutes of Health notes that, although the low-fiber theory of the cause of diverticulosis is the leading theory, it has not yet been proven.[17] ### Genetics[edit] The predisposition to diverticulosis for specific individuals is likely explained by a genetic component, a theory which is supported by studies examining the rates of diverticulosis among twins.[1] The heritability of diverticulosis is estimated to be approximately 40%.[1] ### Intestinal motility[edit] Another theory suggests the degeneration of glial neurons in the myenteric plexus and the interstitial cells of Cajal lead to slowed intestinal movement and consequently fecal content exerts increased pressure on the colon wall resulting in the formation of diverticula.[1] ### Risk factors[edit] 1. Advanced age 2. constipation 3. a diet that is low in dietary fiber (although this claim is controversial) 4. connective tissue disorders (such as Marfan syndrome and Ehlers Danlos Syndrome) that may cause weakness in the colon wall 5. hereditary or genetic predisposition,[18] 6. extreme weight loss 7. heavy meat consumption[19][20][21] ## Pathophysiology[edit] Drawing showing a sigmoid colon with many diverticula The precise mechanisms by which diverticula are formed are unknown.[1] Multiple theories have been proposed including genetic susceptibility, diet, intestinal motility, changes in the microbiome, and inflammation. One leading theory suggests that diverticula form in weakened areas of the colon wall that are subjected to increased pressure.[1] The strength of the colon wall is known to decrease with age.[1] Previous theories proposed that impacted fecal matter and certain foods would get stuck in diverticula (thereby causing trauma), which caused poor blood flow, death of the affected intestinal wall cells, and intestinal perforation.[1] Newer theories have called this paradigm into question.[1] ## Diagnosis[edit] CT scan showing extensive diverticulosis of the sigmoid colon Diverticular disease Whole slide of a transverse section of left colon with diverticulosis Diverticulosis is defined by the presence of multiple pouches (diverticula) in the colon.[22] In people without symptoms, these are usually found incidentally during other investigations.[citation needed] While a good history is often sufficient to form a diagnosis of diverticulosis or diverticulitis, it is important to confirm the diagnosis and rule out other pathology (notably colorectal cancer) and complications. ### Imaging[edit] * Plain abdominal X-ray may show signs of a thickened wall, ileus, constipation, small bowel obstruction or free air in the case of perforation. Plain X-rays are insufficient to diagnose diverticular disease. * Contrast CT is the investigation of choice in acute episodes of diverticulitis and where complications exist. * Colonoscopy will show the diverticulum and rule out malignancy. A colonoscopy should be performed 4–6 weeks after an acute episode. * Barium enema is inferior to colonoscopy in terms of image quality and is usually only performed if the patient has strictures or an excessively tortuous sigmoid colon where colonoscopy is difficult or dangerous. * MRI provides a clear picture of the soft tissue of the abdomen, however its expense often outweighs the benefits when compared to contrast CT or colonoscopy. * There is no blood test for diverticulosis. It is important to note that both barium enema and colonoscopy are contraindicated during acute episodes of diverticulitis, as the barium may leak out into the abdominal cavity, and colonoscopy can cause perforations of the bowel wall. ## Management[edit] Many people with diverticulosis have minimal to no symptoms, and do not require any specific treatment. Colonic stimulants should be avoided. Treatments, like some colon cleansers, that cause hard stools, constipation, and straining, are not recommended.[citation needed] ### Diet[edit] A high-fiber diet and fiber supplements are advisable to prevent constipation.[23][24] The American Dietetic Association recommends 20–35 grams each day. Wheat bran has been shown to reduce intra colonic pressure.[25][26] The US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) says foods such as nuts, popcorn hulls, sunflower seeds, pumpkin seeds, caraway seeds, and sesame seeds have traditionally been labeled as problem foods for people with this condition; however, no scientific data exists to prove this hypothesis. The seeds in tomatoes, zucchini, cucumbers, strawberries, raspberries, and poppy seeds, are not considered harmful by the NIDDK.[2] One study found that nuts and popcorn do not contribute positively or negatively to patients with diverticulosis or diverticular complications.[27][28] ### Complications[edit] Complicated diverticulosis requires treatment of the complication. These complications are often grouped under a single diagnosis of diverticulitis and require skilled medical care of the infection, bleeding and perforation which may include intensive antibiotic treatment, intravenous fluids and surgery. Complications are more common in patients who are taking NSAIDs or aspirin. As diverticulosis occurs in an older population such complications are serious events.[citation needed] ## Epidemiology[edit] The prevalence of diverticulosis progressively increases with age. Approximately 50% of people over the age of 60 and 70% of people over the age of 80 have diverticulosis.[1] This disease is common in the U.S., Britain, Australia, Canada, and is uncommon in Asia and Africa.[5] Large-mouth diverticula are associated with scleroderma. Diverticular disease is more common in collagen disorders such as Ehlers Danlos Syndrome.[29] ## History[edit] The modern emphasis on the value of fiber in the diet began with Thomas L. Cleave.[30] A strong case was made by Neil Painter[31] and Adam Smith[32] that a deficiency of dietary fiber is the cause of diverticular disease. They argued that the colonic muscles needed to contract strongly in order to transmit and expel the small stool associated with a fiber deficient diet. The increased pressure within the segmented section of bowel over years gave rise to herniation at the vulnerable point where blood vessels enter the colonic wall. ## Society and culture[edit] ### Economics[edit] "The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year."[33] ## See also[edit] * Salpingitis isthmica nodosa — diverticulosis of the Fallopian tube ## References[edit] 1. ^ a b c d e f g h i j Feuerstein, JD; Falchuk, KR (August 2016). "Diverticulosis and Diverticulitis". Mayo Clinic Proceedings (Review). 91 (8): 1094–1104. doi:10.1016/j.mayocp.2016.03.012. PMID 27156370. 2. ^ a b c "Diverticular Disease". www.niddk.nih.gov. September 2013. Retrieved 12 June 2016. 3. ^ Tursi A, Papa A, Danese S (September 2015). "Review article: the pathophysiology and medical management of diverticulosis and diverticular disease of the colon". Alimentary Pharmacology & Therapeutics. 42 (6): 664–84. doi:10.1111/apt.13322. PMID 26202723. S2CID 24568867. 4. ^ a b c Tursi, A (March 2016). "Diverticulosis today: unfashionable and still under-researched". Therapeutic Advances in Gastroenterology. 9 (2): 213–28. doi:10.1177/1756283X15621228. PMC 4749857. PMID 26929783. 5. ^ a b Comparato G, Pilotto A, Franzè A, Franceschi M, Di Mario F (2007). "Diverticular disease in the elderly". Digestive Diseases. 25 (2): 151–9. doi:10.1159/000099480. PMID 17468551. 6. ^ Painter NS, Burkitt DP (May 1971). "Diverticular disease of the colon: a deficiency disease of Western civilization". British Medical Journal. 2 (5759): 450–4. doi:10.1136/bmj.2.5759.450. PMC 1796198. PMID 4930390. 7. ^ "Clinical manifestations and diagnosis of colonic diverticular disease". Literature review. 8. ^ Stefánsson T, Ekbom A, Sparèn P, Påhlman L (Aug 2004). "Association between sigmoid diverticulitis and left-sided colon cancer: a nested, population-based, case control study". Scand J Gastroenterol. 39 (8): 743–7. doi:10.1080/00365520410003272. PMID 15513359. S2CID 21100705. 9. ^ Acute lower gastrointestinal bleeding in 1,112 patients admitted to an urban emergency medical center. Gayer C1, Chino A, Lucas C, Tokioka S, Yamasaki T, Edelman DA, Sugawa C. http://www.surgjournal.com/article/S0039-6060(09)00481-4/pdf 10. ^ Barnert J, Messmann H (2008). "Management of lower gastrointestinal tract bleeding". Best Practice & Research. Clinical Gastroenterology. 22 (2): 295–312. doi:10.1016/j.bpg.2007.10.024. PMID 18346685. 11. ^ https://www.cghjournal.org/article/S1542-3565%2813%2900623-X/abstract 12. ^ Tursi A, Papagrigoriadis S (September 2009). "Review article: the current and evolving treatment of colonic diverticular disease". Alimentary Pharmacology & Therapeutics. 30 (6): 532–46. doi:10.1111/j.1365-2036.2009.04072.x. PMID 19549266. S2CID 22765199. 13. ^ Shepherd NA (1992) Diverticular disease. In Oxford Textbook of Pathology, pp. 1256–1258 [J O'D McGee, PG Isaacson and NA Wright, editors]. Oxford: Oxford University Press. 14. ^ Christensen J (1991) Gross and microscopic anatomy of the large intestine. In The Large Intestine Physiology, Pathophysiology and Disease, pp. 13-35 [SF Phillips, JH Pemberton and RG Shorter, editors]. New York: Raven Press. 15. ^ West, AB (2008). "The pathology of diverticulitis". J Clin Gastroenterol. 42 (10): 1137–8. doi:10.1097/MCG.0b013e3181862a9f. PMID 18936652. 16. ^ Drummond, H (1916). "Sacculi of the large intestine with special reference to their relation to the blood vessels of the bowel wall". British Journal of Surgery. 4 (15): 407–413. doi:10.1002/bjs.1800041505. S2CID 72222598. 17. ^ "Understanding Diverticulosis and Diverticulitis - NIH MedicinePlus". Nlm.nih.gov. 2012-08-27. Retrieved 2013-10-04. 18. ^ "Diverticulosis and Diverticulitis". American College of Gastroenterology. 19. ^ Humes D, Smith JK, Spiller RC (14 March 2011). "Colonic diverticular disease: medical treatments for acute diverticulitis". BMJ Clinical Evidence. 2011. PMC 3275154. PMID 21401970. "A prospective cohort study reported that consuming a vegetarian diet and a high intake of dietary fibre were associated with a lower risk of admission to hospital or death from diverticular disease. High meat intake is also a risk factor for developing diverticular disease." 20. ^ Grossi, Enzo; Pace, Fabio (12 May 2016). Human Nutrition from the Gastroenterologist's Perspective. Springer. p. 104. ISBN 9783319303611. "It has been hypothesized that the increased consumption of animal proteins increases the risk of diverticular disease by altering the metabolism of bacteria in the colon or increasing the intake of fat." 21. ^ DiMarino, Anthony J.; Benjamin, Stanley B. (2002). Gastrointestinal Disease: An Endoscopic Approach. SLACK Incorporated. p. 863. ISBN 9781556425110. 22. ^ Pemberton, John H (16 June 2016). "Colonic diverticulosis and diverticular disease: Epidemiology, risk factors, and pathogenesis". UpToDate. Retrieved 13 March 2017. 23. ^ Aldoori, WH; Giovannucci, EL; Rimm, EB; Wing, AL; et al. (1994). "A prospective study of diet and the risk of symptomatic diverticular disease in men". The American Journal of Clinical Nutrition. 60 (5): 757–64. doi:10.1093/ajcn/60.5.757. PMID 7942584. 24. ^ Gear, JS; Ware, A; Fursdon, P; Mann, JI; et al. (1979). "Symptomless diverticular disease and intake of dietary fibre". Lancet. 1 (8115): 511–4. doi:10.1016/S0140-6736(79)90942-5. PMID 85104. S2CID 37933413. 25. ^ Marlett, JA; McBurney, MI; Slavin, JL; American Dietetic, Association (2002). "Position of the American Dietetic Association: health implications of dietary fiber". Journal of the American Dietetic Association. 102 (7): 993–1000. doi:10.1016/S0002-8223(02)90228-2. PMID 12146567. 26. ^ Eglash, A; Lane, CH; Schneider, DM (2006). "Clinical inquiries. What is the most beneficial diet for patients with diverticulosis?". The Journal of Family Practice. 55 (9): 813–5. PMID 16948968. 27. ^ Strate, LL; Liu, YL; Syngal, S; Aldoori, WH; et al. (2008). "Nut, Corn, and Popcorn Consumption and the Incidence of Diverticular Disease". JAMA. 300 (8): 907–914. doi:10.1001/jama.300.8.907. PMC 2643269. PMID 18728264. 28. ^ "Eating Nuts, Popcorn Not Linked With Higher Risk of Diverticulosis". Newswise. 21 August 2008. Retrieved 26 August 2008. 29. ^ Hobson KG, Roberts PL (August 2004). "Etiology and pathophysiology of diverticular disease". Clinics in Colon and Rectal Surgery. 17 (3): 147–53. doi:10.1055/s-2004-832695. PMC 2780060. PMID 20011269. 30. ^ Cleave TL 1974 The Saccharine disease Wright Bristol 31. ^ Painter NS (1975) Diverticular disease of the colon. Heinemann Medical Books 32. ^ Smith, AN (1991). "Diverticular disease of the colon" in The Large Intestine. Ed. Phillips SF, Pemberton JH and Shorter RG. Raven Press. pp. 549–578 33. ^ Peery, AF; Barrett, PR; Park, D; Rogers, AJ; et al. (February 2012). "A high-fiber diet does not protect against asymptomatic diverticulosis". Gastroenterology. 142 (2): 266–72.e1. doi:10.1053/j.gastro.2011.10.035. PMC 3724216. PMID 22062360. ## External links[edit] Classification D * ICD-10: K57 * ICD-9-CM: 562.00 * OMIM: 223320 * MeSH: D004240 * DiseasesDB: 3871 * SNOMED CT: 397881000 External resources * eMedicine: med/3102 Wikimedia Commons has media related to Diverticulosis. * Diverticular Resource Website * Marlett JA, McBurney MI, Slavin JL (2002). "Position of the American Dietetic Association: health implications of dietary fiber". J Am Diet Assoc. 102 (7): 993–1000. doi:10.1016/S0002-8223(02)90228-2. PMID 12146567. Archived from the original on 2016-12-03. Retrieved 2008-08-22. * Diverticulosis—PrimeHealthChannel * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Diverticulosis	c0012819	29,908	wikipedia	https://en.wikipedia.org/wiki/Diverticulosis	2021-01-18T18:49:59	{"mesh": ["D043963"], "icd-9": ["562.00"], "icd-10": ["K57"], "wikidata": ["Q278158"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Otitis" – news · newspapers · books · scholar · JSTOR (September 2014) (Learn how and when to remove this template message) Otitis SpecialtyENT surgery Otitis is a general term for inflammation or infection of the ear, in both humans and other animals. It is subdivided into the following: * Otitis externa, external otitis, or "swimmer's ear", involves the outer ear and ear canal. In external otitis, the ear hurts when touched or pulled. * Otitis media, or middle ear infection, involves the middle ear. In otitis media, the ear is infected or clogged with fluid behind the ear drum, in the normally air-filled middle-ear space. This very common childhood infection sometimes requires a surgical procedure called myringotomy and tube insertion. * Otitis interna, or labyrinthitis, involves the inner ear. The inner ear includes sensory organs for balance and hearing. When the inner ear is inflamed, vertigo is a common symptom. ## External links[edit] Classification D * ICD-9-CM: 380.10 * MeSH: D010031 External resources * MedlinePlus: 001336 * v * t * e Diseases of the outer and middle ear Outer ear * Otitis externa * Otomycosis Middle ear and mastoid * Otitis media * Mastoiditis * Bezold's abscess * Gradenigo's syndrome * Tympanosclerosis * Cholesteatoma * Perforated eardrum Symptoms * Ear pain * Hearing loss Tests * Otoscope * pneumatic * tympanometry * v * t * e Inflammation Symptoms * Flushing (Rubor) * Fever (Calor) * Swelling (Tumor) * Pain (Dolor) * Malaise Mechanism Acute Plasma-derived mediators * Bradykinin * complement * C3 * C5a * MAC * coagulation * Factor XII * Plasmin * Thrombin Cell-derived mediators preformed: * Lysosome granules * biogenic amines * Histamine * Serotonin synthesized on demand: * cytokines * IFN-γ * IL-8 * TNF-α * IL-1 * eicosanoids * Leukotriene B4 * Prostaglandins * Nitric oxide * Kinins Chronic * Macrophage * Epithelioid cell * Giant cell * Granuloma Other * Acute-phase reaction * Vasodilation * Increased vascular permeability * Exudate * Leukocyte extravasation * Chemotaxis Tests * Full blood count * Leukocytosis * C-reactive protein * Erythrocyte sedimentation rate General * Lymphadenopathy * List of inflammed body part states This article about a disease of the ear and mastoid process is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Otitis	c0699744	29,909	wikipedia	https://en.wikipedia.org/wiki/Otitis	2021-01-18T18:46:57	{"mesh": ["D010031"], "umls": ["C0699744"], "icd-9": ["380.10"], "wikidata": ["Q480700"]}
Chordomas are rare malignant tumors arising from embryonic remnants of the notochord in axial skeleton. ## Epidemiology They are predominantly found in adults, and comprise 0.2% of all central nervous system tumors and 2-4% of all primary bone neoplasms, with an estimated prevalence of 1 in 2 million people and a male-to-female ratio of 2:1. ## Clinical description The clinical presentation depends entirely on the location of the chordoma. The main possible locations are the sacrum, intracranially at the clivus and along the spinal axis. When the tumor is intracranial, the most common presenting symptoms are diplopia, swallowing problems and headache. Other neurologic signs also occur, primarily as cranial nerve palsies. Tumors in the spine can cause pain in the area of the tumor (neck, back or tailbone), as well as arm or leg pain, weakness or numbness, bladder and intestinal disturbances. Chordomas are characterized by slow growth, with local destruction of the bone and extension into the adjacent soft tissue. They can metastasize to lymph nodes, lungs, liver and bone. ## Diagnostic methods Diagnosis is made by radiography, computed tomography or magnetic resonance imaging. ## Management and treatment Treatment should be undertaken by expert neurosurgical and radiation oncology teams. Surgery is the primary mode of treatment but excision often remains incomplete despite repeat operations. Radiation in combination with surgery is then often used. High radiation doses (i.e. with proton beams) are required for local control. The role of chemotherapy or targeted therapies is still under investigation. ## Prognosis Prognosis depends on the extent and completeness of the tumor excision. Long-term follow-up is required because of the high rate of recurrence of these tumors. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Chordoma	c0008487	29,910	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178	2021-01-23T17:56:32	{"gard": ["1303"], "mesh": ["D002817"], "omim": ["215400"], "umls": ["C0008487"], "icd-10": ["C76.7"], "synonyms": ["Notochordal sarcoma"]}
This article is about horizontal overlap between upper and lower teeth. For vertical overlap, see Overbite. Overjet Overjet or horizontal overlap. SpecialtyDentistry Overjet is the extent of horizontal (anterior-posterior) overlap of the maxillary central incisors over the mandibular central incisors. In class II (division I) malocclusion the overjet is increased as the maxillary central incisors are protruded. Class II Division I is an incisal classification of malocclusion where the incisal edge of the mandibular incisors lie posterior to the cingulum plateau of the maxillary incisors with normal or proclined maxillary incisors (British Standards Index, 1983). There is always an associated increase in overjet. In the Class II Division 2 incisal classification of malocclusion, the lower incisors occlude posterior to the cingulum plateau of the upper incisors and the upper central incisors are retroclined. The overjet is usually minimal but it may be increased. ## Contents * 1 Signs and symptoms * 1.1 Class II Div I * 2 Classification of the bad bite * 2.1 Incisal Edge-to-Edge * 2.2 Incisal Anterior Open Bite * 2.3 Incisal Class II Div I * 2.4 Incisal Class II Div 2 * 2.5 Causal propositions for orthodontic malocclusion and incisal crowding states * 3 Diagnosis * 4 Health complications * 5 Treatment * 5.1 Class II div 1 * 5.1.1 Early intervention * 5.1.2 Functional appliances * 5.1.2.1 Twin block appliances * 5.1.2.2 Herbst appliance * 5.1.2.3 Headgear * 5.1.3 Fixed appliances * 5.1.4 Late intervention * 6 Epidemiology * 6.1 Class II Div I * 7 History * 7.1 Class II div 1 * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] ### Class II Div I[edit] Benefits associated with orthodontic treatment include a reduction in the susceptibility to caries, periodontal disease and temporomandibular joint dysfunction, whilst also improving speech and masticatory function. However, the supporting evidence is equivocal.[1][2] It may be assumed that correction of an increased overjet will potentially reduce the risk of trauma, as it has been shown that individuals with an overjet greater than 3 mm (0.12 in) are twice as likely to suffer injury to their upper incisors.[3] Table showing the relationship between size of overjet and prevalence of traumatised anterior teeth[4] Overjet (mm) Incidence (%) 5 22 9 24 >9 44 The meta-analysis undertaken in a recent Cochrane review found that 'early orthodontic treatment for children with prominent upper front teeth is more effective in reducing the incidence of incisal trauma than providing one course of orthodontic treatment when the child is in early adolescence'.[5] A number of studies have found that the presence of malocclusion can have a significant impact on an individual’s quality of life and result in reduced self-esteem.[6] Prominent upper incisors may be a target for teasing and bullying and it is now accepted that one reason for undertaking treatment of malocclusion is the psychosocial benefit that it accrues.[7] ## Classification of the bad bite[edit] In 1895 Edward Angle, a mid-North American dentist, published a book on the classification of bad bites - a term he latinised and popularised as malocclusion. The modern discipline of orthodontics was begun by the establishment of the Angle classification of adult first molar relationship. This established that all forms of a bad bite were premised on a natural redundancy of premolar, and in particular third molar teeth (wisdom teeth). Eventually the dual dental specialties of orthodontic and oral surgery were popularised and came to work together in coordinating adelescent dental crowding by the treatment duopoly of extracting excessive teeth, and orthodontically straightening the remaining - especially front - teeth. Once an assessment is made that there is dental crowding (a bad bite), the Angle classification of malocclusion is based only on an assessment of relative position of the upper and lower first adult molar. Class I dental crowding is with a normal molar relationship. Class II dental crowding is with a molar relationship where the relative position of the lower molar is behind the Class I position. Class III is with the abnormal molar position being forward of the normal Class I position. Classifying incisal relationship in the bad bite is made in profile and only of the relative positions upper and lower central incisors. The terms used relate to visual or radiological (lateral cephalometric) measurements of dental overjet and dental overbite. ### Incisal Edge-to-Edge[edit] This describes the incisal relationship where there is both zero overjet and zero overbite, and where the incisal edge of both uppwe and lower central incisors are in direct edge to edge contact. It is considered a traumatic bite in that it accelerates wear and abnormal acquired incisal form, and unaesthetic smile development. ### Incisal Anterior Open Bite[edit] This is where there is no contact between the biting surfaces of the incisor teeth. This prevents both biting and incising. There is a negative incisal overbite, and is independent of overjet measurement. ### Incisal Class II Div I[edit] This incisal relationship is usually where there is a long overjet and deep incisal overbite, and is always in company with a Class II first molar relationship. Instances of long incisal overjet are also associated with Class I or Class III molar relationships. ### Incisal Class II Div 2[edit] This incisal relationship is where there is virtually no incisal overjet, and a very deep incisal overjet, and is always associated with a class II molar relationship. In essence, Class II Div 2 malocclusion is a common description given to extreme crowding, or backward collapse of the anterior front teeth, and is a common presenting complaint by concerned parents of their child's tooth crookedness. Class II malocclusion, either with orominent upper incisors (Class II division 1) or exceeedingly crowded and collapsed upper incisors (Class II division 2) are the dominant presenting orthodontic malocclusionntypes that present to orthodontic offices works wide. They are also the dominant pattern of dental crowding leading to orthodontic premolar extractions, and later impacted wisdom teeth removal by oral surgeons. ### Causal propositions for orthodontic malocclusion and incisal crowding states[edit] The Angle classification is merely a means of describing common states or forms or patterns of adolescent dental crowding. These patterns emerge as baby (deciduous) teeth are lost, and a child's face and overall body are growing. Thus the development of malocclusion and of dental crowding have come to be rationalised as distinct conditions defined by what was originally an arbitrary and simple 19th century classification. As the myth of the veracity of the classification system became entrenched more formally as orthodontic diagnoses, orthodontists attempted to apply epidemiological study as to why these patterns may exist or have become prevalent in modern society. The overriding premises of the overwhelming majority of these studies are that 1\. Malocclusion classifications of dental crowding are in fact diagnostic or disease states, and exist mostly and independently of any other medical condition 2\. That malocclusion occurs as a feature or expression of childhood or adolescent growth, and that treatments can be directed at modifying growth and thus improve the abnormal development of malocclusion 3\. That dental crowding is due to a redundant number of human teeth, and that this redundancy is due to a modern softer diet compared to a more primitive past, and is more conservatively managed by a combination of dental extractions and orthodontic treatments 4\. That being a disease, and that malocclusion and dental crowding is a feature of tooth number redundancy, or oversize of permanent teeth, that epidemiological studies of the natural rates of the various classification states can be made. 5\. That there are no other common associated features of malocclusion outside of the dental relationship. Malocclusion exists as a dental disease specific to itself; and that if there are other conditions or anatomical observations, they exist only to aggravate or impact upon the complexity of the malocclusion, or the orthodontic treatment of it. In orthodontic studies, a number of genetic and environmental factors are postulated to contribute to a Class II division 1 malocclusion:[8] * Skeletal factors − it is generally agreed that the majority of patients with a Class II malocclusion have some degree of skeletal imbalance with either a retrognathic mandible, protrusive maxilla or, most commonly, a combination * Dental factors − crowding, spacing, proclined maxillary anterior teeth * Soft tissue factors − incompetent lips, lower lip trap, tongue thrust * Habits − digit-sucking, use of pacifiers ## Diagnosis[edit] Whenever orthodontic treatment is to be considered, it is essential to carry out a complete patient assessment to get a clear picture of the patient's medical and dental condition before any irreversible treatment (such as extractions) are carried out or the orthodontic treatment causes more harm than benefit. The assessment is also key in establishing the correct diagnosis and likely cause of the malocclusion. This assessment should include the following:[9] * Medical History * Patient's Complaint * History of Trauma * Habits * Extra-Oral Examination * Intra-Oral Examination * Radiograph * Indication of Orthodontic Treatment Need Scoring * Justification for Treatment * Treatment Aims * Treatment Plan The Extra Oral Examination Should Include:[9] * Skeletal Pattern * Anterior-Posterior * Vertical Dimension * Transverse * Soft Tissues * Temporomandibular Joint Examination The Intra Oral Examination Should Include: * Dental health * Lower arch * Upper arch * Teeth in occlusion * Radiographs The presence of dental disease precludes any active orthodontic treatment, even if the malocclusion is severe. This is because orthodontic appliances accumulate plaque and combining this with a high carbohydrate diet and poor oral hygiene can result in extensive decalcification of the teeth and accelerated bone loss if you try to move the teeth when there is active gingivitis and periodontal disease.[10] Overjet is measured from the labial surface of the most prominent incisor to the labial surface of the mandibular incisor. Normally, this measurement is 2–4 mm (0.079–0.157 in). If the lower incisor is anterior to the upper incisors, the overjet is given a negative value.[11] In the UK, an overjet is generally described as increased if it is >3.5 mm (0.14 in). The Index of Orthodontic Treatment Need rates overjet highly on its weighting system, second behind missing teeth. It then grades severity of overjet as:[12] * Grade 3, Borderline need for treatment = increased overjet 3.5 mm (0.14 in) < 6 mm (0.24 in) * Grade 4, Need for treatment = increased overjet 6 mm (0.24 in) < 9 mm (0.35 in) * Grade 5, Need for treatment = increased overjet > 9 mm (0.35 in). Radiographs can aid your diagnosis. Any radiographs taken must be clinically justified in accordance with the IRMER Regulations 2000. Radiographs may help by giving you more information on:[11] * Presence or absence of teeth * Stage of development of adult dentition * Root morphology of teeth * Presence of ectopic or supernumerary * Presence of dental disease * Relationship of the teeth to the skeletal dental bases and their relationship to the cranial base. * Radiographs commonly used in orthodontics assessment include: * Dental panoramic tomography * Cephalometric lateral skull radiograph * Upper standard occlusal radiographs * Periapical Radiographs * Bitewing Radiographs ## Health complications[edit] Untreated overjet can cause the following health complications: * Chewing and speaking difficulties. * Sleep apnoea. * Jaw pain and headaches, that may contribute to the development of Temporomandibular Joint Disorder (TMD). * Gum damage (when teeth contact the gum). * Fractured, worn teeth. * Chapped lips and dry mouth.[13][14][15] ## Treatment[edit] ### Class II div 1[edit] #### Early intervention[edit] Timing of referral for Class II division 1 children is extremely important as late referral may limit the treatment options available, particularly attempts at growth modification. On the other hand, recent evidence strongly suggests that there are few advantages to early treatment (undertaken as a first stage of treatment in the early mixed dentition) for Class II division 1 malocclusion and that starting treatment too early may actually reduce success and long-term outcome. It is therefore now recommended that a single phase of treatment is undertaken once the patient is in the late mixed dentition or early permanent dentition. This is the ideal time for orthodontic referral for the majority of Class II growing patients. The exceptions to this are if there is a significant risk of incisal trauma due to greatly increased overjet, or if the child is being teased or bullied at school. For these patients, early treatment may be indicated and an earlier referral should be made for an orthodontic opinion.[5] Any habits must be completely stopped before treatment can be undertaken otherwise treatment is likely to be unsuccessful or relapse after completion.[16] Early treatment is defined as treatment provided in the early mixed dentition, usually between the ages of 7−9 years. This has also been called two-phase treatment, whereby a second separate definitive phase of treatment is undertaken when the patient reaches the permanent dentition. Late treatment, or one-phase treatment, is a single course of comprehensive treatment undertaken in the permanent dentition around the age of 12−14 years. Early treatment has been advocated to reduce the risk of incisal trauma, improve psychosocial well-being and reduce bullying.[8] It is also been claimed that early treatment can lead to superior outcomes in terms of efficiency, making definitive treatment easier, and efficacy, in that the final result is superior.[17] Further assertions have been made for early treatment in terms of improved skeletal pattern, and reduced need for extractions and orthognathic surgery; however, these have been disproved in recent high quality clinical trials. One high-quality randomized controlled trial compared early and late treatment of Class II division 1 malocclusion with functional appliances. Although differences were found between treated patients and untreated controls after the initial phase, following a second phase of treatment there was no lasting difference in terms of skeletal pattern, extraction pattern or self-esteem. Detrimental effects were seen in those who had undergone early treatment; more appointments, longer total treatment time and associated costs, and a worse final occlusal outcome as indicated by the Peer Assessment Rating (PAR).[18] #### Functional appliances[edit] Functional appliances are a range of fixed and removable appliances that cause their effect by influencing the muscle groups that control position and function of the mandible, transmitting forces to the dentition and basal bone.[17] The result is a decrease in overjet and correction of the buccal segment relationship, caused by both skeletal and dental changes. A recent study quantified the changes seen after a first stage of functional treatment. Skeletal change was attributed to restraint of maxillary forward and downward growth and increased growth and forwarding positioning of the mandible, contributing to 27% of the overjet reduction and 41% of buccal segment correction. Dental changes included retroclination of maxillary incisors, proclination of mandibular incisors and mesial eruption of mandibular molars. The majority of overjet reduction and buccal segment correction is dental, 73% and 59%, respectively.[19] Soft tissue changes include elimination of lip trap and improved lip competence. It has also been postulated that tongue activity and soft tissue pressures from the lips and cheeks might be altered, enhancing the soft tissue environment.[20] ##### Twin block appliances[edit] The Twin Block appliance has been used in most studies evaluating functional appliance treatment as it is considered to be the 'gold standard' against which other appliances should be tested. When compared to other functional appliances, the Twin Block appliance was found to produce a statistically significant reduction in skeletal base discrepancy (ANB = -0.68 degrees; 95% CI -1.32 to -0.04) when compared to other functional appliances, although there was no significant effect from the type of appliance on the final overjet.[5] The Twin Block has also been shown to cause clinically significant beneficial changes to the soft tissues.[21] There are problems associated with the Twin Block including excessive lower incisor proclination, a significant failure-to-complete rate of 25%,[22] and a breakage rate of up to 35%. Lower incisor proclination occurs with most functional appliances and this must be considered during treatment planning and monitored throughout treatment. Twin Block appliances can also cause an increase in vertical dimension, which may be desirable in some cases but may not be beneficial in patients with an increased lower anterior face height. In these patients, careful control of the vertical dimension should be planned.[23] ##### Herbst appliance[edit] The success rate of the Herbst appliance, often considered to be a 'compliance-free' appliance, was found to be much higher than the Twin Block in one study, with a failure-to-complete rate of 12.9%. This is approximately half that of the Twin Block so may be considered in patients where compliance is predicted to be difficult. However, the Herbst is considerably more expensive and demonstrated a higher breakage rate so that the benefits of reduced compliance requirements must be balanced against this.[24] ##### Headgear[edit] Headgear exerts force to the dentition and basal bones via extra-oral traction attached directly to bands on the teeth or to a maxillary splint or functional appliance. The effects are mainly dento-alveolar with some skeletal effect through restriction of maxillary downward and forward growth.[25] Several studies found an additional small effect on mandibular growth when headgear is used in conjunction with an anterior bite plane.[26] The effect of headgear treatment, as early treatment, was compared to one-phase treatment, carried out later, in a study of two trials. Both found a significant reduction in overjet and improvement in skeletal relationship after headgear treatment.[27] There was no difference in any outcomes that could be attributed to treatment timing, with the exception of risk of trauma where the later treatment group showed twice the risk of incisal trauma.[5] The Cochrane review summarizes that 'no significant differences, with respect to final overjet, ANB, or ANB change, were found between the effects of early treatment with headgear and the functional appliances'. However, headgear is highly reliant on good patient compliance, with 12−14 hours a day of wearing required to achieve the effects described. #### Fixed appliances[edit] Fixed appliances can be used alone or in combination with extractions or temporary anchorage devices to retract the maxillary teeth to correct a Class II division 1 malocclusion by dental means only. Class II intermaxillary elastics are used to retract the maxillary teeth against the mandibular teeth, with reciprocal mesialization and proclination of the mandibular teeth. #### Late intervention[edit] Cochrane review showed that, at the end of all treatment, no significant differences were found in overjet, skeletal relationship or PAR score between the children who had a course of early treatment, with either headgear or functional appliances, and those who had not received early treatment. The only outcome to be affected by treatment timing was the incidence of new incisal trauma, which was significantly reduced by early treatment with either functional appliance or headgear (odds ratio 0.59 and 0.47, respectively). The Cochrane review concludes 'the evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is more effective in reducing the incidence of incisal trauma than providing one course in early adolescence. There appears to be no other advantage for providing early treatment'.[5] ## Epidemiology[edit] ### Class II Div I[edit] This malocclusion is common, with an estimated prevalence of 15−20%.[28] There is racial variation with Class II division 1 more common in Caucasian than Latin American, Middle Eastern and Asian populations, and lowest in Black racial groups.[5] ## History[edit] ### Class II div 1[edit] Functional appliances: The first reported use of a mandibular positioning device was the 'Monobloc' by Dr Robin, in France in 1902, for neonates with under-developed mandibles. This was followed by the first functional device for growth modification, the Andresen Activator, in Norway in 1908. A number of German appliances, such as the Herbst appliance in 1934, the Bionator appliance in the 1950s and the Functional Regulator in 1966 followed on. The table below summarizes the various types of functional appliance that are currently in use. The Twin Block, first described by Clark in 1982, consists of two blocks with interlocking 70° bite planes, which cause forward posturing of the mandible. ## See also[edit] * Overbite * Malocclusion * Retrognathia ## References[edit] 1. ^ Hunt NP. Why should the NHS continue to fund orthodontic treatment in the current financial climate? Royal College of Surgeons of England: Faculty Dental Journal 2013; 4: 16−19. 4. 2. ^ Burden DJ. Oral health-related benefits of orthodontic treatment. Semin Orthod 2007; 13: 76−80. 3. ^ Nguyen QV et al. A systematic review of the relationship between overjet size and traumatic dental injuries. Eur J Orthod 1999; 21: 503−515. 4. ^ Roberts-Harry D & Sandy J. Orthodontics. Part 1: Who needs orthodontics? British Dental Journal 195. 433. (25 October 2003) 5. ^ a b c d e f Thiruvenkatachari B et al. Orthodontic treatment for prominent upper front teeth (Class II malocclusion) in children. Cochrane Database Syst Revs 2013; 11: CD003452. 6. ^ Rusanen J et al. Quality of life in patients with severe malocclusion before treatment. Eur J Orthod 2010; 32: 43−48. 7. ^ Seehra J, Newton JT, Dibiase AT. Interceptive orthodontic treatment in bullied adolescents and its impact on self-esteem and oral-health-related quality of life. Eur J Orthod 2013; 35(5): 615−621. 8. ^ a b Barber, S.K., Forde, K.E. & Spencer, R.J. 2015, "Class II division 1: an evidence-based review of management and treatment timing in the growing patient", Dental Update, vol. 42, no. 7, pp. 632-642. 9. ^ a b Roberts-Harry D & Sandy J. 2003. Orthodontics. Part 2: Patient Assessment and Examination I. British Dental Journal 195, 489–493 (08 November 2003) 10. ^ Roberts-Harry D & Sandy J. 2003. Orthodontics. Part 3: Patient assessment and examination II. British Dental Journal 195, 563-565 (22 November 2003). 11. ^ a b Mitchell, Laura. 2013. An Introduction to Orthodontics. 4th ed. Oxford: Oxford University Press. 12. ^ British Orthodontic Society. 2014. Quick Reference Guide to Orthodontic Assessment and Treatment. [Online Guide]. [viewed 7 January 2018] Available from https://www.bos.org.uk 13. ^ Mandal, Ananya (28 June 2019). "What is Orthodontics?". 14. ^ "What's the difference between an overbite and an overjet?". 12 January 2020. 15. ^ "Malocclusion - difference between overbite, overjet and open bite". 2 June 2017. 16. ^ Proffit WR, Fields HW, Sarver DM, eds. Contemporary Orthodontics 5th edn. Oxford: Elsevier Mosby, 2013. 17. ^ a b Proffit WR, Tulloch JF. Preadolescent Class II problems: treat now or wait? Am J Orthod Dentofacial Orthop 2002; 121: 560−562 18. ^ O’Brien K et al. Early treatment for Class II Division 1 malocclusion with the Twin-block appliance: a multi-center, randomized, controlled trial. Am J Orthod Dentofacial Orthop 2009; 135: 573−579. 19. ^ O’Brien K et al. Effectiveness of early orthodontic treatment with the Twin-block appliance: a multicenter, randomized, controlled trial. Part 1: Dental and skeletal effects. Am J Orthod Dentofacial Orthop 2003; 124: 234−243; quiz 339. 20. ^ McDowall RJ, Waring DT. Class II growth modification: evidence of absence or absence of evidence. Orthod Update 2010; 3: 44−50. 21. ^ Morris DO, Illing HM, Lee RT. A prospective evaluation of Bass, Bionator and Twin Block appliances. Part II − The soft tissues. Eur J Orthod 1998; 20: 663−684. 22. ^ O’Brien K et al. Effectiveness of treatment for Class II malocclusion with the Herbst or twin-block appliances: a randomized, controlled trial. Am J Orthod Dentofacial Orthop 2003; 124: 128−137 23. ^ Lee RT, Kyi CS, Mack GJ. A controlled clinical trial of the effects of the Twin Block and Dynamax appliances on the hard and soft tissues. Eur J Orthod 2007; 29: 272−282. 24. ^ O’Brien K et al. Effectiveness of treatment for Class II malocclusion with the Herbst or twin-block appliances: a randomized, controlled trial. Am J Orthod Dentofacial Orthop 2003; 124: 128−137. 25. ^ Ghafari J et al. Headgear versus function regulator in the early treatment of Class II, division 1 malocclusion: a randomized clinical trial. Am J Orthod Dentofacial Orthop 1998; 113: 51−61. 26. ^ Keeling SD et al. Anteroposterior skeletal and dental changes after early Class II treatment with bionators and headgear. Am J Orthod Dentofacial Orthop 1998; 113: 40−50. 27. ^ Tulloch JF, Proffit WR, Phillips C. Outcomes in a 2-phase randomized clinical trial of early Class II treatment. Am J Orthod Dentofacial Orthop 2004; 125: 657−667. 28. ^ Todd JE, Dodd T. Children’s Dental Health in the United Kingdom. London: HMSO, 1985. ## External links[edit] Classification D * ICD-10: K07.2 * ICD-9-CM: 524.26 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Overjet	c0596028	29,911	wikipedia	https://en.wikipedia.org/wiki/Overjet	2021-01-18T18:38:43	{"mesh": ["D057887"], "icd-9": ["524.26"], "icd-10": ["K07.2"], "wikidata": ["Q7113715"]}
Hemeralopia SpecialtyOphthalmology Hemeralopia (from Greek ημέρα hemera, "day", and αλαός alaos, "blindness") is the inability to see clearly in bright light and is the exact opposite of nyctalopia (night blindness), the inability to see clearly in low light. Hemera was the Greek goddess of day, and Nyx was the goddess of night. However, it has been used in an opposite sense by many non-English-speaking doctors.[1] It can be described as insufficient adaptation to bright light. It is also called "heliophobia" and "day blindness".[2] In hemeralopia, daytime vision gets worse, characterised by photoaversion (dislike/avoidance of light) rather than photophobia (eye discomfort/pain in light), which is typical of inflammations of eye. Nighttime vision largely remains unchanged due to the use of rods as opposed to cones (during the day), which are affected by hemeralopia and in turn degrade the daytime optical response. Hence, many patients feel they see better at dusk than in daytime. ## Contents * 1 Causes * 2 Management * 3 See also * 4 References ## Causes[edit] Hemeralopia is known to occur in several ocular conditions. Cone dystrophy and achromatopsia, affecting the cones in the retina, and the anti-epileptic drug trimethadione are typical causes. Adie's pupil, which fails to constrict in response to light; aniridia, which is absence of the iris; and albinism, where the iris is defectively pigmented, may also cause this. Central cataracts, due to the lens clouding, disperses the light before it can reach the retina and is a common cause of hemeralopia and photoaversion in the elderly. Cancer-associated retinopathy (CAR), seen when certain cancers incite the production of deleterious antibodies against retinal components, may cause hemeralopia. Another known cause is a rare genetic condition called Cohen syndrome (aka Pepper syndrome). Cohen syndrome is mostly characterized by obesity, mental retardation and craniofacial dysmorphism due to genetic mutation at locus 8q22–23. Rarely, it may have ocular complications such as hemeralopia, pigmentary chorioretinitis, optic atrophy or retinal/iris coloboma, having a serious effect on the person's vision. Yet another cause of hemeralopia is uni- or bilateral postchiasmatic brain injury.[3] This may also cause concomitant nyctalopia.[3] ## Management[edit] People with hemeralopia may benefit from sunglasses. Wherever possible, environmental illumination should be adjusted to comfortable level.[3] Light-filtering lenses appear to help in people reporting photophobia.[3] Otherwise, treatment relies on identifying and treating any underlying disorder. ## See also[edit] * Adaptation (eye) ## References[edit] 1. ^ Ohba N, Ohba A (December 2006). "Nyctalopia and hemeralopia: the current usage trend in the literature". Br J Ophthalmol. 90 (12): 1548–9. doi:10.1136/bjo.2006.097519. PMC 1857511. PMID 17114591. 2. ^ Gördüren, S. (1950). "Day-Blindness". British Journal of Ophthalmology. 34 (9): 563–567. doi:10.1136/bjo.34.9.563. PMC 1323631. PMID 14777856. 3. ^ a b c d Page 96 in: Zihl, Josef (2000). Rehabilitation of visual disorders after brain injury. East Sussex: Psychology Press. ISBN 0-86377-898-4. Classification D * ICD-10: H53.1 * ICD-9-CM: 368.6 * OMIM: 310500 * MeSH: D014780 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hemeralopia	c0018975	29,912	wikipedia	https://en.wikipedia.org/wiki/Hemeralopia	2021-01-18T18:39:53	{"mesh": ["D014786"], "icd-9": ["368.6"], "icd-10": ["H53.1"], "wikidata": ["Q7757581"]}
Ulnar-mammary syndrome (UMS) is a rare developmental disorder characterized by ulnar defects, mammary and apocrine gland hypoplasia and genital anomalies. Delayed puberty dental anomalies, short stature and obesity have also been described. ## Epidemiology The prevalence is unknown. Approximately 117 cases have been reported in the literature to date. ## Clinical description Upper limb defects are the most common presenting feature of UMS at birth. The limb phenotype ranges from normal limbs, hypoplasia of the distal phalanges of the little fingers or camptodactyly, to absent digits, absent or hypoplastic ulna and a reduced humerus. Abnormalites may be bilateral, but are frequently asymmetric and lower limb defects have not been reported. The variable mammary and apocrine features of UMS may not be apparent until puberty and include mammary gland tissue hypoplasia (leading to absence of breast development and the inability to lactate), areolar or nipple hypoplasia, inverted nipples and apocrine gland hypoplasia (that can result in diminished perspiration and body odor). Associated absence of axillary hair has also been described. Shared facial features of UMS include a wide face tapering to a prominent chin, a broad nasal tip, and a wide nasal base. Genital defects can include micropenis, shawl scrotum, cryptorchidism and imperforate hymen. Delayed puberty, particularly in males, is noted. Short stature is also common in individuals with UMS and a pituitary endocrine deficiency has been suggested as a possible cause. Abnormalities of the teeth with ectopic, hypoplastic or absent canines have been noted in a number of individuals with UMS. Cardiac defects (ventricular septal defects or conduction abnormalities) have been reported in a few cases. ## Etiology UMS is caused by mutations in the TBX3 gene (12q24.21). TBX3 is a member of the T-box gene family. These genes encode transcription factors that have been shown to be important in embryologic development and in the morphogenesis of multiple organ systems. ## Genetic counseling UMS is an autosomal dominant condition commonly reported in families with inter- and intra-familial variability in expression. Genetic counseling is possible. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ulnar-mammary syndrome	c1866994	29,913	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3138	2021-01-23T18:10:07	{"gard": ["118"], "mesh": ["C536937"], "omim": ["181450"], "umls": ["C1866994"], "icd-10": ["Q71.8"], "synonyms": ["Pallister ulnar-mammary syndrome", "Schinzel syndrome", "UMS"]}
Paraneoplastic Pemphigus SpecialtyDermatology Paraneoplastic pemphigus (PNP) is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes. While patients with malignant and benign tumors are both at risk, malignancy is associated with high mortality rates (near 90%). Current treatment focuses on general wound healing and administering corticosteroids, which has not demonstrated a high success rate. Recent research developments aim to treat the underlying tumor in order to alleviate the symptoms of PNP. ## Contents * 1 Signs and symptoms * 2 Mechanism * 2.1 Underlying cause * 2.2 Mechanism behind display of major symptoms * 3 Diagnosis * 3.1 Microscopy * 3.2 Direct immunofluorescence testing * 3.3 Follow-up tests for confirmation * 3.3.1 Indirect immunofluorescence (IDIF) * 3.3.2 Assays * 3.4 Similar diseases with overlapping symptoms * 4 Treatment * 4.1 Wound healing * 4.2 Medication * 4.2.1 Prednisone * 4.2.2 Azathioprine * 4.2.3 Ciclosporin * 4.2.4 Cyclophosphamide * 5 Prognosis * 5.1 Quality of life/ Life expectancy * 5.2 Risk Factors * 6 Recent research * 7 References * 8 External links ## Signs and symptoms[edit] While the presence of lesions is the denominator among patients with PNP, the characteristics of the lesions differ. The five clinical presentations of lesions associated with PNP include: * "Pemphigus-like": Flaccid blister (discrete), crusts over the raw exuding skin lesions * "Pemphigoid-like": Tense blister(s) on brick red erythema * "Erythema multiforme-like": Severe polymorphic skin and/or mucous membrane lesions * "Graft-vs.-host disease-like": Widespread lichenoid eruption with severe mucous membrane involvement * "Lichen planus-like": Small red flat-topped scaly papules It is most common that mucous membrane lesions of the oral cavity are presented first. They can involve the oropharynx, nasopharynx, tongue, and vermilion (red portion) of the lips. They are also known to develop in the conjunctiva of the eye, anogenital (perineum) region, and esophagus. Cutaneous lesions tend to follow the onset of mucosal lesions. The blisters often erupt in waves, usually affecting the upper trunk, head, neck, and proximal extremities. Pemphigoid-like lesions are seen more often on the extremities. Lichenoid lesions are more common among children, presenting on the trunk and limbs, ranging from small red scaly papules to extensive violet to brown papules extending to the face and neck. Within the spectrum of lichenoid presentations are wounds that have features of erythema multiforme and graft-vs.-host disease. Scaly lesions on the palms of the hand and soles of the feet have been noted to coincide with the lichenoid lesions. Lesions of varying morphology may present simultaneously and transform from one type to another as the disease progresses.[1] ## Mechanism[edit] ### Underlying cause[edit] PNP is ultimately caused by the presence of a tumor. There is a strong association between the development of PNP and malignancy of the tumor. However, it is not uncommon for the tumor to be benign, as in the case of afflictions such as thymoma and Castleman's disease. Only one patient without a tumor has met the diagnostic criteria for PNP. However, they rapidly reached their demise and it is suggested they may have had an undiagnosed tumor.[1] ### Mechanism behind display of major symptoms[edit] The underlying tumor causes circulating and tissue-bound antibodies to direct themselves against antigens in the plakin family, which are involved in the intracellular attachment structures in various levels of the skin/respiratory tract/membranes (keeping skin tissue together throughout the body). The number of target antigens varies on a case by case basis. The variability is likely what accounts for the different presentations of PNP. Through immunoprecipitation, target antigens have been found to include desmoglein-3, desmoglein-1, envoplakin, periplakin, desmoplakin 1, desmoplakin 2, and bullous pemphigoid antigen I.[citation needed] The precise mechanism for how tumors are able to induce autoantibodies toward the plakin proteins is unknown. Suggested theories include tumor production of plakin proteins which initiate an autoimmune response against them, and cross-reactivity of tumor antigens and epidermal antigens.[2][3] Once the molecules that hold the various levels of the membranes together are attacked, they are unable to function properly, and the tissue breaks apart. This is manifested as the associated blistering and lesions of PNP.[citation needed] ## Diagnosis[edit] In order to diagnose paraneoplastic pemphigus, several tests may be performed. Initially, samples are obtained via skin biopsy for routine microscopy and direct immunofluorescence (DIF) testing. The skin sample needs to be obtained from an unaffected area adjacent to a lesion. Testing in more detail follows depending on the results from the DIF. Prompt diagnosis of PNP is crucial due to the high mortality rate of the disease. [4] Camisa and Helm revised the original criteria from Anhalt et al.[5] into major and minor signs indicating PNP:[6] Major: * Polymorphic mucocutaneous eruption * Concurrent internal tumor * Serum antibodies with a specific immunoprecipitation pattern Minor: * Histologic evidence of acantholysis (loss of intercellular connections leading to breaking apart of the skin; lesion) * Direct immunofluorescence showing intercellular and basement membrane staining * Indirect immunofluorescence staining with rat bladder epithelium ### Microscopy[edit] Microscopy of the skin sample obtained from the biopsy is used to detect the presence of cleavage within the dermis, epidermal acantholysis (breaking apart of the skin), dyskeratotic keratinocytes and vacuolar changes in the layers of the skin, interfacial dermatitis, and epidermal exocytosis. Presentation of these characteristics suggests PNP.[1] ### Direct immunofluorescence testing[edit] The presence of Immunoglobulin G, A, or M in the epidermis is normal. Detection in other locations such as intercellular and areas below the epidermis (subepidermal), as well as along the dermoepidermal junction (area that joins the epidermis and dermis), suggests paraneoplastic pemphigus.[citation needed] ### Follow-up tests for confirmation[edit] #### Indirect immunofluorescence (IDIF)[edit] Patients with high concentration of antibodies show intercellular, intraepidermal antibodies as well as along the dermoepidermal junction. Patients with low concentration of antibodies only present with them inside the cells (intercellular).[citation needed] If the results are negative, perform the additional assays regardless. Cases have been confirmed that reported with initial negative DIF and IDIF tests.[citation needed] #### Assays[edit] Immunoprecipitation, immunoblotting and enzyme-link immunosorbent assay (ELISA) Poot et al. 2013 determined that immunoprecipitation for antibodies against envoplakin and periplakin or alpha2-macroglobulin-like–1 is the most sensitive test. However, alpha2-macroglobulin-like-1 can also be detected in patients with toxic epidermal necrosis.[2] ### Similar diseases with overlapping symptoms[edit] Bullous Pemphigoid, Cicatricial Pemphigoid, Drug Eruptions. Epidermolysis Bullosa, Epidermolysis Bullosa Acquisita, Erythema Multiforme, Lichen Planus, pemphigus vulgaris, Stevens–Johnson syndrome and toxic epidermal necrolysis.[1][4][7] PNP is most commonly mistaken for pemphigus vulgaris, due to the extreme similarities of the lesions that develop. However, the difference lies in the specificity of the autoreactive antibodies in each case.[8] ## Treatment[edit] ### Wound healing[edit] Initial treatment involves addressing any existing infections that may have occurred due to the broken state of the skin. Existing wounds are treated with warm compresses, non-adherent (non-stick) dressing, and topical antibiotic ointment. Immunosuppressive agents are administered in attempt to decrease blistering; this is not often effective. The first medication given aiming to heal the wounds are high dose corticosteroids. This is followed by steroid sparing agents which may reduce steroid intake and therefore lessen the side effects. Skin lesions are more likely to respond to this line of treatment than mucosal lesions. However, a high level of caution is advised in patients with a confirmed malignancy, where immunosuppression is vital and dictates treatment options. If the initial therapy fails to control the symptoms of PNP, and the condition of the patient deteriorates, a more aggressive approach may be necessary.[9] ### Medication[edit] #### Prednisone[edit] Prednisone is an immunosuppressive agent which affects all of the organ systems. Effects on the cellular level include cell activation, replication, differentiation, and mobility. The overall goal is to decrease blistering (inhibition of immediate and delayed hypersensitivity) through decreasing the production of autoantibodies. In order to suppress the production of antibodies, higher doses must be administered. Lesser doses can be prescribed in order to achieve suppression of monocyte function.[10] #### Azathioprine[edit] Azathioprine is a steroid-sparing agent used in combination with Prednisone. It functions by inhibiting RNA and DNA synthesis.[11] #### Ciclosporin[edit] Ciclosporin is an immunosuppressive agent most often used in organ transplantation that has demonstrated to be effective with skin disorders. It functions by lessening production of autoantibodies and therefore diminishing the development of blisters and erosions. The mechanism of action is by inhibiting the production of T lymphocytes and lymphokines.[12] #### Cyclophosphamide[edit] Cyclophosphamide is an immunomodulator used in combination with systemic steroids to remove bone marrow. This is followed by transplanting peripheral blood stem cells.[13] ## Prognosis[edit] ### Quality of life/ Life expectancy[edit] If the lesions are mild, the patient will be subject to a good deal of pain. If the lesions are severe, the overall quality of life is devastating. The impaired skin barrier function commonly leads to localized infection, which sepsis and death may follow. The pain from the oral and pharyngeal ulcers interfere with eating, which can compromise nutritional health.[citation needed] The general prognosis for PNP is poor. It is more hopeful if the tumor is benign, but in the case of malignant tumors, the mortality rate is roughly 90%. The two most commonly associated types of tumors are non-Hodgkin lymphoma and chronic lymphocytic lymphoma; nearly all of these patients die within two years of diagnosis. This is attributed to the effects of the tumor combined with the negative side effects of the medication administered to treat PNP.[citation needed] Roughly 1/3 of the deaths from PNP stem from pulmonary insufficiency which is brought about by the action of PNP on the respiratory mucosa. It manifests as dyspnea and progresses to bronchiolitis obliterans (non-reversible obstructive lung disease) via an unknown mechanism.[citation needed] ### Risk Factors[edit] As PNP is ultimately caused by the presence of a tumor, it is not contagious. There is no known way to predict who will become afflicted with it. Patients with cancer are therefore a group at risk. Although PNP has been known to affect all age groups, it is more likely to afflict middle-aged to older patients.[14] ## Recent research[edit] The Development of ELISA testing for specific diagnosis of PNP was released in 2009. The research focuses on the specific determination of autoantibodies involved in the mechanism of PNP. Specifically, antibodies against envoplakin and periplakin were being investigated.[15] Further use of ELISA testing on these antibodies confirmed the presence of anti-envoplakin and anti-periplakin autoantibodies in patients with PNP.[16] Further research in 2013 outlined the various types of assays that could be used to determine which antibodies were involved in PNP. Demonstration of certain antibodies in the serum was named as the basis for diagnosis of PNP. This piece labeled PNP as a "multiorgan disease characterized by antibodies against plakins, desmogleins and the α2-macroglobulin-like-1 (A2ML1) protein, in association with an underlying neoplasm".[2] A study concluded in 2009, summarized in 2010, surrounded the surgical removal of the associated tumor as a means to treat PNP. While 7/22 of the subjects perished due to resulting infection from the body's inability to heal itself after surgery, the other 15 cases survived. This study outlined the importance of early detection and prompt treatment as of utmost important in the treatment of PNP.[17] In 2011, a case study of a woman with ulcers on the back of her leg reported as being diagnosed with PNP. The underlying tumors are almost exclusively of B-cell lineage. However, T-cells and CD56+ Natural Killer cells have also been postulated to be associated effectors of paraneoplastic pemphigus. This case demonstrated the rare association between Natural Killer cell lymphoma and PNP, suggesting that Natural Killer cells could be involved in the pathogenesis of PNP. The article warned clinicians to be alert to the possibility that paraneoplastic pemphigus in lymphomas not of B-cell lineage. This added to the already complex, not fully understood pathogenesis of PNP.[18] A study in 2013 outlined the effectiveness of plasma exchange in PNP patients with benign tumors.[19] The University of Toronto has been working to develop a form of treatment that improves the patient's overall quality of life while remaining economically achievable. They believe they have achieved this through fixed-dose rituximab. It has proven to be effective among auto-immune diseases, but the correct administration process for treating PNP is yet to be defined. The results of the study demonstrated varying levels of remission.[20] ## References[edit] Notes 1. ^ a b c d Sehgal, Virendra N.; Srivastava, Govind (2009). "Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome". International Journal of Dermatology. 48 (2): 162–9. doi:10.1111/j.1365-4632.2009.03995.x. PMID 19200194. S2CID 20426868. 2. ^ a b c Poot, A.M.; Diercks, G.F.H.; Kramer, D.; Schepens, I.; Klunder, G.; Hashimoto, T.; Borradori, L.; Jonkman, M.F.; Pas, H.H. (2013). "Laboratory diagnosis of paraneoplastic pemphigus". British Journal of Dermatology. 169 (5): 1016–24. doi:10.1111/bjd.12479. PMID 23796242. S2CID 207070543. 3. ^ Proby, Charlotte; Fujii, Yoshiko; Owaribe, Katsushi; Nishikawa, Takeji; Amagai, Masayuki (1999). "Human Autoantibodies against HD1/Plectin in Paraneoplastic Pemphigus". Journal of Investigative Dermatology. 112 (2): 153–6. doi:10.1046/j.1523-1747.1999.00498.x. PMID 9989789. 4. ^ a b Paraneoplastic Pemphigus~workup at eMedicine 5. ^ Anhalt, Grant J.; Kim, SooChan; Stanley, John R.; Korman, Neil J.; Jabs, Douglas A.; Kory, Mark; Izumi, Hiroshi; Ratrie, Harry; Mutasim, Diya; Ariss-Abdo, Lina; Labib, Ramzy S. (1990). "Paraneoplastic Pemphigus". New England Journal of Medicine. 323 (25): 1729–35. doi:10.1056/NEJM199012203232503. PMID 2247105. 6. ^ Camisa, Charles (1993). "Paraneoplastic Pemphigus Is a Distinct Neoplasia-Induced Autoimmune Disease". Archives of Dermatology. 129 (7): 883–6. doi:10.1001/archderm.1993.01680280071014. PMID 8323311. 7. ^ Frew, John W.; Murrell, Dédée F. (2011). "Paraneoplastic Pemphigus (Paraneoplastic Autoimmune Multiorgan Syndrome): Clinical Presentations and Pathogenesis". Dermatologic Clinics. 29 (3): 419–25, viii. doi:10.1016/j.det.2011.03.018. PMID 21605807. 8. ^ Maverakis, Emanual; Goodarzi, Heidi; Wehrli, Lisa N.; Ono, Yoko; Garcia, Miki Shirakawa (2012). "The Etiology of Paraneoplastic Autoimmunity". Clinical Reviews in Allergy & Immunology. 42 (2): 135–44. doi:10.1007/s12016-010-8248-5. PMID 21246308. S2CID 33226991. 9. ^ Paraneoplastic Pemphigus~treatment at eMedicine 10. ^ "Prednisone Intensol (prednisone) dosing, indications, interactions, adverse effects, and more". 11. ^ "Azasan, Imuran (azathioprine) dosing, indications, interactions, adverse effects, and more". 12. ^ "Neoral, Sandimmune (cyclosporine) dosing, indications, interactions, adverse effects and more". 13. ^ "Cytoxan (cyclophosphamide) dosing, indications, interactions, adverse effects, and more". 14. ^ "Pemphigus - Symptoms and causes". 15. ^ Probst, Christian; Schlumberger, Wolfgang; Stöcker, Winfried; Recke, Andreas; Schmidt, Enno; Hashimoto, Takashi; Zhu, Xue Jun; Zillikens, Detlef; Komorowski, Lars (2009). "Development of ELISA for the specific determination of autoantibodies against envoplakin and periplakin in paraneoplastic pemphigus". Clinica Chimica Acta. 410 (1–2): 13–8. doi:10.1016/j.cca.2009.08.022. PMID 19737550. 16. ^ Huang, Yongchu; Li, Jing; Zhu, Xuejun (2009). "Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in patients with paraneoplastic pemphigus". Archives of Dermatological Research. 301 (10): 703–9. doi:10.1007/s00403-008-0901-y. PMID 18820940. S2CID 862396. 17. ^ Zhang, Jun; Qiao, Qi-lu; Chen, Xi-xue; Liu, Ping; Qiu, Jian-xing; Zhao, Hu; Zhao, Jian-xun; Liu, Yu-cun; Wan, Yuan-lian (2011). "Improved outcomes after complete resection of underlying tumors for patients with paraneoplastic pemphigus: a single-center experience of 22 cases". Journal of Cancer Research and Clinical Oncology. 137 (2): 229–34. doi:10.1007/s00432-010-0874-z. PMID 20390428. S2CID 22375666. 18. ^ Gill, Harinder; Trendell-Smith, Nigel J.; Loong, Florence; Chan, Johnny Chun-Yin; Kwong, Yok-Lam (2011). "Paraneoplastic pemphigus due to natural-killer/T-cell lymphoma". British Journal of Haematology. 154 (2): 160. doi:10.1111/j.1365-2141.2011.08645.x. PMID 21517813. S2CID 40794144. 19. ^ Kitagawa, C; Nakajima, K; Aoyama, Y; Fujioka, A; Nakajima, H; Tarutani, M; Tsuruta, D; Hashimoto, T; Sano, S (2014). "A Typical Case of Paraneoplastic Pemphigus Without Detection of Malignancy: Effectiveness of Plasma Exchange". Acta Dermato Venereologica. 94 (3): 359–61. doi:10.2340/00015555-1742. PMID 24162880. 20. ^ Heelan, Kara; Al-Mohammedi, Faisal; Smith, Myles J.; Knowles, Sandra; Lansang, Perla; Walsh, Scott; Shear, Neil H. (2014). "Durable Remission of Pemphigus With a Fixed-Dose Rituximab Protocol". JAMA Dermatology. 150 (7): 703–8. doi:10.1001/jamadermatol.2013.6739. PMID 24500264. ## External links[edit] Classification D External resources * eMedicine: derm/1064452 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Paraneoplastic pemphigus	c1112570	29,914	wikipedia	https://en.wikipedia.org/wiki/Paraneoplastic_pemphigus	2021-01-18T19:01:19	{"umls": ["C1112570"], "icd-10": ["L10.8"], "orphanet": ["63455"], "wikidata": ["Q3899003"]}
A number sign (#) is used with this entry because of evidence that orofacial cleft-15 (OFC15) is caused by mutation in the DLX4 gene (601911) on chromosome 17q21. One such family has been reported. For a discussion of genetic heterogeneity of nonsyndromic cleft/lip palate (CL/P), see OFC1 (119530). Clinical Features Wu et al. (2015) studied a Hispanic mother and son with bilateral cleft lip and palate and minor dysmorphic features. The mother had CL/P repaired in early childhood. On examination at 16 years of age, her speech was hyponasal and she exhibited high anterior hairline, sparse eyebrows, prominent ears, hypertelorism, euryblepharon, lagophthalmos, and mild ectropion of the lower eyelids. She also had marked midface hypoplasia with an anterior crossbite, and the lateral incisors were missing. Her son was also born with bilateral CL/P and showed similar facial dysmorphism, with sparse eyebrows, prominent ears, bulbous nasal tip, euryblepharon, lagophthalmos, and mild ectropion of the lower eyelids. In addition, he had cryptorchidism and bilateral inguinal hernias. There was no family history of cleft lip or palate. Molecular Genetics In a Hispanic woman with bilateral CL/P and minor facial dysmorphism, who was negative for mutation in genes known to be associated with CL/P, Wu et al. (2015) performed whole-exome sequencing and identified heterozygosity for a 1-bp deletion in the DLX4 gene (601911.0001) that was also present in her affected son but was not found in public variant databases. Analysis of DLX4 in 3 patients with blepharocheilodontic syndrome (see 119580) and in 155 patients with nonsyndromic CL, CL/P, or CP did not reveal any mutations. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- High anterior hairline \- Midface hypoplasia Ears \- Prominent ears Eyes \- Sparse eyebrows \- Sparse eyelashes \- Hypertelorism \- Euryblepharon \- Lagophthalmos \- Mild ectropion of lower eyelids \- Epicanthal folds \- Upslanting palpebral fissures Nose \- Bulbous nasal tip Mouth \- Cleft lip, bilateral \- Cleft palate, bilateral Teeth \- Anterior crossbite \- Absence of lateral incisors ABDOMEN External Features \- Bilateral inguinal hernia GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKIN, NAILS, & HAIR Skin \- Single palmar creases Hair \- High anterior hairline VOICE \- Hyponasal speech MISCELLANEOUS \- Based on report of a Hispanic mother and son (last curated February 2016) MOLECULAR BASIS \- Caused by mutation in the distal-less homeobox-4 gene (DLX4, 601911.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	OROFACIAL CLEFT 15	c0158646	29,915	omim	https://www.omim.org/entry/616788	2019-09-22T15:47:54	{"doid": ["0080408"], "omim": ["616788"], "orphanet": ["199306"]}
A rare inherited disorder of leucine metabolism characterized by a highly variable clinical picture ranging from metabolic crisis in infancy to asymptomatic adults. ## Epidemiology The birth prevalence in Europe is estimated at 1/50,000-1/30,000. The introduction of neonatal screening programs based on tandem mass spectrometry has revealed a high frequency of this disorder, and it now appears to be the most common organic aciduria in some populations. ## Clinical description Patients with 3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD) have a variable clinical phenotype with the vast majority of patients being asymptomatic and a small subgroup displaying symptoms of an organic aciduria, usually in association with environmental triggering factors. Many newborns now diagnosed through expanded newborn screening tests remain asymptomatic, indicating that the disease has a very low clinical penetrance. Most symptomatic patients have normal growth and development until presenting with an acute metabolic crisis, usually following a minor infection, fasting or introduction of a protein-rich diet, between the ages of 2-33 months. Symptoms include vomiting, coma and apnea. Rarely, neurological abnormalities (i.e. metabolic stroke, hemiparesis, and encephalopathy), weakness, muscular hypotonia and developmental delay have been reported. Between episodes of metabolic crisis patients are usually asymptomatic. Some patients with 3-MCCD may not develop symptoms until adulthood, manifesting with weakness and fatigue, while others may never show symptoms. ## Etiology 3-MCCD is due to mutations in the MCCC1 (3q27.1) or MCCC2 (5q12-q13) genes. These two genes encode MCCase subunit alpha and MCCase subunit beta, which together catalyze the fourth step in the leucine catabolic pathway. Mutations in these genes lead to reduced or absent 3-MCC activity, thereby allowing the toxic byproducts of leucine processing to build up and cause clinical symptoms. Evidence is emerging that consanguinity with homozygosity for damaging mutations in a second rare disease gene may be associated with non-specific severe phenotypes of 3-MCCD. ## Diagnostic methods Newborn screening using tandem mass spectrometry reveals an elevation of C5-hydroxy acylcarnitine on blood spots. Urine organic acid analysis shows elevation of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. Carnitine serum levels can be decreased. Lymphocyte and fibroblast assays show low to absent 3-MCC activity while other carboxylase enzymes have normal activity. Laboratory findings during an acute metabolic crisis include metabolic acidosis, hypoglycemia, and in some cases, mild hyperammonemia. Molecular genetic testing identifying two disease causing alleles confirms diagnosis. Newborn screening programs are available in the U.S. and some European countries. ## Differential diagnosis The differential diagnosis includes other organic acidurias such as multiple carboxylase deficiency as well as Reye's syndrome. ## Antenatal diagnosis Antenatal diagnosis is possible in families with known disease causing mutations. ## Genetic counseling 3-MCCD is inherited autosomal recessively and genetic counseling is recommended. ## Management and treatment Early diagnosis may help in properly managing 3-MCCD and reducing the risk of severe metabolic crisis. Treatment is often not necessary in asymptomatic individuals. Some patients may require oral L-carnitine supplementation. A diet restricted in leucine is usually not warranted. Avoidance of fasting and of other precipitating stresses is recommended (mainly in infants and young children), as is the regular monitoring of free carnitine concentrations. An emergency regimen (IV glucose and the correction of acidosis) is recommended during intercurrent illness. ## Prognosis The prognosis is usually good but depends on the severity of symptoms experienced. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	3-methylcrotonyl-CoA carboxylase deficiency	c0268600	29,916	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=6	2021-01-23T19:09:27	{"gard": ["10954"], "mesh": ["C535308"], "omim": ["210200", "210210"], "umls": ["C0268600"], "icd-10": ["E71.1"], "synonyms": ["3-methylcrotonylglycinuria", "MCC deficiency", "MCCD"]}
17-beta hydroxysteroid dehydrogenase 3 deficiencyis an inherited condition that affects male sexual development. People with this condition are genetically male and have testes, but do not produce enough testosterone. Most people with this condition are born with external genitalia that appear female. In some cases, the external genitalia are ambiguous or appear male but are abnormal in size and/or appearance. During puberty, people with this condition typically go on to develop male secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern body hair. 17-beta hydroxysteroid dehydrogenase 3 deficiency is caused by mutations in the HSD17B3 gene and is inherited in an autosomal recessive pattern. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	17-beta hydroxysteroid dehydrogenase 3 deficiency	c0268296	29,917	gard	https://rarediseases.info.nih.gov/diseases/5659/17-beta-hydroxysteroid-dehydrogenase-3-deficiency	2021-01-18T18:02:26	{"mesh": ["C537805"], "omim": ["264300"], "umls": ["C0268296"], "orphanet": ["752"], "synonyms": ["17 alpha ketosteroid reductase deficiency of testis", "17 alpha KSR deficiency", "Neutral 17 beta hydroxysteroid oxidoreductase deficiency", "Male pseudoherma-phroditism with gynecomastia", "17 beta hydroxysteroid dehydrogenase III deficiency"]}
A rare infantile epilepsy syndrome characterized by early onset of seizures of variable type and severity, potentially associated with a spectrum of clinical signs and symptoms including delay or lack of psychomotor development, intellectual disability, poor or absent speech development, behavioral abnormalities, hypotonia, movement disorders, spasticity, microcephaly, and dysmorphic facial features, among others. Brain imaging findings are also variable and may include cerebral atrophy or white matter abnormalities. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Undetermined early-onset epileptic encephalopathy	c4538788	29,918	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=442835	2021-01-23T17:46:23	{"omim": ["301008", "614558", "615476", "615833", "615871", "615905", "616056", "616211", "616339", "616346", "616366", "616409", "617020", "617105", "617106", "617132", "617153", "617162", "617166", "617829", "617830", "617831", "617836", "617854", "617938", "618008", "618012", "618201", "618396", "618437", "618468", "618557", "618559", "618910", "618916"], "icd-10": ["G40.4"], "synonyms": ["Undetermined EOEE"]}
Lethal congenital contracture syndrome Lethal congenital contracture syndrome has an autosomal recessive pattern of inheritance. Lethal congenital contracture syndrome 1 (LCCS1), also called Multiple contracture syndrome, Finnish type,[1] is an autosomal recessive genetic disorder characterized by total immobility of a fetus, detectable at around the 13th week of pregnancy. LCCS1 invariably leads to prenatal death before the 32nd gestational week. LCCS1 is one of 40 Finnish heritage diseases. It was first described in 1985 and since then, approximately 70 cases have been diagnosed.[2] ## Contents * 1 Characteristics * 2 Cause * 3 Genetics * 3.1 Population genetics * 3.2 Mapping * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Characteristics[edit] LCCS1 is characterized by total lack of the movements of the fetus, and is detectable at 13th week of pregnancy. It is accompanied by oedema, small chin, small lungs, crooked joints and occasional skin webs of the neck and elbows. The fetus has characteristic pattern of malpositions recognizable even in severely macerated fetuses with club feet and hyperextension of the knees but the elbows and wrists showing flexion contractures.[3] Neuropathological analysis shows lack of anterior horn motoneurons and severe atrophy of the ventral spinal cord. The skeletal muscles are severely hypoplastic.[4] ## Cause[edit] The defective gene associated with LCCS1 is mRNA export mediator GLE1 at chromosome 9q34. In more than 40 families the fetus has been homozygous for A->G substitution (c.432-10A>G) located in intron 3 of GLE1 creating an illegitimate splice acceptor site resulting in nine extra nucleotides in the GLE1 cDNA (GLE1 FinMajor mutation). In one family the fetus has been compound heterozygous for GLE1 FinMajor and R→H substitution in exon 12.[5] A slightly milder phenotype with survival beyond 32nd gestational week also characterized by foetal akinesia, arthrogryposis and anterior horn cell loss (Lethal arthrogryposis with anterior horn cell disease, LAAHD) was also shown to be allelic to LCCS1 and result from mutations in GLE1. ## Genetics[edit] LCCS1 is inherited in an autosomal recessive manner.[4] This means the defective gene responsible for the disorder (GLE1) is located on an autosome (chromosome 9), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. ### Population genetics[edit] LCCS1 belongs to Finnish heritage of diseases and cases have been confirmed until now (2009) only in Finland. The prevalence is 1 in 25000 births.[6] The carrier frequency is 1% in whole Finland and 2% in North-Eastern part of Finland where the birthplaces of ancestors of affected individual show clustering. ### Mapping[edit] Mäkelä-Bengs et al. (1997,1998) performed a genome-wide screening and linkage analysis and assigned the LCCS locus to a defined region of 9q34.[7] ## Diagnosis[edit] A doctor will diagnosis the child within the First 10 to 14 days after birth ## Treatment[edit] This section is empty. You can help by adding to it. (December 2017) ## See also[edit] * Lethal arthrogryposis with anterior horn cell disease ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 255310 2. ^ Norio R (2003). "The Finnish disease heritage III: the individual diseases". Hum. Genet. 112 (5–6): 486–487. doi:10.1007/s00439-002-0877-1. PMID 12627297. S2CID 26741302. 3. ^ Herva R, Leisti J, Kirkinen P, Seppänen U (1985). "A lethal autosomal recessive syndrome of multiple congenital contractures". Am. J. Med. Genet. 20 (3): 431–439. doi:10.1002/ajmg.1320200303. PMID 3993672. 4. ^ a b Herva R, Conradi N, Kalimo H, Leisti J, Sourander P (1988). "A lethal autosomal recessive syndrome of multiple congenital contractures. Neuropathological analysis of five fetal cases". Am. J. Med. Genet. 29 (1): 67–76. doi:10.1002/ajmg.1320290109. PMID 3344776. 5. ^ Nousiainen HO, Kestilä M, Pakkasjärvi N, Honkala H, Kuure S, Tallila J, Vuopala K, Ignatius J, Herva R, Peltonen L (2008). "Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease". Nature Genetics. 40 (2): 155–157. doi:10.1038/ng.2007.65. PMC 2684619. PMID 18204449. 6. ^ Pakkasjärvi N, Ritvanen A, Herva R, Peltonen L, Kestilä M, Ignatius J (2006). "Lethal congenital contracture syndrome (LCC) and other lethal arthrogryposes in Finland – an epidemiological study". Am. J. Med. Genet. 140A (17): 1834–1839. doi:10.1002/ajmg.a.31381. PMID 16892327. S2CID 23457002. 7. ^ Mäkelä-Bengs P, Järvinen N, Vuopala K, Suomalainen A, Palotie A, Peltonen L (1997). "The assignment the lethal congenital contracture syndrome (LCCS) locus to chromosome 9q33-34". Am. J. Hum. Genet. 61 (suppl): A30. ## External links[edit] Classification D * OMIM: 253310 * MeSH: C537194 External resources * Orphanet: 294965 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Lethal congenital contracture syndrome	c1854664	29,919	wikipedia	https://en.wikipedia.org/wiki/Lethal_congenital_contracture_syndrome	2021-01-18T18:48:24	{"gard": ["3227"], "mesh": ["C537194"], "umls": ["C1854664"], "orphanet": ["1486"], "wikidata": ["Q6533262"]}
Autoimmune polyglandular syndrome type 1 is an inherited autoimmune condition that affects many of the body's organs. Symptoms often begin in childhood or adolescence and may include mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. This syndrome can cause a variety of additional signs and symptoms, such as weak teeth (enamel hypoplasia) and chronic diarrhea or constipation. Also, about 60% of the women with APS-1 who are younger than 30 years of age develop primary ovarian insufficiency. Complications of APS-1 can affect the bones, joints, skin, and nails, the gonads (ovaries and testicles), the eyes, the thyroid, and several internal organs (kidneys, liver, lungs and the spleen). Anemia may also be present due to a lack of production of the red blood cells. Type 1 diabetes also occurs in some patients with this condition. APS-1 is progressive, with symptoms appearing at different time intervals (chronic mucocutaneous candidiasis and hypoparathyroidism classically appear early in childhood, whereas adrenal insufficiency usually start in the second decade of life). Diagnosis is suspected when there are at least two of these features, specially in young people. APS-1 is caused by variations (mutations) in the AIRE gene. Inheritance is autosomal recessive. Treatment may include hormone-replacement, and medication for candidiasis, as well as specific treatment of any complications. Patients with APS-1 are best followed by an endocrinologist and other specialists. Most people with APS-1, develop earlier and more severe symptoms than people with a related disease known as autoimmune polyendocrine syndrome type 2 (APS-2). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autoimmune polyglandular syndrome type 1	c0085859	29,920	gard	https://rarediseases.info.nih.gov/diseases/8466/autoimmune-polyglandular-syndrome-type-1	2021-01-18T18:01:58	{"mesh": ["D016884"], "omim": ["240300"], "umls": ["C0085859"], "orphanet": ["3453"], "synonyms": ["APS 1", "Autoimmune polyendocrine syndrome type 1", "Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)", "Hypoadrenocorticism with hypoparathyroidism and superficial moniliasis", "Autoimmune polyendocrinopathy syndrome type 1", "Polyglandular autoimmune syndrome type 1", "PGA 1", "PGA-I", "Whitaker syndrome", "Type I Polyglandular Autoimmune Syndrome", "Autoimmune polyglandular syndrome type I"]}
Spondyloepimetaphyseal dysplasia with multiple dislocations is a rare genetic primary bone dysplasia disorder characterized by midface hypoplasia, short stature, generalized joint laxity, multiple joint dislocations (most frequently of knees and hips), limb malalignment (genu valgum/varum) and progressive spinal deformity (e.g. kyphosis/scoliosis). Radiography reveals distinctive slender metacarpals and metatarsals, as well as small, irregular epiphyses, metaphyseal irregularities with vertical striations, constricted femoral necks and mild platyspondyly, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spondyloepimetaphyseal dysplasia with multiple dislocations	c1863732	29,921	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93360	2021-01-23T17:14:41	{"gard": ["9866"], "mesh": ["C535784"], "omim": ["603546"], "umls": ["C1863732"], "icd-10": ["Q77.7"], "synonyms": ["SEMD-MD", "SEMDJL2", "Spondyloepimetaphyseal dysplasia with joint laxicity, Hall type", "Spondyloepimetaphyseal dysplasia with joint laxity type 2", "Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type", "Spondyloepimetaphyseal dysplasia with multiple dislocations, Hall type"]}
## Summary ### Clinical characteristics. Fibrodysplasia ossificans progressiva (FOP) is characterized by congenital bilateral hallux valgus malformations and early-onset heterotopic ossification, which may be spontaneous or precipitated by trauma including intramuscular vaccinations. Painful, recurrent soft-tissue swellings (flare-ups) may precede localized heterotopic ossification. Heterotopic ossification can occur at any location, but typically affects regions in close proximity to the axial skeleton in the early/mild stages, before progressing to the appendicular skeleton. This can lead to restriction of movement due to ossification impacting joint mobility. Problems with swallowing and speaking can occur with ossification affecting the jaw, head, and neck, and restriction of the airway and breathing may lead to thoracic insufficiency syndrome. ### Diagnosis/testing. The diagnosis of FOP is established in a proband with heterotopic ossification, hallux valgus malformations, and/or a heterozygous pathogenic variant in ACVR1 identified by molecular genetic testing. ### Management. Treatment of manifestations: Avoid intramuscular injections and arterial punctures. Fall prevention using household safety measures and ambulatory devices; use of protective headgear to reduce sequelae of falls; prompt medical attention after a fall with consideration of prophylactic corticosteroid use; management by a dietician for those with feeding difficulties; preventative dental care with precautions to avoid injury; orthodontic treatment with a practitioner with experience in FOP; consultation with an expert anesthetist with experience in FOP prior to elective anesthesia; use of singing, swimming, incentive spirometry; positive pressure ventilation when indicated for mechanical respiratory difficulties including thoracic insufficiency syndrome; anti-inflammatory medications for flare-ups; consider corticosteroids for flare-ups of the submandibular region or jaw, major joints, after significant soft-tissue trauma, and for prophylaxis prior to dental and surgical procedures. Conservative management for scoliosis. Consider bisphosphonates for corticosteroid-induced osteopenia; fractures should be managed by an expert in FOP; hearing aids and appliances for conductive hearing impairment; encourage hydration and avoidance of high protein and high salt intake to prevent renal stones; occupational therapy; warm water hydrotherapy for mobility difficulties; lower extremity elevation, DVT prophylaxis, and supportive stockings while avoiding traumatic compression for lymphedema. Psychological support. Surveillance: Annual clinical evaluation including evaluation for scoliosis with orthopedist or geneticist familiar with FOP; annual nutrition evaluation and examination for jaw ankylosis; baseline pulmonary function assessment, sleep assessment, and echocardiogram before age ten years followed by annual clinical evaluation of respiratory status; annual evaluation for fracture risk; audiology assessment every 12 to 24 months; annual assessment for signs and symptoms of nephrocalcinosis, gastrointestinal complications, and skin integrity; dental examinations every six months; Doppler ultrasound if DVT is suspected. Agents/circumstances to avoid: Avoid procedures that predispose to soft-tissue injury, including intramuscular injections such as vaccinations, arterial punctures, dental procedures, procedures related to anesthesia, biopsies, removal of heterotopic bone, and all nonemergent surgical procedures. Avoid contact sports, overstretching of soft tissues, muscle fatigue, and passive range of motion. Avoid falls. In individuals with thoracic insufficiency syndrome, avoid supplemental oxygen, which can suppress respiratory drive. ### Genetic counseling. FOP is inherited in an autosomal dominant manner. The majority of affected individuals represent simplex cases (i.e., a single occurrence in a family) resulting from a de novo ACVR1 pathogenic variant. Rarely, an individual diagnosed with FOP has an affected parent. If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to sibs is 50%. Once the ACVR1 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis There are no formal diagnostic criteria for fibrodysplasia ossificans progressiva (FOP). ### Suggestive Findings FOP should be suspected in individuals with the following clinical and radiographic findings. Clinical findings * Congenital hallux valgus deformity that is most often bilateral * Progressive heterotopic ossification (extraosseous bone formation) that may manifest as a palpable mass. Ossification is either spontaneous or in response to soft-tissue trauma, including iatrogenic trauma from vaccinations or surgical procedures. * Painful, recurrent soft-tissue swellings (flare-ups) that may precede localized heterotopic ossification. This may occur in the form of scalp nodules in infancy, which may be an early or presenting feature. * Limb reduction defects that may affect the fingers in atypical or nonclassic FOP and may be mistaken for a brachydactyly syndrome in individuals who have not yet developed heterotopic ossifications Imaging findings (see Figure 1) #### Figure 1. Characteristic features of FOP. A photograph (A) and radiograph (B) of the feet in an affected boy age 15 years with classic FOP show short, malformed halluces with a single, dysplastic phalanx in each great toe. A photograph of his back (C) and a radiograph (more...) * Prenatal ultrasound may identify a hallux valgus deformity as early as 23 weeks' gestation [Maftei et al 2015]. * Radiographs of the halluces demonstrate short, malformed first metatarsals and a single dysplastic phalanx. * Radiographs of affected areas demonstrate heterotopic ossification (extraosseous bone formation). Note: Individuals with suspected FOP should avoid biopsy, elective surgery, and immunizations until diagnosis is confirmed [Kaplan et al 2019]. ### Establishing the Diagnosis The diagnosis of FOP is established in a proband with hallux valgus malformations, heterotopic ossification, and/or a heterozygous pathogenic variant in ACVR1 identified by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive features described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas individuals in whom the diagnosis of FOP has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and radiographic findings suggest the diagnosis of FOP, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of ACVR1 to detect the most common pathogenic variant (c.617G>A; p.Arg206His) and other missense variants associated with FOP. Note: Since FOP occurs through a gain-of-function mechanism and large intragenic deletions or duplications have not been reported, testing for intragenic deletions or duplication is not indicated in individuals in whom a diagnosis of FOP is strongly suspected. Pathogenic loss of function variants in ACVR1 such as nonsense, frameshift, and splice-site variants have not been described. * A skeletal dysplasia multigene panel that includes ACVR1 and other genes of interest (see Differential Diagnosis) may be considered to identify the genetic cause of the condition at the most reasonable cost, compared to comprehensive genomic testing, while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the diagnosis of FOP has not been considered, including in individuals with atypical phenotypic features and/or the absence of congenital hallux malformation, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) may be the best option. Exome sequencing is most commonly used; genome sequencing is an increasingly used alternative. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Fibrodysplasia Ossificans Progressiva View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ACVR1Sequence analysis 3100% 4 Gene-targeted deletion/duplication analysis 5None reported 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. The pathogenic variant c.617G>A (p.Arg206His) has been identified in more than 97% of affected individuals. All additional pathogenic variants have been located in the glycine-serine(GS)-rich domain or the protein kinase domain [Shore et al 2006a, Zhang et al 2013]. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. ## Clinical Characteristics ### Clinical Description Fibrodysplasia ossificans progressiva (FOP) is characterized by congenital bilateral hallux valgus malformations and early-onset heterotopic ossification, which may be spontaneous or precipitated by trauma, including intramuscular vaccinations [Pignolo et al 2016]. To date, more than 800 individuals with over 20 pathogenic variants in ACVR1 have been reported (overview in Kaplan et al [2019]). The following description of the phenotypic features associated with this condition is based on these reports and reports of classic FOP phenotype in individuals who did not have molecular genetic testing. ### Table 2. Select Features of Fibrodysplasia Ossificans Progressiva View in own window Feature% of Persons with Feature 1Comment Bilateral congenital hallux valgus malformations>97% * Hallux valgus, malformed 1st metatarsal, &/or monophalangism * Often 1st clinical feature * Present in 100% of persons w/common c.617G>A (p.Arg206His) variant & classic phenotype Heterotopic ossification~100% * Age dependent * Episodic * May be triggered by soft-tissue injury incl vaccinations 2 Inflammatory soft-tissue swellings~100%May be spontaneous or triggered by trauma Scalp nodules~40% * Localized manifestation of soft-tissue swelling * May be an early or presenting feature when observed in neonatal period or infancy Other skeletal manifestationsOsteochondromas~90%Proximal medial tibia is most common site. Cervical spine fusions~80%Affecting C2 to C7 Short broad femoral neck~70% Scoliosis~65%May be rapidly progressive Thumb malformations~50% Distal limb reduction defects<3%May be misdiagnosed as a brachydactyly syndrome 1\. Kaplan et al [2009], Piram et al [2011], Kaplan et al [2019] 2\. Shore & Kaplan [2008] Hallux valgus malformation. Hallux valgus malformations are present from birth and may be identifiable on prenatal imaging [Maftei et al 2015]. The first metatarsal is short with a hallux valgus malformation and/or monophalangism with a single dysplastic phalanx (see Figure 1) [Towler et al 2020]. Additional hallux malformations can include a delta-shaped, dysplastic proximal phalanx. Hallux valgus malformations are most often bilateral but can be unilateral or absent in a minority of individuals with atypical FOP. Heterotopic ossification * Extraosseous bone formation (abnormal bone formation in soft connective tissues outside of the normal skeleton) may manifest as a palpable hard lump or mass. Onset of ossification in individuals with the most common pathogenic variant (c.617G>A; p.Arg206His) is age one to ten years, while onset of heterotopic ossification may be later in some individuals with atypical FOP. * Heterotopic ossification can be spontaneous or in response to soft-tissue trauma, including iatrogenic trauma from intramuscular vaccinations, falls, and surgical procedures. Painful, recurrent soft-tissue swelling may precede localized heterotopic ossification. * Heterotopic ossification can occur at any location, typically affecting regions in close proximity to the axial skeleton in the early/mild stages, before progressing to the appendicular skeleton. This can lead to restriction of movement due to ossification affecting joint mobility. Ossification of the jaw, head, and neck can affect swallowing and speaking. * Heterotopic ossification occurring in the thoracic region, submandibular region, throat, or other locations near the airway may impact the airway or respiratory function. In addition, costovertebral involvement, ossification of intercostal muscles, paravertebral muscles, and aponeuroses, as well as progressive spinal deformity with kyphoscoliosis may lead to thoracic insufficiency syndrome, the predominant cause of mortality. Pneumonia, hypoxemia, hypercarbia, pulmonary hypertension, and right-sided heart failure may occur in individuals with thoracic insufficiency syndrome. * Heterotopic ossification may be misdiagnosed as tumors or isolated osteochondromas such as those seen in hereditary multiple osteochondromas, especially if the hallux malformations are not recognized. Soft-tissue swellings * Soft-tissue swellings (flare-ups) may be spontaneous or follow an injury. They are characterized by painful swellings in soft connective tissue including skeletal muscles, tendons, ligaments, fascia, and aponeuroses. They may precede the development of localized heterotopic ossification. * Scalp nodules occurring in neonates and infants have been described in 40% of individuals from a national disease registry [Piram et al 2011]. The nodules were large, firm, immobile, and tender, with rapid growth when they first appear. They generally regress spontaneously without treatment. The overlying skin was normal. Scalp nodules may be a localized manifestation of the soft-tissue swellings. Additional skeletal malformations and manifestations variably seen: * Variable thumb malformations may be present in some individuals, including hypoplasia and dysplastic phalanges. * Limb reduction defects affecting the fingers may be seen in atypical FOP. * Cervical spine fusions between C2 and C7 may be noted on cervical spine radiographs and may contribute to limitations in mobility as heterotopic ossification progresses. This occurs from intra-articular ankylosis of facet joints and early degenerative changes of the cervical spine. * Scoliosis affects up to 65% of individuals, may be rapidly progressive due to paravertebral lesions, and may contribute to thoracic insufficiency syndrome. * Pelvic radiographs may identify congenital short broad femoral necks, which rarely affect function. * Developmental hip dysplasia is present in 60% of individuals with acute hip pain. * Osteochondromas are reported in up to 90% of individuals, with the proximal medial tibia the most common location. * Enchondromas, a benign tumor originating in cartilaginous tissue, have been described in several individuals [Tabas et al 1993, Rafati et al 2016]; the prevalence is unknown. Fractures. Individuals with FOP are at increased risk for fractures of both normotropic and heterotopic bone due to the increased risk for falls, immobility, and corticosteroid-related osteopenia. Fractures in individuals with FOP usually heal with minimal heterotopic bone formation. Open reduction and internal fixation can lead to rapid onset of heterotopic ossification and is not recommended. Hearing loss. Conductive hearing loss is present in 50% of individuals with FOP and may be slowly progressive. Onset is usually in childhood and may result from middle ear ossification. In some individuals, a sensorineural component may be present. Acute hearing loss is not usually associated with FOP and should prompt evaluation for other causes. Renal stones. Individuals with FOP have a threefold increased risk of renal stones, which may be due to a combination of immobilization coupled with increased bone turnover. There has been no comprehensive study of stone composition in individuals with FOP. Lymphedema may occur with flare-ups affecting the limbs. This may be acute, subacute, or chronic. In some individuals, underlying deep vein thrombosis may be present. ### Genotype-Phenotype Correlations The c.617G>A (p.Arg206His) pathogenic variant is associated with the classic FOP phenotype, including bilateral hallux valgus malformations and early-onset heterotopic ossification [Kaplan et al 2009]. Specific gain-of-function variants at amino acid residue 328 (p.Gly328Arg [c.982G>A and c.982G>C], p.Gly328Trp [c.982G>T], and p.Gly328Glu [c.983G>A]) have been associated with a characteristic phenotype that includes limb reduction defects, which may be misdiagnosed as an amniotic band defect or a brachydactyly syndrome, most commonly brachydactyly type B [Kaplan et al 2009]. ### Penetrance The penetrance of gain-of-function variants in ACVR1 is estimated to be near complete; there are no reported individuals with nonpenetrance [Shore et al 2006b]. Among reported individuals with the most common pathogenic variant (c.617G>A; p.Arg206His), none are unaffected. ### Prevalence Based on studies in French [Baujat et al 2017] and British [Connor & Evans 1982] populations, the prevalence of FOP is estimated at one in one million (0.6-1.36 :1,000,000). Individuals with FOP have been reported in diverse ethnic populations, and no racial, ethnic, gender, or geographic predisposition has been identified. ## Differential Diagnosis The diagnosis of fibrodysplasia ossificans progressiva (FOP) is often missed, due in part to the rarity of the condition. Nearly 90% of individuals with FOP initially receive a misdiagnosis, with two thirds undergoing unnecessary and potentially dangerous procedures that lead to permanent harm and lifelong disability in as many as 50% [Kitterman et al 2005]. Disorders that may present with clinical features similar to those of FOP are summarized in Table 3. ### Table 3. Genes of Interest in the Differential Diagnosis of Fibrodysplasia Ossificans Progressiva View in own window Gene(s)DisorderMOIClinical Features of Differential Diagnosis Disorder Overlapping w/FOPDistinguishing from FOP EXT1 EXT2Hereditary multiple osteochondromasADMultiple osteochondromas arising from growth plate in juxtaphyseal region of long bones or from surface of flat bones * No hallux malformations * No heterotopic ossification GNASProgressive osseous heteroplasia (see Disorders of GNAS Inactivation)AD 1Extensive bone formation (episodic & cumulative) w/in soft connective tissues * No hallux malformations or inflammatory soft-tissue swellings * Individuals w/POH typically develop ossification w/in superficial dermal layer of the skin (which is unaffected in FOP. * Predominance of membranous rather than endochondral bone formation PTPN11Metachondromatosis (OMIM 156250)ADOsteochondromas & enchondromas * No hallux malformations * No heterotopic ossification ROR2Brachydactyly type B1 (OMIM 113000)ADDistal limb (terminal) reduction-type defects w/brachydactylyNo heterotopic ossification AD = autosomal dominant; FOP = fibrodysplasia ossificans progressiva; MOI = mode of inheritance; POH = progressive osseous heteroplasia 1\. Disorders of GNAS inactivation are inherited in an autosomal dominant manner, with the specific phenotype determined by the parental origin of the defective allele. Disorders to consider in individuals presenting with an isolated clinical feature characteristic of FOP [Kaplan et al 2008]: * Hallux malformations may represent isolated congenital malformations (e.g., isolated brachydactyly) or juvenile bunions. * Tumor-like swellings may be associated with sarcoma, desmoid tumor, aggressive juvenile fibromatosis, or lymphedema. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with fibrodysplasia ossificans progressiva (FOP), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Fibrodysplasia Ossificans Progressiva View in own window System/ConcernEvaluationComment OverallClinical staging based on published criteria (see Table 5) Hallux malformationsFunctional assessment w/orthopedist &/or physiotherapistRarely requires intervention Heterotopic ossificationClinical assessment of extent of heterotopic ossification & impact on functionAvoid elective medical, surgical, & dental procedures. Thoracic insufficiency syndromeConsider pulmonary & sleep studiesIf clinical concern for mechanical respiratory insufficiency Painful, recurrent soft-tissue swellingHistory & physical exam for areas of soft-tissue swelling OtherConsultation w/clinical geneticist &/or genetic counselor Note: Further evaluation may be indicated for participation in clinical trials. ### Table 5. Clinical Staging of Fibrodysplasia Ossificans Progressiva View in own window FeatureClinical Stage Early/MildModerateLate/SevereProfoundEnd Stage History of flare-upsNone; or if present, limited to scalp, neck, or backMostly limited to axial regions & upper limbsIn any locationIn any locationIn any location Body regions affectedNeck, back, upper limbsNeck, back, chest, upper & lower limbsNeck, back, chest, upper & lower limbs, jawNeck, back, chest, upper & lower limbs, jaw & distal limbs (wrists & ankles)Ankyloses of most or all joints Thoracic insufficiency (TI)Limited chest expansionRigid chest wall, no chest expansion, diaphragmatic breathingSymptomatic TI syndrome (pulmonary hypertension & right-sided heart failure)SymptomaticTI syndrome (pulmonary hypertension & right-sided heart failure) Other complicationsPneumonia, pressure ulcersRecurrent respiratory infections ADLsNo or minimal assistance required due to mild joint limitations or physical delay in developmental milestonesSome assistance requiredAssistance needed for most activitiesDependent for all ADLsDependent for all ADLs AmbulationUnaffected or cannot evaluate due to very young ageWalks; may use wheelchair in extenuating circumstances (e.g., long distances)Walks w/assistive device &/or uses wheelchairWheelchair boundMostly bed bound CAJIS≤45-1819-24≥24≥28 Adapted from Pignolo & Kaplan [2018] ADLs = activities of daily living; CAJIS = cumulative analog joint involvement scale (for FOP) 1\. See Kaplan et al [2017] ### Treatment of Manifestations There is currently no definitive medical treatment for FOP and management is supportive. Clinical trials investigating experimental treatments are in progress (see Therapies Under Investigation). Guidelines for the management of individuals with FOP have been developed by a multidisciplinary team of experts [Kaplan et al 2019]. A hallmark of FOP management is prevention of soft-tissue injury and muscle damage to prevent inflammatory soft-tissue swellings and heterotopic ossification [Kaplan et al 2019]. ### Table 6. Treatment of Manifestations in Individuals with Fibrodysplasia Ossificans Progressiva View in own window Manifestation/ConcernTreatmentConsiderations/Other Prevention of soft-tissue & muscle injuryAvoid intramuscular injections.Routine DTP vaccinations are particularly harmful. Avoid arterial punctures.Routine venipuncture poses minimal risk. Biopsies of lesions are never indicated.Biopsies are likely to cause heterotopic ossification. Precautions during dental care * Avoid overstretching of jaw. * Care w/local anesthesia Fall-related injuriesFall prevention * Modification of activity * Improved household safety (e.g., install handrails, secure loose carpeting, remove objects from walkways, eliminate uneven flooring.) * Use of ambulatory devices Reduce sequelae of fallsUse of protective headgear Treatment following a fall * Prompt medical attention * Consider head & neck injuries to be serious until proven otherwise. * Consider prophylactic corticosteroid use. Feeding difficulties due to jaw ankylosis when heterotopic ossification affects jaw regionReferral to dietician to consider supplemental intake or modified food consistency Dental care * Preventative dental care from a young age * Consult FOP expert prior to dental procedures. * Dental care may be affected by spontaneous or post-traumatic jaw ankylosis. * Consider corticosteroids for prophylaxis prior to dental & surgical procedures. Orthodontic concernsOrthodontic treatment by practitioner w/experience w/FOP Requirement for anesthesiaConsult w/expert anesthetist w/experience w/FOP prior to elective anesthesia. * If general anesthesia is required, an awake intubation by nasotracheal fiber-optic technique should be performed because of neck malformations, jaw ankylosis, sensitive airway, & risk of an obstructing neck flare-up. * Highly skilled FOP-aware anesthesiologists should be present for all elective intubations. Mechanical respiratory difficulties incl thoracic insufficiency syndrome * Singing, swimming, incentive spirometry * Positive pressure ventilation when indicated * Avoid respiratory infections. * Consider subcutaneous vaccination for influenza & pneumococcus in the proband. 1 * Recommend pertussis & influenza vaccination in family members. 2 * Avoid supplemental oxygen, which can suppress respiratory drive. Painful, recurrent soft-tissue swelling (flare-ups) * NSAIDs or COX-2 inhibitors (oral or topical) * Other anti-inflammatory medications including mast cell stabilizers, leukotriene inhibitors * Consider corticosteroids, particularly for flare-ups affecting the submandibular region or jaw, major joints, & after significant soft-tissue trauma. 1 * Consider oral corticosteroids for prophylaxis prior to dental & surgical procedures. 1 * Consider prophylactic treatment to prevent gastrointestinal complications due to NSAIDs or COX-2 inhibitors. * Avoid narcotic analgesia if possible. * No definitive evidence for use of bisphosphonates or imatinib Scalp nodulesNo treatment requiredUsually spontaneously regress ScoliosisConservative managementAvoid traditional operative approaches. Corticosteroid-induced osteopeniaConsider bisphosphonates according to standard treatment protocolsBisphosphonates may play role in managing soft-tissue swellings. 1 FracturesConsult w/FOP expert * Fractures usually heal w/minimal heterotopic bone formation. * Avoid open reduction & internal fixation, which can precipitate heterotopic ossification. Conductive hearing impairmentHearing aids & appliances Renal stones * Encourage fluid intake (1.5-2 L/day). * Avoid high-protein & high-salt diets. Problems w/ADLsOT Mobility issuesWarm water hydrotherapyAvoid passive joint movement. Lymphedema * Elevate legs during sleep & while recumbent. * DVT prophylaxis * Supportive stockings while avoiding traumatic compression DepressionPsychological support ADLs = activities of daily living; DVT = deep vein thrombosis; NSAID = nonsteroidal anti-inflammatory drug; OT = occupational therapy 1\. See Kaplan et al [2019]. 2\. Anti-influenza medication (oseltamivir) at first sign of influenza-like illness, while contacting medical practitioner Note: Treatments for which no definitive evidence supports their use in FOP include chemotherapy, radiotherapy, bone marrow transplantation, and the chronic use of antiangiogenic agents, calcium binders, colchicine, fluoroquinolone antibiotics, propranolol, mineralization inhibitors, PPAR-gamma antagonists, and TNF-α inhibitors [Kaplan et al 2019]. ### Surveillance ### Table 7. Recommended Surveillance for Individuals with Fibrodysplasia Ossificans Progressiva View in own window System/ConcernEvaluationFrequency Musculoskeletal * Clinical eval w/orthopedist &/or clinical geneticist w/experience in managing FOP * Careful eval for scoliosis, which may be progressive At least annually; more frequently when clinically indicated Feeding problems * Anthropometric assessment * Nutrition eval to monitor weight & caloric intake * Clinical history & physical exam for jaw ankylosis Annually Mechanical respiratory difficulties, incl thoracic insufficiency syndrome * Clinical history & physical exam for signs/symptoms of respiratory disease * Pulmonary assessments & sleep assessments * Echocardiogram * Baseline pulmonary function assessment, sleep assessments, & echocardiogram before age 10 yrs (earlier if indicated) * Annual clinical eval w/investigations as clinically indicated to guide specific respiratory therapies, incl positive pressure ventilation Fracture risk * If corticosteroid treatment has been extensive, consider eval for corticosteroid-induced osteopenia/osteoporosis. * Eval for fall risk Annually & as clinically indicated Hearing lossAudiology assessmentEvery 12-24 mos NephrocalcinosisClinical assessment for signs/symptoms of nephrocalcinosisAnnually w/additional investigations as clinically indicated according to signs/symptoms GastrointestinalClinical assessment for signs/symptoms of gastric complications due to NSAID & corticosteroid managementAnnually & as clinically indicated Pressure soresEval of skin integrityAt each clinical visit Oral healthAge-appropriate dental examEvery 6 mos LymphedemaDoppler ultrasound if underlying DVT suspectedAs clinically indicated Based on Kaplan et al [2019] DVT = deep vein thrombosis; NSAID = nonsteroidal anti-inflammatory drug ### Agents/Circumstances to Avoid It is imperative that iatrogenic harm is limited by avoiding procedures that predispose to soft-tissue injury, including intramuscular injections such as vaccinations, dental procedures, procedures related to anesthesia, biopsies, removal of heterotopic bone, and all nonemergent surgical procedures [Kaplan et al 2019]. Other activities to avoid include soft-tissue injuries, contact sports, overstretching of soft tissues, muscle fatigue, and passive range of motion (caution is required during treatment with physical therapists) [Kaplan et al 2019]. Falls should be actively avoided. Protective headwear should be considered for children who have upper limb involvement to prevent fall-induced head injury. Mobility aids may be effective in reducing falls in all age groups [Kaplan et al 2019]. In individuals with thoracic insufficiency syndrome, avoid supplemental oxygen, which can suppress respiratory drive. Administration of vaccinations must be carefully managed in individuals with FOP. Detailed guidelines are available [Kaplan et al 2019] (see pdf). In brief, intramuscular vaccinations and all diphtheria-tetanus-pertussis (DTP) type vaccinations should be avoided. When the benefit outweighs the risk, subcutaneous vaccinations may be given at least six to eight weeks following recovery from soft-tissue flare-ups. Vaccinations to prevent respiratory disease (influenza, pneumococcal) are particularly important, and family members of individuals with FOP should receive influenza and pertussis vaccinations. ### Evaluation of Relatives at Risk It may be appropriate to clarify the genetic status of apparently asymptomatic young sibs of an affected individual in order to identify individuals at risk of iatrogenic harm (e.g., intramuscular injections) and other sources of trauma that may precipitate heterotopic ossification. Note: For adult at-risk family members of a proband with classic FOP, molecular genetic testing in the absence of supportive physical examination findings (i.e., hallux deformity and signs of heterotopic ossification) is not usually required. However, for the evaluation of adult family members of a proband with atypical FOP, molecular genetic testing is recommended because manifestations of FOP may not be clinically apparent on physical examination. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management It is not known whether women with FOP have impaired fertility. Pregnancy in women with FOP is uncommon, as the disease manifestations at reproductive age limit reproductive potential. FOP poses major life-threatening risks to mother and fetus due to potential mechanical restrictions secondary to heterotopic ossification affecting the pelvis and surrounding regions, as well as breathing difficulties in later pregnancy secondary to restrictive chest wall disease. There is an increased risk of thromboembolism exacerbated by immobility. Ideally, pregnancy in a woman with FOP should be provided at a high-risk pregnancy center and follow established guidelines for the management of pregnancy in women with FOP (see Kaplan et al [2019]). See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation Research to develop treatments for FOP has focused on targeted inhibition of the ACVR1 receptor, ACVR1 ligands, BMP pathway signaling, pre-osseous chondrogenic heterotopic ossification, and inflammatory triggers of disease activity. Palovarotene is a RAR-gamma agonist that reduces BMP signaling and may reduce the volume of heterotopic ossification. REGN2477 is an antibody that binds to activin A and blocks its activity. By binding and blocking activin A, REN2477 may prevent the formation and stop the growth of heterotopic ossification in individuals with FOP. REGN2477 is currently in Phase II clinical trials in individuals older than age 18 years. Sirolimus is an mTOR inhibitor that may reduce heterotopic ossification. Sirolimus is currently in Phase II clinical trials in individuals older than age six years. Several other agents are currently undergoing safety and tolerability assessment in Phase I clinical trials. Further information on therapies under investigation is available in Kaplan et al [2019]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for further information on clinical studies for FOP. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Fibrodysplasia Ossificans Progressiva	c0016037	29,922	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK558090/	2021-01-18T21:25:58	{"mesh": ["D009221"], "synonyms": ["Myositis Ossificans Progressiva", "Progressive Ossifying Myositis"]}
Response to a terrifying, traumatic, or surprising experience This article is about the psychological condition sometimes called shock. For the circulatory condition, see Shock (circulatory). This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) The examples and perspective in this article may not include all significant viewpoints. Please improve the article or discuss the issue. (September 2012) (Learn how and when to remove this template message) This article needs to be updated. Please update this article to reflect recent events or newly available information. (March 2018) (Learn how and when to remove this template message) Acute stress reaction SpecialtyPsychiatry Part of a series on Emotions * Acceptance * Affection * Amusement * Anger * Angst * Anguish * Annoyance * Anticipation * Anxiety * Apathy * Arousal * Awe * Boredom * Confidence * Contempt * Contentment * Courage * Curiosity * Depression * Desire * Disappointment * Disgust * Distrust * Doubt * Ecstasy * Embarrassment * Empathy * Enthusiasm * Envy * Euphoria * Faith * Fear * Frustration * Gratification * Gratitude * Greed * Grief * Guilt * Happiness * Hatred * Hope * Horror * Hostility * Humiliation * Interest * Jealousy * Joy * Kindness * Loneliness * Love * Lust * Nostalgia * Outrage * Panic * Passion * Pity * Pleasure * Pride * Rage * Regret * Rejection * Remorse * Resentment * Sadness * Self-pity * Shame * Shock * Shyness * Social connection * Sorrow * Suffering * Surprise * Trust * Wonder * Worry * v * t * e Acute stress disorder (ASD, also known as acute stress reaction, psychological shock, mental shock, or simply shock) is a psychological response to a terrifying, traumatic, or surprising experience. Acute stress disorder is not fatal, but it may bring about delayed stress reactions (better known as posttraumatic stress disorder, or PTSD) if not correctly addressed.[1][2] ## Contents * 1 Types of ASD * 1.1 Sympathetic (also known as "fight or flight" response) * 1.2 Parasympathetic * 2 Signs and symptoms * 3 Causes * 4 Pathophysiology * 5 Diagnosis * 6 Treatment * 7 History * 8 References * 9 External links ## Types of ASD[edit] ### Sympathetic (also known as "fight or flight" response)[edit] Sympathetic acute stress disorder is caused by the release of excessive adrenaline and norepinephrine into the nervous system. These hormones may speed up a person's pulse and respiratory rate, dilate pupils, or temporarily mask pain. This type of ASD developed as an evolutionary advantage to help humans survive dangerous situations. The "fight or flight" response may allow for temporarily-enhanced physical output, even in the face of severe injury. However, other physical illnesses become more difficult to diagnose, as ASD masks the pain and other vital signs that would otherwise be symptomatic.[1] ### Parasympathetic[edit] Parasympathetic acute stress disorder is characterised by feeling faint and nauseous. This response is fairly often triggered by the sight of blood. In this stress response, the body releases acetylcholine. In many ways, this reaction is the opposite of the sympathetic response, in that it slows the heart rate and can cause the patient to either regurgitate or temporarily lose consciousness. The evolutionary value of this is unclear, although it may have allowed for prey to appear dead to avoid being eaten.[1] ## Signs and symptoms[edit] The DSM-IV specifies that acute stress disorder must be accompanied by the presence of dissociative symptoms, which largely differentiates it from posttraumatic stress disorder. Dissociative symptoms include a sense of numbing or detachment from emotional reactions, a sense of physical detachment – such as seeing oneself from another perspective – decreased awareness of one's surroundings, the perception that one's environment is unreal or dreamlike, and the inability to recall critical aspects of the traumatic event (dissociative amnesia).[3] In addition to these characteristics, ASD can be present in the following four distinct symptom clusters;[4] Intrusion symptom cluster Recurring and distressing dreams, flashbacks, and/or memories related to the traumatic event. Intense/prolonged psychological distress or somatic reactions to internal or external traumatic cues. Negative mood cluster A persistent inability to experience positive emotions such as happiness, loving feelings, or satisfaction. Avoidance symptom cluster The avoidance of distressing memories, thoughts, feelings (or external reminders of them) that are closely associated with the traumatic event. Arousal symptom cluster Sleep disturbances, hyper-vigilance, difficulties with concentration, easily startled, and irritability/anger/aggression.[4] ## Causes[edit] There are several theoretical perspectives on trauma response, including cognitive, biological, and psycho-biological. While PTSD-specific, these theories are still useful in understanding acute stress disorder, as the two disorders share many symptoms.[3] A recent study found that even a single stressful event may have long-term consequences on cognitive function. This result calls the traditional distinction between the effects of acute and chronic stress into question.[5] ## Pathophysiology[edit] Stress is characterised by specific physiological responses to adverse or noxious stimuli. Hans Selye was the first to coin the term "general adaptation syndrome" to suggest that stress-induced physiological responses proceed through the stages of alarm, resistance, and exhaustion.[6] The sympathetic branch of the autonomic nervous system gives rise to a specific set of physiological responses to physical or psychological stress. The body's response to stress is also termed a "fight or flight" response, and it is characterised by an increase in blood flow to the skeletal muscles, heart, and brain, a rise in heart rate and blood pressure, dilation of pupils, and an increase in the amount of glucose released by the liver.[7] The onset of an acute stress response is associated with specific physiological actions in the sympathetic nervous system, both directly and indirectly through the release of adrenaline and, to a lesser extent, noradrenaline from the medulla of the adrenal glands. These catecholamine hormones facilitate immediate physical reactions by triggering increases in heart rate and breathing, constricting blood vessels. An abundance of catecholamines at neuroreceptor sites facilitates reliance on spontaneous or intuitive behaviours often related to combat or escape.[8] Normally, when a person is in a serene, non-stimulated state, the firing of neurons in the locus ceruleus is minimal. A novel stimulus, once perceived, is relayed from the sensory cortex of the brain through the thalamus to the brain stem. That route of signalling increases the rate of noradrenergic activity in the locus ceruleus, and the person becomes more alert and attentive to their environment.[9] If a stimulus is perceived as a threat, a more intense and prolonged discharge of the locus ceruleus activates the sympathetic division of the autonomic nervous system.[10] The activation of the sympathetic nervous system leads to the release of norepinephrine from nerve endings acting on the heart, blood vessels, respiratory centres, and other sites. The ensuing physiological changes constitute a major part of the acute stress response. The other major player in the acute stress response is the hypothalamic-pituitary-adrenal axis. Stress activates this axis and produces neuro-biological changes. These chemical changes increase the chances of survival by bringing the physiological system back to homeostasis.[11] The autonomic nervous system controls all automatic functions in the body and contains two subsections within it that aid the response to an acute stress reaction. These two subunits are the sympathetic nervous system and the parasympathetic nervous system. The sympathetic response is colloquially known as the "fight or flight" response, indicated by accelerated pulse and respiration rates, pupil dilation, and a general feeling of anxiety and hyper-awareness. This is caused by the release of epinephrine and norepinephrine from the adrenal glands. The epinephrine and norepinephrine strike the beta receptors of the heart, which feeds the heart's sympathetic nerve fibres to increase the strength of heart muscle contraction; as a result, more blood gets circulated, increasing the heart rate and respiratory rate. The sympathetic nervous system also stimulates the skeletal system and muscular system to pump more blood to those areas to handle the acute stress. Simultaneously, the sympathetic nervous system inhibits the digestive system and the urinary system to optimise blood flow to the heart, lungs, and skeletal muscles. This plays a role in the alarm reaction stage. The parasympathetic response is colloquially known as the "rest and digest" response, indicated by reduced heart and respiration rates, and, more obviously, by a temporary loss of consciousness if the system is fired at a rapid rate. The parasympathetic nervous system stimulates the digestive system and urinary system to send more blood to those systems to increase the process of digestion. To do this, it must inhibit the cardiovascular system and respiratory system to optimise blood flow to the digestive tract, causing low heart and respiratory rates. The parasympathetic nervous system plays no role in acute stress response.[12][13] Studies have shown that patients with acute stress disorder have overactive right amygdalae and prefrontal cortices; both structures are involved in the fear-processing pathway.[2] ## Diagnosis[edit] According to the DSM-V, symptom presentation must last for three consecutive days to be classified as acute stress disorder. If symptoms persist past one month, the diagnosis of PTSD is explored.[4] There must be a clear temporal connection between the impact of an exceptional stressor and the onset of symptoms; onset is usually within a few minutes or days but may occur up to one month after the stressor. Also, the symptoms show a mixed and rapidly changing picture; although "daze" depression, anxiety, anger, despair, hyper-activity, and withdrawal may all be seen, no one symptom dominates for long. The symptoms usually resolve rapidly where removal from the stressful environment is possible. In cases where the stress continues, the symptoms usually begin to diminish after 24–48 hours and are usually minimal after about three days. The DSM-V specifies that there is a higher prevalence rate of ASD among females compared to males due to higher risk of experiencing traumatic events and neurobiological gender differences in stress response.[4] ## Treatment[edit] This disorder may resolve itself with time or may develop into a more severe disorder, such as PTSD. However, results of Creamer, O'Donnell, and Pattison's (2004) study of 363 patients suggests that a diagnosis of acute stress disorder had only limited predictive validity for PTSD. Creamer et al. found that re-experiences of the traumatic event and arousal were better predictors of PTSD.[14] Early pharmacotherapy may prevent the development of post-traumatic symptoms.[15] Additionally, early trauma-focused cognitive behavioural therapy (TFCBT) for those with a diagnosis of ASD can protect an individual from developing chronic PTSD.[16] Studies have been conducted to assess the efficacy of counselling and psychotherapy for people with acute stress disorder. Cognitive behavioural therapy, which includes exposure and cognitive restructuring, was found to be effective in preventing PTSD in patients diagnosed with acute stress disorder with clinically significant results at six-month follow-up appointments. A combination of relaxation, cognitive restructuring, imaginal exposure, and in-vivo exposure was superior to supportive counselling.[17] Mindfulness-based stress reduction programmes also appear to be effective for stress management.[18] In a wilderness context where counselling, psychotherapy, and cognitive behavioural therapy is unlikely to be available, the treatment for acute stress reaction is very similar to the treatment of cardiogenic shock, vascular shock, and hypovolemic shock; that is, allowing the patient to lie down, providing reassurance, and removing the stimulus that prompted the reaction. In traditional shock cases, this generally means relieving injury pain or stopping blood loss. In an acute stress reaction, this may mean pulling a rescuer away from the emergency to calm down or blocking the sight of an injured friend from a patient.[12] ## History[edit] The term "acute stress disorder" was first used to describe the symptoms of soldiers during World War I and II, and it was therefore also termed "combat stress reaction" (CSR). Approximately 20% of U.S. troops displayed symptoms of CSR during WWII. It was assumed to be a temporary response of healthy individuals to witnessing or experiencing traumatic events. Symptoms include depression, anxiety, withdrawal, confusion, paranoia, and sympathetic hyperactivity.[3] The APA officially included the term ASD in the DSM-IV in 1994. Before that, symptomatic individuals within the first month of trauma were diagnosed with adjustment disorder. According to the DSM-IV, acute stress reaction refers to the symptoms experienced immediately to 48-hours after exposure to a traumatic event. In contrast, acute stress disorder is defined by symptoms experienced 48-hours to one-month following the event. Symptoms experienced for longer than one month are consistent with a diagnosis of PTSD.[3] Initially, being able to describe different ASRs was one of the goals of introducing ASD. Some criticisms surrounding ASD's focal point include issues with ASD recognising other distressing emotional reactions, like depression and shame. Emotional reactions similar to these may then be diagnosed as adjustment disorder under the current system of trying to diagnose ASD.[19] ## References[edit] 1. ^ a b c Isaac, Jeff. (2013). Wilderness and rescue medicine. Jones & Bartlett Learning. ISBN 9780763789206. OCLC 785442005. 2. ^ a b Reynaud, Emmanuelle; Guedj, Eric; Trousselard, Marion; El Khoury-Malhame, Myriam; Zendjidjian, Xavier; Fakra, Eric; Souville, Marc; Nazarian, Bruno; Blin, Olivier; Canini, Frédéric; Khalfa, Stephanie (2015). "Acute stress disorder modifies cerebral activity of amygdala and prefrontal cortex". Cognitive Neuroscience. 6 (1): 39–43. doi:10.1080/17588928.2014.996212. PMID 25599382. S2CID 12378221. 3. ^ a b c d Bryant, R.; Harvey, A. (2000). Acute Stress Disorder: A Handbook Of Theory, Assessment, And Treatment. Washington, D.C.: American Psychological Association. pp. 3–40, 87–134. 4. ^ a b c d American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5 ed.). Arlington, VA: American Psychiatric Publishing. 5. ^ Musazzi, L; Tornese, P; Sala, N; Popoli, M (2016). "Acute stress is not acute: Sustained enhancement of glutamate release after acute stress involves readily releasable pool size and synapsin I activation". Molecular Psychiatry. 22 (9): 1226–1227. doi:10.1038/mp.2016.175. PMID 27698433. S2CID 7077097. Lay summary – Neuroscience News (November 23, 2016). 6. ^ Butler, G (1993). "Definitions of stress". Occasional Paper (Royal College of General Practitioners) (61): 1–5. PMC 2560943. PMID 8199583. 7. ^ Widmaier, Eric P. (2015). Vander's Human Physiology: The Mechanisms Of Body Function. Boston: McGraw-Hill Education. p. 182. ISBN 978-1-259-60779-0. 8. ^ Eiden, Lee E. (2013). "Neuropeptide–Catecholamine Interactions in Stress". A New Era of Catecholamines in the Laboratory and Clinic. Advances in Pharmacology. 68. pp. 399–404. doi:10.1016/B978-0-12-411512-5.00018-X. ISBN 9780124115125. ISSN 1054-3589. PMC 3928117. PMID 24054154. 9. ^ McEwen, Bruce S.; Bowles, Nicole P.; Gray, Jason D.; Hill, Matthew N.; Hunter, Richard G.; Karatsoreos, Ilia N.; Nasca, Carla (2015). "Mechanisms of stress in the brain". Nature Neuroscience. 18 (10): 1353–1363. doi:10.1038/nn.4086. ISSN 1097-6256. PMC 4933289. PMID 26404710. 10. ^ Robins, Clive J. (1993). "Cognitive therapy with inpatients. J. Wright, M. Thase, A. Beck, J. Ludgate (eds). Guilford Press, New York, 1993. 445 pp., $36.95". Depression. 1 (6): 329–330. doi:10.1002/depr.3050010609. ISSN 1062-6417. 11. ^ Tsigos, Constantine; Chrousos, George P (October 2002). "Hypothalamic–pituitary-adrenal axis, neuroendocrine factors and stress". Journal of Psychosomatic Research. 53 (4): 865–871. doi:10.1016/s0022-3999(02)00429-4. ISSN 0022-3999. PMID 12377295. 12. ^ a b Isaac, Jeffrey E.; Johnson, David E. (2013). Wilderness and Rescue Medicine. Burlington, MA: Jones & Bartlett Learning. pp. 27–8. ISBN 978-0-7637-8920-6. 13. ^ VanPutte, C. L., Regan, J., Russo, A., Seeley, R. R., Stephens, T. D., Tate, P., & Seeley, R. R. (2014). Seeley's anatomy & physiology. New York, NY: McGraw-Hill. 14. ^ Creamer, Mark; o'Donnell, Meaghan L; Pattison, Phillipa (2004). "The relationship between acute stress disorder and posttraumatic stress disorder in severely injured trauma survivors". Behaviour Research and Therapy. 42 (3): 315–28. doi:10.1016/s0005-7967(03)00141-4. PMID 14975772. 15. ^ Vaiva, G; Ducrocq, F; Jezequel, K; Averland, B; Lestavel, P; Brunet, A; Marmar, C. R (2003). "Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma". Biological Psychiatry. 54 (9): 947–9. doi:10.1016/s0006-3223(03)00412-8. PMID 14573324. S2CID 3064619. 16. ^ Kornør, Hege; Winje, Dagfinn; Ekeberg, Øivind; Weisæth, Lars; Kirkehei, Ingvild; Johansen, Kjell; Steiro, Asbjørn (September 2008). "Early trauma-focused cognitive-behavioural therapy to prevent chronic post-traumatic stress disorder and related symptoms: A systematic review and meta-analysis". BMC Psychiatry. 8: 8. doi:10.1186/1471-244x-8-81. PMC 2559832. PMID 18801204. 17. ^ Lambert, M.J., ed. (2004). Bergin and Garfield's Handbook of Psychotherapy and Behavioral Change. New York: Wiley.[page needed] 18. ^ Sharma, Manoj; Rush, Sarah E (2014). "Mindfulness-Based Stress Reduction as a Stress Management Intervention for Healthy Individuals". Journal of Evidence-Based Complementary & Alternative Medicine. 19 (4): 271–86. doi:10.1177/2156587214543143. PMID 25053754. 19. ^ Bryant, Richard A.; Friedman, Matthew J.; Spiegel, David; Ursano, Robert; Strain, James (September 2011). "A review of acute stress disorder in DSM-5". Depression and Anxiety. 28 (9): 802–817. doi:10.1002/da.20737. PMID 21910186. S2CID 46689852. ## External links[edit] Classification D * ICD-10: F43.0 * ICD-9-CM: 308 * MeSH: D040701 * v * t * e Emotions (list) Emotions * Acceptance * Adoration * Aesthetic emotions * Affection * Agitation * Agony * Amusement * Anger * Angst * Anguish * Annoyance * Anticipation * Anxiety * Apathy * Arousal * Attraction * Awe * Boredom * Calmness * Compassion * Confidence * Contempt * Contentment * Courage * Cruelty * Curiosity * Defeat * Depression * Desire * Despair * Disappointment * Disgust * Distrust * Ecstasy * Embarrassment * Vicarious * Empathy * Enthrallment * Enthusiasm * Envy * Euphoria * Excitement * Fear * Flow (psychology) * Frustration * Gratification * Gratitude * Greed * Grief * Guilt * Happiness * Hatred * Hiraeth * Homesickness * Hope * Horror * Hostility * Humiliation * Hygge * Hysteria * Indulgence * Infatuation * Insecurity * Inspiration * Interest * Irritation * Isolation * Jealousy * Joy * Kindness * Loneliness * Longing * Love * Limerence * Lust * Mono no aware * Neglect * Nostalgia * Outrage * Panic * Passion * Pity * Self-pity * Pleasure * Pride * Grandiosity * Hubris * Insult * Vanity * Rage * Regret * Social connection * Rejection * Remorse * Resentment * Sadness * Melancholy * Saudade * Schadenfreude * Sehnsucht * Self-confidence * Sentimentality * Shame * Shock * Shyness * Sorrow * Spite * Stress * Suffering * Surprise * Sympathy * Tenseness * Trust * Wonder * Worry World views * Cynicism * Defeatism * Nihilism * Optimism * Pessimism * Reclusion * Weltschmerz Related * Affect * consciousness * in education * measures * in psychology * Affective * computing * forecasting * neuroscience * science * spectrum * Affectivity * positive * negative * Appeal to emotion * Emotion * and art * and memory * and music * and sex * classification * evolution * expressed * functional accounts * group * homeostatic * perception * recognition * in conversation * in animals * regulation * interpersonal * work * Emotional * aperture * bias * blackmail * competence * conflict * contagion * detachment * dysregulation * eating * exhaustion * expression * intelligence * and bullying * intimacy * isolation * lability * labor * lateralization * literacy * prosody * reasoning * responsivity * security * selection * symbiosis * well-being * Emotionality * bounded * Emotions * and culture * in decision-making * in the workplace * in virtual communication * history * moral * self-conscious * social * social sharing * sociology * Feeling * Gender and emotional expression * Group affective tone * Interactions between the emotional and executive brain systems * Meta-emotion * Pathognomy * Pathos * Social emotional development * Stoic passions * Theory * affect * appraisal * discrete emotion * somatic marker * constructed emotion * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acute stress disorder	c0029488	29,923	wikipedia	https://en.wikipedia.org/wiki/Acute_stress_disorder	2021-01-18T18:44:11	{"mesh": ["D040701"], "umls": ["C0029488"], "icd-10": ["F43.0"], "wikidata": ["Q424221"]}
White coat hypertension Other namesWhite coat syndrome A white coat and scrubs White coat hypertension (WHT), more commonly known as white coat syndrome, is a form of labile hypertension[1] in which people exhibit a blood pressure level above the normal range, in a clinical setting, although they do not exhibit it in other settings.[2] It is believed that the phenomenon is due to anxiety experienced during a clinic visit.[3] The patient's daytime ambulatory blood pressure is used as a reference as it takes into account ordinary levels of daily stress. Many problems have been incurred in the diagnosis and treatment of white coat hypertension. The term "masked hypertension" can be used to describe the contrasting phenomenon, where a patient's blood pressure is above the normal range during daily living, although it isn't above the normal range when the patient is in a clinic setting.[4] ## Contents * 1 Diagnosis * 2 Implications for treatment * 3 References * 4 External links ## Diagnosis[edit] In studies, white coat hypertension can be defined as the presence of a defined hypertensive average blood pressure in a clinic setting, although it isn't present when the patient is at home.[5] Diagnosis is made difficult as a result of the unreliable measures taken from the conventional methods of detection. These methods often involve an interface with health care professionals and frequently results are tarnished by a list of factors including variability in the individual’s blood pressure, technical inaccuracies, anxiety of the patient,[6] recent ingestion of pressor substances, and talking, amongst many other factors. The most common measure of blood pressure is taken from a noninvasive instrument called a sphygmomanometer. "A survey showed that 96% of primary care physicians habitually use a cuff size too small,"[7] adding to the difficulty in making an informed diagnosis. For such reasons, white coat hypertension cannot be diagnosed with a standard clinical visit. It can be reduced (but not eliminated) with automated blood pressure measurements over 15 to 20 minutes in a quiet part of the office or clinic.[8] Patients with white coat hypertension do not exhibit the signs indicative of trepidation and their increased blood pressure is often not accompanied by tachycardia.[9] This is supported by studies that repeatedly indicate that 15%–30% of those thought to have mild hypertension as a result of clinic or office recordings display normal blood pressure and no unusual response to pressure stimulus. These persons did not show any specific characteristics such as age that may be indicative of a higher susceptibility to white coat hypertension.[10] Ambulatory blood pressure monitoring and patient self-measurement using a home blood pressure monitoring device is being increasingly used to differentiate those with white coat hypertension or experiencing the white coat effect from those with chronic hypertension. This does not mean that these methods are without fault. Daytime ambulatory values, despite taking into account stresses of everyday life when taken during the patient's daily routine, are still susceptible to the effects of daily variables such as physical activity, stress and duration of sleep. Ambulatory monitoring has been found to be the more practical and reliable method in detecting patients with white coat hypertension and for the prediction of target organ damage. Even as such, the diagnosis and treatment of white coat hypertension remains controversial. Recent studies showed that home blood pressure monitoring is as accurate as a 24-hour ambulatory monitoring in determining blood pressure levels.[11] Researchers at the University of Turku, Finland studied 98 patients with untreated hypertension. They compared patients using a home blood pressure device and those wearing a 24-hour ambulatory monitor. Researcher Dr. Niiranen said that "home blood pressure measurement can be used effectively for guiding anti-hypertensive treatment". Dr. Stergiou added that home tracking of blood pressure "is more convenient and also less costly than ambulatory monitoring." Use of breathing patterns has been proposed as a technique for identifying white coat hypertension.[12] In one Turkish study of 438 consecutive patients, 38% were normotensive, 43% had white coat hypertension, 2% had masked hypertension, and 15% had sustained hypertension. Even patients taking medication for sustained hypertension who are normotensive at home may exhibit white coat hypertension in the office setting.[13] ## Implications for treatment[edit] In general, individuals with white coat hypertension have lower morbidity than patients with sustained hypertension, but higher morbidity than the clinically normotensive.[14] However all published trials on the consequences of high blood pressure and the benefits of treating, are based on one-time measurement in clinical settings rather than the generally lower readings obtained from ambulatory recordings. The debate and conflicting ideas revolve around whether or not it would be feasible to treat white coat hypertension, as there still is no conclusive evidence that a temporary rise in blood pressure during office visits has an adverse effect on health. In fact, many cross sectional studies have shown that "target-organ damage (as exemplified by left ventricular hypertrophy) is less in white-coat hypertensive patients than in sustained hypertensive patients even after the allowance has been made for differences in clinic pressure".[7] Many believe that patients with "white coat" hypertension do not require even very small doses of antihypertensive therapy as it may result in hypotension, but must still be careful as patients may show signs of vascular changes and may eventually develop hypertension. Even patients with established hypertension that is well-controlled based on home blood pressure monitoring may experience elevated readings during office visits. ## References[edit] 1. ^ Mann, Samuel J. (2009). "The Clinical Spectrum of Labile Hypertension: A Management Dilemma". The Journal of Clinical Hypertension. 11 (9): 491–497. doi:10.1111/j.1751-7176.2009.00155.x. PMID 19751461. S2CID 9378265. 2. ^ "Hypertension: Overview". eMedicine. 3. ^ Swan, Norman (20 June 2010). Health Minutes - Hypertension. Retrieved 27 August 2010. 4. ^ Pickering TG, Eguchi K, Kario K (June 2007). "Masked hypertension: a review" (–). Hypertens. Res. 30 (6): 479–88. doi:10.1291/hypres.30.479. PMID 17664850. 5. ^ Ruxer J, Mozdzan M, Baranski M, Wozniak-Sosnowska U, Markuszewski L (October 2007). ""White coat hypertension" in type 2 diabetic patients". Pol. Arch. Med. Wewn. 117 (10): 452–6. PMID 18320786. 6. ^ Jhalani, Juhee a; Goyal, Tanya a; Clemow, Lynn a; Schwartz, Joseph E. b; Pickering, Thomas G. a; Gerin, William a (December 2005). "Anxiety and outcome expectations predict the white-coat effect". Blood Pressure Monitoring. Lippincott Williams & Wilkins, Inc. 10 (6): 317–319. doi:10.1097/00126097-200512000-00006. PMID 16496447. S2CID 2058260. 7. ^ a b Pickering T (1994). "Blood pressure measurement and detection of hypertension". Lancet. 344 (8914): 31–5. doi:10.1016/S0140-6736(94)91053-7. PMID 7912303. S2CID 41756474. 8. ^ Pickering, TG; Hall, JE; Appel, LJ; et al. (2005). "Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research". Hypertension. 45 (5): 142–61. doi:10.1161/01.HYP.0000150859.47929.8e. PMID 15611362.CS1 maint: multiple names: authors list (link) See p. 146, Masked Hypertension or Isolated Ambulatory Hypertension. 9. ^ Pickering T, James G, Boddie C, Harshfield G, Blank S, Laragh J (1988). "How common is white coat hypertension?". JAMA. 259 (2): 225–8. doi:10.1001/jama.259.2.225. PMID 3336140. 10. ^ McGrath B (1996). "Is white-coat hypertension innocent?". Lancet. 348 (9028): 630. doi:10.1016/S0140-6736(05)65069-6. PMID 8782749. S2CID 6990525. \- commentary on: Glen S, Elliott H, Curzio J, Lees K, Reid J (1996). "White-coat hypertension as a cause of cardiovascular dysfunction". Lancet. 348 (9028): 654–7. doi:10.1016/S0140-6736(96)02303-3. PMID 8782756. S2CID 35890241. 11. ^ Niiranen TJ, Kantola IM, Vesalainen R, Johansson J, Ruuska MJ (May 2006). "A comparison of home measurement and ambulatory monitoring of blood pressure in the adjustment of antihypertensive treatment". Am. J. Hypertens. 19 (5): 468–74. doi:10.1016/j.amjhyper.2005.10.017. PMID 16647616. 12. ^ Thalenberg JM, Póvoa RM, Bombig MT, de Sá GA, Atallah AN, Luna Filho B (October 2008). "Slow breathing test increases the suspicion of white-coat hypertension in the office". Arq. Bras. Cardiol. 91 (4): 243–9, 267–73. doi:10.1590/s0066-782x2008001600010. PMID 19009177. 13. ^ Helvaci MR, Seyhanli M (2006). "What a high prevalence of white coat hypertension in society!". Intern. Med. 45 (10): 671–4. doi:10.2169/internalmedicine.45.1650. PMID 16778338. 14. ^ Khan TV, Khan SS, Akhondi A, Khan TW (2007). "White coat hypertension: relevance to clinical and emergency medical services personnel". MedGenMed. 9 (1): 52. PMC 1924974. PMID 17435652. ## External links[edit] Classification D * MeSH: D059466 * DiseasesDB: 14138 * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	White coat hypertension	c0262534	29,924	wikipedia	https://en.wikipedia.org/wiki/White_coat_hypertension	2021-01-18T18:36:03	{"mesh": ["D059466"], "umls": ["C0262534"], "wikidata": ["Q1777563"]}
Brachymetatarsia Other namesHypoplastic metatarsal X-ray of congenital brachymetatarsia involving fourth metatarsal bone SpecialtyMedical genetics, rheumatology Brachymetatarsia is a condition in which there is one or more abnormally short or overlapping toe bones (metatarsals).[1] This condition may result due to a congenital defect or it may be an acquired condition.[1] It most frequently involves the fourth metatarsal. If it involves the first metatarsal, the condition is known as Morton's syndrome.[1] Treatment is via a number of differing surgical procedures.[1] ## Contents * 1 Diagnosis * 1.1 Differential diagnosis * 2 Treatment * 3 Epidemiology * 4 References ## Diagnosis[edit] ### Differential diagnosis[edit] Congenital causes include: Aarskog syndrome, Turner syndrome, Albright's hereditary osteodystrophy, maternal ingestion of thalidomide during pregnancy and Apert syndrome. Can be caused by a trauma, although the exact mechanism is not known.[1] ## Treatment[edit] Bilateral brachymetatarsia of the fourth metatarsal Symptoms may be treated by wearing wider shoes to relieve pressure, or patient can wear padding around the toes. Surgery is also an option, if the pain and discomfort cannot be treated, or for cosmetic reasons. In this procedure, the short metatarsal is typically cut and a piece of bone is grafted between the two ends. In some cases an external fixator may be attached to the metatarsal with pins. Within the external fixator is an adjustable screw that must be turned (per doctors' orders) to lengthen the gap between bone segments, so the bone will regrow to the appropriate shape. Following surgery, crutches or a knee scooter should be used to keep all weight off the surgically repaired foot for 3 months. After this period, orthopedic shoes or boots may be used.[2] ## Epidemiology[edit] Brachymetatarsia is found to occur more frequently in women than men.[1] ## References[edit] 1. ^ a b c d e f Schimizzi A, Brage M (September 2004). "Brachymetatarsia". Foot Ankle Clin. 9 (3): 555–70, ix. doi:10.1016/j.fcl.2004.05.002. PMID 15324790. 2. ^ http://www.healthcommunities.com [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Brachymetatarsia	c0265650	29,925	wikipedia	https://en.wikipedia.org/wiki/Brachymetatarsia	2021-01-18T19:07:17	{"icd-10": ["M21.6", "Q72.8"], "wikidata": ["Q2923350"]}
A number sign (#) is used with this entry because of evidence that aniridia-3 (AN3) is caused by heterozygous mutation in the TRIM44 gene (612298) on chromosome 11p13. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of aniridia, see AN1 (106210). Clinical Features Zhang et al. (2015) studied a 4-generation Chinese family in which 8 patients had aniridia without systemic abnormalities. The patients ranged in age from 7 to 55 years, and all had complete bilateral defects of the iris. Visual acuity gradually decreased over time due to the irregular lens opacity caused by lack of iris block and direct exposure to the sun. Visual impairment was exacerbated by associated complications, including cataract and glaucoma. Cataract was observed in patients over the age of 10 years. None of the patients exhibited congenital corneal opacity. Mapping In 7 affected and 13 unaffected members of a 4-generation Chinese family segregating autosomal dominant aniridia, Zhang et al. (2015) performed linkage and haplotype analysis and identified a shared haplotype in the 7 patients at chromosome 11p13, with a maximum lod score of 2.72 at D11S907 (theta = 0). Molecular Genetics In a 4-generation Chinese family with aniridia mapping to chromosome 11p13, negative for mutation in the coding and splicing regions of the PAX6 (607108), FOXC1 (601090), and PITX2 (601542) genes, Zhang et al. (2015) performed whole-exome sequencing and identified 4 patient-specific mutations: 2 variants in the 3-prime UTR of PAX6, and 2 missense mutations in the TRIM44 gene (612298), located approximately 4 Mb from PAX6. Functional analysis indicated that the 2 PAX6 variants were unlikely to contribute to the pathogenesis of aniridia in this pedigree. However, the identified TRIM44 G155R substitution (612298.0001), which is located at a conserved residue and was not found in public variant databases, showed significantly stronger suppression of PAX6 expression than wildtype. The other TRIM44 variant involved a nonconserved residue, was found in Asian and European populations of the ExAC database, and exhibited suppression of PAX6 at a similar level as wildtype TRIM44. Zhang et al. (2015) concluded that TRIM44 is a negative regulator that restricts expression of PAX6 and that the G155R mutation significantly enhances its activity, representing a novel pathogenic mechanism for aniridia. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Decreased visual acuity, progressive \- Bilateral defects of the iris \- Cataract \- Glaucoma (in some patients) MISCELLANEOUS \- Progressive decreased visual acuity due to gradual development of cataract caused by exposure to sun \- Based on report of one 4-generation Chinese family (last curated October 2016) MOLECULAR BASIS \- Caused by mutation in the tripartite motif-containing protein-44 gene (TRIM44, 612298.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ANIRIDIA 3	c0003076	29,926	omim	https://www.omim.org/entry/617142	2019-09-22T15:46:42	{"mesh": ["D015783"], "omim": ["617142"], "orphanet": ["250923"]}
Waxy skin SpecialtyDermatology Waxy skin is a cutaneous condition observed in roughly 50% of diabetic patients with longstanding disease.[1]:540 ## See also[edit] * Diabetic dermadromes * Limited joint mobility * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Waxy skin	None	29,927	wikipedia	https://en.wikipedia.org/wiki/Waxy_skin	2021-01-18T18:42:21	{"wikidata": ["Q7975738"]}
## Clinical Features Neuhauser et al. (1976) described tremor, nystagmus, and duodenal ulcer in multiple persons in a kindred. Essential tremor developed in 12 of 17 affected members. Alcohol controlled the tremor temporarily. Severely affected members became alcoholics. The most severely affected persons showed cerebellar signs. Nystagmus occurred often in the absence of tremor and was usually congenital. Duodenal ulcer appeared to be a pleiotropic effect. It sometimes preceded onset of tremor. Inheritance The transmission pattern of tremor, nystagums, and duodenal ulcer in the family reported by Neuhauser et al. (1976) was consistent with autosomal dominant inheritance. Misc \- Response to alcohol \- Cerebellar signs \- Nystagmus Neuro \- Essential tremor GI \- Duodenal ulcer Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	TREMOR, NYSTAGMUS, AND DUODENAL ULCER	c1860860	29,928	omim	https://www.omim.org/entry/190310	2019-09-22T16:32:26	{"mesh": ["C536406"], "omim": ["190310"], "orphanet": ["3350"]}
Water–electrolyte imbalance Diagram of ion concentrations and charge across a semi-permeable cellular membrane. SpecialtyNephrology Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Electrolyte disturbances are involved in many disease processes, and are an important part of patient management in medicine.[1][2] The causes, severity, treatment, and outcomes of these disturbances can vastly differ depending on the implicated electrolyte.[3] The most serious electrolyte disturbances involve abnormalities in the levels of sodium, potassium or calcium. Other electrolyte imbalances are less common and often occur in conjunction with major electrolyte changes. The kidney is the most important organ in maintaining appropriate fluid and electrolyte balance, but other factors such as hormonal changes and physiological stress play a role.[2] Chronic laxative abuse or severe diarrhea or vomiting can lead to dehydration and electrolyte imbalance. People suffering from malnutrition are at especially high risk for an electrolyte imbalance. Severe electrolyte imbalances must be treated carefully as there are risks with overcorrecting too quickly, which can result in arrhythmias, brain herniation, or refeeding syndrome depending on the cause of imbalance.[4][5][6] ## Contents * 1 General function * 2 Sodium * 2.1 Hypernatremia * 2.1.1 Causes * 2.1.2 Symptoms * 2.1.3 Treatment * 2.2 Hyponatremia * 2.2.1 Causes * 2.2.2 Symptoms * 2.2.3 Treatment * 3 Potassium * 3.1 Hyperkalemia * 3.1.1 Causes * 3.1.2 Symptoms * 3.1.3 Treatment * 3.2 Hypokalemia * 3.2.1 Causes * 3.2.2 Symptoms * 3.2.3 Treatment * 4 Calcium * 4.1 Hypercalcemia * 4.1.1 Causes * 4.1.2 Symptoms * 4.1.3 Treatment * 4.2 Hypocalcemia * 4.2.1 Causes * 4.2.2 Symptoms * 4.2.3 Treatment * 5 Magnesium * 5.1 Hypermagnesemia * 5.1.1 Causes * 5.1.2 Symptoms * 5.1.3 Treatment * 5.2 Hypomagnesemia * 5.2.1 Causes * 5.2.2 Symptoms * 5.2.3 Treatment * 6 Chloride * 6.1 Hyperchloremia * 6.1.1 Causes * 6.1.2 Symptoms * 6.1.3 Treatment * 6.2 Hypochloremia * 6.2.1 Causes * 6.2.2 Symptoms * 6.2.3 Treatment * 7 Dietary sources * 7.1 Sodium * 7.2 Potassium * 7.3 Calcium * 7.4 Magnesium * 8 See also * 9 References * 10 External links ## General function[edit] Electrolytes are important because they are what cells (especially nerve, heart and muscle cells) use to maintain voltages across their cell membranes. Electrolytes have different functions, and an important one is to carry electrical impulses between cells.[citation needed] Kidneys work to keep the electrolyte concentrations in blood constant despite changes in the body.[4][6] For example, during heavy exercise, electrolytes are lost in sweat, particularly in the form of sodium and potassium.[6] The kidneys can also generate dilute urine to balance sodium levels.[6] These electrolytes must be replaced to keep the electrolyte concentrations of the body fluids constant. Hyponatremia, or low sodium, is the most commonly seen type of electrolyte imbalance.[7][8] Treatment of electrolyte imbalance depends on the specific electrolyte involved and whether the levels are too high or too low.[3] The level of aggressiveness of treatment and choice of treatment may change depending on the severity of the disturbance.[3] If the levels of an electrolyte are too low, a common response to electrolyte imbalance may be to prescribe supplementation. However, if the electrolyte involved is sodium, the issue is not a deficiency of sodium, but rather a water excess, causing the imbalance. Supplementation for these people may correct the electrolyte imbalance but at the expense of volume overload, which can be dangerous particularly for neonates.[4] Because each individual electrolyte affects physiological function differently, they must be considered separately when discussing causes, treatment, and complications. ## Sodium[edit] Sodium is the most abundant electrolyte in the blood.[citation needed] Sodium and its homeostasis in the human body is highly dependent on fluids. The human body is approximately 60% water, a percentage which is also known as total body water. The total body water can be divided into two compartments called extracellular fluid (ECF) and intracellular fluid (ICF). The majority of the sodium in the body stays in the extracellular fluid compartment.[9] This compartment consists of the fluid surrounding the cells and the fluid inside the blood vessels. ECF has a sodium concentration of approximately 140 mEq/L.[9] Because cells membranes are permeable to water and not sodium, the movement of water across membranes affects the concentration of sodium in the blood. Sodium acts as a force that pulls water across membranes, and water moves from places with lower sodium concentration to places with higher sodium concentration. This happens through a process called osmosis.[9] When evaluating sodium imbalances, both total body water and total body sodium must be considered.[3] ### Hypernatremia[edit] Main article: Hypernatremia Hypernatremia means that the concentration of sodium in the blood is too high. An individual is considered to be having high sodium at levels above 145 mEq/L of sodium. Hypernatremia is not common in individuals with no other health concerns.[3] Most individuals with this disorder have either experienced loss of water from diarrhea, altered sense of thirst, inability to consume water, inability of kidneys to make concentrated urine, or increased salt intake.[3][9] #### Causes[edit] There are three types of hypernatremia each with different causes.[3] The first is dehydration along with low total body sodium. This is most commonly caused by heatstroke, burns, extreme sweating, vomiting, and diarrhea.[3] The second is low total body water with normal body sodium. This can be caused by diabetes insipidus, renal disease, hypothalamic dysfunction, sickle cell disease, and certain drugs.[3] The third is increased total body sodium which is caused by increased ingestion, Conn's syndrome, or Cushing's syndrome.[3] #### Symptoms[edit] Symptoms of hypernatremia may vary depending on type and how quickly the electrolyte disturbance developed.[9] Common symptoms are dehydration, nausea, vomiting, fatigue, weakness, increased thirst, excess urination. Patients may be on medications that caused the imbalance such as diuretics or nonsteroidal anti-inflammatory drugs.[9] Some patients may have no obvious symptoms at all.[9] #### Treatment[edit] It is crucial to first assess the stability of the patient. If there are any signs of shock such as tachycardia or hypotension, these must be treated immediately with IV saline infusion.[3][9] Once the patient is stable, it is important to identify the underlying cause of hypernatremia as that may affect the treatment plan.[3][9] The final step in treatment is to calculate the patients free water deficit, and to replace it at a steady rate using a combination of oral or IV fluids.[3][9] The rate of replacement of fluids varies depending on how long the patient has been hypernatremic. Lowering the sodium level too quickly can cause cerebral edema.[9] ### Hyponatremia[edit] Main article: Hyponatremia Hyponatremia means that the concentration of sodium in the blood is too low. It is generally defined as a concentration lower than 135 mEq/L.[3] This relatively common electrolyte disorder can indicate the presence of a disease process, but in the hospital setting is more often due to administration of Hypotonic fluids.[10][3] The majority of hospitalized patients only experience mild hyponatremia, with levels above 130 mEq/L. Only 1-4% of patients experience levels lower than 130 mEq/L.[10] #### Causes[edit] Hyponatremia has many causes including heart failure, chronic kidney disease, liver disease, treatment with thiazide diuretics, psychogenic polydipsia, syndrome of inappropriate antidiuretic hormone secretion.[3] It can also be found in the postoperative state, and in the setting of accidental water intoxication as can be seen with intense exercise.[3] Common causes in pediatric patients may be diarrheal illness, frequent feedings with dilute formula, water intoxication via excessive consumption, and enemas.[3] pseudohyponatremia is a false low sodium reading that can be caused by high levels of fats or proteins in the blood.[10][3] Dilutional hyponatremia can happen in diabetics as high glucose levels pull water into the blood stream causing the sodium concentration to be lower.[10][3] Diagnosis of the cause of hyponatremia relies on three factors: volume status, plasma osmolality, urine sodium levels and urine osmolality.[10][3] #### Symptoms[edit] Many individuals with mild hyponatremia will not experience symptoms. Severity of symptoms is directly correlated with severity of hyponatremia and rapidness of onset.[3] General symptoms include loss of appetite, nausea, vomiting, confusion, agitation, and weakness.[10][3] More concerning symptoms involve the central nervous system and include seizures, coma, and death due to brain herniation.[10][3] These usually do not occur until sodium levels fall below 120 mEq/L.[3] #### Treatment[edit] Considerations for treatment include symptom severity, time to onset, volume status, underlying cause, and sodium levels.[10] If the sodium level is <120 mEq/L, the person can be treated with hypertonic saline as extremely low levels are associated with severe neurological symptoms.[10] In non-emergent situations, it is important to correct the sodium slowly to minimize risk of osmotic demyelination syndrome.[10][3] If a person has low total body water and low sodium they are typically given fluids.[3] If a person has high total body water (such as due to heart failure or kidney disease) they may be placed on fluid restriction, salt restriction, and treated with a diuretic.[3] If a person has a normal volume of total body water, they may be placed on fluid restriction alone.[3] ## Potassium[edit] Potassium resides mainly inside the cells of the body, so its concentration in the blood can range anywhere from 3.5 mEq/L to 5 mEq/L.[10] The kidneys are responsible for excreting the majority of potassium from the body.[10] This means their function is crucial for maintaining a proper balance of potassium in the blood stream. ### Hyperkalemia[edit] Main article: Hyperkalemia Hyperkalemia means the concentration of potassium in the blood is too high. This occurs when the concentration of potassium is >5 mEq/L.[3][10] It can lead to cardiac arrhythmias and even death.[3] As such it is considered to be the most dangerous electrolyte disturbance.[3] #### Causes[edit] Hyperkalemia is typically caused by decreased excretion by the kidneys, shift of potassium to the extracellular space, or increased consumption of potassium rich foods in patients with kidney failure.[3] The most common cause of hyperkalemia is lab error due to potassium released as blood cells from the sample break down.[10] Other common causes are kidney disease, cell death, acidosis, and drugs that affect kidney function.[3] #### Symptoms[edit] Part of the danger of hyperkalemia is that it is often asymptomatic, and only detected during normal lab work done by primary care physicians.[3] As potassium levels get higher, individuals may begin to experience nausea, vomiting, and diarrhea.[3] Patients with severe hyperkalemia, defined by levels above 7 mEq/L, may experience muscle cramps, numbness, tingling, absence of reflexes, and paralysis.[3][10] Patients may experience arrhythmias that can result in death.[3][10] #### Treatment[edit] There are three mainstays of treatment of hyperkalemia. These are stabilization of cardiac cells, shift of potassium into the cells, and removal of potassium from the body.[3][10] Stabilization of cardiac muscle cells is done by administering calcium intravenously.[3] Shift of potassium into the cells is done using both insulin and albuterol inhalers.[3] Excretion of potassium from the body is done using either hemodialysis, loop diuretics, or a resin that causes potassium to be excreted in the fecal matter.[3] ### Hypokalemia[edit] Main article: Hypokalemia The most common electrolyte disturbance, hypokalemia means that the concentration of potassium is <3.5 mEq/L.[3] It often occurs concurrently with low magnesium levels.[3] #### Causes[edit] Low potassium is caused by increased excretion of potassium, decreased consumption of potassium rich foods, movement of potassium into the cells, or certain endocrine diseases.[3] Excretion is the most common cause of hypokalemia and can be caused by diuretic use, metabolic acidosis, diabetic ketoacidosis, hyperaldosteronism, and renal tubular acidosis.[3] Potassium can also be lost through vomiting and diarrhea.[10] #### Symptoms[edit] Hypokalemia is often asymptomatic, and symptoms may not appear until potassium concentration is <2.5 mEq/L.[10] Typical symptoms consist of muscle weakness and cramping. Low potassium can also cause cardiac arrythmias.[3][10] #### Treatment[edit] Hypokalemia is treated by replacing the body's potassium. This can occur either orally or intravenously.[3][10] Because low potassium is usually accompanied by low magnesium, patients are often given magnesium alongside potassium.[10] ## Calcium[edit] Though calcium is the most plentiful electrolyte in the body, a large percentage of it is used to form the bones.[10] It is mainly absorbed and excreted through the GI system.[10] The majority of calcium resides extracellularly, and it is crucial for the function of neurons, muscle cells, function of enzymes, and coagulation.[10] The normal range for calcium concentration in the body is 8.5 - 10.5 mg/dL.[11] The parathyroid gland is responsible for sensing changes in calcium concentration and regulating the electrolyte with parathyroid hormone.[12] ### Hypercalcemia[edit] Main article: Hypercalcaemia Hypercalcemia describes when the concentration of calcium in the blood is too high. This occurs above 10.5 mg/dL.[3] #### Causes[edit] The most common causes of hypercalcemia are certain types of cancer, hyperparathyroidism, hyperthyroidism, pheochromocytoma, excessive ingestion of vitamin D, sarcoidosis, and tuberculosis.[3] Hyperparathyroidism and malignancy are the predominate causes.[10] It can also be caused by muscle cell breakdown, prolonged immobilization, dehydration.[3] #### Symptoms[edit] The predominant symptoms of hypercalcemia are abdominal pain, constipation, kidney stones, extreme thirst, excessive urination, nausea and vomiting.[3][10] In severe cases where the calcium concentration is >14 mg/dL, individuals may experience confusion, altered mental status, coma, and seizure.[3][10] #### Treatment[edit] Primary treatment of hypercalcemia consists of administering IV fluids.[3] If the hypercalcemia is severe and/or associated with cancer, it may be treated with bisphosphonates.[3][10] For very severe cases, hemodialysis may be considered for rapid removal of calcium from the blood.[3][10] ### Hypocalcemia[edit] Main article: Hypocalcaemia Hypocalcemia describes when calcium levels are too low in the blood, usually less than 8.5 mg/dL. #### Causes[edit] Hypoparathyroidism and vitamin D deficiency are common causes of hypocalcemia.[3] It can also be caused by malnutrition, blood transfusion, ethylene glycol intoxication, and pancreatitis.[3] #### Symptoms[edit] Neurological and cardiovascular symptoms are the most common manifestations of hypocalcemia.[3][10] Patients may experience muscle cramping or twitching, and numbness around the mouth and fingers. They may also have shortness of breath, low blood pressure, and cardiac arrhythmias.[3] #### Treatment[edit] Patients with hypocalcemia may be treated with either oral or IV calcium.[3] Typically, IV calcium is reserved for patients with severe hypocalcemia.[3][10] It is also important to check magnesium levels in patients with hypocalcemia and to replace magnesium if it is low.[10] ## Magnesium[edit] Magnesium is mostly found in the bones and within cells. Approximately 1% of total magnesium in the body is found in the blood.[13] Magnesium is important in control of metabolism and is involved in numerous enzyme reactions. A normal range is 0.70 - 1.10 mmol/L.[13] The kidney is responsible for maintaining the magnesium levels in this narrow range. ### Hypermagnesemia[edit] Main article: Hypermagnesemia Hypermagnesemia, or abnormally high levels of magnesium in the blood, is relatively rare in individuals with normal kidney function.[14] This is defined by a magnesium concentration >2.5 mg/dL. #### Causes[edit] Hypermagnesemia typically occurs in individuals with abnormal kidney function. This imbalance can also occur with use of antacids or laxatives that contain magnesium. Most cases of hypermagnesemia can be prevented by avoiding magnesium-containing medications. #### Symptoms[edit] Mild symptoms include nausea, flushing, tiredness. Neurologic symptoms are seen most commonly including decreased deep tendon reflexes. Severe symptoms include paralysis, respiratory failure, and bradycardia progressing to cardiac arrest. #### Treatment[edit] If kidney function is normal, stopping the source of magnesium intake is sufficient. Diuretics can help increase magnesium excretion in the urine. Severe symptoms may be treated with dialysis to directly remove magnesium from the blood. ### Hypomagnesemia[edit] Main article: Magnesium deficiency Hypomagnesemia, or low magnesium levels in the blood, can occur in up to 12% of hospitalized patients.[15] Symptoms or effects of hypomagnesemia can occur after relatively small deficits. #### Causes[edit] Major causes of hypomagnesemia are from gastrointestinal losses such as vomiting and diarrhea. Another major cause is from kidney losses from diuretics, alcohol use, hypercalcemia, and genetic disorders. Low dietary intake can also contribute to magnesium deficiency. #### Symptoms[edit] Hypomagnesemia is typically associated with other electrolyte abnormalities, such as hypokalemia and hypocalcemia. For this reason, there may be overlap in symptoms seen in these other electrolyte deficiencies. Severe symptoms include arrhythmias, seizures, or tetany. #### Treatment[edit] The first step in treatment is determining whether the deficiency is caused by a gastrointestinal or kidney problem. People with no or minimal symptoms are given oral magnesium; however, many people experience diarrhea and other gastrointestinal discomfort. Those who cannot tolerate or receive magnesium, or those with severe symptoms can receive intravenous magnesium. Hypomagnesemia may prevent the normalization of other electrolyte deficiencies. If other electrolyte deficiencies are associated, normalizing magnesium levels may be necessary to treat the other deficiencies. ## Chloride[edit] Chloride, after sodium, is the second most abundant electrolyte in the blood, and most abundant in the extracellular fluid.[16] Most of the chloride in the body is from salt (NaCl) in the diet.[17] Chloride is part of gastric acid (HCl), which plays a role in absorption of electrolytes, activating enzymes, and killing bacteria. The levels of chloride in the blood can help determine if there are underlying metabolic disorders.[18] Generally, chloride has an inverse relationship with bicarbonate, an electrolyte that indicates acid-base status.[18] Overall, treatment of chloride imbalances involve addressing the underlying cause rather than supplementing or avoiding chloride. ### Hyperchloremia[edit] Main article: Hyperchloremia #### Causes[edit] Hyperchloremia, or high chloride levels, is usually associated with excess chloride intake (e.g., saltwater drowning), fluid loss (e.g., diarrhea, sweating), and metabolic acidosis.[16] #### Symptoms[edit] Patients are usually asymptomatic with mild hyperchloremia. Symptoms associated with hyperchloremia are usually caused by the underlying cause of this electrolyte imbalance.[19] #### Treatment[edit] Treat the underlying cause, which commonly includes increasing fluid intake.[19] ### Hypochloremia[edit] Main article: Hypochloremia #### Causes[edit] Hypochloremia, or low chloride levels, are commonly associated with gastrointestinal (e.g., vomiting) and kidney (e.g., diuretics) losses.[18] Greater water or sodium intake relative to chloride also can contribute to hypochloremia.[18] #### Symptoms[edit] Patients are usually asymptomatic with mild hypochloremia. Symptoms associated with hypochloremia are usually caused by the underlying cause of this electrolyte imbalance.[20] #### Treatment[edit] Treat the underlying cause, which commonly includes increasing fluid intake.[20] ## Dietary sources[edit] Diet significantly contributes to our electrolyte stores and blood levels. Below are a list of foods that are associated with higher levels of these electrolytes. ### Sodium[edit] It is recommended that an individual consumes less than 2,300 mg of sodium daily as part of a healthy diet.[21] A significant portion of our sodium intake comes from a just a few types of food, which can be surprising as large sources of sodium may not taste salty.[22][23] * Breads * Soups * Cured meats and cold cuts * Cheese * Savory snacks (e.g., chips, crackers, pretzels) ### Potassium[edit] Good sources of potassium are found in a variety of fruits and vegetables.[24] Recommend potassium intake for adults ranges from 2,300 mg to 3,400 mg depending on age and gender.[25] * Beans and lentils * Dark leafy greens (e.g., spinach, kale) * Apples * Apricots * Potatoes * Squash * Bananas * Dates ### Calcium[edit] Dairy is a major contributor of calcium to diet in the United States.[26] The recommended calcium intake for adults range from 1,000 mg to 1,300 mg depending on age and gender.[26] * Yogurt * Cheese * Milk * Tofu * Canned sardines ### Magnesium[edit] Magnesium is found in a variety of vegetables, meats, and grains.[27] Foods high in fiber generally are a source of magnesium.[28] The recommended magnesium intake for adults range from 360 mg to 420 mg depending on age and gender.[28] * Epsom salt * Nuts and seeds (e.g., pumpkin seeds, almonds, peanuts)[27] * Dark leafy greens (e.g., spinach)[27] * Beans[27] * Fortified cereals ## See also[edit] * Acidosis * Alkalosis * Dehydration * Malnutrition * Starvation * Sports drink ## References[edit] 1. ^ Alfarouk, Khalid O.; Ahmed, Samrein B. M.; Ahmed, Ahmed; Elliott, Robert L.; Ibrahim, Muntaser E.; Ali, Heyam S.; Wales, Christian C.; Nourwali, Ibrahim; Aljarbou, Ahmed N.; Bashir, Adil H. H.; Alhoufie, Sari T. S.; Alqahtani, Saad Saeed; Cardone, Rosa A.; Fais, Stefano; Harguindey, Salvador; Reshkin, Stephan J. (7 April 2020). "The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer". Cancers. 12 (4): 898. doi:10.3390/cancers12040898. PMC 7226178. PMID 32272658. 2. ^ a b Balcı, Arif Kadri; Koksal, Ozlem; Kose, Ataman; Armagan, Erol; Ozdemir, Fatma; Inal, Taylan; Oner, Nuran (2013). "General characteristics of patients with electrolyte imbalance admitted to emergency department". World Journal of Emergency Medicine. 4 (2): 113–116. doi:10.5847/wjem.j.issn.1920-8642.2013.02.005. ISSN 1920-8642. PMC 4129840. PMID 25215103. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj Walls, Ron M.; Hockberger, Robert S.; Gausche-Hill, Marianne (2018). Rosen's Emergency Medicine: Concepts and Clinical Practice. Philadelphia, PA: Elsevier. pp. 1516–1532. ISBN 978-0-323-35479-0. 4. ^ a b c Bockenhauer, D; Zieg, J (September 2014). "Electrolyte disorders". Clinics in Perinatology. 41 (3): 575–90. doi:10.1016/j.clp.2014.05.007. PMID 25155728. 5. ^ Tisdall, M; Crocker, M; Watkiss, J; Smith, M (January 2006). "Disturbances of sodium in critically ill adult neurologic patients: a clinical review". Journal of Neurosurgical Anesthesiology. 18 (1): 57–63. doi:10.1097/01.ana.0000191280.05170.0f. PMC 1513666. PMID 16369141. 6. ^ a b c d Moritz, ML; Ayus, JC (November 2002). "Disorders of water metabolism in children: hyponatremia and hypernatremia". Pediatrics in Review. 23 (11): 371–80. doi:10.1542/pir.23-11-371. PMID 12415016. S2CID 40511233. 7. ^ Dineen, R; Thompson, CJ; Sherlock, M (June 2017). "Hyponatraemia – presentations and management". Clinical Medicine. 17 (3): 263–69. doi:10.7861/clinmedicine.17-3-263. PMC 6297575. PMID 28572229. 8. ^ Ályarez L, E; González C, E (June 2014). "[Pathophysiology of sodium disorders in children]". Revista chilena de pediatria (Review). 85 (3): 269–80. doi:10.4067/S0370-41062014000300002. PMID 25697243. 9. ^ a b c d e f g h i j k Tintinalli, Judith E.; Stapczynski, J. Stephan; Ma, O. John; Yealy, Donald M.; Meckler, Garth D.; Cline, David M. (2016). Tintinalli's Emergency Medicine: A Comprehensive Study Guide. New York, NY: McGraw-Hill. ISBN 978-0-07-179476-3. 10. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag Tintinalli, JE; Stapczynski, J; Ma, O; Yealy, DM; Meckler, GD; Cline, DM (2016). Tintinalli's Emergency Medicine: A Comprehensive Study Guide. New York, NY: McGraw-Hill. ISBN 978-0-07-179476-3. 11. ^ Goldstein, David A. (1990), Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.), "Serum Calcium", Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.), Butterworths, ISBN 978-0-409-90077-4, PMID 21250094, retrieved 2020-03-11 12. ^ Bove-Fenderson, Erin; Mannstadt, Michael (2018-10-01). "Hypocalcemic disorders". Best Practice & Research Clinical Endocrinology & Metabolism. SI: Metabolic bone disease. 32 (5): 639–656. doi:10.1016/j.beem.2018.05.006. ISSN 1521-690X. PMID 30449546. 13. ^ a b Glasdam, Sidsel-Marie; Glasdam, Stinne; Peters, Günther H. (2016-01-01), Makowski, Gregory S. (ed.), "Chapter Six - The Importance of Magnesium in the Human Body: A Systematic Literature Review", Advances in Clinical Chemistry, Elsevier, 73: 169–193, doi:10.1016/bs.acc.2015.10.002, PMID 26975973 14. ^ Van Laecke, Steven (2019-01-02). "Hypomagnesemia and hypermagnesemia". Acta Clinica Belgica. 74 (1): 41–47. doi:10.1080/17843286.2018.1516173. ISSN 1784-3286. PMID 30220246. 15. ^ Wong, E. T.; Rude, R. K.; Singer, F. R.; Shaw, S. T. (March 1983). "A high prevalence of hypomagnesemia and hypermagnesemia in hospitalized patients". American Journal of Clinical Pathology. 79 (3): 348–352. doi:10.1093/ajcp/79.3.348. ISSN 0002-9173. PMID 6829504. 16. ^ a b Nagami, Glenn T. (2016-07-01). "Hyperchloremia – Why and how". Nefrología. 36 (4): 347–353. doi:10.1016/j.nefro.2016.04.001. ISSN 0211-6995. PMID 27267918. 17. ^ Powers, F. (September 1999). "The role of chloride in acid-base balance". Journal of Intravenous Nursing. 22 (5): 286–291. ISSN 0896-5846. PMID 10776193. 18. ^ a b c d Berend, Kenrick; van Hulsteijn, Leonard Hendrik; Gans, Rijk O. B. (April 2012). "Chloride: the queen of electrolytes?". European Journal of Internal Medicine. 23 (3): 203–211. doi:10.1016/j.ejim.2011.11.013. ISSN 1879-0828. PMID 22385875. 19. ^ a b "Hyperchloremia (High Chloride) - Managing Side Effects - Chemocare". chemocare.com. Retrieved 2020-03-27. 20. ^ a b "Hypochloremia (Low Chloride) - Managing Side Effects - Chemocare". chemocare.com. Retrieved 2020-03-27. 21. ^ "2015-2020 Dietary Guidelines \| health.gov". health.gov. Retrieved 2020-03-27. 22. ^ "CDC - DHDSP - Top 10 Sources of Sodium". www.cdc.gov. 2018-10-03. Retrieved 2020-03-27. 23. ^ "What We Eat In America (WWEIA) Database \| Ag Data Commons". data.nal.usda.gov. Retrieved 2020-03-27. 24. ^ "Blood Pressure : How to eat more potassium". www.bloodpressureuk.org. Retrieved 2020-03-27. 25. ^ "Office of Dietary Supplements - Potassium". ods.od.nih.gov. Retrieved 2020-03-27. 26. ^ a b "Office of Dietary Supplements - Calcium". ods.od.nih.gov. Retrieved 2020-03-27. 27. ^ a b c d "Magnesium-Rich Food Information". Cleveland Clinic. Retrieved 2020-03-25. 28. ^ a b "Office of Dietary Supplements - Magnesium". ods.od.nih.gov. Retrieved 2020-03-27. ## External links[edit] Classification D * ICD-10: E86-E87 * ICD-9-CM: 276 * MeSH: D014883 * v * t * e Electrolyte imbalances Sodium * High * Salt poisoning * Low * Hypotonic * Isotonic * Cerebral salt-wasting syndrome Potassium * High * Low Chloride * High * Low Calcium * High * Low * Symptoms and signs * Chvostek sign * Trousseau sign * Milk-alkali syndrome * Disorders of calcium metabolism * Calcinosis (Calciphylaxis, Calcinosis cutis) * Calcification (Metastatic calcification, Dystrophic calcification) * Familial hypocalciuric hypercalcemia Phosphate * High * Low Magnesium * High * Low [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Electrolyte imbalance	c0043065	29,929	wikipedia	https://en.wikipedia.org/wiki/Electrolyte_imbalance	2021-01-18T18:32:51	{"mesh": ["D014883"], "icd-9": ["276"], "icd-10": ["E87", "E86"], "wikidata": ["Q1326943"]}
Hereditary coproporphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks and, more rarely, by the presence of cutaneous lesions. ## Epidemiology The prevalence in Europe is estimated at about 1/1,000,000. ## Clinical description The disease manifests after puberty and preferentially affects women. Patients suffer neuro-visceral attacks, which can persist for several weeks and manifest as intense abdominal pain (in 85-95% of cases), and neurological and psychological symptoms. The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and constipation. Psychological symptoms are variable: irritability, emotionality, depression, considerable anxiety and, more rarely, auditory and visual hallucinations, disorientation, mental confusion. Neurological manifestations can affect the central nervous system as much as the peripheral nervous system (myalgia, paresis, ascending flaccid paralysis of the limbs, or convulsions) and can lead to severe complications such as motor paralysis. Tachycardia and hyponatremia are common during attacks. In cases with cardiac arrhythmia and respiratory paralysis (rare), attacks can be fatal. The attacks are most commonly triggered by exogenous factors (porphyrinogenic drugs, alcohol, infections, a hypo-calorific diet, stress), and/or endogenous factors (hormonal, linked to menstrual cycle). In 30% of cases patients present with cutaneous lesions as a result of photosensitivity. These lesions predominate in areas exposed to the sun (hands, face). They manifest as bullae that cause differing degrees of pain and that leave scars that are often hyperpigmented. ## Etiology Hereditary coproporphyria is caused by a deficiency of coproporphyrinogen oxidase (CPO, the sixth enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid, ALA and porphobilinogen, PBG). The enzyme deficiency is caused by mutationsof the CPOX gene coding for CPO (3q12). Transmission is autosomal dominant. ## Diagnostic methods The observation of reddish or dark brown urine evokes the diagnosis of the disease. Diagnosis is based on evidence of elevated concentrations of ALA, PBG and of uroporphyrins and coproporphyrins in the urine. ## Differential diagnosis Differential diagnoses include acute intermittent porphyria and, especially, variegate porphyria (see these terms). ## Genetic counseling Genetic counseling should be offered to patients and families to identify individuals susceptible to developing or transmitting the disease. ## Management and treatment When an acute attack is confirmed, urgent treatment with an injection of human hemin and/or perfusion of carbohydrates is required. Management includes the suppression of triggering factors, relief from pain (opiates), vomiting and anxiety, and the prevention of attacks (by avoiding triggering factors, particularly drugs). ## Prognosis With early diagnosis and management, attacks from porphyria are rarely fatal. Acute attacks are more rare than in cases of acute intermittent porphryia and, if the triggering factors are eliminated, the disease is rarely progressive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hereditary coproporphyria	c0162531	29,930	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79273	2021-01-23T18:02:45	{"gard": ["6619"], "mesh": ["D046349"], "omim": ["121300"], "umls": ["C0162531"], "icd-10": ["E80.2"]}
## Description Thymomas are low-grade epithelial cancers of the thymus. Familial occurrence of thymoma is rare. Clinical Features Matani and Dristsas (1973) reported a Greek sibship of 3, demonstrating familial occurrence of thymoma. One of the 3 sibs, a 2-year-old girl, died of respiratory insufficiency resulting from a lymphocytic thymoma. Her 9-month-old brother died 2 years earlier of the same cause. The eldest sib, a male, and the parents were healthy. No reference was made concerning parental consanguinity. Thymomas are notably rare in persons of this young age. Wick et al. (1982) described 2 brothers who developed malignant epithelial tumors of the thymus. One had thymic carcinoma with death in his late 50s; the other had an invasive spindle cell thymoma with associated hypogammaglobulinemia. The authors thought the occurrence particularly significant because thymic tumors are rare and malignant forms especially so. Nicodeme et al. (2005) studied a family bearing the constitutional chromosome translocation t(14;20)(q24;p12). Eleven of 27 family members had the translocation breakpoint; of these 11, 3 had thymoma and 4 others had 5 different autoimmune diseases (109100), namely, diabetes mellitus type I, Graves disease, pernicious anemia, Sjogren disease, and autoimmune pancytopenia. FISH studies demonstrated that the 14q24 breakpoint was in intron 5 of the RAD51L1 gene (602948), and the 20p breakpoint was 100 kb telomeric to the BMP2 gene (112261). RAD51L1 is a tumor-suppressing gene implicated in many tumors (e.g., uterine leiomyomas and pulmonary chondroid hamartomas) and involved in recombinational repair of DNA double-strand breaks. BMP2 belongs to the TGF-beta superfamily and is involved in the maturation of T lymphocytes in the thymic stroma. Dysregulation of RAD51L1 and/or BMP2 was thought to explain the familial occurrence of thymomas and autoimmune diseases. Population Genetics Nicodeme et al. (2005) stated that familial thymoma has a prevalence of 0.1 to 0.4 per 100,000. Molecular Genetics ### Somatic Mutation Petrini et al. (2014) analyzed 28 thymic epithelial tumors using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970 T-A) in the GTF2I gene (601679) at high frequency in type A thymomas, a relatively indolent subtype. In a series of 274 thymic epithelial tumors, Petrini et al. (2014) detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified. Therefore, GTF2I mutation correlated with better survival. GTF2I beta and delta isoforms were expressed in thymic epithelial tumors, and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas carried a higher number of mutations than thymomas (average of 43.5 and 18.4, respectively). INHERITANCE \- Somatic mutation RESPIRATORY \- Respiratory insufficiency IMMUNOLOGY \- Thymoma NEOPLASIA \- Thymoma ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	THYMOMA, FAMILIAL	c0040100	29,931	omim	https://www.omim.org/entry/274230	2019-09-22T16:21:42	{"mesh": ["D013945"], "omim": ["274230"], "orphanet": ["99867"], "synonyms": ["Alternative titles", "THYMIC NEOPLASIA"]}
A rare multiple congenital anomalies/neurodevelopmental disorder characterized by five major features: intellectual disability (typically mild to moderate), visceral malformations (frequently congenital heart defects), persistence of fetal fingertip pads, post-natal short stature, skeletal anomalies (brachymesophalangy, brachydactyly V, spinal column abnormalities and fifth digit clinodactyly) and specific facial features (arched and broad eyebrows, long palpebral fissures, eversion of the lower eyelid, large prominent, cupped ears, depressed nasal tip and short columella). Various additional features are frequently observed. ## Epidemiology The prevalence of Kabuki syndrome (KS) is estimated at 1/32000 birth and seems a frequent etiology in malformed fetus. ## Clinical description Presentation is typically with neonatal/infantile hypotonia and feeding difficulties (affecting more than 70%). KS associates developmental delay and intellectual disability in 90% of patients. Intellectual disability is frequently mild to moderate; however, the spectrum ranges from normal intellect to severe disability. Verbal language acquisition and memory are usually better than visuospatial or processing speed. Individuals with KS usually achieve walking and language milestones. Heart malformations are observed in around 50% of patients. Kidney malformations, deafness, and seizures of different types are observed in 20%. Immune deficiency and recurrent infection are frequent. Autoimmune features increase with age affecting around 20% of the adults with KS. Scoliosis and patellar luxation require frequent screening and should be monitored carefully at puberty. Missing teeth are frequently observed. Obesity could arise from the age of 5 and requires monitoring. Growth hormone deficiency is observed in 25-30%. Premature thelarche occurs in 30% of females. ## Etiology KS is usually due to de novo pathogenic variants in about 70% of patients fulfilling the diagnostic criteria. For the majority of patients (56% to 75%), KS is due to mutations in KMT2D (12q13.12) and for the minority of patients (5%), KS is due to mutations in KDM6A (xp11.2). ## Diagnostic methods Diagnosis is evoked on clinical examination, and confirmed using genetic studies. ## Differential diagnosis Differential diagnosis includes CHARGE, 3MC, and Hardikar syndromes, KAT6B-related disorders, and other genetic disorders involving chromatin regulation. ## Antenatal diagnosis For parents of an index individual, detection of KS by amniocentesis in subsequent pregnancies should be discussed. KS could be identified using exome sequencing during pregnancy screening for malformative syndromes. ## Genetic counseling Transmission of KMT2D-related KS is autosomal dominant; however, in most situations, the pathogenic variants arise de novo and thus the risk of sibling recurrence is low. The estimated recurrence risk to siblings is 1% based on the possibility of parental germline mosaicism. Transmission of KDM6A-related KS is X-linked with males slightly more affected than females. ## Management and treatment Management requires a lifelong multidisciplinary approach. Regular follow‐up by a clinical geneticist, pediatrician, ophthalmologist, psychologist/psychiatrist, speech therapist, physiotherapist and ophthalmologist will have a major impact. Feeding difficulties may require tube feeding (nasogastric or gastrostomy). Developmental assessments are required in order to tailor medical services to each individual's needs. Other specialists can be required, such as a cardiologist, gastroenterologist, nephrologist, immunologist, ENT (ear, nose and throat) or stomatologist. Special attention is need for fine graphomotor and visuals difficulties. ## Prognosis The prognosis is usually good. A specific survey is required for autoimmune and kidney problems. Autonomy may be limited and affected individuals will sometimes require life-long support from caregivers. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Kabuki syndrome	c0796004	29,932	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2322	2021-01-23T18:38:30	{"gard": ["6810"], "mesh": ["C537705"], "omim": ["147920", "300867"], "umls": ["C0796004"], "icd-10": ["Q87.0"], "synonyms": ["Kabuki make-up syndrome", "Niikawa-Kuroki syndrome"]}
Rapid-onset dystonia-parkinsonism (RDP) is a very rare movement disorder, characterized by the abrupt onset of parkinsonism and dystonia, often triggered by physical or psychological stress. ## Epidemiology The prevalence is unknown. Fewer than 100 patients have been described worldwide to date. ## Clinical description RDP typically presents in childhood or early adulthood (but age of onset can range from 4-55 years) with the abrupt onset of dystonia along with parkinsonism (bradykinesia and postural instability) with a rostrocaudal gradient and prominent bulbar symptoms (dysarthria and dysphagia) that do not respond to dopaminergic medication. Symptoms may develop over several minutes to 30 days, after which time they stabilize. Often onset is triggered by physical exertion, fever, extreme heat, childbirth, excessive alcohol consumption or emotional stress. Some patients experience mild upper limb dystonia (mainly in the hands) and cramping before disease onset occurs. In most cases the disease stabilizes, but a few cases have been reported where a second episode of worsening of symptoms occurred 1-9 years after initial onset. In rare cases seizures, anxiety and depression have been reported. Recently, a variant phenotype in infants (<4 years of age) has been reported with initially episodic hypotonia, gait ataxia, motor delay, and speech and swallowing difficulties. ## Etiology RDP is caused by several missense mutations in the ATP1A3 gene (19q13.2) encoding the sodium/potassium-transporting ATPase subunit alpha-3 protein, which is important for maintaining the electrochemical gradients of potassium and sodium across the plasma membrane. These mutations are thought to lead to neuronal dysfunction. Other genes, which have not yet been identified, may also be involved. ## Diagnostic methods Diagnosis is based on the sudden onset of clinical manifestations (parkinsonism and dystonia), the finding of low homovanillic acid concentrations in cerebrospinal fluid (CSF), normal brain imaging studies and the lack of response to levodopa (L-dopa) therapy. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies show normal dopamine reuptake in dopamine transporters. A mutation in the ATP1A3 gene may confirm diagnosis. ## Differential diagnosis Differential diagnosis includes other forms of dystonia-parkinsonism, such as young adult-onset parkinsonism, dopa-responive dystonia (DRD), dystonia 16 (DYT16) and X-linked dystonia parkinsonism (DYT3). Unlike DYT3 and other forms of young-onset parkinsonism, RDP is not a neurodegenerative disorder. ## Antenatal diagnosis Prenatal diagnosis is possible in families where a disease causing mutation is known. ## Genetic counseling RDP is inherited in an autosomal dominant manner with reduced penetrance, and genetic counseling is possible and recommended. De novo mutations are also observed. ## Management and treatment There is no effective treatment for RDP at present. L-dopa is ineffective. Pallidal deep brain stimulation (DBS) has shown limited or no therapeutic effects. If present, seizures, anxiety and depression can be treated with standard therapy. High-dose benzodiazepines and possibly other muscle relaxants may offer some symptomatic relief. All known triggers of RDP should be avoided. Physical therapy is recommended. ## Prognosis There is no effect on life expectancy, but quality of life is severely affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Rapid-onset dystonia-parkinsonism	c1868681	29,933	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=71517	2021-01-23T17:55:28	{"gard": ["9628"], "mesh": ["C538001"], "omim": ["128235"], "umls": ["C1868681"], "icd-10": ["G24.1"], "synonyms": ["DYT12", "Dystonia 12"]}
Large for gestational age Other namesMacrosomia LGA: A healthy 11-pound (5.0 kg) newborn child, delivered vaginally without complications (41 weeks; fourth child; no gestational diabetes) SpecialtyObstetrics, pediatrics Large for gestational age (LGA) describes full-term or post-term infants that are born of high birth weight.[1] The term LGA or large for gestational age is defined by birth weight above the 90th percentile for their gestational age and gender.[2] In infants with birth weight above the 97th percentile in their gestational age and gender group, research has shown that greater risk of long-term health complications and fatal outcomes are present in LGA infants.[3] Specifically, large for gestational age can be characterized by macrosomia, referring to a fetal growth beyond a certain threshold (threshold ranging from a body weight of 4,000 grams to above 5,000 grams).[4] Experts in Obstetrics and Gynecology currently use a grading system to evaluate LGA infants, where their birth weight may help identify risks associated with their birth, including labor complications of both mother and child, potential long-term health complications of the neonate and infant mortality.[3] ## Contents * 1 Presentation * 1.1 Complications * 1.1.1 Neonatal * 1.1.2 Maternal * 2 Risk factors * 2.1 Maternal diabetes * 2.2 Genetics * 2.3 Other risk factors * 3 Diagnosis * 4 Management * 5 Epidemiology * 6 References * 7 External links ## Presentation[edit] ### Complications[edit] #### Neonatal[edit] Common risks in LGA babies include shoulder dystocia,[3] hypoglycemia,[3] brachial plexus injuries,[5] metatarsus adductus, hip subluxation [6] and talipes calcaneovalgus, due to intrauterine deformation.[6] Shoulder dystocia occurs when the anterior shoulder becomes impacted on the maternal pubic symphysis during birth.[7] The doctor or midwife will try to push the baby's anterior shoulder downward to pass through the birth canal and clear the woman's pubic symphysis. This can be difficult if the child is LGA, since the birth canal is 10 cm when fully dilated for most women and there may not be much room to move the baby. If shoulder dystocia occurs, there are various maneuvers which can be performed by the birth attendant to try to deliver the shoulders. These generally involve trying to turn the shoulders into the oblique, using suprapubic pressure to disimpact the anterior shoulder from above the pubic symphysis, or delivering the posterior arm first.[8] If these do not resolve the situation, the provider may intentionally snap the baby's clavicle (bone that holds shoulder in place) in a procedure called cleidotomy in order to displace the shoulder and allow the child to be delivered.[9][10] Other methods to deliver the baby as a last resort when all else have failed are the Zavanelli maneuver and symphysiotomy.[9][10] The Zavanelli maneuver involves flexing and pushing the fetal head back into the birth canal, and an emergency cesarean section is then performed.[10] Symphysiotomy allows childbirth by surgically dividing the pubic bone to widen the pelvis and it is performed after a failed Zavanelli maneuver.[10] Newborns with shoulder dystocia are at risk of temporary or permanent nerve damage to the baby's arm, or other injuries such as humeral fracture.[8] In non-diabetic women, shoulder dystocia happens 0.65% of the time in babies that weigh less than 8 pounds 13 ounces (4,000 g), 6.7% of the time in babies that weigh 8 pounds 13 ounces (4,000 g) to 9 pounds 15 ounces (4,500 g), and 14.5% of the time in babies that weigh more than 9 pounds 15 ounces (4,500 g).[11] In diabetic women, shoulder dystocia happens 2.2% of the time in babies that weigh less than 8 pounds 13 ounces (4,000 g), 13.9% of the time in babies that weigh 8 pounds 13 ounces (4,000 g) to 9 pounds 15 ounces (4,500 g), and 52.5% of the time in babies that weigh more than 9 pounds 15 ounces (4,500 g).[11] Although big babies are at higher risk for shoulder dystocia, most cases of shoulder dystocia happen in smaller babies because there are many more small and normal-size babies being born than big babies.[12] Researchers have been unable to predict who will have shoulder dystocia and who will not.[13] LGA babies are at higher risk of hypoglycemia in the neonatal period, independent of whether the mother has diabetes.[14] Hypoglycemia, as well as hyperbilirubinemia and polycythemia, occur as a result of hyperinsulinemia in the fetus.[15] High birth weight may impact the baby in the long term. Macrosomic neonates are at a higher risk of being overweight and obese than their normal-weight counterparts later in life.[4][16] Studies have shown that the long-term overweight risk is doubled when the birth weight is greater than 4,000 g.[17] The risk of having type 2 diabetes mellitus in adult life is 19% higher among macrosomic babies with birth weights heavier than 4,500 g compared to those with birth weights between 4,000 g and 4,500 g.[18] #### Maternal[edit] Maternal complications in pregnancies with macrosomia include emergency cesarean section, postpartum hemorrhage and obstetric anal sphincter injury.[19] The risk of maternal complications in pregnancies with newborns weighing between 4,000 g and 4,500 g is two-fold greater than in pregnancies without macrosomia. In pregnancies with newborns weighing over 4,500 g, the risk is approximately three-fold greater.[19] ## Risk factors[edit] ### Maternal diabetes[edit] One of the primary risk factors of LGA is poorly-controlled maternal diabetes, particularly gestational diabetes (GD), as well as preexisting diabetes mellitus (DM) (preexisting type 2 is associated more with macrosomia, while preexisting type 1 can be associated with microsomia).[20] The risk of having a macrosomic fetus is three times greater in mothers with diabetes than those without diabetes.[21] DM increases maternal plasma glucose levels as well as insulin, stimulating fetal growth of subcutaneous fat.[21] The LGA newborn exposed to maternal DM usually only has an increase in weight, not a change in body length or head size.[21] ### Genetics[edit] Genetics plays a role in having an LGA baby. Taller, heavier parents tend to have larger babies.[22] Genetic disorders of overgrowth (e.g. Beckwith–Wiedemann syndrome, Sotos syndrome, Perlman syndrome, Simpson-Golabi-Behmel syndrome [23]) are often characterized by macrosomia.[24][25] ### Other risk factors[edit] * Gestational age: pregnancies that go beyond 40 weeks increase incidence of an LGA infant [21] * Fetal sex: male infants tend to weigh more than female infants [5] * Obesity prior to pregnancy and maternal weight gain above recommended guidelines during pregnancy [26][27][28] * Multiparity: giving birth to previous LGA infants vs. non-LGA infants [5] * Frozen embryo transfer as fertility treatment, as compared with fresh embryo transfer or no artificial assistance [29][30] ## Diagnosis[edit] Diagnosing fetal macrosomia cannot be performed until after birth, as evaluating a baby's weight in the womb may be inaccurate.[21] While ultrasound has been the primary method for diagnosing LGA, this form of fetal weight assessment remains imprecise, as the fetus is a highly variable structure in regards to density and weight— no matter the gestational age.[21] Ultrasonography involves an algorithm that incorporates biometric measurements of the fetus, such as biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL), to calculate the estimated fetal weight (EFW).[31] Variability of fetal weight estimations has been linked to differences due to sensitivity and specificity of ultrasound algorithms as well as to the individual performing the ultrasound examination.[32] In addition to sonography, fetal weight can also be assessed using clinical and maternal methods. Clinical methods for estimating fetal weight involves measuring the mother's symphysis-fundal height and performing Leopold's maneuvers, which can help with determining the fetus position in utero in addition to size.[32] However, as this method relies heavily on practitioner experience and technique, it does not provide an accurate and definite diagnosis of an LGA infant and only would only serve as a potential indication of suspected macrosomia.[32] Fetal weight can also be estimated through a mother's subjective assessment of the fetus size, but this method is dependent on a mother's experience with past pregnancies and may not be clinically useful.[32] There are new methods being studied for their accuracy in predicting fetal weight, such as measuring fetal soft tissue, but more research needs to be done to find a consistent, reliable method.[33] ## Management[edit] Induction of labor at or near term for women with a baby of suspected macrosomia has been proposed as a treatment method, as it stops fetal growth and results in babies with a lower birth weight, fewer bone fractures, and less incidence of shoulder dystocia.[7] However, this method could increase the number of women with perineal tears, and failed inductions can prompt the need for emergency cesarean sections.[7] LGA babies are more than two times likely to be delivered by Cesarean section, compared to infants under 4000 grams (below the threshold of macrosomia).[34] Predicting a baby’s weight can be inaccurate and women could be worried unnecessarily, and request their labor to be induced without a medical reason.[7] Doctors disagree whether women should be induced for suspected macrosomia and more research is needed to find out what is best for women and their babies.[7] Elective cesarean section has also been presented as a potential delivery method for infants of suspected macrosomia, as it can serve to prevent possible birth trauma. However, the American College of Obstetricians and Gynecologists recommends that cesarean delivery should only be considered if the fetus is an estimated weight of at least 5,000 grams in non-diabetic mothers and at least 4,500 grams in diabetic mothers. [35] A number needed to treat analysis determined that approximately 3,700 women with suspected fetal macrosomia would have to undergo an unnecessary cesarean section in order to prevent one incident of brachial plexus injuries secondary to shoulder dystocia.[5] Management of gestational diabetes through dietary modifications and anti-diabetic medications has been shown to decrease the incidence of LGA.[36] The use of metformin to control maternal blood glucose levels has shown to be more effective than using insulin alone in reducing the likelihood of fetal macrosomia.[37] There is a 20% lower chance of having an LGA baby when using metformin to manage diabetes compared to using insulin.[38] Modifiable risk factors that increase the incidence of LGA births, such as gestational weight gain above recommended BMI guidelines, can be managed with lifestyle modifications, including maintaining a balanced diet and exercising.[39][40] Such interventions can help mothers achieve the recommended gestational weight and lower the incidence of fetal macrosomia in obese and overweight women.[39][40] The World Health Organization also recommends that mothers aim for their recommended BMI prior to conception.[28] In general, obese mothers or women with excessive gestational weight gain may have higher risk of pregnancy complications (ranging from LGA, shoulder dystocia, etc.). [41] ## Epidemiology[edit] In healthy pregnancies without pre-term or post-term health complications, large for gestational age, or fetal macrosomia have been observed to affect around 12% of newborns. [7] By comparison, women with gestational diabetes are at an increased risk of giving birth to LGA babies, where ~15-45% of neonates may be affected.[7] In 2017, the National Center of Health Statistics found that 7.8% of live-born infants born in the United States meet the definition of macrosomia, where their birth weight surpasses the threshold of 4000 grams (above ~8.8 pounds).[7] Women in Europe and the United States tend to have higher pre-term body weight and have increased gestational weight during pregnancy compared to women in east Asia.[42] Thus, women in Europe and the United States, with higher gestational weight gain, tend to have higher associated risk of LGA infants, macrosomia and cesarean.[42] In European countries, the prevalence of births of newborns weighing between 4,000 g and 4,499 g is 8% to 21%, and in Asian countries the prevalence is between 1% and 8%.[43] In general, rates of LGA infants have increased 15-25% in many countries including the United States, Canada, Germany, Denmark, Scotland and more in the past 20-30 years, suggesting an increase in LGA births worldwide.[44] ## References[edit] 1. ^ Henriksen T (2008). "The macrosomic fetus: a challenge in current obstetrics". Acta Obstetricia et Gynecologica Scandinavica. 87 (2): 134–45. doi:10.1080/00016340801899289. PMID 18231880. S2CID 38118355. 2. ^ McGrath RT, Glastras SJ, Hocking SL, Fulcher GR (August 2018). "Large-for-Gestational-Age Neonates in Type 1 Diabetes and Pregnancy: Contribution of Factors Beyond Hyperglycemia". Diabetes Care. 41 (8): 1821–1828. doi:10.2337/dc18-0551. PMID 30030258. S2CID 207369659. 3. ^ a b c d Boulet SL, Alexander GR, Salihu HM, Pass M (May 2003). "Macrosomic births in the united states: determinants, outcomes, and proposed grades of risk". American Journal of Obstetrics and Gynecology. 188 (5): 1372–8. doi:10.1067/mob.2003.302. PMID 12748514. 4. ^ a b Barth Jr WH, Jackson R, et al. (Committee on Practice Bulletins—Obstetrics) (January 2020). "Macrosomia: ACOG Practice Bulletin, Number 216". Obstetrics and Gynecology. 135 (1): e18–e35. doi:10.1097/AOG.0000000000003606. PMID 31856124. 5. ^ a b c d Zamorski MA, Biggs WS (January 2001). "Management of suspected fetal macrosomia". American Family Physician. 63 (2): 302–6. PMID 11201695. 6. ^ a b Lapunzina P, Camelo JS, Rittler M, Castilla EE (February 2002). "Risks of congenital anomalies in large for gestational age infants". The Journal of Pediatrics. 140 (2): 200–4. doi:10.1067/mpd.2002.121696. PMID 11865271. 7. ^ a b c d e f g h Boulvain M, Irion O, Dowswell T, Thornton JG, et al. (Cochrane Pregnancy and Childbirth Group) (May 2016). "Induction of labour at or near term for suspected fetal macrosomia". The Cochrane Database of Systematic Reviews (5): CD000938. doi:10.1002/14651858.CD000938.pub2. PMC 7032677. PMID 27208913. 8. ^ a b Young BC, Ecker JL (February 2013). "Fetal macrosomia and shoulder dystocia in women with gestational diabetes: risks amenable to treatment?". Current Diabetes Reports. 13 (1): 12–8. doi:10.1007/s11892-012-0338-8. PMID 23076441. S2CID 4385185. 9. ^ a b Politi S, D'emidio L, Cignini P, Giorlandino M, Giorlandino C (July 2010). "Shoulder dystocia: an Evidence-Based approach". Journal of Prenatal Medicine. 4 (3): 35–42. PMC 3279180. PMID 22439059. 10. ^ a b c d Hill MG, Cohen WR (2016). "Shoulder dystocia: prediction and management". Women's Health. 12 (2): 251–61. doi:10.2217/whe.15.103. PMC 5375046. PMID 26901875. 11. ^ a b Rouse DJ, Owen J, Goldenberg RL, Cliver SP (November 1996). "The effectiveness and costs of elective cesarean delivery for fetal macrosomia diagnosed by ultrasound". JAMA. 276 (18): 1480–6. doi:10.1001/jama.1996.03540180036030. PMID 8903259. 12. ^ Morrison JC, Sanders JR, Magann EF, Wiser WL (December 1992). "The diagnosis and management of dystocia of the shoulder". Surgery, Gynecology & Obstetrics. 175 (6): 515–22. PMID 1448731. 13. ^ Gross TL, Sokol RJ, Williams T, Thompson K (June 1987). "Shoulder dystocia: a fetal-physician risk". American Journal of Obstetrics and Gynecology. 156 (6): 1408–18. doi:10.1016/0002-9378(87)90008-1. PMID 3591856. 14. ^ Rozance PJ (February 2014). "Update on neonatal hypoglycemia". Current Opinion in Endocrinology, Diabetes and Obesity. 21 (1): 45–50. doi:10.1097/MED.0000000000000027. PMC 4012366. PMID 24275620. 15. ^ Mayer C, Joseph KS (February 2013). "Fetal growth: a review of terms, concepts and issues relevant to obstetrics". Ultrasound in Obstetrics & Gynecology. 41 (2): 136–45. doi:10.1002/uog.11204. PMID 22648955. 16. ^ Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C (October 2005). "Being big or growing fast: systematic review of size and growth in infancy and later obesity". BMJ. 331 (7522): 929. doi:10.1136/bmj.38586.411273.E0. PMC 1261184. PMID 16227306. 17. ^ Schellong K, Schulz S, Harder T, Plagemann A (2012). Hernandez AV (ed.). "Birth weight and long-term overweight risk: systematic review and a meta-analysis including 643,902 persons from 66 studies and 26 countries globally". PLOS ONE. 7 (10): e47776. Bibcode:2012PLoSO...747776S. doi:10.1371/journal.pone.0047776. PMC 3474767. PMID 23082214. 18. ^ Knop MR, Geng TT, Gorny AW, Ding R, Li C, Ley SH, Huang T (December 2018). "Birth Weight and Risk of Type 2 Diabetes Mellitus, Cardiovascular Disease, and Hypertension in Adults: A Meta-Analysis of 7 646 267 Participants From 135 Studies". Journal of the American Heart Association. 7 (23): e008870. doi:10.1161/JAHA.118.008870. PMC 6405546. PMID 30486715. 19. ^ a b Beta J, Khan N, Khalil A, Fiolna M, Ramadan G, Akolekar R (September 2019). "Maternal and neonatal complications of fetal macrosomia: systematic review and meta-analysis". Ultrasound in Obstetrics & Gynecology. 54 (3): 308–318. doi:10.1002/uog.20279. PMID 30938004. 20. ^ Leipold H, Worda C, Gruber CJ, Kautzky-Willer A, Husslein PW, Bancher-Todesca D (August 2005). "Large-for-gestational-age newborns in women with insulin-treated gestational diabetes under strict metabolic control". Wiener Klinische Wochenschrift. 117 (15–16): 521–5. doi:10.1007/s00508-005-0404-1. PMID 16160802. S2CID 7465313. 21. ^ a b c d e f Kc K, Shakya S, Zhang H (2015). "Gestational diabetes mellitus and macrosomia: a literature review". Annals of Nutrition & Metabolism. 66 Suppl 2 (Suppl. 2): 14–20. doi:10.1159/000371628. PMID 26045324. S2CID 6536421. 22. ^ Christian M, Gustafsson J. Pediatrik (2 uppl ed.). ISBN 9789147112968. OCLC 1001668564. 23. ^ Sajorda BJ, Gonzalez-Gandolfi CX, Hathaway ER, Kalish JM (1993–2020). "Simpson-Golabi-Behmel Syndrome Type 1". GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle. PMID 20301398. 24. ^ "Beckwith-Wiedemann syndrome". Genetics Home Reference. Retrieved 2020-07-30. 25. ^ Vora N, Bianchi DW (October 2009). "Genetic considerations in the prenatal diagnosis of overgrowth syndromes". Prenatal Diagnosis. 29 (10): 923–9. doi:10.1002/pd.2319. PMC 4426974. PMID 19609940. 26. ^ Boubred F, Pauly V, Romain F, Fond G, Boyer L (2020-06-05). Farrar D (ed.). "The role of neighbourhood socioeconomic status in large for gestational age". PLOS ONE. 15 (6): e0233416. Bibcode:2020PLoSO..1533416B. doi:10.1371/journal.pone.0233416. PMC 7274403. PMID 32502147. 27. ^ Henriksen T (February 2008). "The macrosomic fetus: a challenge in current obstetrics". Acta Obstetricia et Gynecologica Scandinavica. 87 (2): 134–45. doi:10.1080/00016340801899289. PMID 18231880. S2CID 38118355. 28. ^ a b Goldstein RF, Abell SK, Ranasinha S, Misso M, Boyle JA, Black MH, et al. (June 2017). "Association of Gestational Weight Gain With Maternal and Infant Outcomes: A Systematic Review and Meta-analysis". JAMA. 317 (21): 2207–2225. doi:10.1001/jama.2017.3635. PMC 5815056. PMID 28586887. 29. ^ Berntsen S, Pinborg A (May 2018). "Large for gestational age and macrosomia in singletons born after frozen/thawed embryo transfer (FET) in assisted reproductive technology (ART)". Birth Defects Research. 110 (8): 630–643. doi:10.1002/bdr2.1219. PMID 29714057. S2CID 25437950. 30. ^ Orvieto R, Kirshenbaum M, Gleicher N (2020). "Is Embryo Cryopreservation Causing Macrosomia-and What Else?". Frontiers in Endocrinology. 11: 19. doi:10.3389/fendo.2020.00019. PMC 6997460. PMID 32047479. 31. ^ Coomarasamy A, Connock M, Thornton J, Khan KS (November 2005). "Accuracy of ultrasound biometry in the prediction of macrosomia: a systematic quantitative review". BJOG. 112 (11): 1461–6. doi:10.1111/j.1471-0528.2005.00702.x. PMID 16225563. S2CID 34330598. 32. ^ a b c d Ray EM, Alhusen JL (2016). "The Suspected Macrosomic Fetus at Term: A Clinical Dilemma". Journal of Midwifery & Women's Health. 61 (2): 263–9. doi:10.1111/jmwh.12414. PMID 26869131. 33. ^ Warska A, Maliszewska A, Wnuk A, Szyszka B, Sawicki W, Cendrowski K (March 2018). "Current knowledge on the use of ultrasound measurements of fetal soft tissues for the assessment of pregnancy development". Journal of Ultrasonography. 18 (72): 50–55. doi:10.15557/JoU.2018.0008. PMC 5911719. PMID 29844941. 34. ^ Steer P (February 2004). "The management of large and small for gestational age fetuses". Seminars in Perinatology. 28 (1): 59–66. doi:10.1053/j.semperi.2003.10.013. PMID 15058903. 35. ^ "Safe Prevention of the Primary Cesarean Delivery". www.acog.org. Retrieved 2020-08-04. 36. ^ Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L (July 2013). "Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research". Annals of Internal Medicine. 159 (2): 123–9. doi:10.7326/0003-4819-159-2-201307160-00661. PMID 23712381. S2CID 21881403. 37. ^ Guo L, Ma J, Tang J, Hu D, Zhang W, Zhao X (2019). "Comparative Efficacy and Safety of Metformin, Glyburide, and Insulin in Treating Gestational Diabetes Mellitus: A Meta-Analysis". Journal of Diabetes Research. 2019: 9804708. doi:10.1155/2019/9804708. PMC 6875019. PMID 31781670. 38. ^ Butalia S, Gutierrez L, Lodha A, Aitken E, Zakariasen A, Donovan L (January 2017). "Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis". Diabetic Medicine. 34 (1): 27–36. doi:10.1111/dme.13150. PMID 27150509. S2CID 3418227. 39. ^ a b World Health Organization (2016). WHO recommendations on antenatal care for a positive pregnancy experience. Geneva, Switzerland. ISBN 978-92-4-154991-2. OCLC 974355266. 40. ^ a b "Weight Gain During Pregnancy \| Pregnancy \| Maternal and Infant Health C". www.cdc.gov. 2019-01-17. Retrieved 2020-08-04. 41. ^ Santos S, Voerman E, Amiano P, Barros H, Beilin LJ, Bergström A, et al. (July 2019). "Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts". BJOG. 126 (8): 984–995. doi:10.1111/1471-0528.15661. PMC 6554069. PMID 30786138. 42. ^ a b Goldstein RF, Abell SK, Ranasinha S, Misso ML, Boyle JA, Harrison CL, et al. (August 2018). "Gestational weight gain across continents and ethnicity: systematic review and meta-analysis of maternal and infant outcomes in more than one million women". BMC Medicine. 16 (1): 153. doi:10.1186/s12916-018-1128-1. PMC 6117916. PMID 30165842. 43. ^ Culliney KA, Parry GK, Brown J, Crowther CA, et al. (Cochrane Pregnancy and Childbirth Group) (April 2016). "Regimens of fetal surveillance of suspected large-for-gestational-age fetuses for improving health outcomes". The Cochrane Database of Systematic Reviews. 4: CD011739. doi:10.1002/14651858.CD011739.pub2. PMC 7081118. PMID 27045604. 44. ^ Miller V, Saxena S, Farhan M (2010). "Management of large-for-gestational-age pregnancy in non-diabetic women". The Obstetrician & Gynaecologist. 12 (4): 250–256. doi:10.1576/toag.12.4.250.27617. ## External links[edit] Classification D * ICD-10: P08 * ICD-9-CM: 766 * MeSH: D005320 * DiseasesDB: 21929 External resources * MedlinePlus: 002251 * eMedicine: med/3279 * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Large for gestational age	c0015938	29,934	wikipedia	https://en.wikipedia.org/wiki/Large_for_gestational_age	2021-01-18T18:42:19	{"gard": ["10155"], "mesh": ["D005320"], "icd-9": ["656.6", "766"], "icd-10": ["O36.6", "P08"], "wikidata": ["Q1886514"]}
Recessive X-linked ichthyosis (RXLI) is a genodermatosis belonging to the Mendelian Disorders of Cornification (MeDOC) and characterized by generalized hyperkeratosis and scaling of the skin. ## Epidemiology RXLI affects almost exclusively males. It is the second most common type of ichthyosis with an estimated prevalence of 1 / 2,000 to 1 / 6,000 males. ## Clinical description Onset may occur within the first days of life with the development of generalized non-erythematous, polygonal, loosely adherent scales. These scales later evolve into grayish or blackish adherent scales that are pronounced on the trunk, the extensor and flexor sites of the extremities, and the neck (giving the ''dirty-neck'' appearance). Skin's folds, palms and soles, are normally spared. Scaling improves with age and during summer. Delayed birth (insufficient cervical dilatation) may be observed. Extracutaneous manifestations like testicular maldescent and/or corneal opacities are possible for rare cases, if the ichthyosis is part of a disease syndrome (syndromic RXLI; see this term). ## Etiology X-linked ichthyosis is an epidermal lipid metabolism anomaly due to inactivating mutations or deletions in the steroid sulfatase STS gene (Xp22.3). STS codes for a lipid hydrolase of the stratum corneum that participates in the regulation of permeability barrier homeostasis and desquamation by catalyzing the hydrolysis of steroid sulfates (e.g. cholesterol sulfate CSO4, sulfated steroid hormones). STS deficiency leads to increased amounts of CSO4 that inhibit epidermal serine proteases, which in turn results in decreased desquamation of corneocytes with retention hyperkeratosis. There are some much more rare syndromic RXLI cases that are due to contiguous gene deletion affecting neighbouring genes of the STS gene. This can be observed in Kallman syndrome, hypergonadotropic hypogonadism, ocular albinism type 1 (see these terms), or hypertrophic pyloric stenosis. ## Diagnostic methods Diagnosis is based on clinical findings and family history (scaling in male relatives, history of delayed birth). It is confirmed by biochemical (serum protein electrophoresis, STS activity test of fibroblasts or leukocytes) and molecular/cytogenetic analyses (polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH)). Histology or ultrastructure of the skin is helpful for the differentiation of ichthyosis vulgaris. ## Differential diagnosis Differential diagnosis includes ichthyosis vulgaris, autosomal recessive congenital ichthyosis (ARCI), namely lamellar ichthyosis, syndromic RLXI, or multiple sulfatase deficiency (see these terms). ## Antenatal diagnosis Maternal urine and serum steroid measurements may show decreased estrogen levels. Therefore, RXLI may be detected in utero, when maternal estriol levels are measured for prenatal screening for Down syndrome and other disorders. ## Genetic counseling XLRI is transmitted as an X-linked recessive trait: it affects males and is inherited through female carriers. Female patients have rarely been reported. ## Management and treatment Treatment consists in hydrating and softening the skin with the use of lubricating bath oils and emollients containing humectants and keratolytics (e. g. urea, lactic acid, and glycolic acid). For adult patients systemic retinoids are an option, e. g. during winter, when the ichthyosis is often more severe. ## Prognosis RXLI represents a benign form of ichthyosis. The ichthyosis is life-long but hyperkeratosis and scaling may improve with age. Life expectancy is normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Recessive X-linked ichthyosis	c0079588	29,935	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=461	2021-01-23T17:20:33	{"gard": ["7904"], "mesh": ["D016114"], "omim": ["300001", "308100"], "umls": ["C0079588", "C2717836", "C2720163"], "icd-10": ["Q80.1"], "synonyms": ["RXLI", "Steroid sulfatase deficiency", "X-linked ichthyosis", "XLI"]}
## Summary ### Clinical characteristics. Individuals with ETV6 thrombocytopenia and predisposition to leukemia most often present with a lifelong history of thrombocytopenia, which is usually in the mild to moderate range. No syndromic features or associations are consistently shared across pedigrees. Affected individuals also have a moderate risk of developing a hematologic malignancy (with B-cell acute lymphoblastic leukemia [B-ALL] being the most common) and possibly other malignant solid tumors, particularly colorectal cancer. ### Diagnosis/testing. The diagnosis of ETV6 thrombocytopenia and predisposition to leukemia is established in a proband by identification of a heterozygous germline pathogenic variant in ETV6 by molecular genetic testing. ### Management. Treatment of manifestations: For clinical bleeding, local measures with consideration of antifibrinolytic agents, desmopressin, and/or platelet transfusion if bleeding is moderate to severe. For neoplasm, standard neoplasm-specific therapy with consideration of indications for stem cell transplantation, eligibility, and available donors. Prevention of secondary complications: For individuals with a history of moderate or severe bleeding, antifibrinolytic agents or desmopressin may be considered prior to surgical procedures to reduce bleeding complications. Platelet transfusions should be used judiciously, particularly in women of childbearing age, to reduce the risk of alloimmunization. Surveillance: Complete blood count with differential every six to 12 months and consideration of bone marrow aspirate and biopsy annually. The frequency of such screening must be weighed against the burden of the screening protocol, particularly in young children. The exact frequency of CBC and bone marrow evaluations should be determined on a case-by-case basis by the physician and in consideration of patient/family preferences. Agents/circumstances to avoid: For those with a history of bleeding, avoidance of medications that decrease platelet function (e.g., aspirin, nonsteroidal anti-inflammatories) and avoidance of participation in contact sports are recommended. Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of clinical surveillance for malignancy and management of potential significant thrombocytopenia. Pregnancy management: Platelet counts should be monitored during pregnancy and prior to delivery. Platelet transfusions prior to invasive procedures (e.g., epidural analgesia or cæsarean section) or at the time of delivery may be considered in those with a history of bleeding or severe thrombocytopenia, on a case-by-case basis. ### Genetic counseling. ETV6 thrombocytopenia and predisposition to leukemia is inherited in an autosomal dominant manner. To date, all affected individuals have inherited the ETV6 pathogenic variant from a parent, although in some instances the heterozygous parent did have any known clinical findings. The offspring of an individual with ETV6 thrombocytopenia and predisposition to leukemia are at 50% risk of inheriting the ETV6 pathogenic variant. Once the ETV6 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ETV6 thrombocytopenia and predisposition to leukemia is a nonsyndromic genetic disorder of thrombocytopenia and high risk of leukemia without any other known congenital anomalies. Formal clinical diagnostic criteria have not been published. ### Suggestive Findings ETV6 thrombocytopenia and predisposition to leukemia should be considered in individuals with the following clinical and laboratory findings and family history. Clinical findings * Absent-to-moderate bleeding tendencies (e.g., menorrhagia, epistaxis, easy bruising, gum bleeding) * Hematologic malignancies, including: * B-cell acute lymphoblastic leukemia (B-ALL), which is the most common * Acute myeloid leukemia (AML) * Myelodysplastic syndrome (MDS) * Myeloproliferative neoplasms (MPN) * Mixed phenotype acute leukemia (MPAL) * Multiple myeloma * Possibly solid tumors, especially colorectal cancer Laboratory findings * Persistent and unexplained mild-to-moderate thrombocytopenia (platelet counts are often >75x109/L) with typically normal platelet size and occasionally accompanied by a high mean platelet volume * Normal white blood cell count * Normal hemoglobin concentration, sometimes with a high mean erythrocyte corpuscular volume (MCV) * Abnormal bone marrow histology with small hyperchromatic megakaryocytes, disseminated toxic granulations, and dysplastic eosinophils in the absence of frank myelodysplasia Family history * One or more relatives with thrombocytopenia, acute leukemia, AND/OR solid tumors (particularly colorectal cancer) consistent with an autosomal dominant inheritance pattern * Note: Absence of a known family history of thrombocytopenia, acute leukemia or solid tumors does not preclude the diagnosis. ### Establishing the Diagnosis The diagnosis of ETV6 thrombocytopenia and predisposition to leukemia is established in a proband by identification of a heterozygous germline pathogenic variant in ETV6 by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of ETV6 thrombocytopenia and predisposition to leukemia has not been considered may be diagnosed using genomic testing (see Option 2). #### Option 1 When the clinical and laboratory findings suggest the diagnosis of ETV6 thrombocytopenia and predisposition to leukemia, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of ETV6 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. * A multigene panel that includes ETV6 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. It is important to note that: (1) The genes included in panels and the diagnostic sensitivity of the testing for each gene vary by laboratory and are likely to change over time; (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview and some panels may not include this gene; (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician; and (4) The methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the diagnosis of ETV6 thrombocytopenia and predisposition to leukemia is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. Note: A diagnosis of ETV6 thrombocytopenia and predisposition to leukemia should not be confused with individuals who have malignancies with somatic chromosome rearrangements involving ETV6 (see Genetically Related Disorders and Cancer and Benign Tumors). ### Table 1. Molecular Genetic Testing Used in ETV6-Related Thrombocytopenia and Predisposition to Leukemia View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ETV6Sequence analysis 323/26 4 Gene-targeted deletion/duplication analysis 52/26 6, 7 Karyotype1/26 8 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Di Paola & Porter [2019] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Paulsson et al [2010] reported one affected individual with an intragenic deletion involving exon 2. 7\. Ross et al [2019] described a family in which individuals had a contiguous gene deletion that included ETV6. Rampersaud et al [2019] reported a germline 75-base-pair deletion of ETV6 at the intron 6-exon 7 junction in all affected individuals. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by Ross et al [2019]) may not be detected by these methods. 8\. Järviaho et al [2019] described a pedigree in which two second-degree relatives developed B-ALL and were found to have a constitutional, balanced translocation involving ETV6 (t(12;14)(p13.2;q23.1). An additional seven family members were found to harbor the same translocation but did not have a history of leukemia. No family members had thrombocytopenia. ## Clinical Characteristics ### Clinical Description Individuals with ETV6 thrombocytopenia and predisposition to leukemia most often present with a lifelong history of thrombocytopenia, which is usually in the mild to moderate range. No syndromic features or associations are consistently shared across pedigrees. Affected individuals also have a moderate risk of developing a hematologic malignancy (with B-cell acute lymphoblastic leukemia [B-ALL] being the most common) and possibly other malignant solid tumors, particularly colorectal cancer. To date, a total of 100 individuals from 26 families have been identified with a germline pathogenic variant in ETV6 [Paulsson et al 2010, Di Paola & Porter 2019, Rampersaud et al 2019, Ross et al 2019]. The following description of the phenotypic features associated with this condition is based on these reports. #### Thrombocytopenia Thrombocytopenia is found in more than 90% of affected individuals at the time of diagnosis. However, most affected individuals have normal hemostasis or only a mild bleeding tendency. Bleeding history * Most affected individuals do not develop severe spontaneous bleeding episodes. * Reported bleeding symptoms have included menorrhagia, epistaxis, easy bruising, and gum bleeding [Hock & Shimamura 2017]. Complete blood counts * Most reported platelet counts are between 100-150x109/L. * Some affected individuals have platelet counts as low as 32x109/L, but severe thrombocytopenia (<20 x 109/L) is rarely seen without concurrent myelodysplastic syndrome. * Platelet size is usually normal by automated method (mean platelet volume) or microscopic analysis, although some affected individuals exhibit increased platelet volume. Platelet structure and function studies. While abnormal platelet aggregation studies have been observed in a few individuals, no abnormal pattern on platelet membrane receptor distribution has been observed to date. Platelets have also shown abnormal clot retraction and spreading on fibrinogen surfaces [Poggi et al 2017, Di Paola & Porter 2019]. #### Bone Marrow Biopsy Bone marrow aspirates in those without concurrent leukemias have revealed dyserythropoiesis, megakaryocyte hyperplasia, and small hypolobulated megakaryocytes [Di Paola & Porter 2019]. #### Lymphoid and Myeloid Malignancies About 30% of individuals with ETV6 thrombocytopenia and predisposition to leukemia develop a hematologic malignancy. * Reported age range at time of diagnosis of a hematologic malignancy is between two and 82 years, with an average and median age of onset of 22 and 11 years, respectively [Di Paola & Porter 2019]. * About two thirds of affected individuals who develop a hematologic malignancy will have B-cell acute lymphoblastic leukemia. * Other reported malignancies: * Other forms of acute lymphoblastic leukemia * Myelodysplastic syndrome (MDS) * Acute myeloid leukemia (AML) * Mixed phenotype acute leukemia * Diffuse large B-cell lymphoma * Polycythemia vera Children with ETV6 thrombocytopenia and predisposition to leukemia may be more likely to have hyperdiploid leukemia and be older at the time of diagnosis of leukemia than sporadic cases of leukemia [Moriyama et al 2015]. There is currently no evidence that the presence of a heterozygous germline ETV6 pathogenic variant influences response to therapy, nor are there any recommendations to alter standard therapy based on the presence of a heterozygous germline ETV6 pathogenic variant. #### Solid Tumors There may be an increased risk for the development of solid tumors in those with ETV6 thrombocytopenia and predisposition to leukemia. While the exact risk has not been defined, at least seven molecularly confirmed individuals have a reported history of malignant solid tumors diagnosed before age 50 years, including two with colorectal cancer [Di Paola & Porter 2019]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been identified. ### Penetrance The penetrance of thrombocytopenia in this disorder is thought to exceed 90%. The penetrance of malignancy, specifically lymphoid and myeloid, is estimated at 30%. ### Prevalence The prevalence of ETV6 thrombocytopenia and predisposition to leukemia is unknown. To date, around 100 individuals have been reported to have this disorder. ## Differential Diagnosis ### Table 2. Genes of Interest in the Differential Diagnosis of ETV6 Thrombocytopenia and Predisposition to Leukemia View in own window GeneDisorder 1Associated MalignanciesHematologic Findings ANKRD26ANKRD26 thrombocytopeniaMDS/AML AUL CLL CMLThrombocytopenia CYCSThrombocytopenia 4 (OMIM 612004)NoneThrombocytopenia w/normal-sized platelets FLI1Bleeding disorder, platelet type 21 (OMIM 617443)NoneThrombocytopenia w/large platelets RUNX1Familial platelet disorder w/predisposition to acute myelogenous leukemia (OMIM 601399)MDS/AML T-ALL Hairy cell leukemiaThrombocytopenia (can have normal platelet counts) AML = acute myeloid leukemia; AUL = acute undifferentiated leukemia; CLL = chronic lymphocytic leukemia; CML = chronic myeloid leukemia; MDS = myelodysplastic syndrome; T-ALL = T-cell acute lymphoblastic leukemia 1\. Disorders in this table are inherited in an autosomal dominant manner. ## Management Expert and consensus clinical guidelines for the management of inherited thrombocytopenia and leukemia predisposition syndromes, including those with germline ETV6 pathogenic variants, have been proposed [Porter et al 2017, Dupuis & Gachet 2018]. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ETV6 thrombocytopenia and predisposition to leukemia, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with ETV6 Thrombocytopenia and Predisposition to Leukemia View in own window System/ConcernEvaluationComment Hematologic/ OncologicCBC w/differentialIncl peripheral smear for detection of hematologic neoplasms Consider platelet aggregation studies.If available & platelet count allows Consider bone marrow biopsy & aspirate.Particularly if cytopenias are present on CBC Consider referral to hematologist/oncologist.Consider referral to a center w/expertise in predisposition to malignancy, as a multidisciplinary team may help refine optimal management. Genetic counselingConsultation w/clinical geneticist &/or genetic counselorTo incl genetic counseling, ideally in a center w/experience in predisposition to hematologic malignancy CBC = complete blood count ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with ETV6 Thrombocytopenia and Predisposition to Leukemia View in own window Manifestation/ ConcernTreatmentConsiderations/Other Clinical bleedingLocal measures Antifibrinolytic agents; desmopressinIf bleeding is moderate or severe Platelet transfusionFor acute, moderate-to-severe bleeding 1 NeoplasmStandard neoplasm-specific therapyConsider indications for stem cell transplantation, eligibility, & available donors. Confirm by targeted molecular genetic testing that potential related donors do not have ETV6 thrombocytopenia w/predisposition to leukemia. 2 1\. Dupuis & Gachet [2018] 2\. Godley [2014] ### Prevention of Secondary Complications For individuals with a history of moderate or severe bleeding, antifibrinolytic agents or desmopressin may be considered prior to surgical procedures to reduce bleeding complications. Platelet transfusions should be used judiciously – particularly in women of childbearing age – to reduce the risk of alloimmunization. ### Surveillance Individuals with ETV6 thrombocytopenia and leukemia predisposition should adhere to published population-based cancer screening guidelines, including for breast and colon cancers. In addition to education regarding the signs and symptoms of hematologic malignancies, the following surveillance should be considered. ### Table 5. Recommended Surveillance for Individuals with ETV6 Thrombocytopenia and Predisposition to Leukemia View in own window System/ConcernEvaluationFrequency Hematology/ OncologyCBC w/differentialEvery 6 to 12 mos 1, 2, 3 Bone marrow aspirate & biopsy 4Annually 1, 2 CBC = complete blood count 1\. The benefit of this screening regimen is currently unknown. 2\. The frequency of such screening must be weighed against the burden of the screening protocol, particularly in young children. The frequency of CBC and bone marrow evaluations should be determined on a case-by-case basis by the physician and in consideration of patient/family preferences. 3\. If changes in the CBC with differential are persistent for 2-4 weeks, particularly cytopenias, consider an additional bone marrow aspirate and biopsy. 4\. To include morphology, cytogenetics, fluorescence in situ hybridization (FISH) (e.g., for chromosomes 5q, 7q, 8, and 20q) and molecular studies (depending on morphology, cytogenetics, and/or FISH) [Di Paola & Porter 2019]. ### Agents/Circumstances to Avoid For individuals with ETV6 thrombocytopenia and predisposition to leukemia and a history of bleeding, medications that decrease platelet function (e.g., aspirin, nonsteroidal anti-inflammatories) should be avoided. Similarly, participation in contact sports is not recommended. ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of clinical surveillance for malignancy and management of potential significant thrombocytopenia. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Platelet counts should be monitored during pregnancy and prior to delivery, in collaboration with a hematologist. Platelet transfusions prior to invasive procedures (e.g., epidural analgesia or cæsarean section) or at the time of delivery may be considered in those with a history of bleeding or severe thrombocytopenia on a case-by-case basis. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ETV6 Thrombocytopenia and Predisposition to Leukemia	None	29,936	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK564234/	2021-01-18T21:28:53	{"synonyms": ["ETV6-Linked Leukemia / Familial Thrombocytopenia Syndrome", "Thrombocytopenia 5 (THC5)"]}
Argininemia Other namesArginase deficiency[1] Arginine SpecialtyNeurology, medical genetics, endocrinology SymptomsLethargy, Dehydration[2][3] CausesMutations in the ARG1 gene[4][5] Diagnostic methodUrinary orotic acid concentration[2] TreatmentProtein intake limited, Sodium benzoate[3] Argininemia, is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high; the nervous system is especially sensitive to the effects of excess ammonia.[2][6] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 References * 6 Further reading * 7 External links ## Signs and symptoms[edit] The presentation of argininemia, in those that are affected, is consistent with the following:[2][3] * Lethargy * Dehydration * Hypotonia * Growth is stunted * Microcephaly * Seizures ## Genetics[edit] Argininemia has an autosomal recessive pattern of inheritance. Mutations in the ARG1 gene cause argininemia, which belongs to a class of genetic diseases called urea cycle disorders.[4][5] The urea cycle is a sequence of reactions that occurs in liver cells (hepatocytes). This cycle processes excess nitrogen, generated when protein is used by the body, making urea that is excreted via the kidneys.[7] The ARG1 gene provides instructions for making an enzyme called arginase, this enzyme controls the last steps of the urea cycle, which produces urea by extracting nitrogen from arginine.[4] In people with arginase deficiency, arginase is missing, and arginine is not broken down properly. consequently, urea cannot be produced and excess nitrogen accumulates in the blood in the form of ammonia. Ammonia and arginine are thought to cause neurological problems and other symptoms of arginase deficiency.[2] This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome,[6] and two copies of the defective gene are required to inherit the disorder. Both parents of an individual with an autosomal recessive disorder are carriers of one copy of the gene, but usually do not have the disorder.[medical citation needed] ## Diagnosis[edit] The diagnosis for argininemia can usually be done using fetal blood sample.[8] One can look for the following indicators as to the presence of the condition:[2] * Plasma ammonia concentration. * Urinary orotic acid concentration * Red blood cell arginase enzyme activity (measurement) ## Treatment[edit] Glycerol phenylbutyrate The treatment for infants (individuals) with argininemia is the following, including medications:[3] * Protein intake limited * Sodium benzoate * Sodium phenylbutyrate * Carglumic acid * Glycerol phenylbutyrate * Palonosetron * Ondansetron hydrochloride ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 207800 2. ^ a b c d e f Wong, Derek; Cederbaum, Stephen; Crombez, Eric A. (1 January 1993). "Arginase Deficiency". GeneReviews. PMID 20301338. Retrieved 20 November 2016.update 2014 3. ^ a b c d "Arginase Deficiency: Background, Pathophysiology, Epidemiology". eMedicine. 15 April 2016. Retrieved 28 November 2016. 4. ^ a b c Reference, Genetics Home. "ARG1 gene". Genetics Home Reference. Retrieved 28 November 2016. 5. ^ a b Ah Mew, Nicholas; Lanpher, Brendan C.; Gropman, Andrea; Chapman, Kimberly A.; Simpson, Kara L.; Summar, Marshall L. (1 January 1993). "Urea Cycle Disorders Overview". GeneReviews. Retrieved 20 November 2016.update 2015 6. ^ a b Reference, Genetics Home. "arginase deficiency". Genetics Home Reference. Retrieved 20 November 2016. 7. ^ Hames, David; Hooper, Nigel (2005). Instant Notes in Biochemistry. Annales de Biologie Clinique. 58 (3rd ed.). Hoboken: Taylor & Francis Ltd. p. 408. ISBN 9780203967621. PMID 11098183. Retrieved 28 November 2016. 8. ^ Wyllie, Robert; Hyams, Jeffrey S.; Kay, Marsha (2015). Pediatric Gastrointestinal and Liver Disease. Elsevier Health Sciences. p. 886. ISBN 9780323370219. ## Further reading[edit] * (editors), Jean-Marie Saudubray, Georges van den Berghe, John H. Walter; Berghe, Georges van den; Walter, John H. (2012). Inborn metabolic diseases diagnosis and treatment (5th ed.). Berlin: Springer. ISBN 9783642157202. Retrieved 28 November 2016.CS1 maint: extra text: authors list (link) * Piña-Garza, J. Eric (2013). Fenichel's Clinical pediatric neurology a signs and symptoms approach (7th ed.). Oxford: Saunders. ISBN 978-1455748129. Retrieved 28 November 2016. ## External links[edit] Classification D * ICD-10: E72.2 * ICD-10-CM: E72.21 * OMIM: 207800 * MeSH: D020162 * DiseasesDB: 29677 External resources * eMedicine: ped/132 * GeneReviews: Arginase Deficiency * Orphanet: 90 Scholia has a topic profile for Argininemia. * v * t * e Inborn error of amino acid metabolism K→acetyl-CoA Lysine/straight chain * Glutaric acidemia type 1 * type 2 * Hyperlysinemia * Pipecolic acidemia * Saccharopinuria Leucine * 3-hydroxy-3-methylglutaryl-CoA lyase deficiency * 3-Methylcrotonyl-CoA carboxylase deficiency * 3-Methylglutaconic aciduria 1 * Isovaleric acidemia * Maple syrup urine disease Tryptophan * Hypertryptophanemia G G→pyruvate→citrate Glycine * D-Glyceric acidemia * Glutathione synthetase deficiency * Sarcosinemia * Glycine→Creatine: GAMT deficiency * Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine * Carnosinemia * Histidinemia * Urocanic aciduria Proline * Hyperprolinemia * Prolidase deficiency Glutamate/glutamine * SSADHD G→propionyl-CoA→ succinyl-CoA Valine * Hypervalinemia * Isobutyryl-CoA dehydrogenase deficiency * Maple syrup urine disease Isoleucine * 2-Methylbutyryl-CoA dehydrogenase deficiency * Beta-ketothiolase deficiency * Maple syrup urine disease Methionine * Cystathioninuria * Homocystinuria * Hypermethioninemia General BC/OA * Methylmalonic acidemia * Methylmalonyl-CoA mutase deficiency * Propionic acidemia G→fumarate Phenylalanine/tyrosine Phenylketonuria * 6-Pyruvoyltetrahydropterin synthase deficiency * Tetrahydrobiopterin deficiency Tyrosinemia * Alkaptonuria/Ochronosis * Tyrosinemia type I * Tyrosinemia type II * Tyrosinemia type III/Hawkinsinuria Tyrosine→Melanin * Albinism: Ocular albinism (1) * Oculocutaneous albinism (Hermansky–Pudlak syndrome) * Waardenburg syndrome Tyrosine→Norepinephrine * Dopamine beta hydroxylase deficiency * reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine * aspartate) * Argininemia * Argininosuccinic aciduria * Carbamoyl phosphate synthetase I deficiency * Citrullinemia * N-Acetylglutamate synthase deficiency * Ornithine transcarbamylase deficiency/translocase deficiency Transport/ IE of RTT * Solute carrier family: Cystinuria * Hartnup disease * Iminoglycinuria * Lysinuric protein intolerance * Fanconi syndrome: Oculocerebrorenal syndrome * Cystinosis Other * 2-Hydroxyglutaric aciduria * Aminoacylase 1 deficiency * Ethylmalonic encephalopathy * Fumarase deficiency * Trimethylaminuria * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Argininemia	c0268548	29,937	wikipedia	https://en.wikipedia.org/wiki/Argininemia	2021-01-18T18:36:28	{"gard": ["5840"], "mesh": ["D020162"], "umls": ["C0268548"], "orphanet": ["90"], "wikidata": ["Q890367"]}
Ependymoma Micrograph of an ependymoma. H&E stain. SpecialtyOncology An ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymomas is the fourth ventricle. Rarely, ependymomas can occur in the pelvic cavity. Syringomyelia can be caused by an ependymoma. Ependymomas are also seen with neurofibromatosis type II. ## Contents * 1 Signs and symptoms * 2 Morphology * 3 Ependymoma tumors * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] Source:[1] * severe headache * visual loss (due to papilledema) * vomiting * bilateral Babinski sign * drowsiness (after several hours of the above symptoms) * gait change (rotation of feet when walking) * impaction/constipation * back flexibility ## Morphology[edit] Ependymomas are composed of cells with regular, round to oval nuclei. There is a variably dense fibrillary background. Tumor cells may form gland-like round or elongated structures that resemble the embryologic ependymal canal, with long, delicate processes extending into the lumen; more frequently present are perivascular pseudorosettes in which tumor cells are arranged around vessels with an intervening zone consisting of thin ependymal processes directed toward the wall of the vessel.[2] It has been suggested that ependymomas are derived from radial glia, despite their name suggesting an ependymal origin.[3] * Micrograph of a myxopapillary ependymoma. HPS stain. * Ependymoma of 4.ventricle in MRI. * Ependymoma of 4.ventricle in MRI. * Ependymoma of 4.ventricle in MRI. Left without, right with contrast-enhancement. ## Ependymoma tumors[edit] Ependymomas make up about 5% of adult intracranial gliomas and up to 10% of childhood tumors of the central nervous system (CNS). Their occurrence seems to peak at age 5 years and then again at age 35. They develop from cells that line both the hollow cavities of the brain and the canal containing the spinal cord, but they usually arise from the floor of the fourth ventricle, situated in the lower back portion of the brain, where they may produce headache, nausea and vomiting by obstructing the flow of cerebrospinal fluid. This obstruction may also cause hydrocephalus. They may also arise in the spinal cord, conus medullaris and supratentorial locations.[4] Other symptoms can include (but are not limited to): loss of appetite, difficulty sleeping, temporary inability to distinguish colors, uncontrollable twitching, seeing vertical or horizontal lines when in bright light, and temporary memory loss. It should be remembered that these symptoms also are prevalent in many other illnesses not associated with ependymoma. About 10% of ependymomas are benign myxopapillary ependymoma (MPE).[citation needed] MPE is a localized and slow-growing low-grade tumor, which originates almost exclusively from the lumbosacral nervous tissue of young patients.[5] On the other hand, it is the most common tumor of the lumbosacral canal comprising about 90% of all tumoral lesions in this region.[6] Although some ependymomas are of a more anaplastic and malignant type, most of them are not anaplastic. Well-differentiated ependymomas are usually treated with surgery. For other ependymomas, total surgical removal is the preferred treatment in addition to radiation therapy. The malignant (anaplastic) varieties of this tumor, malignant ependymoma and the ependymoblastoma, are treated similarly to medulloblastoma but the prognosis is much less favorable. Malignant ependymomas may be treated with a combination of radiation therapy and chemotherapy. Ependymoblastomas, which occur in infants and children younger than 5 years of age, may spread through the cerebrospinal fluid and usually require radiation therapy. The subependymoma, a variant of the ependymoma, is apt to arise in the fourth ventricle but may occur in the septum pellucidum and the cervical spinal cord. It usually affects people over 40 years of age and more often affects men than women.[citation needed] Extraspinal ependymoma (EEP), also known as extradural ependymoma, may be an unusual form of teratoma[7] or may be confused with a sacrococcygeal teratoma.[8] ## Treatment[edit] Guidelines for initial management for ependymoma are maximum surgical resection followed by radiation.[9] Chemotherapy is of limited use and reserved for special cases including young children and those with tumor present after resection. Prophylactic craniospinal irradiation is of variable use and is a source of controversy given that most recurrence occurs at the site of resection and therefore is of debatable efficacy.[10][9] Confirmation of cerebrospinal infiltration warrants more expansive radiation fields. Prognosis of recurrence is poor and often indicates palliative care to manage symptoms.[11] ## References[edit] 1. ^ PRITE 2010 Part II q.13 2. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). "Ch. 28 The central nervous system". Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN 0-7216-0187-1.[page needed] 3. ^ Poppleton, H; Gilbertson, R J (2006). "Stem cells of ependymoma". British Journal of Cancer. 96 (1): 6–10. doi:10.1038/sj.bjc.6603519. PMC 2360214. PMID 17179988. 4. ^ Goel, Ayush; Gaillard, Frank. "Ependymoma". Radiopaedia.org. Retrieved 12 September 2014. 5. ^ Mehrjardi, Mohammad Zare; Mirzaei, Samira; Haghighatkhah, Hamid Reza (2017). "The many faces of primary cauda equina myxopapillary ependymoma: Clinicoradiological manifestations of two cases and review of the literature". Romanian Neurosurgery. 31 (3): 385–90. doi:10.1515/romneu-2017-0062. 6. ^ Duong, Linh M; McCarthy, Bridget J; McLendon, Roger E; Dolecek, Therese A; Kruchko, Carol; Douglas, Lynda L; Ajani, Umed A (2012). "Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors, United States, 2004-2007". Cancer. 118 (17): 4220–7. doi:10.1002/cncr.27390. PMC 4484585. PMID 22907705. 7. ^ Aktuğ, Tanju; Hakgüder, Gülce; Sarioğlu, Sülen; Akgür, Feza M; Olguner, Mustafa; Pabuçcuoğlu, Uğur (2000). "Sacrococcygeal extraspinal ependymomas: The role of coccygectomy". Journal of Pediatric Surgery. 35 (3): 515–8. doi:10.1016/S0022-3468(00)90228-8. PMID 10726703. 8. ^ Hany, Manuela A; Bouvier, Raymonde; Ranchère, Dominique; Bergeron, Christophe; Schell, Matthias; Chappuis, Jean-Paul; Philip, Thierry; Frappaz, Didier (2009). "Case Report: A Preterm Infant with an Extradural Myxopapillary Ependymoma Component of a Teratoma and High Levels of α-Fetoprotein". Pediatric Hematology and Oncology. 15 (5): 437–41. doi:10.3109/08880019809016573. PMID 9783311. 9. ^ a b Reni, M (2003). "Guidelines for the treatment of adult intra-cranial grade II-III ependymal tumours". Forum (Genoa, Italy). 13 (1): 90–8. PMID 14732890. 10. ^ Merchant, T. E; Fouladi, M (2005). "Ependymoma: New therapeutic approaches including radiation and chemotherapy". Journal of Neuro-Oncology. 75 (3): 287–99. doi:10.1007/s11060-005-6753-9. PMID 16195801. 11. ^ Merchant, T. E; Boop, F. A; Kun, L. E; Sanford, R. A (2008). "A retrospective study of surgery and reirradiation for recurrent ependymoma". International Journal of Radiation OncologyBiologyPhysics. 71 (1): 87–97. doi:10.1016/j.ijrobp.2007.09.037. PMID 18406885. ## External links[edit] * Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke) Classification D * ICD-10: C71 * ICD-9-CM: 191.9, 225.0, 237.5 * ICD-O: M9391/3-9394/1 * MeSH: D004806 * DiseasesDB: 29452 External resources * eMedicine: med/700 * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ependymoma	c0014474	29,938	wikipedia	https://en.wikipedia.org/wiki/Ependymoma	2021-01-18T18:41:10	{"gard": ["6353"], "mesh": ["D004806"], "icd-9": ["191.9", "225.0", "237.5"], "icd-10": ["C71"], "orphanet": ["251636"], "wikidata": ["Q1346753"]}
Hartnup disease is a metabolic disorder characterized by abnormal transport of certain amino acids in the kidney and gastrointestinal system. It is a type of aminoaciduria. The condition may be diagnosed based on the results of newborn screening tests. Most people with the condition have no symptoms (asymptomatic). For those who do show symptoms, the onset of the disease is usually between the ages of 3 and 9; occasionally the disease may present in adulthood. Mental development is usually normal, though a few cases with intellectual impairment have been reported. The signs and symptoms of Hartnup disease incude skin photosensitivity, neurologic findings, psychiatric symptoms, and ocular (eye) findings. Hartnup disease is caused by mutations in the SLC6A19 gene and is inherited in an autosomal recessive manner.[1][2] People with Hartnup disease may benefit from a high-protein diet, protection from sunlight, vitamin supplementation, and avoidance of certain drugs/medications. In some cases, treatment with nicotinamide supplements and tryptophan ethyl ester may be indicated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hartnup disease	c0018609	29,939	gard	https://rarediseases.info.nih.gov/diseases/6569/hartnup-disease	2021-01-18T18:00:09	{"mesh": ["D006250"], "omim": ["234500"], "umls": ["C0018609"], "orphanet": ["2116"], "synonyms": ["HND", "Hartnup disorder"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-52 (MRT52) is caused by homozygous mutation in the LMAN2L gene (609552) on chromosome 2q11. One such family has been reported. Clinical Features Rafiullah et al. (2016) reported a large multigenerational consanguineous Pakistani family in which 7 individuals had global developmental delay and severe intellectual disability with poor speech. Ranging in age from 7 to 25 years, all were completely dependent for all activities of daily living. The patients also had mild seizures in early childhood that spontaneously remitted by around 5 years of age. Two of the patients died at age 7 and 16 years. None had dysmorphic features. Inheritance The transmission pattern of MRT52 in the family reported by Rafiullah et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of a Pakistani family with MRT52, Rafiullah et al. (2016) identified a homozygous missense mutation in the LMAN2L gene (R53Q; 609552.0001). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Patient cells had no evidence of glycosylation defects. Additional functional studies were not performed. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Global developmental delay \- Intellectual disability, severe \- Seizures, mild MISCELLANEOUS \- Onset in infancy \- Seizures remit spontaneously by age 5 years \- One consanguineous Pakistani family has been reported (last curated March 2016) MOLECULAR BASIS \- Caused by mutation in the LMAN2-like protein gene (LMAN2L, 609552.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MENTAL RETARDATION, AUTOSOMAL RECESSIVE 52	c4225168	29,940	omim	https://www.omim.org/entry/616887	2019-09-22T15:47:32	{"omim": ["616887"], "orphanet": ["88616"], "synonyms": ["AR-NSID", "NS-ARID"]}
Branchiooculofacial syndrome (BOFS) is a very rare genetic disorder that is apparent at birth. Only about 50 cases of BOFS had been reported in the medical literature. Like its name implies, BOFS is characterized by skin defects, eye abnormalities, and distinctive facial features. Among the reported cases thus far, the symptoms may vary from mild to severe. BOFS is caused by mutations in the TFAP2A gene and inherited as an autosomal dominant trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Branchiooculofacial syndrome	c0376524	29,941	gard	https://rarediseases.info.nih.gov/diseases/3212/branchiooculofacial-syndrome	2021-01-18T18:01:42	{"mesh": ["D019280"], "omim": ["113620"], "umls": ["C0376524"], "orphanet": ["1297"], "synonyms": ["BOFS syndrome", "Branchial clefts with characteristic facies growth retardation imperforate nasolacrimal duct and premature aging", "Hemangiomatous branchial clefts-lip pseudocleft syndrome", "Lip pseudocleft-hemangiomatous branchial cyst syndrome"]}
A rare, primary bone dysplasia characterized by severe growth retardation, short stature, cortical thickening and medullary stenosis of long bones, delayed closure of the anterior fontanelle, absent diploic space in the skull bones, prominent forehead, macrocephaly, dental anomalies, eye problems (hypermetropia and pseudopapilledema), and hypocalcemia due to hypoparathyroidism, sometimes resulting in convulsions. Intelligence is normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal dominant Kenny-Caffey syndrome	c4316787	29,942	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93325	2021-01-23T17:05:27	{"gard": ["83"], "mesh": ["C537020"], "omim": ["127000"], "icd-10": ["Q87.1"]}
A rare disease with malignant hyperthermia characterized by exercise-induced life-threatening hyperthermia with a body temperature over 40°C and signs of encephalopathy ranging from confusion to convulsions or coma. Incidence increases with rising ambient temperature and relative humidity. Manifestations may include rhabdomyolysis (presenting with myalgia, muscle weakness, and myoglobinuria), tachycardia, and in severe cases multiorgan failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Exercise-induced malignant hyperthermia	c4544037	29,943	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=466650	2021-01-23T18:33:44	{"icd-10": ["T88.3"], "synonyms": ["Exertional heat stroke"]}
A number sign (#) is used with this entry because of evidence that developmental delay with short stature, dysmorphic facial features, and sparse hair (DEDSSH) is caused by homozygous mutation in the DPH1 gene (603527) on chromosome 17p13. Clinical Features Alazami et al. (2015) reported 4 patients from a consanguineous Saudi family (10DG0934) with syndromic intellectual disability. Loucks et al. (2015) provided more clinical details of these patients. The patients had delayed psychomotor development and an unusual skull shape, mainly scaphocephaly with or without craniosynostosis. Other features included short stature, hypertelorism, downslanting palpebral fissures, epicanthal folds, low-set ears, depressed nasal bridge, and micrognathia, as well as sparse hair of the scalp, eyelashes, and eyebrows. Brain imaging showed posterior malformations, including Dandy-Walker malformation, cerebellar vermis hypoplasia, and posterior fossa cyst. Three patients had a ventricular septal defect and 3 had a renal anomaly. Three patients died between 8 months and 4 years of age. Loucks et al. (2015) reported 4 children, including 2 sibs, from a North American genetic isolate with a neurodevelopmental syndrome. The patients presented in the neonatal period with dysmorphic features and thereafter showed developmental delay and short stature. Dysmorphic features included scaphocephaly, prominent forehead, and sparse eyebrows and hair and hypoplastic toenails, reminiscent of an ectodermal dysplasia. Other more variable features included epicanthal folds, downslanting palpebral fissures, and dental anomalies. One patient had recurrent hematuria and proteinuria associated with mild focal interstitial nephritis on biopsy, but renal function was normal. Brain CT scan of 1 patient was essentially normal. Two sibs, ages 23 and 18, had moderate cognitive impairment and could not live independently. Inheritance The transmission pattern of DEDSSH in the families reported by Loucks et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 4 affected individuals from a consanguineous Saudi family with DEDSSH, Alazami et al. (2015) identified a homozygous missense mutation in the DPH1 gene (L234P; 603527.0001). The family was part of a large cohort of 143 multiplex consanguineous families with various neurodevelopmental disorders who underwent whole-exome sequencing. Functional studies of the variant were not performed. In 4 patients from a North American genetic isolate with DEDSSH, Loucks et al. (2015) identified a homozygous missense mutation in the DPH1 gene (M6K; 603527.0002). The mutation was found by a combination of linkage analysis and exome sequencing and confirmed by Sanger sequencing. The carrier frequency of the variant was 0.46% in this population, consistent with a founder effect. Functional studies of the variant and studies of patient cells were not performed. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Scaphocephaly \- Trigonocephaly Face \- Prominent forehead \- Micrognathia Ears \- Low-set ears Eyes \- Hypertelorism \- Downslanting palpebral fissures \- Epicanthal folds \- Sparse eyebrows \- Sparse eyelashes Nose \- Depressed nasal bridge Teeth \- Dental anomalies CARDIOVASCULAR Heart \- Ventricular septal defect (1 family) GENITOURINARY Kidneys \- Renal anomalies (in some patients) SKELETAL Skull \- Craniosynostosis SKIN, NAILS, & HAIR Nails \- Hypoplastic toenails Hair \- Sparse hair NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Posterior fossa abnormalities (in some patients) \- Cerebellar vermis hypoplasia (in some patients) \- Dandy-Walker malformation (in some patients) MISCELLANEOUS \- Onset at birth \- Death in childhood may occur \- Two unrelated families have been reported (last curated April 2016) MOLECULAR BASIS \- Caused by mutation in the homolog of the S. cerevisiae DPH1 gene (DPH1, 603527.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FACIAL FEATURES, AND SPARSE HAIR	c4310801	29,944	omim	https://www.omim.org/entry/616901	2019-09-22T15:47:30	{"omim": ["616901"], "orphanet": ["459061"], "synonyms": ["Alternative titles", "Developmental delay-short stature-dysmorphic features-sparse hair syndrome", "LOUCKS-INNES SYNDROME"]}
Mast cell sarcoma is a rare, neoplastic disease characterized by locally destructive sarcoma-like growth of a solitary mass, composed of atypical mast cells, and without systemic involvement. It can affect any organ and the symptoms depend on the location. Cells are medium to large, pleomorphic or epithelioid, with oval, bilobed or multilobulated nuclei, sometimes prominent multinucleated giant cells. The disease closely resembles other neoplasms and may share associated markers, however the tumor is positive for mast cell tryptase. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mast cell sarcoma	c0036221	29,945	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66661	2021-01-23T18:02:05	{"mesh": ["D012515"], "umls": ["C0036221"], "icd-10": ["C96.2"]}
Neurofibromatosis (NF) type 3 (NF3), also known as schwannomatosis, is the least frequent form of the rare genetic disorder neurofibromatosis. It is clinically and genetically distinct from NF1 and NF2 and is characterized by the development of multiple schwannomas (nerve sheath tumors), without involvement of the vestibular nerves. NF3 develops in adulthood and is often associated with chronic pain. Dysesthesia and paresthesia may also be present. Common localizations include the spine, peripheral nerves, and the cranium. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Schwannomatosis	c0917817	29,946	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93921	2021-01-23T18:13:53	{"gard": ["4768"], "mesh": ["C536641", "D017253"], "omim": ["162091", "162260", "615670"], "umls": ["C0917817", "C1335929", "C2931480"], "icd-10": ["Q85.0"], "synonyms": ["NF3", "Neurilemmomatosis", "Neurofibromatosis type 3"]}
Retrolisthesis Grade 1 retrolistheses of C3 on C4 and C4 on C5 SpecialtyOrthopedics A retrolisthesis is a posterior displacement of one vertebral body with respect to the subjacent vertebra to a degree less than a luxation (dislocation). Retrolistheses are most easily diagnosed on lateral x-ray views of the spine. Views where care has been taken to expose for a true lateral view without any rotation offer the best diagnostic quality. Retrolistheses are found most prominently in the cervical spine and lumbar region but can also be seen in the thoracic area. ## Contents * 1 Classification * 2 Signs and symptoms * 3 Diagnosis * 3.1 Grading * 3.2 Joint stability * 4 Management * 5 References ## Classification[edit] Retrolisthesis can be classified as a form of spondylolisthesis, since spondylolisthesis is often defined in the literature as displacement in any direction.[1][2] Yet, medical dictionaries usually define spondylolisthesis specifically as the forward or anterior displacement of a vertebra over the vertebra inferior to it (or the sacrum).[3][4] Retrolisthesis is also called retrospondylolisthesis.[5] ## Signs and symptoms[edit] Retrolisthesis may lead to symptoms of greatly varying intensity and distribution. This is because of the variable nature of the impact on nerve tissue and of the mechanical impact on the spinal joints themselves.[citation needed] Structural instability may be experienced as a local uneasiness through to a more far reaching structural compensatory distortion involving the whole spine. If the joints are stuck in a retrolisthesis configuration there may also be changes to range of motion.[citation needed] Pain may be experienced as a result of irritation to the sensory nerve roots by bone depending on the degree of displacement and the presence of any rotatory positioning of the individual spinal motion segments. The soft tissue of the disc is often caused to bulge in retrolistheses. These cannot be determined by plain films, as the x-ray passes through the soft tissue. A study by Giles et al., stated that sixteen of the thirty patients (53%) had retrolisthesis of L5 on S1 ranging from 2–9 mm; these patients had either intervertebral disc bulging or protrusion on CT examination ranging from 3–7 mm into the spinal canal. Fourteen patients (47%) without retrolisthesis (control group) did not show any retrolisthesis and the CT did not show any bulge/protrusion. On categorizing x-ray and CT pathology as being present or not, the well positioned i.e. true lateral plain x-ray film revealed a sensitivity and specificity of 100% ([95% Confidence Interval. = [89%–100%]) for bulge/protrusion in this preliminary study.” (7)[citation needed] Spinal cord compressions are also possible with patients experiencing pain, rigidity and neurologic signs that may follow some distance along nerves to cause symptoms at some distance from the location of the retrolisthesis. ## Diagnosis[edit] Retrolisthesis of L5-S1 Complete Retrolisthesis - The body of one vertebra is posterior to both the vertebral body of the segment of the spine above as well as below.[citation needed] Stairstepped Retrolisthesis - The body of one vertebra is posterior to the body of the spinal segment above, but is anterior to the one below.[citation needed] Partial Retrolisthesis - The body of one vertebra is posterior to the body of the spinal segment either above or below. (3)[citation needed] ### Grading[edit] Since the vertebral body in a retrolisthesis moves in a posterior direction, the grading used for spondylolistheses is of little use. It is however useful to divide the anterior to posterior dimension of the intervertebral foramina (IVF) (4) into four equal units. A posterior displacement of up to ¼ of the IVF is graded as Grade 1, ¼ to ½ as Grade 2, ½ to ¾ as Grade 3, ¾ to total occlusion of the IVF as Grade 4. Alternatively, a measurement of the amount of displacement can also made by measuring the bone displacement in millimetres.[citation needed] Retrolistheses can be caused by injury[citation needed] and the resulting instability of the connecting soft tissues especially ligaments, discs, muscles, tendons and fascia. They may also involve muscles through spasm as a result of nerve malfunction due to pressure caused by the posterior displacement of the vertebra encroaching on the contents of the IVF. The IVF's contents include spinal (sensory and motor) nerves, arteries, veins and lymphatic vessels which cater to the nutritional and waste removal needs of the spinal cord. Degenerative spinal changes are often seen at the levels where a retrolisthesis is found. These changes are more pronounced as time progresses after injury, and are evidenced by end plate osteophytosis, disc damage, disc narrowing, desiccation and disc bulging. “A retrolisthesis hyperloads at least one disc and puts shearing forces on the anterior longitudinal ligament, the annular rings, nucleus pulposus, cartilage end plates and capsular ligaments. The bulging, twisting and straining tissues attached to the endplates pull, push and stretch it. It is worsened with time, becoming irreversible.” This is the etiology of degenerative joint disease. (5) Associated radiological findings include a vacuum phenomenon (in the nucleus pulposis of the adjacent intervertebral disc), reduction of disc height with corresponding loss of the disc space, marginal sclerosis of the adjacent vertebral bodies, osteophyte formation and apophyseal joint instability. With a retrolisthesis there is always a less than ideal positioning of spinal segments. There is also always a reduced anterior to posterior dimension of the spinal canal compared to the way it is supposed to be. The greater the posterior displacement, the more significant it is for producing a dysfunctional spinal cord or even a cauda equina syndrome.[citation needed] ### Joint stability[edit] Joint stability is easily evaluated by the use of flexion and extension lateral x-ray views of the spine. A summary of part of the DRE tables (6) give a guide as to the implications of the joint instability. If either translation or angular change is determined from flexion to extension to the degree shown in the table below, then Category IV instability is present. See also Joint stability.[citation needed] Translation is a gliding motion where one bone of a joint glides over its neighbour.[citation needed] ## Management[edit] This section is empty. You can help by adding to it. (November 2019) ## References[edit] 1. ^ Introduction to chapter 17 in: Thomas J. Errico, Baron S. Lonner, Andrew W. Moulton (2009). Surgical Management of Spinal Deformities. Elsevier Health Sciences. ISBN 9781416033721.CS1 maint: multiple names: authors list (link) 2. ^ Page 250 in: Walter R. Frontera, Julie K. Silver, Thomas D. Rizzo (2014). Essentials of Physical Medicine and Rehabilitation (3 ed.). Elsevier Health Sciences. ISBN 9780323222723.CS1 maint: multiple names: authors list (link) 3. ^ "spondylolisthesisplay". Merriam-Webster medical dictionary. Retrieved 2017-09-07. 4. ^ "spondylolisthesis". Farlex medical dictionary. Retrieved 2017-09-07., in turn citing: * Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. Copyright date 2003 * Dorland's Medical Dictionary for Health Consumers. Copyright date 2007 * The American Heritage Medical Dictionary. Copyright date 2007 * Mosby's Medical Dictionary, 9th edition * McGraw-Hill Concise Dictionary of Modern Medicine. Copyright date 2002 * Collins Dictionary of Medicine. Copyright date 2005 5. ^ Dorland's (2012). Illustrated Medical Dictionary (32nd ed.). Elsevier Saunders. p. 1636. ISBN 978-1-4160-6257-8. 6\. Hadley, Lee A. (MD), (1973) “Anatomicoroentgenographic Studies of the Spine”. 390. 7\. Cocchiarella L., Andersson, G. “American Medical Association Guides to the Evaluation of Permanent Impairment”, 5th edition, Tables 15- 3, 15-4, 15-5. 8\. Giles, L.G.F.; Muller R.; and Winter G.J. (2006) “Lumbosacral disc bulge or protrusion suggested by lateral lumbosacral plain x-ray film – preliminary results.” Journal of Bone and Joint Surgery. British Volume, Vol 88-B, Issue SUPP_III, 450. * v * t * e Spinal disease Deforming Spinal curvature * Kyphosis * Lordosis * Scoliosis Other * Scheuermann's disease * Torticollis Spondylopathy inflammatory * Spondylitis * Ankylosing spondylitis * Sacroiliitis * Discitis * Spondylodiscitis * Pott disease non inflammatory * Spondylosis * Spondylolysis * Spondylolisthesis * Retrolisthesis * Spinal stenosis * Facet syndrome Back pain * Neck pain * Upper back pain * Low back pain * Coccydynia * Sciatica * Radiculopathy Intervertebral disc disorder * Schmorl's nodes * Degenerative disc disease * Spinal disc herniation * Facet joint arthrosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Retrolisthesis	c1562792	29,947	wikipedia	https://en.wikipedia.org/wiki/Retrolisthesis	2021-01-18T19:03:16	{"umls": ["C1562792"], "wikidata": ["Q4393723"]}
Neonatal cholestasis defines persisting conjugated hyperbilirubinemia in the newborn [1]with conjugated bilirubin levels exceeding 15% (5.0 mg/dL) of total bilirubin level. The disease is either due to defects in bile excretion from hepatocytes or impaired bile flow.General presentations in neonates include abdominal pain and general GI upset. Physical examination may show palpable liver and enlarged spleen. Differential diagnosis typically presents with a host of possibilities, many of them not treatable. Histopathology shows dilated bile duct system at all levels and bile duct proliferation in response to back pressure. The incidence has been found to be about 1:2,500 live births.[citation needed] ## See also[edit] * Neonatal jaundice ## References[edit] 1. ^ Feldman, Amy G.; Sokol, Ronald J. (1 February 2013). "Neonatal Cholestasis". NeoReviews. 14 (2): 10.1542/neo.14–2–e63. doi:10.1542/neo.14-2-e63. ISSN 1526-9906. PMC 3827866. PMID 24244109. This article about a disorder arising in the perinatal period is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neonatal cholestasis	c1112213	29,948	wikipedia	https://en.wikipedia.org/wiki/Neonatal_cholestasis	2021-01-18T18:41:34	{"wikidata": ["Q6993476"]}
## Summary The purpose of this overview is to increase the awareness of clinicians regarding maturity-onset diabetes of the young (MODY) and its genetic causes and management. The following are the goals of this overview: ### Goal 1. Describe the clinical characteristics of MODY. ### Goal 2. Review the genetic causes of MODY. ### Goal 3. Provide an evaluation strategy to identify the genetic cause of MODY in a proband (when possible). ### Goal 4. Inform (when possible) medical management of MODY based on genetic cause. ### Goal 5. Inform risk assessment and surveillance of at-risk relatives for early detection and treatment of MODY. ## Diagnosis ## Clinical Characteristics ## Differential Diagnosis ## Management [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Maturity-Onset Diabetes of the Young Overview	None	29,949	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK500456/	2021-01-18T21:12:39	{"synonyms": ["MODY Overview"]}
Cocaine intoxication Other namesCocaine toxicity, cocaine poisoning Cocaine SpecialtyToxicology Cocaine intoxication refers to the pharmacological and subjective effects of cocaine on the body, primarily through its effects on neurotransmitter receptors in the brain. The short-term effects are usually described as feeling stimulating, euphoric, sensual or agitating. ## Contents * 1 Signs and symptoms * 1.1 Overdose * 1.2 Withdrawal * 2 Pathophysiology * 3 Management * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Cocaine increases alertness, feelings of well-being, euphoria, energy, competence, sociability, and sexuality. Mild adverse effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause chronic complications like insomnia, weight loss, anorexia, persistent tachycardia, heart failure, kidney failure, hallucinations, and paranoid delusions.[1] Depression with suicidal ideation may develop in heavy users.[2] Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons.[3] Chronic intranasal usage can degrade the cartilage separating the nostrils (the nasal septum), which can eventually lead to its complete disappearance.[4] Studies have shown that cocaine usage during pregnancy triggers premature labor[5] and may lead to abruptio placentae.[6] In cases of severe acute intoxication, potentially lethal adverse effects include prolonged episodes of arrhythmia (i.e., a group of abnormal heart rhythms that also include tachycardia), heavy hypoglycemia, tremors, convulsions, hyperthermia (i.e., markedly increased core temperature), untreated uremia, myocardial infarction, stroke, and sudden cardiac arrest.[7] ### Overdose[edit] US yearly overdose deaths involving cocaine.[8] US. Opioid involvement in cocaine overdose deaths. Green line is cocaine and any opioid. Gray line is cocaine without any opioids. Yellow line is cocaine and other synthetic opioids.[8] Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes abnormally fast heart rhythms and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, acute respiratory failure (i.e., hypoxemia, with or without hypercapnia), stroke, cerebral hemorrhage, and sudden cardiac arrest.[9] Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in kidney failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 14,600 deaths occurred in the US in 2017 due to cocaine overdose.[8] Because of the increase in heart rate, cocaine users can be prone to elevated body temperatures, tremors, chest pains, and subject to nausea and vomiting. Some psychological symptoms due to an overdose include paranoia, delirium, anxiety as well as panicked feelings.[10] Some signs of an overdose of cocaine are difficulty breathing, loss of urine control, bluish color of the skin, loss of awareness or surroundings, and high blood pressure. Although not as common, death can be caused from an over intoxication of cocaine.[11] Most severe overdoses occur when users combine cocaine with other substances like alcohol or heroin, which increase the effects and heighten the chances of having a dangerous overdose. Treating an overdose can be done by bringing back blood flow to the heart, and restoring the body with oxygen rich blood, especially for the brain to reduce the risk of stroke.[12] Cocaine overdoses have fluctuated over the years. From 2006 to 2010 there has been a decline in the number of reported cases. Though, from 2010 to 2015 there has been an increase in the reported cases involving over cocaine Intoxication. As far as gender goes, it's found that males have a much higher chance of overdosing than females. The ratio of male to female cocaine overdoses is 3:1.[13] ### Withdrawal[edit] Cocaine withdrawal isn't as severe as the withdrawal from other substances. For example, substances like alcohol and benzodiazepines can involve severe physical withdrawal symptoms while cocaine results in mostly psychological symptoms. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia, hypersomnia, anger, increased appetite, weight gain, psychomotor retardation, agitation, depression, and anxiety. According to a study done by Gawin and Kleber in 1986, there are three phases in the withdrawal process. They observed the behavior of 30 cocaine-dependent individuals. Phase one, the crash, is characterized by acute dysphoria, irritability and anxiety, increased desire for sleep, exhaustion, increased appetite, decreased craving to use. Phase two, withdrawal, is characterized by increasing craving to use, poor concentration, some irritability and some lethargy, which persisted for up to 10 weeks. Lastly, phase three is characterized by the intermittent craving to use in the context of external cues.[14] Cocaine and its metabolites are completely eliminated from the body by 3 days.[15] There are not any FDA-approved medications that specifically help treat cocaine withdrawal, however, there are some useful medications that could possibly help individuals overcome their addiction. One example is propranolol. Propranolol is a beta blocker that has been approved to treat hypertension, angina, anxiety, and other related psychological problems. Buprenorphine and naltrexone are two substances that act as an effective treatment in the earlier stages of withdrawal. ## Pathophysiology[edit] Cocaine pharmacodynamics involve multiple complex mechanisms. Although it has a short half-life (~ 1 hour),[15] cocaine metabolites, which rise in concentrations several hours after cocaine ingestion, persist in circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction.[16] This drug binds and blocks monoamine (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. Cocaine's acute effect in the central nervous system is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain). When this effect ceases due to metabolism of cocaine, depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the cocaine user may experience dysphoria, or a "crash" after the initial high. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation.[17] Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Similar to local anesthetics such as lidocaine, cocaine blocks sodium channels and interferes with action potential propagation.[18] This Vaughn-Williams class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.[19][20][21][22] ## Management[edit] A "cocaine alert" sign posted by GGD Amsterdam: the sign reminds people to "Call 112 for an ambulance." Emergency treatment of cocaine-associated high body temperature consists of giving a benzodiazepine and physical cooling. Cooling is best accomplished with tepid water misting and cooling with a fan.[23][24] There is no specific antidote for cocaine. The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with benzodiazepines.[25] Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A review of cocaine cardiovascular toxicity found benzodiazepines may not always reliably lower heart rate and blood pressure.[26] Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate.[26] Nitroglycerin is useful for cocaine-induced chest pain, but the possibility of reflex tachycardia must be considered.[27] Alpha-blockers such as phentolamine have been recommended[25] and may be used to treat cocaine-induced hypertension and coronary arterial vasoconstriction, but these agents do not reduce heart rate.[26][28] Furthermore, phentolamine is rarely used, not readily available in many emergency departments, and many present-day clinicians are unfamiliar with its use. The use of beta-blockers for cocaine toxicity has been a relative contraindication despite limited evidence. The phenomenon of “unopposed alpha-stimulation,” in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in people using cocaine, is controversial.[29][30] This rarely-encountered and unpredictable adverse effect has resulted in some clinicians advocating for an absolute contraindication of all beta-blockers, including specific, non-specific, and mixed.[31] Many clinicians have disregarded this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia.[32][33][34][35][36] Of the 1,744 people in the aforementioned systematic review,[26] only 7 adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1).[37][38][39][40][41] Some detractors of beta-blockers for cocaine-induced chest pain have cited minimal acute mortality and the short half-life of the medication, making it unnecessary to aggressively treat any associated tachycardia and hypertension.[31][42] However, the long-term effect of cocaine use and development of heart failure, with early mortality, high morbidity, and tremendous demand on hospital utilization should be taken under consideration.[43][44][45] Although the use of beta blockers is still controversial, notwithstanding decades of clinical practice and a massive production of peer-reviewed research papers[46] (more details are in the next section), the intravenous racemic mixture[47] of Labetalol, a non-selective β blocker and selective α1 blocker is recommended for treating concomitant hypertension and tachycardia.[26][48][49] The use of Labetalol is approved by a AHA/ACC guideline for people who have used cocaine and methamphetamine with unstable angina/non-STEMI.[50] Calcium channel blockers may also be used to treat hypertension and coronary arterial vasoconstriction,[51] but fail to lower tachycardia based on all cocaine-related studies.[26] Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil are preferable, as dihydropyridine agents such as nifedipine have much higher risk of reflex tachycardia (however, clinicians can prevent reflex tachycardia by administering beta-blockers some minutes before using the latter class of CCBs). People who are agitated are best treated with benzodiazepines, though antipsychotics such as haloperidol and olanzapine may also be useful.[26] The alpha-2 agonist dexmedetomidine may also be useful for agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports.[26] Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports. ## See also[edit] * Cocaine Anonymous * Cocaine dependence * Crack cocaine § Crack lung * List of deaths from drug overdose and intoxication ## References[edit] 1. ^ Glauser, Jonathan; Queen, John R. (2007-02-01). "An overview of non-cardiac cocaine toxicity". The Journal of Emergency Medicine. 32 (2): 181–186. doi:10.1016/j.jemermed.2006.05.044. ISSN 0736-4679. PMID 17307630. 2. ^ Narvaez, Joana C. M.; Jansen, Karen; Pinheiro, Ricardo T.; Kapczinski, Flávio; Silva, Ricardo A.; Pechansky, Flávio; Magalhães, Pedro V. (2014-08-01). "Psychiatric and substance-use comorbidities associated with lifetime crack cocaine use in young adults in the general population". Comprehensive Psychiatry. 55 (6): 1369–1376. doi:10.1016/j.comppsych.2014.04.021. ISSN 1532-8384. PMID 24933652. 3. ^ Little, Karley Y.; Ramssen, Eric; Welchko, Ryan; Volberg, Vitaly; Roland, Courtney J.; Cassin, Bader (2009-08-15). "Decreased brain dopamine cell numbers in human cocaine users". Psychiatry Research. 168 (3): 173–180. doi:10.1016/j.psychres.2008.10.034. ISSN 0165-1781. PMID 19233481. S2CID 27618292. 4. ^ Trimarchi, M.; Bussi, M.; Sinico, R. A.; Meroni, Pierluigi; Specks, U. (2013-02-01). "Cocaine-induced midline destructive lesions - an autoimmune disease?". Autoimmunity Reviews. 12 (4): 496–500. doi:10.1016/j.autrev.2012.08.009. ISSN 1873-0183. PMID 22940554. 5. ^ Cain, Mary A.; Bornick, Patricia; Whiteman, Valerie (2013-03-01). "The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy". Clinical Obstetrics and Gynecology. 56 (1): 124–132. doi:10.1097/GRF.0b013e31827ae167. ISSN 1532-5520. PMID 23314714. 6. ^ Flowers, D.; Clark, J. F.; Westney, L. S. (1991-03-01). "Cocaine intoxication associated with abruptio placentae". Journal of the National Medical Association. 83 (3): 230–232. ISSN 0027-9684. PMC 2627035. PMID 2038082. 7. ^ Zimmerman, Janice L. (2012-10-01). "Cocaine intoxication". Critical Care Clinics. 28 (4): 517–526. doi:10.1016/j.ccc.2012.07.003. ISSN 1557-8232. PMID 22998988. 8. ^ a b c Overdose Death Rates. By National Institute on Drug Abuse (NIDA). 9. ^ O'Leary, Michael E; Hancox, Jules C (2010). "Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias". British Journal of Clinical Pharmacology. 69 (5): 427–442. doi:10.1111/j.1365-2125.2010.03629.x. ISSN 0306-5251. PMC 2856043. PMID 20573078. 10. ^ Editorial Staff. "Cocaine Overdose: Symptoms and Dangers". American Addiction Centers. Retrieved 2019-10-21. 11. ^ "Cocaine intoxication: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2019-10-21. 12. ^ Abuse, National Institute on Drug. "Cocaine". www.drugabuse.gov. Retrieved 2019-10-21. 13. ^ Editorial Staff. "Cocaine Overdose: Symptoms and Dangers". American Addiction Centers. Retrieved 2019-10-29. 14. ^ "Department of Health \| The cocaine withdrawal syndrome". www1.health.gov.au. Retrieved 2019-10-29. 15. ^ a b Jufer, R. A.; Wstadik, A.; Walsh, S. L.; Levine, B. S.; Cone, E. J. (2000-10-01). "Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers". Journal of Analytical Toxicology. 24 (7): 467–477. doi:10.1093/jat/24.7.467. ISSN 0146-4760. PMID 11043648. 16. ^ Brogan, Walter C.; Lange, Richard A.; Kim, Anatole S.; Moliterno, David J.; Hillis, L. David (1991-08-01). "Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin". Journal of the American College of Cardiology. 22nd Bethesda Conference: Congenital heart disease after childhood: An edpanding patient population. 18 (2): 581–586. doi:10.1016/0735-1097(91)90617-I. ISSN 0735-1097. PMID 1906905. 17. ^ Heesch, C. M.; Wilhelm, C. R.; Ristich, J.; Adnane, J.; Bontempo, F. A.; Wagner, W. R. (2000-06-01). "Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans". Heart. 83 (6): 688–695. doi:10.1136/heart.83.6.688. ISSN 1468-201X. PMC 1760877. PMID 10814631. 18. ^ Hariman, Robert J.; Liu, Dong; Loeb, Henry S.; McKieman, Thomas L.; Scanlon, Patrick J.; Bauman, Jerry L. (1996-02-01). "Competitive binding between cocaine and lidocaine". Journal of the American College of Cardiology. 27 (2): 80. doi:10.1016/S0735-1097(96)80520-1. 19. ^ Williams, Mark J.; Adinoff, Bryon (2008-07-01). "The role of acetylcholine in cocaine addiction". Neuropsychopharmacology. 33 (8): 1779–1797. doi:10.1038/sj.npp.1301585. ISSN 0893-133X. PMC 2667818. PMID 17928814. 20. ^ Haile, Colin N.; Mahoney, James J.; Newton, Thomas F.; De La Garza, Richard (2012-05-01). "Pharmacotherapeutics directed at deficiencies associated with cocaine dependence: focus on dopamine, norepinephrine and glutamate". Pharmacology & Therapeutics. 134 (2): 260–277. doi:10.1016/j.pharmthera.2012.01.010. ISSN 1879-016X. PMC 3341931. PMID 22327234. 21. ^ Narayanan, Sanju; Mesangeau, Christophe; Poupaert, Jacques H.; McCurdy, Christopher R. (2011-01-01). "Sigma receptors and cocaine abuse". Current Topics in Medicinal Chemistry. 11 (9): 1128–1150. doi:10.2174/156802611795371323. ISSN 1873-4294. PMID 21050176. 22. ^ Kivell, Bronwyn M.; Ewald, Amy W. M.; Prisinzano, Thomas E. (2014-01-01). Salvinorin A analogs and other κ-opioid receptor compounds as treatments for cocaine abuse. Advances in Pharmacology. 69. pp. 481–511. doi:10.1016/B978-0-12-420118-7.00012-3. ISBN 9780124201187. ISSN 1557-8925. PMC 4128345. PMID 24484985. 23. ^ Smith, Caroline J.; Johnson, John M. (2016-04-01). to hyperthermia.pdf "Responses to hyperthermia. Optimizing heat dissipation by convection and evaporation: Neural control of skin blood flow and sweating in humans" Check `\|url=` value (help) (PDF). Autonomic Neuroscience: Basic & Clinical. 196: 25–36. doi:10.1016/j.autneu.2016.01.002. ISSN 1872-7484. PMID 26830064. S2CID 3790152. 24. ^ Richards, John R.; Colby, Daniel K. (2016-01-01). "Stimulant-induced hyperthermia and ice-water submersion: Practical considerations". Clinical Toxicology. 54 (1): 69–70. doi:10.3109/15563650.2015.1104536. ISSN 1556-9519. PMID 26515112. S2CID 207553540. 25. ^ a b McCord, J; Jneid, H; Hollander, JE; de Lemos, JA; Cercek, B; Hsue, P; Gibler, WB; Ohman, EM; Drew, B; Philippides, G; Newby, LK; American Heart Association Acute Cardiac Care Committee of the Council on Clinical, Cardiology (Apr 8, 2008). "Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology". Circulation. 117 (14): 1897–907. doi:10.1161/CIRCULATIONAHA.107.188950. PMID 18347214. 26. ^ a b c d e f g h Richards, John R.; Garber, Dariush; Laurin, Erik G.; Albertson, Timothy E.; Derlet, Robert W.; Amsterdam, Ezra A.; Olson, Kent R.; Ramoska, Edward A.; Lange, Richard A. (2016-06-01). "Treatment of cocaine cardiovascular toxicity: a systematic review". Clinical Toxicology. 54 (5): 345–364. doi:10.3109/15563650.2016.1142090. ISSN 1556-9519. PMID 26919414. S2CID 5165666. 27. ^ Ma, Sheng-xing; Schmid, Phillip G.; Long, John P. (1994-01-01). "Noradrenergic mechanisms and the cardiovascular actions of nitroglycerin". Life Sciences. 55 (21): 1595–1603. doi:10.1016/0024-3205(94)00325-4. PMID 7968233. 28. ^ Lange, Richard A.; Cigarroa, Ricardo G.; Yancy, Clyde W. Jr.; Willard, John E.; Popma, Jeffrey J.; Sills, Michael N.; McBride, Wade; Kim, Anatole S.; Hillis, L. David (1989-12-07). "Cocaine-Induced Coronary-Artery Vasoconstriction". New England Journal of Medicine. 321 (23): 1557–1562. doi:10.1056/NEJM198912073212301. ISSN 0028-4793. PMID 2573838. 29. ^ Schurr, James W.; Gitman, Brenda; Belchikov, Yuly (2014-12-01). "Controversial therapeutics: the β-adrenergic antagonist and cocaine-associated cardiovascular complications dilemma". Pharmacotherapy. 34 (12): 1269–1281. doi:10.1002/phar.1486. ISSN 1875-9114. PMID 25224512. S2CID 5282953. 30. ^ Freeman, Kalev; Feldman, James A. (2008-02-01). "Cocaine, myocardial infarction, and beta-blockers: time to rethink the equation?". Annals of Emergency Medicine. 51 (2): 130–134. doi:10.1016/j.annemergmed.2007.08.020. ISSN 1097-6760. PMID 17933425. 31. ^ a b Gupta, Amit K.; Greller, Howard A.; Hoffman, Robert Steven (2010-11-08). "Beta-blockers and cocaine: still a bad idea". Archives of Internal Medicine. 170 (20): 1859–1860, author reply 1860. doi:10.1001/archinternmed.2010.398. ISSN 1538-3679. PMID 21059982. 32. ^ Dattilo, Philip B.; Hailpern, Susan M.; Fearon, Kerrie; Sohal, Davendra; Nordin, Charles (2008-02-01). "Beta-blockers are associated with reduced risk of myocardial infarction after cocaine use". Annals of Emergency Medicine. 51 (2): 117–125. doi:10.1016/j.annemergmed.2007.04.015. ISSN 1097-6760. PMID 17583376. 33. ^ Rangel, Carlos; Shu, Richard G.; Lazar, Lawrence D.; Vittinghoff, Eric; Hsue, Priscilla Y.; Marcus, Gregory M. (2010-05-24). "Beta-blockers for chest pain associated with recent cocaine use". Archives of Internal Medicine. 170 (10): 874–879. doi:10.1001/archinternmed.2010.115. ISSN 1538-3679. PMID 20498415. 34. ^ Ibrahim, Morhaf; Maselli, Diego Jose; Hasan, Reham; Hamilton, Andrew (2013-03-01). "Safety of β-blockers in the acute management of cocaine-associated chest pain". The American Journal of Emergency Medicine. 31 (3): 613–616. doi:10.1016/j.ajem.2012.09.027. ISSN 1532-8171. PMID 23122421. 35. ^ Fanari, Zaher; Kennedy, Kevin K.; Lim, Michael J.; Laddu, Abhay A.; Stolker, Joshua M. (2014-06-01). "Comparison of in-hospital outcomes for beta-blocker use versus non-beta blocker use in patients presenting with cocaine-associated chest pain". The American Journal of Cardiology. 113 (11): 1802–1806. doi:10.1016/j.amjcard.2014.03.010. ISSN 1879-1913. PMID 24742472. 36. ^ Gupta, Navdeep; Washam, Jeffrey B.; Mountantonakis, Stavros E.; Li, Shuang; Roe, Matthew T.; de Lemos, James A.; Arora, Rohit (2014-03-01). "Characteristics, management, and outcomes of cocaine-positive patients with acute coronary syndrome (from the National Cardiovascular Data Registry)". The American Journal of Cardiology. 113 (5): 749–756. doi:10.1016/j.amjcard.2013.11.023. ISSN 1879-1913. PMID 24388623. 37. ^ Ramoska, Edward; Sacchetti, Alfred D (1985-11-01). "Propranolol-induced hypertension in treatment of cocaine intoxication". Annals of Emergency Medicine. 14 (11): 1112–1113. doi:10.1016/s0196-0644(85)80934-3. ISSN 0196-0644. PMID 4051280. 38. ^ Fareed, Fareed N.; Chan, Gar; Hoffman, Robert S. (2007-12-01). "Death temporally related to the use of a Beta adrenergic receptor antagonist in cocaine associated myocardial infarction". Journal of Medical Toxicology. 3 (4): 169–172. doi:10.1007/bf03160934. ISSN 1556-9039. PMC 3550023. PMID 18072171. 39. ^ Sand, I.Charles; Brody, Steven L.; Wrenn, Keith D.; Slovis, Corey M. (1991-03-01). "Experience with esmolol for the treatment of cocaine-associated cardiovascular complications". The American Journal of Emergency Medicine. 9 (2): 161–163. doi:10.1016/0735-6757(91)90182-j. ISSN 0735-6757. PMID 1671639. 40. ^ Lange, Richard A.; Cigarroa, Ricardo G.; Flores, Eduardo D.; McBride, Wade; Kim, Anatole S.; Wells, Peter J.; Bedotto, John B.; Danziger, Robert S.; Hillis, L. David (1990-06-15). "Potentiation of Cocaine-Induced Coronary Vasoconstriction by Beta-Adrenergic Blockade". Annals of Internal Medicine. 112 (12): 897–903. doi:10.7326/0003-4819-112-12-897. ISSN 0003-4819. PMID 1971166. 41. ^ Izquierdo Gómez, María Manuela; Domínguez-Rodríguez, Alberto; Gálvez Rodríguez, Manuel; Marrero Rodríguez, Francisco (2009-04-01). "Reflections on beta-adrenergic receptor blockers and cocaine use. A case in point". Revista Española de Cardiología. 62 (4): 455–456. doi:10.1016/s1885-5857(09)71677-9. ISSN 1579-2242. PMID 19401135. 42. ^ Hollander, Judd (December 28, 2011). "Update on Cocaine Myocardial Ischemia". Archived from the original on January 11, 2017. 43. ^ Casartelli, Alessandro; Dacome, Lisa; Tessari, Michela; Pascali, Jennifer; Bortolotti, Federica; Trevisan, Maria Teresa; Bosco, Oliviero; Cristofori, Patrizia; Tagliaro, Franco (2014-01-01). "Cocaine-associated increase of atrial natriuretic peptides: an early predictor of cardiac complications in cocaine users?". Heart Asia. 6 (1): 100–107. doi:10.1136/heartasia-2013-010482. ISSN 1759-1104. PMC 4832714. PMID 27326180. 44. ^ Liaudet, Lucas; Calderari, Belinda; Pacher, Pal (2014-11-01). "Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity" (PDF). Heart Failure Reviews. 19 (6): 815–824. doi:10.1007/s10741-014-9418-y. ISSN 1573-7322. PMID 24398587. S2CID 22420796. 45. ^ Walsh, David W.; McVey, Molly C.; Gass, Abigal; Zhang, Jingwen; Mauldin, Patrick D.; Rockey, Don C. (2016-06-24). "Identification of high resource utilizing patients on internal medicine hospital services". Journal of Investigative Medicine. 64 (7): jim–2016–000118. doi:10.1136/jim-2016-000118. ISSN 1708-8267. PMID 27342424. S2CID 4547095. 46. ^ Shin, Doosup; Lee, Eun Sun; Bohra, Chandrashekar; Kongpakpaisarn, Kullatham (2019). "In-Hospital and Long-Term Outcomes of Beta-Blocker Treatment in Cocaine Users: A Systematic Review and Meta-analysis". Cardiology Research. 10 (1): 40–47. doi:10.14740/cr831. ISSN 1923-2829. PMC 6396807. PMID 30834058. 47. ^ Robertson D, Biaggioni, I. Adrenoceptor Antagonist Drugs. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12th ed. San Francisco, CA: McGraw Hill Lange Medical; 2012: 151-168. ISBN 978-0-07-176401-8. 48. ^ Boehrer, James D.; Moliterno, David J.; Willard, John E.; Hillis, L.David; Lange, Richard A. (1993-06-01). "Influence of labetalol on cocaine-induced coronary vasoconstriction in humans". The American Journal of Medicine. 94 (6): 608–610. doi:10.1016/0002-9343(93)90212-8. ISSN 0002-9343. PMID 8506886. 49. ^ Richards, John R.; Lange, Richard A. (2016-02-01). "Labetalol and cardiovascular consequences of cocaine use". Trends in Cardiovascular Medicine. 26 (2): 202–203. doi:10.1016/j.tcm.2015.05.002. ISSN 1873-2615. PMID 26116092. 50. ^ Anderson, Jeffrey L.; Adams, Cynthia D.; Antman, Elliott M.; Bridges, Charles R.; Califf, Robert M.; Casey, Donald E.; Chavey, William E.; Fesmire, Francis M.; Hochman, Judith S. (2013-06-11). "2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Journal of the American College of Cardiology. 61 (23): e179–347. doi:10.1016/j.jacc.2013.01.014. ISSN 1558-3597. PMID 23639841. 51. ^ Negus, Brian H.; Willard, John E.; Hillis, L.David; Glamann, D.Brent; Landau, Charles; Snyder, Richard W.; Lange, Richard A. (1994-03-01). "Alleviation of cocaine-induced coronary vasoconstriction with intravenous verapamil". The American Journal of Cardiology. 73 (7): 510–513. doi:10.1016/0002-9149(94)90684-x. ISSN 0002-9149. PMID 8141094. ## External links[edit] Classification D * ICD-10: F14.0 * ICD-9-CM: 305.6 * MeSH: D019970 External resources * MedlinePlus: 000946 * eMedicine: article/813959 * v * t * e Psychoactive substance-related disorder General * SID * Substance intoxication / Drug overdose * Substance-induced psychosis * Withdrawal: * Craving * Neonatal withdrawal * Post-acute-withdrawal syndrome (PAWS) * SUD * Substance abuse / Substance-related disorders * Physical dependence / Psychological dependence / Substance dependence Combined substance use * SUD * Polysubstance dependence * SID * Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases * Alcoholic cardiomyopathy * Alcohol flush reaction (AFR) Gastrointestinal diseases * Alcoholic liver disease (ALD): * Alcoholic hepatitis * Auto-brewery syndrome (ABS) Endocrine diseases * Alcoholic ketoacidosis (AKA) Nervous system diseases * Alcohol-related dementia (ARD) * Alcohol intoxication * Hangover Neurological disorders * Alcoholic hallucinosis * Alcoholic polyneuropathy * Alcohol-related brain damage * Alcohol withdrawal syndrome (AWS): * Alcoholic hallucinosis * Delirium tremens (DTs) * Fetal alcohol spectrum disorder (FASD) * Fetal alcohol syndrome (FAS) * Korsakoff syndrome * Positional alcohol nystagmus (PAN) * Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis) * Wernicke encephalopathy (WE) Respiratory tract diseases * Alcohol-induced respiratory reactions * Alcoholic lung disease SUD * Alcoholism (alcohol use disorder (AUD)) * Binge drinking Caffeine * SID * Caffeine-induced anxiety disorder * Caffeine-induced sleep disorder * Caffeinism * SUD * Caffeine dependence Cannabis * SID * Cannabis arteritis * Cannabinoid hyperemesis syndrome (CHS) * SUD * Amotivational syndrome * Cannabis use disorder (CUD) * Synthetic cannabinoid use disorder Cocaine * SID * Cocaine intoxication * Prenatal cocaine exposure (PCE) * SUD * Cocaine dependence Hallucinogen * SID * Acute intoxication from hallucinogens (bad trip) * Hallucinogen persisting perception disorder (HPPD) Nicotine * SID * Nicotine poisoning * Nicotine withdrawal * SUD * Nicotine dependence Opioids * SID * Opioid overdose * SUD * Opioid use disorder (OUD) Sedative / hypnotic * SID * Kindling (sedative–hypnotic withdrawal) * benzodiazepine: SID * Benzodiazepine overdose * Benzodiazepine withdrawal * SUD * Benzodiazepine use disorder (BUD) * Benzodiazepine dependence * barbiturate: SID * Barbiturate overdose * SUD * Barbiturate dependence Stimulants * SID * Stimulant psychosis * amphetamine: SUD * Amphetamine dependence Volatile solvent * SID * Sudden sniffing death syndrome (SSDS) * Toluene toxicity * SUD * Inhalant abuse [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cocaine intoxication	c0009176	29,950	wikipedia	https://en.wikipedia.org/wiki/Cocaine_intoxication	2021-01-18T18:38:44	{"icd-9": ["305.6"], "icd-10": ["T40.5", "F14.0"], "orphanet": ["90068"], "synonyms": [], "wikidata": ["Q5139133"]}
Monomelic amyotrophy (MA) is a rare benign lower motor neuron disorder characterized by muscular weakness and wasting in the distal upper extremities during adolescence followed by a spontaneous halt in progression and a stabilization of symptoms. ## Epidemiology The prevalence is unknown. It is seen mainly in Asian countries (particularly in Japan and India) with only a very few cases reported in Europe and the United States. A nation-wide survey conducted from 1996 to 1998 in Japan found 333 identified cases with the estimated prevalence being approximately 1/33, 300. ## Clinical description MA is seen more frequently in males (male to female ratio of 20:1) with an age of onset in the second to third decade of life (ages 14-25). Muscle weakness and wasting begins in the hand or forearm on one side. There is no pain associated with this muscular atrophy, nor sensory changes. Progression is slow, usually over a 3-9 year time span, followed by a halt and stabilization of symptoms. Occasionally it can destabilize and continue progression after the age of 40. In rare cases it can progress to the opposite limb. Additional rare manifestations include worsening of symptoms with exposure to cold (cold paresis), muscle cramps, cold hands, irregular coarse tremor and/or contraction fasciculations. O'Sullivan-McLeod syndrome (see this term), considered to be a variant of MA, presents with weakness in the intrinsic hand muscles. It begins unilaterally but eventually spreads to the opposite limb with an asymmetrical distribution. ## Etiology The exact etiology is unknown. One theory is that MA is caused by the anterior shift of the cervical dural sac, due to repeated neck flexion, leading to the compression of the anterior aspect of the spinal cord against the posterior margin of the vertebral body. Autoimmunity, toxins and infections have been proposed as possible causes, but more evidence is needed. Since there have been several familial cases of MA reported (<1% of MA patients), genetic susceptibility could also be a factor. ## Diagnostic methods Diagnosis is based on clinical imaging and electromyography findings. Magnetic resonance imaging (MRI) shows distinctive images of the anterior horn being compressed when a patient is in the maximum cervical anteflexion position (snake eyes sign). Atrophy in the lower cervical spinal cord is also visible. Nerve conduction tests show reduced compound muscle action potential of the median and ulnar nerves in the affected limb and F-wave studies show reduced frequency and prolonged minimum latency in these muscles. ## Differential diagnosis Poliomyelitis, multifocal motor neuropathy with conduction block, syringomyelia (see these terms), anterior interosseous or deep ulnar neuropathy, cervical vertebral abnormalities, spinal cord tumors, brachial plexopathy and trauma must be excluded. ## Management and treatment There is no cure for MA. Treatment is conservative and with early detection aims to slow the progression of muscle wasting. A cervical collar worn in the early stages of disease has been shown to halt progress of the disease in some cases, as it prevents neck flexion. Muscle strengthening exercises and hand coordination training can also be helpful. ## Prognosis MA is not life threatening but can cause a social disability in those with a complete loss of hand function. Early intervention can minimize progression of disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Monomelic amyotrophy	c1865384	29,951	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65684	2021-01-23T19:01:48	{"gard": ["9697"], "mesh": ["C538253"], "omim": ["602440"], "umls": ["C1865384"], "icd-10": ["G12.8"], "synonyms": ["Benign focal amyotrophy", "Hirayama disease", "JMADUE", "Juvenile muscular atrophy of distal upper extremity", "Juvenile muscular atrophy of the distal upper limb"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Punding" – news · newspapers · books · scholar · JSTOR (December 2019) Punding, a possible symptom of dopamine dysregulation syndrome (DDS), is the repetition of complex motor behaviours such as collecting or arranging objects. Punding is a term that was coined originally to describe complex prolonged, purposeless, and stereotyped behaviour in phenmetrazine and chronic amphetamine users, by Swedish forensic psychiatrist G. Rylander, in 1968.[1] It was later described in Parkinson's disease.[2] It has also been described in methamphetamine and cocaine users, as well as in some patients with gambling addictions, and hypersexuality.[3] Punding activity is characterized by compulsive fascination with and performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting household objects. For example, punding may consist of activities such as: * collecting pebbles and lining them up as perfectly as possible, * disassembling wristwatches and putting them back together again, * building hundreds of small wooden boxes * trying but failing to systematically remove the entire contents of all the drawers and shelves in the home and sort through all their contents. People engaging in punding find immersion in such activities comforting, even when it serves no purpose, and generally find it very frustrating to be diverted from them. They are not generally aware that there is a compulsive element, but will continue even when they have good reason to stop. Rylander describes a burglar who started punding and could not stop, even though he was suffering from an increasing apprehension of being caught.[4] Interrupting can lead to various responses, including violent rage.[5] ## See also[edit] * Knolling * Stimming * Tweaking (behavior) ## Notes[edit] 1. ^ Folke Sjöqvist; Malcolm Tottie, eds. (1969). "Clinical and Medico-criminological aspects of addiction to Central Stimulating Drugs". Abuse of Central Stimulants: Symposium Arranged by the Swedish Committee on International Health Relations, Stockholm, November 25–27, 1968. Almqvist & Wiksell: 257. 2. ^ Evans AH; Katzenschlager R; Paviour D; et al. (April 2004). "Punding in Parkinson's disease: its relation to the dopamine dysregulation syndrome". Mov. Disord. 19 (4): 397–405. doi:10.1002/mds.20045. PMID 15077237. S2CID 23886073. 3. ^ Graham NA, Hammond CJ, Gold MS (2009). "Drug-induced compulsive behaviors: exceptions to the rule". Mayo Clin. Proc. 84 (9): 846–7, author reply 847. doi:10.4065/84.9.846. PMC 2735437. PMID 19720785. 4. ^ Lester Grinspoon; Peter Hedblom (1975). The Speed Culture: Amphetamine Use and Abuse in America. Harvard Paperbacks Series. Harvard University Press. p. 104. ISBN 9780674831926. 5. ^ Elaine A. Moore (2010). The Amphetamine Debate: The Use of Adderall, Ritalin and Related Drugs for Behavior Modification, Neuroenhancement and Anti-Aging Purposes. McFarland health topics. 10. McFarland. p. 186. ISBN 9780786480128. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Punding	c1963933	29,952	wikipedia	https://en.wikipedia.org/wiki/Punding	2021-01-18T18:30:06	{"umls": ["C1963933"], "wikidata": ["Q20827012"]}
Inflammation of the intestine causing diarrhea with blood Dysentery Other namesBloody diarrhea A person with dysentery in a Burmese hospital, 1943 SpecialtyInfectious disease SymptomsBloody diarrhea, abdominal pain, fever[1][2] ComplicationsDehydration[3] DurationLess than a week[4] CausesUsually Shigella or Entamoeba histolytica[1] Risk factorsContamination of food and water with feces due to poor sanitation[5] Diagnostic methodBased on symptoms, Stool test PreventionHand washing, food safety[4] TreatmentDrinking sufficient fluids, antibiotics (severe cases)[4] FrequencyCommon in the developing world[6] Deaths> million a year[6] Dysentery is a type of gastroenteritis that results in diarrhea with blood.[1][7] Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation.[2][8][5] Complications may include dehydration.[3] The cause of dysentery is usually the bacteria Shigella, in which case it is known as shigellosis, or the amoeba Entamoeba histolytica.[1] Other causes may include certain chemicals, other bacteria, other protozoa, or parasitic worms.[2] It may spread between people.[4] Risk factors include contamination of food and water with feces due to poor sanitation.[5] The underlying mechanism involves inflammation of the intestine, especially of the colon.[2] Efforts to prevent dysentery include hand washing and food safety measures while traveling in areas of high risk.[4] While the condition generally resolves on its own within a week, drinking sufficient fluids such as oral rehydration solution is important.[4] Antibiotics such as azithromycin may be used to treat cases associated with travelling in the developing world.[8] While medications used to decrease diarrhea such as loperamide are not recommended on their own, they may be used together with antibiotics.[8][4] Shigella results in about 165 million cases of diarrhea and 1.1 million deaths a year with nearly all cases in the developing world.[6] In areas with poor sanitation nearly half of cases of diarrhea are due to Entamoeba histolytica.[5] Entamoeba histolytica affects millions of people and results in greater than 55,000 deaths a year.[9] It commonly occurs in less developed areas of Central and South America, Africa, and Asia.[9] Dysentery has been described at least since the time of Hippocrates.[10] ## Contents * 1 Signs and symptoms * 2 Mechanism * 2.1 Amoebic dysentery * 2.2 Bacillary dysentery * 2.3 Other bacteria * 3 Diagnosis * 3.1 Physical exam * 3.2 Stool and blood tests * 4 Prevention * 4.1 Vaccine * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 History * 9 Notable cases * 10 See also * 11 References * 12 External links ## Signs and symptoms[edit] The most common form of dysentery is bacillary dysentery, which is typically a mild sickness, causing symptoms normally consisting of mild gut pains and frequent passage of stool or diarrhea. Symptoms normally present themselves after 1–3 days, and are usually no longer present after a week. The frequency of urges to defecate, the large volume of liquid feces ejected, and the presence of blood, mucus, or pus depends on the pathogen causing the disease. Temporary lactose intolerance can occur, as well. In some caustic occasions, severe abdominal cramps, fever, shock, and delirium can all be symptoms.[2][11][12][13] In extreme cases, people may pass more than one liter of fluid per hour. More often, individuals will complain of diarrhea with blood, accompanied by extreme abdominal pain, rectal pain and a low-grade fever. Rapid weight loss and muscle aches sometimes also accompany dysentery, while nausea and vomiting are rare. In many cases there can be cascading cramps that affect the muscles surrounding the entire upper intestine; sometimes severe enough to cause the lining of the intestine to separate from the wall, leading to systemic infection. On rare occasions, the amoebic parasite will invade the body through the bloodstream and spread beyond the intestines. In such cases, it may more seriously infect other organs such as the brain, lungs, and most commonly the liver.[14] ## Mechanism[edit] Cross-section of diseased intestines. Colored lithograph c. 1843 Dysentery results from bacterial, or parasitic infections. Viruses do not generally cause the disease.[7] These pathogens typically reach the large intestine after entering orally, through ingestion of contaminated food or water, oral contact with contaminated objects or hands, and so on. Each specific pathogen has its own mechanism or pathogenesis, but in general, the result is damage to the intestinal linings, leading to the inflammatory immune responses. This can cause elevated physical temperature, painful spasms of the intestinal muscles (cramping), swelling due to fluid leaking from capillaries of the intestine (edema) and further tissue damage by the body's immune cells and the chemicals, called cytokines, which are released to fight the infection. The result can be impaired nutrient absorption, excessive water and mineral loss through the stools due to breakdown of the control mechanisms in the intestinal tissue that normally remove water from the stools, and in severe cases, the entry of pathogenic organisms into the bloodstream. Anemia may also arise due to the blood loss through diarrhea.[citation needed] Bacterial infections that cause bloody diarrhea are typically classified as being either invasive or toxogenic. Invasive species cause damage directly by invading into the mucosa. The toxogenic species do not invade, but cause cellular damage by secreting toxins, resulting in bloody diarrhea. This is also in contrast to toxins that cause watery diarrhea, which usually do not cause cellular damage, but rather they take over cellular machinery for a portion of life of the cell.[15] Some microorganisms – for example, bacteria of the genus Shigella – secrete substances known as cytotoxins, which kill and damage intestinal tissue on contact. Shigella is thought to cause bleeding due to invasion rather than toxin, because even non-toxogenic strains can cause dysentery, but E. coli with shiga-like toxins do not invade the intestinal mucosa, and are therefore toxin dependent. Definitions of dysentery can vary by region and by medical specialty. The U. S. Centers for Disease Control and Prevention (CDC) limits its definition to "diarrhea with visible blood".[16] Others define the term more broadly.[17] These differences in definition must be taken into account when defining mechanisms. For example, using the CDC definition requires that intestinal tissue be so severely damaged that blood vessels have ruptured, allowing visible quantities of blood to be lost with defecation. Other definitions require less specific damage. ### Amoebic dysentery[edit] Main article: Amoebiasis Amoebiasis, also known as amoebic dysentery, is caused by an infection from the amoeba Entamoeba histolytica,[18] which is found mainly in tropical areas.[19] Proper treatment of the underlying infection of amoebic dysentery is important; insufficiently treated amoebiasis can lie dormant for years and subsequently lead to severe, potentially fatal, complications. When amoebae inside the bowel of an infected person are ready to leave the body, they group together and form a shell that surrounds and protects them. This group of amoebae is known as a cyst, which is then passed out of the person's body in the feces and can survive outside the body. If hygiene standards are poor – for example, if the person does not dispose of the feces hygienically – then it can contaminate the surroundings, such as nearby food and water. If another person then eats or drinks food or water that has been contaminated with feces containing the cyst, that person will also become infected with the amoebae. Amoebic dysentery is particularly common in parts of the world where human feces are used as fertilizer. After entering the person's body through the mouth, the cyst travels down into the stomach. The amoebae inside the cyst are protected from the stomach's digestive acid. From the stomach, the cyst travels to the intestines, where it breaks open and releases the amoebae, causing the infection. The amoebae can burrow into the walls of the intestines and cause small abscesses and ulcers to form. The cycle then begins again.[citation needed] ### Bacillary dysentery[edit] Main article: Bacillary dysentery Dysentery may also be caused by shigellosis, an infection by bacteria of the genus Shigella, and is then known as bacillary dysentery (or Marlow syndrome). The term bacillary dysentery etymologically might seem to refer to any dysentery caused by any bacilliform bacteria, but its meaning is restricted by convention to Shigella dysentery. ### Other bacteria[edit] Some strains of Escherichia coli cause bloody diarrhea. The typical culprits are enterohemorrhagic Escherichia coli, of which O157:H7 is the best known. ## Diagnosis[edit] A diagnosis may be made by taking a history and doing a brief examination. Dysentery should not be confused with hematochezia, which is the passage of fresh blood through the anus, usually in or with stools. ### Physical exam[edit] The mouth, skin, and lips may appear dry due to dehydration. Lower abdominal tenderness may also be present.[14] ### Stool and blood tests[edit] Cultures of stool samples are examined to identify the organism causing dysentery. Usually, several samples must be obtained due to the number of amoebae, which changes daily.[14] Blood tests can be used to measure abnormalities in the levels of essential minerals and salts.[14] ## Prevention[edit] Efforts to prevent dysentery include hand washing and food safety measures while traveling in areas of high risk.[4] ### Vaccine[edit] Although there is currently no vaccine that protects against Shigella infection, several are in development.[20][21] Vaccination may eventually become a part of the strategy to reduce the incidence and severity of diarrhea, particularly among children in low-resource settings. For example, Shigella is a longstanding World Health Organization (WHO) target for vaccine development, and sharp declines in age-specific diarrhea/dysentery attack rates for this pathogen indicate that natural immunity does develop following exposure; thus, vaccination to prevent this disease should be feasible. The development of vaccines against these types of infection has been hampered by technical constraints, insufficient support for coordination, and a lack of market forces for research and development. Most vaccine development efforts are taking place in the public sector or as research programs within biotechnology companies.[citation needed] ## Treatment[edit] Dysentery is managed by maintaining fluids using oral rehydration therapy. If this treatment cannot be adequately maintained due to vomiting or the profuseness of diarrhea, hospital admission may be required for intravenous fluid replacement. In ideal situations, no antimicrobial therapy should be administered until microbiological microscopy and culture studies have established the specific infection involved. When laboratory services are not available, it may be necessary to administer a combination of drugs, including an amoebicidal drug to kill the parasite, and an antibiotic to treat any associated bacterial infection. If shigellosis is suspected and it is not too severe, letting it run its course may be reasonable — usually less than a week. If the case is severe, antibiotics such as ciprofloxacin or TMP-SMX may be useful. However, many strains of Shigella are becoming resistant to common antibiotics, and effective medications are often in short supply in developing countries. If necessary, a doctor may have to reserve antibiotics for those at highest risk for death, including young children, people over 50, and anyone suffering from dehydration or malnutrition. Amoebic dysentery is often treated with two antimicrobial drugs such as metronidazole and paromomycin or iodoquinol.[22] ## Prognosis[edit] With correct treatment, most cases of amoebic and bacterial dysentery subside within 10 days, and most individuals achieve a full recovery within two to four weeks after beginning proper treatment. If the disease is left untreated, the prognosis varies with the immune status of the individual patient and the severity of disease. Extreme dehydration can delay recovery and significantly raises the risk for serious complications.[23] ## Epidemiology[edit] Insufficient data exists, but Shigella is estimated to have caused the death of 34,000 children under the age of five in 2013, and 40,000 deaths in people over five years of age.[20] Amoebiasis infects over 50 million people each year, of whom 50,000 die (one per thousand).[24] ## History[edit] The seed, leaves, and bark of the kapok tree have been used in traditional medicine by indigenous peoples of the rainforest regions in the Americas, west-central Africa, and Southeast Asia in this disease.[25][26][27] Bacillus subtilis was marketed throughout America and Europe from 1946 as an immunostimulatory aid in the treatment of gut and urinary tract diseases such as rotavirus and Shigella,[28] but declined in popularity after the introduction of consumer antibiotics. ## Notable cases[edit] A Red Army soldier dies of dysentery after eating unwashed vegetables. This is a common way of contracting dysentery. From a health advisory pamphlet given to soldiers. * 685 – Constantine IV, the Byzantine emperor, died of dysentery in September 685. * 1183 – Henry the Young King died of dysentery at the castle of Martel on 11 June 1183. * 1216 – John, King of England died of dysentery at Newark Castle on 18 October 1216.[29] * 1270 – Louis IX of France died of dysentery in Tunis while commanding his troops for the Eighth Crusade on 25 September 1270. * 1307 – Edward I of England caught dysentery on his way to the Scottish border and died in his servants' arms on 6 July 1307. * 1322 – Philip V of France died of dysentery at the Abbey of Longchamp (site of the present hippodrome in the Bois de Boulogne) in Paris while visiting his daughter, Blanche, who had taken her vows as a nun there in 1322. He died on January 3, 1322. * 1376 – Edward the Black Prince son of Edward III of England and heir to the English throne. Died of apparent dysentery in June, after a months-long period of illness during which he predicted his own imminent death, in his 46th year. * 1422 – King Henry V of England died suddenly on 31 August 1422 at the Château de Vincennes, apparently from dysentery,[30] which he had contracted during the siege of Meaux. He was 35 years old and had reigned for nine years. * 1536 – Erasmus, Dutch renaissance humanist and theologian. At Basel.[31] * 1596 – Sir Francis Drake, vice admiral, died of dysentery on 28 January 1596 whilst anchored off the coast of Portobelo.[32] * 1605 – Akbar, ruler of the Mughal Empire of South Asia, died of dysentery. On 3 October 1605, he fell ill with an attack of dysentery, from which he never recovered. He is believed to have died on or about 27 October 1605, after which his body was buried at a mausoleum in Agra, present-day India.[33] * 1675 – Jacques Marquette died of dysentery on his way north from what is today Chicago, traveling to the mission where he intended to spend the rest of his life.[34] * 1676 – Nathaniel Bacon died of dysentery after taking control of Virginia following Bacon's Rebellion. He is believed to have died in October 1676, allowing Virginia's ruling elite to regain control.[35] * 1680 \- Shivaji, founder and ruler of the Maratha Empire of South Asia, died of dysentery on 3 April 1680. In 1680, Shivaji fell ill with fever and dysentery, dying around 3–5 April 1680 at the age of 52 on the eve of Hanuman Jayanti. He was cremated at Raigad Fort, where his Samadhi is built in Mahad, Raigad district of Maharashtra, India.[36] [37] * 1827 – Queen Nandi kaBhebhe, (mother of Shaka Zulu) died of dysentery on October 10, 1827.[38] * 1896 – Phan Đình Phùng, a Vietnamese revolutionary who led rebel armies against French colonial forces in Vietnam, died of dysentery as the French surrounded his forces on January 21, 1896.[39] * 1930 – The French explorer and writer, Michel Vieuchange, died of dysentery in Agadir on 30 November 1930, on his return from the "forbidden city" of Smara. He was nursed by his brother, Doctor Jean Vieuchange, who was unable to save him. The notebooks and photographs, edited by Jean Vieuchange, went on to become bestsellers.[40][41] * 1942 – The Selarang Barracks incident in the summer of 1942 during World War II involved the forced crowding of 17,000 Anglo-Australian prisoners-of-war (POWs) by their Japanese captors in the areas around the barracks square for nearly five days with little water and no sanitation after the Selarang Barracks POWs refused to sign a pledge not to escape. The incident ended with the surrender of the Australian commanders due to the spreading of dysentery among their men.[42] ## See also[edit] * Medicine portal * Cholera, a bacterial infection of the small intestine which produces severe diarrhea requiring Laudanum (Deodorized Tincture of Opium known as DTO) Not to be confused with paregoric. * Oregon trail, a pioneering computer game in which dysentery was a prominent cause of death. ## References[edit] 1. ^ a b c d "Dysentery". who.int. Archived from the original on 5 December 2014. Retrieved 28 November 2014. 2. ^ a b c d e "Dysentery" at Dorland's Medical Dictionary 3. ^ a b "WHO EMRO \| Dysentery \| Health topics". www.emro.who.int. Retrieved 15 November 2019. 4. ^ a b c d e f g h "Dysentery". nhs.uk. 18 October 2017. Retrieved 15 November 2019. 5. ^ a b c d Marie, C; Petri WA, Jr (30 August 2013). "Amoebic dysentery". BMJ Clinical Evidence. 2013. PMC 3758071. PMID 23991750. 6. ^ a b c "Dysentery (Shigellosis)" (PDF). WHO. November 2016. p. 2. Retrieved 15 November 2019. 7. ^ a b "Controlling the Spread of Infections\|Health and Safety Concerns". www.cdc.gov. Retrieved 15 November 2019. 8. ^ a b c Tribble, DR (September 2017). "Antibiotic Therapy for Acute Watery Diarrhea and Dysentery". Military Medicine. 182 (S2): 17–25. doi:10.7205/MILMED-D-17-00068. PMC 5650106. PMID 28885920. 9. ^ a b Shirley, DT; Farr, L; Watanabe, K; Moonah, S (July 2018). "A Review of the Global Burden, New Diagnostics, and Current Therapeutics for Amebiasis". Open Forum Infectious Diseases. 5 (7): ofy161. doi:10.1093/ofid/ofy161. PMC 6055529. PMID 30046644. 10. ^ Grove, David (2013). Tapeworms, Lice, and Prions: A compendium of unpleasant infections. OUP Oxford. p. PT517. ISBN 9780191653452. 11. ^ DuPont, H. L. (1978). "Interventions in diarrheas of infants and young children". J. Am. Vet. Med. Assoc. 173 (5 Pt 2): 649–53. PMID 359524. 12. ^ DeWitt, T. G. (1989). "Acute diarrhoea in children". Pediatr Rev. 11 (1): 6–13. doi:10.1542/pir.11-1-6. PMID 2664748. 13. ^ "Dysentery symptoms". National Health Service. Archived from the original on 23 March 2010. Retrieved 22 January 2010. 14. ^ a b c d "Dysentery-Diagnosis". mdguidelines.com. Archived from the original on 14 July 2011. Retrieved 17 November 2010. 15. ^ Ryan, Jason (2016). Boards and Beyond: Infectious Disease (Version 9-26-2016 ed.). 16. ^ "Laboratory Methods for the Diagnosis of Epidemic Dysentery and Cholera" (PDF). WHO/CDS/CSR/EDC/99.8. Centers for Disease Control and Prevention. Atlanta, Georgia 1999. Archived from the original (PDF) on 5 March 2012. 17. ^ "Dysentery". TheFreeDictionary's Medical dictionary. 18. ^ WHO (1969). "Amoebiasis. Report of a WHO Expert Committee". WHO Technical Report Series. 421: 1–52. PMID 4978968. 19. ^ Amebic+Dysentery at the US National Library of Medicine Medical Subject Headings (MeSH) 20. ^ a b Mani, Sachin; Wierzba, Thomas; Walker, Richard I (2016). "Status of vaccine research and development Shigella". Vaccine. 34 (26): 2887–2894. doi:10.1016/j.vaccine.2016.02.075. PMID 26979135. 21. ^ "WHO vaccine pipeline tracker". World Health Organization. Archived from the original on 25 July 2016. Retrieved 21 July 2016. 22. ^ "Chapter 3 Infectious Diseases Related To Travel". CDC. 1 August 2013. Archived from the original on 14 July 2014. Retrieved 9 June 2014. 23. ^ mdguidelines.com. "Dysentery-Prognosis". Archived from the original on 14 July 2011. Retrieved 17 November 2010. 24. ^ Byrne, Joseph Patrick (2008). Encyclopedia of Pestilence, Pandemics, and Plagues: A-M. ABC-CLIO. pp. 175–176. ISBN 978-0-313-34102-1. 25. ^ "Kapok Tree". Blue Planet and Biomoes. Archived from the original on 22 February 2012. Retrieved 7 February 2012. 26. ^ "Ceiba pentandra". Human Uses and Cultural Importance. Archived from the original on 15 February 2012. Retrieved 7 February 2012. 27. ^ "Kapok Emergent Tree Of Tropical Rain Forest Used To Treat Asthma Dysentery Fever Kidney Diseases". encyclocenter.com. Archived from the original on 10 May 2012. Retrieved 27 April 2018. 28. ^ Mazza, P. (1994). "The use of Bacillus subtilis as an antidiarrhoeal microorganism". Boll. Chim. Farm. 133 (1): 3–18. PMID 8166962. 29. ^ Warren, W. Lewis (1991). King John. London: Methuen. p. 253. ISBN 978-0-413-45520-8. 30. ^ "BBC – History – Henry V". bbc.co.uk. Archived from the original on 13 February 2018. Retrieved 27 April 2018. 31. ^ Herbermann, Charles, ed. (1913). "Desiderius Erasmus" . Catholic Encyclopedia. New York: Robert Appleton Company. 32. ^ "BBC – History – Sir Francis Drake". bbc.co.uk. Archived from the original on 12 February 2018. Retrieved 27 April 2018. 33. ^ Majumdar 1984, pp. 168–169 harvnb error: no target: CITEREFMajumdar1984 (help) 34. ^ [1] Archived March 8, 2013, at the Wayback Machine 35. ^ Foner, Eric (2012). Give Me Liberty! An American History (brief ed.). New York, London: W. W. Norton and Company. ISBN 9780393920321. 36. ^ * Sarkar, Jadunath (1920) [1919], Shivaji and His Times (Second ed.), London: Longmans, Green and Co. 37. ^ Sarkar, Shivaji and His Times 1920, p. 382. 38. ^ cite Morris, Donald R. (1998). The Washing of the Spears: A History of the Rise of the Zulu Nation Under Shaka and Its Fall in the Zulu War of 1879 39. ^ Marr, David G. (1970). Vietnamese anticolonialism, 1885–1925. Berkeley, California: University of California. p. 68. ISBN 978-0-520-01813-6. 40. ^ Meaux, Antoine de (2004). L'ultime désert: vie et mort de Michel Vieuchange (in French). Paris: Phébus. pp. 29, 245–249 & 253\. ISBN 978-2-85940-997-5. 41. ^ Vieuchange, Michel (1988) [1932]. Smara: The Forbidden City. Fletcher Allen, Edgar (translation); Vieuchange, Jean (editor; introduction, notes, postscript); Claudel, Paul (preface). (Reprinted ed.). New York: Ecco. ISBN 978-0-88001-146-4. 42. ^ Thompson, Peter (2005). The Battle For Singapore—The True Story of the Greatest Catastrophe of World War II. United Kingdom: Portraits Books. pp. 389–390. ISBN 978-0-7499-5085-9. ## External links[edit] Classification D * ICD-10: A09.0, A03.9, A06.0, A07.9 * ICD-9-CM: 004, 007.9, 009.0 * MeSH: D004403 * v * t * e Parasitic disease caused by Excavata protozoa Discicristata Trypanosomatida Trypanosomiasis * T. brucei * African trypanosomiasis * T. cruzi * Chagas disease Leishmaniasis * Leishmania major / L. mexicana / L. aethiopica / L. tropica * Cutaneous leishmaniasis * L. braziliensis * Mucocutaneous leishmaniasis * L. donovani / infantum * Visceral leishmaniasis Schizopyrenida * Naegleria fowleri * Primary amoebic meningoencephalitis Trichozoa Diplomonadida * Giardia lamblia (Giardiasis) Trichomonadida * Trichomonas vaginalis * Trichomoniasis * Dientamoeba fragilis * Dientamoebiasis * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum Authority control * GND: 4178684-1 * NDL: 00570574 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Dysentery	c0013369	29,953	wikipedia	https://en.wikipedia.org/wiki/Dysentery	2021-01-18T18:50:49	{"mesh": ["D004403"], "umls": ["C0013369"], "icd-10": ["A09.0", "A06.0", "A03.9", "A07.9"], "wikidata": ["Q129279"]}
Loeys–Dietz syndrome Other namesAortic aneurysm syndrome due to TGF-beta receptors anomalies This condition is inherited in an autosomal dominant manner[1] Pronunciation * /ˌloʊiːzˈdiːts/ LOH-eez-DEETS[2] SpecialtyCardiology, rheumatology, medical genetics Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome.[3][4][5] The disorder is marked by aneurysms in the aorta, often in children, and the aorta may also undergo sudden dissection in the weakened layers of the wall of the aorta. Aneurysms and dissections also can occur in arteries other than the aorta. Because aneurysms in children tend to rupture early, children are at greater risk for dying if the syndrome is not identified. Surgery to repair aortic aneurysms is essential for treatment. There are five types of the syndrome, labelled types I through V, which are distinguished by their genetic cause. Type 1, Type 2, Type 3, Type 4 and Type 5 are caused by mutations in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3 respectively. These five genes encoding transforming growth factors play a role in cell signaling that promotes growth and development of the body's tissues. Mutations of these genes cause production of proteins without function. The skin cells for individuals with Loeys–Dietz syndrome are not able to produce collagen, the protein that allows skin cells to be strong and elastic. This causes these individuals to be susceptible to different tears in the skin such as hernias. Although the disorder has an autosomal pattern of inheritance, this disorder results from a new gene mutation in 75% of cases and occurs in people with no history of the disorder in their family. In other cases it is inherited from one affected parent.[6] Loeys–Dietz syndrome was identified and characterized by pediatric geneticists Bart Loeys and Harry "Hal" Dietz at Johns Hopkins University in 2005. ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Types (old nomenclature) * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References * 7 Further reading * 8 External links ## Signs and symptoms[edit] There is considerable variability in the phenotype of Loeys–Dietz syndrome, from mild features to severe systemic abnormalities. The primary manifestations of Loeys–Dietz syndrome are arterial tortuosity (winding course of blood vessels), widely spaced eyes (hypertelorism), wide or split uvula, and aneurysms at the aortic root. Other features may include cleft palate and a blue/gray appearance of the white of the eyes. Cardiac defects and club foot may be noted at birth.[7] There is overlap in the manifestations of Loeys–Dietz and Marfan syndromes, including increased risk of ascending aortic aneurysm and aortic dissection, abnormally long limbs and fingers, and dural ectasia (a gradual stretching and weakening of the dura mater that can cause abdominal and leg pain). Findings of hypertelorism (widely spaced eyes), bifid or split uvula, and skin findings such as easy bruising or abnormal scars may distinguish Loeys–Dietz from Marfan syndrome.[citation needed] Affected individuals often develop immune system related problems such as allergies to food, asthma, hay fever, and inflammatory disorders such as eczema or inflammatory bowel disease. Findings of Loeys–Dietz syndrome may include:[citation needed] * Skeletal/spinal malformations: craniosynostosis, Scoliosis, spinal instability and spondylolisthesis, Kyphosis * Sternal abnormalities: pectus excavatum, pectus carinatum * Contractures of fingers and toes (camptodactyly) * Long fingers and lax joints * Weakened or missing eye muscles (strabismus) * Club foot * Premature fusion of the skull bones (craniosynostosis) * Joint hypermobility * Congenital heart problems including patent ductus arteriosus (connection between the aorta and the lung circulation) and atrial septal defect (connection between heart chambers) * Translucency of the skin with velvety texture * Abnormal junction of the brain and medulla (Arnold–Chiari malformation) * Bicuspid aortic valves * Criss-crossed pulmonary arteries ## Cause[edit] ### Types (old nomenclature)[edit] Several genetic causes of Loeys–Dietz syndrome have been identified. A de novo mutation in TGFB3, a ligand of the TGF ß pathway, was identified in an individual with a syndrome presenting partially overlapping symptoms with Marfan Syndrome and Loeys–Dietz Syndrome.[8] Type Gene Locus OMIM Description 1A TGFBR1 9q22 609192 Also known as Furlong disease 1B TGFBR2 3p22 610168 2A TGFBR1 9q22 608967 2B TGFBR2 3p22 610380 Previously known as Marfan syndrome type 2 3 SMAD3 613795 Also known as Aneurysms-osteoarthritis syndrome 4 TGFB2 614816 5 TGFB3 615582 ## Diagnosis[edit] Diagnosis involves consideration of physical features and genetic testing. Presence of split uvula is a differentiating characteristic from Marfan Syndrome, as well as the severity of the heart defects. Loeys–Dietz Syndrome patients have more severe heart involvement and it is advised that they be treated for enlarged aorta earlier due to the increased risk of early rupture in Loeys–Dietz patients. Because different people express different combinations of symptoms and the syndrome was first identified in 2005, many doctors may not be aware of its existence.[citation needed] ## Treatment[edit] As there is no known cure, Loeys–Dietz syndrome is a lifelong condition. Due to the high risk of death from aortic aneurysm rupture, patients should be followed closely to monitor aneurysm formation, which can then be corrected with vascular surgery.Previous research in laboratory mice has suggested that the angiotensin II receptor antagonist losartan, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial sponsored by the National Institutes of Health is currently underway to explore the use of losartan to prevent aneurysms in Marfan syndrome patients. Both Marfan syndrome and Loeys–Dietz syndrome are associated with increased TGF-beta signaling in the vessel wall. Therefore, losartan also holds promise for the treatment of Loeys–Dietz syndrome. In those patients in which losartan is not halting the growth of the aorta, irbesartan has been shown to work and is currently also being studied and prescribed for some patients with this condition.[citation needed] If an increased heart rate is present, a cardioselective beta-1 blocker, with or without losartan, is sometimes prescribed to reduce the heart rate to prevent any extra pressure on the tissue of the aorta. Likewise, strenuous physical activity is discouraged in patients, especially weight lifting and contact sports.[9] ## Epidemiology[edit] The incidence of Loeys–Dietz syndrome is unknown; however, Type 1 and 2 appear to be the most common.[6] ## References[edit] 1. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Loeys Dietz syndrome". www.orpha.net. Retrieved 27 July 2017. 2. ^ "Research and Treatment \| Loeys-Dietz Syndrome". Johns Hopkins Medicine. 10 August 2018. Retrieved 8 November 2020. 3. ^ Loeys BL, Schwarze U, Holm T, et al. (2006). "Aneurysm syndromes caused by mutations in the TGF-beta receptor". N. Engl. J. Med. 355 (8): 788–98. doi:10.1056/NEJMoa055695. PMID 16928994. 4. ^ LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM (2007). "Severe aortic and arterial aneurysms associated with a TGFBR2 mutation". Nature Clinical Practice Cardiovascular Medicine. 4 (3): 167–71. doi:10.1038/ncpcardio0797. PMC 2561071. PMID 17330129. 5. ^ Loeys BL, Chen J, Neptune ER, et al. (March 2005). "A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2". Nat. Genet. 37 (3): 275–81. doi:10.1038/ng1511. hdl:1854/LU-330238. PMID 15731757. S2CID 24499542. 6. ^ a b Loeys–Dietz syndrome at NLM Genetics Home Reference 7. ^ "Loeys-Dietz Syndrome". The Marfan Foundation. 27 June 2013. 8. ^ Rienhoff HY, Yeo C-Y, Morissette R, Khrebtukova I, Melnick J, Luo S, Leng N, Kim Y-J, Schroth G, Westwick J, Vogel H, McDonnell N, Hall JG, Whitman M. 2013. A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis, and clinical features overlapping with Marfan and Loeys–Dietz syndrome. Am J Med Genet Part A. 161A:2040–2046. 9. ^ Loeys, BL; Dietz, HC (1993). "Loeys-Dietz Syndrome". In Adam, MP; Ardinger, HH; Pagon, RA (eds.). GeneReviews®. Seattle (WA): University of Washington, Seattle. ## Further reading[edit] * Bertoli-Avella, A. M; Gillis, E; Morisaki, H; Verhagen, J. M. A; De Graaf, B. M; Van De Beek, G; Gallo, E; Kruithof, B. P. T; Venselaar, H; Myers, L. A; Laga, S; Doyle, A. J; Oswald, G; Van Cappellen, G. W. A; Yamanaka, I; Van Der Helm, R. M; Beverloo, B; De Klein, A; Pardo, L; Lammens, M; Evers, C; Devriendt, K; Dumoulein, M; Timmermans, J; Bruggenwirth, H. T; Verheijen, F; Rodrigus, I; Baynam, G; Kempers, M; et al. (2015). "Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections". Journal of the American College of Cardiology. 65 (13): 1324–1336. doi:10.1016/j.jacc.2015.01.040. PMC 4380321. PMID 25835445. ## External links[edit] * orphan.net LDS-Syndrome Classification D * ICD-10: Q87.89 * OMIM: 609192 610168 * MeSH: D055947 * DiseasesDB: 34032 * SNOMED CT: 446263001 External resources * GeneReviews: Loeys-Dietz Syndrome * Orphanet: 60030 * v * t * e Cell surface receptor deficiencies G protein-coupled receptor (including hormone) Class A * TSHR (Congenital hypothyroidism 1) * LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty) * FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis) * GnRHR (Gonadotropin-releasing hormone insensitivity) * EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2) * AVPR2 (Nephrogenic diabetes insipidus 1) * PTGER2 (Aspirin-induced asthma) Class B * PTH1R (Jansen's metaphyseal chondrodysplasia) Class C * CASR (Familial hypocalciuric hypercalcemia) Class F * FZD4 (Familial exudative vitreoretinopathy 1) Enzyme-linked receptor (including growth factor) RTK * ROR2 (Robinow syndrome) * FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome) * FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome) * FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome) * INSR (Donohue syndrome * Rabson–Mendenhall syndrome) * NTRK1 (Congenital insensitivity to pain with anhidrosis) * KIT (KIT Piebaldism, Gastrointestinal stromal tumor) STPK * AMHR2 (Persistent Müllerian duct syndrome II) * TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia) * TGFBR1/TGFBR2 (Loeys–Dietz syndrome) GC * GUCY2D (Leber's congenital amaurosis 1) JAK-STAT * Type I cytokine receptor: GH (Laron syndrome) * CSF2RA (Surfactant metabolism dysfunction 4) * MPL (Congenital amegakaryocytic thrombocytopenia) TNF receptor * TNFRSF1A (TNF receptor associated periodic syndrome) * TNFRSF13B (Selective immunoglobulin A deficiency 2) * TNFRSF5 (Hyper-IgM syndrome type 3) * TNFRSF13C (CVID4) * TNFRSF13B (CVID2) * TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A) Lipid receptor * LRP: LRP2 (Donnai–Barrow syndrome) * LRP4 (Cenani–Lenz syndactylism) * LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1) * LDLR (LDLR Familial hypercholesterolemia) Other/ungrouped * Immunoglobulin superfamily: AGM3, 6 * Integrin: LAD1 * Glanzmann's thrombasthenia * Junctional epidermolysis bullosa with pyloric atresia EDAR (EDAR hypohidrotic ectodermal dysplasia) * PTCH1 (Nevoid basal-cell carcinoma syndrome) * BMPR1A (BMPR1A juvenile polyposis syndrome) * IL2RG (X-linked severe combined immunodeficiency) See also cell surface receptors [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Loeys–Dietz syndrome	c1836635	29,954	wikipedia	https://en.wikipedia.org/wiki/Loeys%E2%80%93Dietz_syndrome	2021-01-18T18:28:05	{"gard": ["10788"], "mesh": ["D055947"], "umls": ["C1836635", "C2697932"], "orphanet": ["60030"], "wikidata": ["Q3508669"]}
A rare chromosomal anomaly syndrome, resulting from a partial deletion of the long arm of chromosome 20, with a highly variable phenotype typically characterized by global developmental delay with important speech and language deficits, intellectual disability, hypotonia, epilepsy, behavioral anomalies (e.g. autism spectrum disorder behaviors) and hand and feet skeletal malformations. Craniofacial dysmorphism, including microcephaly, high forehead, hypertelorism, broad nasal bridge, bulbous nasal tip, malformed ears, long philtrum, thin upper lip, and microretrognathia, may be occasionally associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Distal monosomy 20q	None	29,955	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96152	2021-01-23T18:15:27	{"icd-10": ["Q93.5"], "synonyms": ["Distal deletion 20q", "Monosomy 20qter", "Telomeric deletion 20q"]}
Superior limbic keratoconjunctivitis This condition affects cornea and limbus SpecialtyOphthalmology Superior limbic keratoconjunctivitis is an ocular disease[1] characterized by episodes of recurrent inflammation of the superior cornea and limbus, as well as of the superior tarsal and bulbar conjunctiva.[citation needed] Even though the pathophysiology remains unclear, it is thought that mechanical trauma from tight upper lids or loose redundant conjunctiva could lead to the disruption of normal epithelium. This mechanical hypothesis is supported by the increased lid apposition of exophthalmic thyroid patients, who are known to have an increased incidence of superior limbic keratoconjunctivitis.[citation needed] Patients present with red eye, burning, tearing, foreign body sensation, mild photophobia. Inflammation and thickening of the conjunctiva is observed, especially at the limbus. Lubrication is an effective treatment for this pathology.[citation needed] ## References[edit] 1. ^ "Superior limbic keratoconjunctivitis \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-09-30. ## External links[edit] Classification D External resources * eMedicine: article/1194578 This article about the eye is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Superior limbic keratoconjunctivitis	c0339229	29,956	wikipedia	https://en.wikipedia.org/wiki/Superior_limbic_keratoconjunctivitis	2021-01-18T18:35:41	{"gard": ["10940"], "umls": ["C0339229"], "orphanet": ["88633"], "wikidata": ["Q7643645"]}
## Summary ### Clinical characteristics. Saul-Wilson syndrome (SWS) is a skeletal dysplasia characterized by profound short stature, distinctive craniofacial features, short distal phalanges of fingers and toes, and often clubfoot. Early development (primarily speech and motor) is delayed; cognition is normal. Other findings can include hearing loss (conductive, sensorineural, and mixed), lamellar cataracts, and/or rod-cone retinal dystrophy. To date, 16 affected individuals have been reported. ### Diagnosis/testing. The diagnosis of SWS is established in a proband with marked short stature, typical facial and skeletal features, and a heterozygous pathogenic variant in COG4 identified by molecular genetic testing. To date only two COG4 variants, both resulting in a p.Gly516Arg missense change, have been reported. ### Management. Treatment of manifestations: Skeletal dysplasia or physiatry clinic (orthopedist, OT/PT/ rehabilitation specialist) to address repair of clubfoot, possible C1-C2 subluxation and/or spinal cord compression, mobility issues in those with residual foot deformities (post clubfoot repair), osteoarticular pain; standard treatment for feeding issues, speech delay, cataracts and retinal dystrophy, and hearing loss. Surveillance: Routine follow up of growth and feeding, developmental progress and educational needs, musculoskeletal issues including mobility, osteoarticular pain, bone fragility, possible cataracts and/or retinal dystrophy, hearing loss. Agents/circumstances to avoid: Participation in gymnastics and jumping on a trampoline until atlanto-axial instability is excluded. ### Genetic counseling. SWS is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Sib recurrence has been observed in one family and is thought to result from germline mosaicism in a parent. The risk to offspring of an individual with SWS of inheriting the COG4 pathogenic variant is 50%. Once the COG4 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis Formal diagnostic criteria for Saul-Wilson syndrome have not been established. ### Suggestive Findings Saul-Wilson syndrome should be suspected in individuals with the following clinical, laboratory, and imaging findings [Ferreira et al 2018]. Clinical findings * Skeletal * Profound short stature (typically of prenatal onset) * Clubfoot * Short distal phalanges of fingers and toes (Figure 1) * Distinctive craniofacial features (Figure 1) * Progeroid facial appearance (more striking during infancy) * Sparse hair and sparse eyebrows * Prominent forehead with prominent scalp veins * Enlargement and delayed closure of the anterior fontanelle (earliest known closure 21 months; still open at age 3 years in one child) * Narrow nasal bridge with convex nasal ridge * Prominent columella (developing in late childhood) * Thin vermilion of the upper lip * Mild micrognathia * Eyes * Blue sclerae (during the first few months of life) * Lamellar cataracts * Rod-cone dystrophy * Hearing loss (conductive, sensorineural, and mixed) * Early developmental delay (primarily speech) with normal cognition #### Figure 1 A, C, and D. Note prominent forehead, scalp veins, and columella, as well as thin vermilion of the upper lip. B. Note short distal phalanges of the fingers. Laboratory findings * Elevated hepatic transaminases * Intermittent neutropenia Skeletal radiographs (Figure 2) #### Figure 2 A. Babygram obtained at age 11 months. Note coxa valga, overtubulation of the long bones, and lucencies of the proximal femora. B. Lateral cervical spine radiograph obtained at age eight months highlighting hypoplasia of the odontoid process * Long bones * Short long bones * Overtubulation with thin diaphyses and flared metaphyses * Lucency of proximal femora * Coxa valga * Megaepiphyses * Hand * Small hands with short metacarpals and short phalanges * Accessory ossification centers of the proximal metacarpals * Cone-shaped epiphyses of the phalanges * Ivory epiphyses of the distal phalanges (in late childhood) * Spine * Hypoplasia of the odontoid process of C2 * Hypoplasia of T12 or L1 * Platyspondyly (vertebral bodies become taller with age) * Irregularities of the endplates of the vertebral bodies (in later life) ### Establishing the Diagnosis The diagnosis of Saul-Wilson syndrome is established in a proband with marked short stature, typical facial and skeletal features, and a heterozygous pathogenic variant in COG4 identified by molecular genetic testing (see Table 1). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because Saul-Wilson syndrome is rare, individuals with the distinctive findings described in Suggestive Findings in whom the diagnosis is recognized are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of Saul-Wilson syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1: Single-Gene Testing Sequence analysis of COG4 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Note: (1) Since only two variants, both resulting in a p.Gly516Arg missense change, have been reported to date, targeted analysis for these variants could be performed first to confirm a clinical diagnosis of Saul-Wilson syndrome. (2) Since Saul-Wilson syndrome occurs through a gain-of-function mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant. #### Option 2: Genomic Testing Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Saul-Wilson Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method COG4Sequence analysis 314/14 4 Gene-targeted deletion/duplication analysis 5None detected 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Ferreira et al [2018] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Since Saul-Wilson syndrome occurs through a gain-of-function mechanism and large intragenic deletions or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant. ## Clinical Characteristics ### Clinical Description Saul-Wilson syndrome is a skeletal dysplasia characterized by profound short stature, distinctive craniofacial features, short distal phalanges of fingers and toes, and often clubfoot. Early development (primarily speech) is delayed; cognition is normal. Other findings can include hearing loss (conductive, sensorineural, and mixed), lamellar cataracts, and/or rod-cone retinal dystrophy. A total of 16 individuals with Saul-Wilson syndrome have been reported to date. Saul-Wilson syndrome was first described in a small-for-gestational-age infant with bulging fontanelles, clubfoot, blue sclerae, and blunted fingertips; over time, growth was delayed and the child developed bilateral cataracts, and hearing loss as the result of frequent otitis media [Saul 1982]. Three additional individuals with similar features were reported [Saul & Wilson 1990, Hersh et al 1994]. Subsequently the diagnosis of Saul-Wilson syndrome was entertained in a child without typical facial features [Chinen et al 2015], but the diagnosis could not be confirmed by molecular genetic testing. Fourteen individuals were described in 2018, including two originally reported in the 1990s [Ferreira et al 2018]. Since that publication, a few additional individuals with Saul-Wilson syndrome worldwide have been diagnosed [Author, personal observation]. The clinical findings discussed in this section are based on these reports. #### Growth Individuals with Saul-Wilson syndrome show impaired postnatal growth, and several also had intrauterine growth restriction (IUGR). Mean length, weight, and head circumference at birth: * Length. 44.1 cm (range 38.0-49.0) * Weight. 2.09 kg (range 1.45-2.80) * Head circumference. 31.7 cm (range 29.0-34.0) Z-scores at birth: * Length. -2.3 ± 1.5 SD (range -0.4 to -5.1) * Weight. -2.4 ± 0.7 SD (range -1.2 to -3.8) * Head circumference: -2.0 ± 0.9 SD (range -0.8 to -3.9) Standard deviation scores decline sharply over the first few months of life. At last examination: * Stature. -6.3 ± 1.8 SD (range -3.5 to -9.8) * Weight. -4.0 ± 1.2 SD (range -1.1 to -5.8) * Head circumference. -1.7 ± 1.7 SD (range 0.8 to -5.0) Based on data available from three adults * Mean height, weight, and head circumference at skeletal maturity: * Height. 107.6 cm * Weight. 30.5 kg * Head circumference. 50.2 cm * Z-scores at skeletal maturity: * Height. -8.9 ± 0.8 SD (range -8.3 to -9.8) * Weight. -4.3 ± 0.6 SD (range -3.6 to -4.8) * Head circumference. -3.9 ± 1.6 SD (-2.7 to -5.0) Growth charts for clinical use are currently under development. Despite absolute microcephaly, head circumferences exceed the height by more than 2 SD, with consequent relative macrocephaly. #### Development Speech delay (8/11) and motor delay (12/14) are common, probably related to the presence of hearing loss and skeletal deformities, respectively; cognitive development does not appear to be affected. #### Ophthalmologic Features The majority of affected individuals develop lamellar cataracts during the first few years of life (10/13), and several developed retinal involvement (6/9). Retinal pigmentary changes can be seen in the periphery as early as the toddler years. During adolescence and early adulthood, a rod-cone dystrophy (5/9) becomes evident with constricted visual fields and night blindness. Macular cystic changes were also described (2/4). One individual had myelinated retinal nerve fibers [Ferreira et al 2020]. #### Skeletal Features Shortening of the distal phalanges of fingers and toes is appreciated on physical examination (12/14). This finding, apparent at birth, did not progress over time. The majority of individuals (10/14) had clubfoot, and in some cases residual deformity even after multiple attempts at surgical repair [Ferreira et al 2020]. Pectus deformity (5/14) and cervical spinal cord compression (3/7) have also been reported. Bone fragility has been suggested, as several individuals (4/14) developed fractures with minimal or no known trauma [Ferreira et al 2020]. One of these individuals had poor fracture healing, which was also described in the original patient [Saul & Wilson 1990]. Nonunion with pseudoarthrosis has been seen in two individuals [Saul & Wilson 1990, Ferreira et al 2020]. Although DXA scans for two individuals reported bone mineral density (BMD) <2 SD below the mean, the height-adjusted BMD [Zemel et al 2010, Zemel et al 2011] was normal in both [Author, personal observation]. Osteoarticular pain was reported by all three adults. Two had confirmed degenerative joint disease, leading to joint replacement surgeries in one individual in her 20s [Ferreira et al 2020]. The combination of megaepiphyses with coxa valga, leading to acetabulum-femoral epiphyseal incongruence, may contribute to premature osteoarthropathy of the hip. #### Other Hearing loss, seen in the majority of affected individuals over time, can be conductive, sensorineural, or mixed. In one child hearing impairment associated with inner-ear malformations was detected on newborn hearing screen. MRI findings. Ventriculomegaly was seen in 5/9 and spinal cord syrinx in 1/4 individuals. Spinal cord compression was observed in 3/7: in one child with soft-tissue pannus surrounding the odontoid process, it was seen as early as age four years, and in another child with cervical spine instability, as late as age 14 years. Intermittent neutropenia, though not appreciated in the first two months of life, was seen in all 12 individuals subsequently evaluated for this finding [Ferreira et al 2020]. The earliest known age of onset is three months, and it still occurred in adults. While intermittent neutropenia could be one possible explanation for the frequent (although rarely life-threatening) respiratory infections experienced in the first years of life, the neutropenia persisted into adulthood whereas the number of respiratory infections decreased over time. Asymptomatic elevation of liver transaminases. Elevated aspartate aminotransferase was observed in 6/8 individuals and elevated alanine aminotransferase in 3/8, without abnormalities in other liver function tests, such as serum albumin, coagulation parameters, alkaline phosphatase, and bilirubin [Ferreira et al 2020]. ### Genotype-Phenotype Correlations No genotype-phenotype correlation is possible because all affected individuals have the same amino acid substitution. ### Penetrance Penetrance is thought to be 100%. ### Prevalence Sixteen individuals have been reported to date. Three additional individuals are known to have the diagnosis of Saul-Wilson syndrome [Author, personal observation]. There is no known geographic predilection. ## Differential Diagnosis ### Table 2. Disorders Interest in the Differential Diagnosis of Saul-Wilson Syndrome View in own window Differential DisorderCauseMOIFeatures of Differential Disorder Overlapping w/SWSDistinguishing from SWS Silver-Russell syndromeChromosome 11p15.5- or chromosome 7-relatedSee footnote 1. * Short stature (largely prenatal onset w/no postnatal catch-up growth) * Relative macrocephaly w/enlarged anterior fontanelle * Frontal prominence * Blue sclerae * Ivory epiphyses * Limb-length asymmetry, multiple café au lait spots, & hypoglycemia * No spondyloepimetaphyseal changes, ocular signs, hearing loss, neutropenia, or ↑ transaminases Osteogenesis imperfecta (see COL1A1/2 Osteogenesis Imperfecta)COL1A1 COL1A2 (>15 genes) 2AD 2 * Blue sclerae * Bone fragility * Hearing loss * Dentinogenesis imperfecta * No spondyloepimetaphyseal changes, cataracts, retinal degeneration, neutropenia, or ↑ transaminases Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720)PCNTAR * Profound prenatal-onset short stature * Microcephaly * Low-hanging columella * Thin bones w/metaphyseal widening * Metacarpal pseudoepiphyses * Ivory epiphyses * Vascular issues * No shortening of distal phalanges or frontal prominence Wiedemann- Rautenstrauch syndrome (OMIM 264090)POLR3AAR * Early progeroid features * Poor growth * Frontal prominence * Delayed closure of anterior fontanelle * Prominent scalp veins * Convex nasal ridge * Thin vermilion of upper lip * Intellectual disability 3 * No shortening of distal phalanges Hallermann- Streiff syndrome (OMIM 234100)UnknownUnknown * Short stature * Cataracts * Micrognathia * Prominent scalp veins * Slender diaphyses Distinct facial gestalt (e.g., characteristic thin nose & more pronounced micrognathia) Floating-Harbor syndromeSRCAPAD * Profound prenatal-onset short stature * Low-hanging columella * Thin vermilion of upper lip * Speech delay Distinct facial gestalt (e.g., distinctive prominent nose) AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; SWS = Saul-Wilson syndrome 1\. In most families, a proband with SRS represents a simplex case (a single affected family member) and has SRS as the result of an apparent de novo epigenetic or genetic alteration (e.g., loss of paternal methylation at the H19/IGF2 imprinting center 1 or maternal uniparental disomy for chromosome 7). 2\. The majority of individuals diagnosed with osteogenesis imperfect (OI) have the disorder as the result of a pathogenic variant in COL1A1 or COL1A2. COL1A1/2-OI is inherited in an autosomal dominant manner. OI caused by pathogenic variants in other genes (see OMIM PS166200) may be associated with autosomal recessive, autosomal dominant, or X-linked inheritance. 3\. Intellectual disability is not typically observed in Saul-Wilson syndrome. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Saul-Wilson syndrome, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Saul-Wilson Syndrome View in own window System/ConcernEvaluationComment ConstitutionalMeasurement of HT, WT, & HCAssess for evidence of linear growth failure using SWS-specific growth charts. Gastrointestinal/ FeedingGastroenterology / nutrition / feeding team evaluationAvoid overfeeding. DevelopmentDevelopmental assessmentTo incl motor & speech/language evaluation MusculoskeletalRefer to physiatry clinic (OT/PT/ rehabilitation specialist).To evaluate fine & gross motor skills, mobility, & activities of daily living Refer to orthopedist. * Mgmt of clubfoot * Assess osteoarticular pain. Obtain history of bone fractures. Spine * Flexion-extension radiographs of lateral cervical spine * Flexion-extension MRI if instability & compression seen on radiographs or interpretation is limited (e.g., in young individuals w/delayed ossification of cervical vertebral bodies) Evaluate for cervical instability & risk of spinal cord compression EyesOphthalmologic evaluationTo incl assessment for rod-cone dystrophy in individuals old enough to cooperate: * BCVA * Refractive error * Assessment of dark adaptation * Full-field ERG * Spectral-domain OCT Young children: assess visual acuity & refractive error as a baseline. Children & adolescents: assess for cataracts. HearingAudiologic evaluation 1Assess for SNHL & conductive hearing loss. HematologyComplete blood count w/absolute neutrophil countTo evaluate for neutropenia LiverAspartate aminotransferase, alanine aminotransferaseTo evaluate for ↑ liver enzymes Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselor Family support/resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support. BCVA = best-corrected Snellen visual acuity; BMD = bone mineral density; ERG = electroretinography; FTT = failure to thrive; HC = head circumference; HT = height; OCT = optical coherence tomography; OT = occupational therapy; PT = physical therapy; SNHL= sensorineural hearing loss; SWS = Saul-Wilson syndrome; WT = weight 1\. See Hereditary Hearing Loss and Deafness Overview for details about audiologic evaluations. ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with Saul-Wilson Syndrome View in own window Manifestation/ ConcernTreatmentConsiderations/Other Delayed developmentSee Developmental Delay Management Issues. MusculoskeletalSkeletal dysplasia or physiatry clinic (orthopedics, OT/PT/ rehabilitation specialist)Address mobility issues in those w/residual foot deformities (post-club foot repair), osteoarticular pain. Cervical spine compressionSurgical mgmt for medullopathy (C1-C2 fixation) by an expert familiar w/skeletal dysplasias & spine involvementGiven possibility of C1-C2 subluxation &/or spinal cord compression, follow best practices in perioperative mgmt of those w/skeletal dysplasias. 1 Cataract / Retinal dystrophyStandard treatment(s) as recommended by ophthalmologistCataracts: Consider surgery when dense to prevent amblyopia Retinal dystrophy: * Night vision scopes or selected wavelength filters 2 * Community vision services in teen yrs / young adulthood 3 Hearing lossPer treating otolaryngologist: * Myringotomy tubes * Hearing aids Community hearing services through early intervention or school district 4 NeutropeniaPer treating immunologist or infectious disease specialistIf frequent infections: consider GCSF to improve absolute neutrophil counts. 5 Family/ Community * Ensure appropriate social work involvement to connect families w/local resources, respite, & support. * Coordinate care to manage multiple subspecialty appointments. Consider involvement in adaptive sports or Special Olympics. GCSF = granulocyte colony-stimulating factor; OT = occupational therapist; PT = physical therapist 1\. White et al [2017]. Including cervical spine imaging prior to general anesthesia. 2\. See Nonsyndromic Retinitis Pigmentosa Overview for information about management. 3\. In the US, publicly funded agencies at the state level provide services for the visually impaired or those with progressive eye disorders; services include vocational training, mobility training, and skills for independent living. 4\. See Hereditary Hearing Loss and Deafness Overview for information about management. 5\. Ferreira et al [2020] #### Developmental Disability Management Issues The following information represents typical management recommendations for individuals with developmental disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider: * Individualized education plan (IEP) services: * An IEP provides specially designed instruction and related services to children who qualify. * IEP services will be reviewed annually to determine whether any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * Vision and hearing consultants should be a part of the child's IEP team to support access to academic material. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. ### Surveillance ### Table 5. Recommended Surveillance for Individuals with Saul-Wilson Syndrome View in own window System/ConcernEvaluationFrequency ConstitutionalMeasure HT, WT, & HC using growth curves standardized for SWS.At each visit DevelopmentMonitor developmental progress / educational needs.At each visit in young children MusculoskeletalTo evaluate fine & gross motor skills, mobility, & activities of daily livingAnnually Assess osteoarticular pain.At each visit starting in young adulthood DXA for bone fragilityAs needed based on history * Flexion-extension radiograph * Flexion-extension MRI if instability & compression on radiographs or limited interpretation on radiographs Per orthopedist based on clinical findings or planned surgery EyesComplete eye examination for: * Those known to have rod-cone dystrophy: BVCA, refractive error, dark adaptation, & visual field testing * Those not known to have rod-cone dystrophy (see Table 3) * All patients: cataracts Annually HearingAudiologic evaluation to determine type & extent of hearing loss or success of interventionAnnually OtherObtain complete blood counts to assess neutrophil count.Annually (or as needed during acute infections) BCVA = best-corrected Snellen visual acuity; DXA = dual-energy X-ray absorptiometry; HC = head circumference; HT = height; SWS = Saul-Wilson syndrome; WT = weight ### Agents/Circumstances to Avoid Participation in gymnastics and jumping on a trampoline should be avoided until atlanto-axial instability is excluded. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Pregnancy of an affected woman has not been documented to date, although regular menstrual cycles and a normal hormone profile in two adult females suggest no impairment of the ability to conceive [Ferreira et al 2020]. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Saul-Wilson Syndrome	c1300285	29,957	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK554080/	2021-01-18T20:57:20	{"synonyms": ["Microcephalic Osteodysplastic Dysplasia"]}
A rare mature T-cell neoplasm characterized by proliferation of small to medium-sized prolymphocytes with a mature post-thymic T-cell phenotype, involving the peripheral blood, bone marrow, lymph nodes, liver, spleen, and sometimes the skin. T-cell receptor genes are clonally rearranged. Patients typically present with hepatosplenomegaly, generalized lymphadenopathy, high leukocyte count with normal serum immunoglobulins, anemia, and thrombocytopenia. HTLV-1 serology is negative. The disease course is aggressive with generally poor prognosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	T-cell prolymphocytic leukemia	c2363142	29,958	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86871	2021-01-23T17:50:36	{"mesh": ["D015461"], "umls": ["C0023494", "C2363142"], "icd-10": ["C91.6"], "synonyms": ["T-PLL", "T-cell chronic lymphocytic leukemia"]}
Goldberg-Shprintzen megacolon syndrome (GOSHS) is a very rare genetic condition characterized by a swollen, irritated colon (megacolon); characteristic facial features; a small head, and intellectual disability. Most people with GOSHS also are born with Hirschsprung disease, a condition in which the colon is missing nerve cells, leading to intestinal blockage. Some patients with this condition have a defect in the iris of the eye (coloboma), brain and other central nervous system abnormalities, an opening in the roof of the mouth (cleft palate) and short stature. This condition is caused by changes (mutations) in the KIAA1279 (also known as K1F1BP) gene, and appears to be inherited in an autosomal recessive pattern. GOSHS is diagnosed based on the signs and symptoms and through genetic testing. Treatment is based on the symptoms and may include surgery. This condition has been described in only about 15 individuals to date, and the long-term outlook for people with GOSHS is unclear. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Goldberg-Shprintzen megacolon syndrome	c1836123	29,959	gard	https://rarediseases.info.nih.gov/diseases/9849/goldberg-shprintzen-megacolon-syndrome	2021-01-18T18:00:14	{"mesh": ["C537279"], "omim": ["609460"], "umls": ["C1836123"], "orphanet": ["66629"], "synonyms": ["Goldberg-Shprintzen syndrome", "GOSHS"]}
## Description Mseleni joint disease is a familial degenerative osteoarthropathy affecting several hundred persons in a remote rural region of northern Zululand, South Africa. The condition presents in childhood and progresses relentlessly, leading to severe physical handicap by early adulthood (summary by Agarwal et al., 1997). Clinical Features Persons with Mseleni joint disease develop discomfort in the large joints in mid-childhood. The onset is insidious without inflammation or swelling. The weight-bearing joints are primarily affected and by late-childhood walking is difficult (Lockitch et al., 1973; du Toit, 1979). By early adulthood, prosthetic hip joint replacement is often necessary. Radiographic investigations show that in mid-childhood the femoral capital epiphyses are flattened and irregular, with patchy sclerosis and lucency. Similar changes are present in all other joints, maximal in the weight-bearing regions. The changes become increasingly marked, the joint spaces narrow, and eventually the appearances are indistinguishable from those of conventional osteoarthropathy. Involvement of the spine is variable but some degree of platyspondyly is usual, with irregularity and sclerosis of the vertebral endplates. The skeleton is somewhat porotic and protusio acetabulae may occur (Lockitch et al., 1973; du Toit, 1979; Agarwal et al., 1997). In Mseleni joint disease, mild dwarfism often occurs (du Toit, 1979). Viljoen et al. (1993) identified 8 members of affected families who had severe short stature (adult height 130 cm), marked brachydactyly of fingers and toes, and some radiologic findings of Mseleni joint disease. Agarwal et al. (1997) noted that the clinical and radiographic manifestations of Mseleni joint disease are similar to those of Handigodu joint disease (613343) and suggested that they may represent the same entity. Pathogenesis In a study of affected and unaffected persons from the same population, Ballo et al. (1996) found no association between Mseleni joint disease and the HLA system. Inheritance Although Mseleni joint disease clusters in families, there is no obvious mode of mendelian genetic transmission (Nurse et al., 1974; Viljoen et al., 1993). Ballo et al. (1996) noted that assessment of affected kindreds had not shown any evidence of genomic imprinting. They also noted that all attempts to identify a causative environmental agent had been unproductive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MSELENI JOINT DISEASE	c2931420	29,960	omim	https://www.omim.org/entry/613342	2019-09-22T15:58:54	{"mesh": ["C537086"], "omim": ["613342"], "orphanet": ["2619"]}
## Description Asperger syndrome is considered to be a form of childhood autism (see, e.g., 209850). The DSM-IV (American Psychiatric Association, 1994) specifies several diagnostic criteria for Asperger syndrome, which has many of the same features as autism. In general, patients with Asperger syndrome and autism exhibit qualitative impairment in social interaction, as manifest by impairment in the use of nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. Gillberg et al. (2001) described the development of the Asperger syndrome (and high-functioning autism) Diagnostic Interview (ASDI), which they claimed has a strong validity in the diagnosis of the disorder. For a discussion of genetic heterogeneity of Asperger syndrome, see ASPG1 (608638). Mapping Ylisaukko-oja et al. (2004) performed a genomewide scan on 17 Finnish families ascertained for Asperger syndrome with a strictly defined phenotype. They obtained evidence for linkage on chromosome 3p24-p14 with a maximum 2-point lod score of 2.50 at theta = 0.00 for marker D3S2432. Rehnstrom et al. (2006) enlarged the study of Asperger syndrome in Finnish families by analyzing an independent set of 12 novel extended Asperger families with 54 individuals having Asperger syndrome or Asperger-like symptoms. The new dataset, like the first (Ylisaukko-oja et al., 2004), supported linkage to 3p24-p21. When statistical analyses were performed including the families from the original genomewide screen, a maximum multipoint nonparametric linkage score of 3.83 was obtained at marker D3S2432. The results of the linkage study were further supported by evidence of association in the region. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ASPERGER SYNDROME, SUSCEPTIBILITY TO, 4	c1864961	29,961	omim	https://www.omim.org/entry/609954	2019-09-22T16:05:24	{"omim": ["609954"]}
Period of intense fear of sudden onset For other uses, see Panic attack (disambiguation). Panic attack A depiction of someone experiencing a panic attack, being reassured by another person. SpecialtyPsychiatry SymptomsPeriods of intense fear, palpitations, sweating, shaking, shortness of breath, numbness[1][2] ComplicationsSelf-harm, suicide[2] Usual onsetOver minutes[2] DurationSeconds to hours[3] CausesPanic disorder, social anxiety disorder, post-traumatic stress disorder, drug use, depression, medical problems[2][4] Risk factorsSmoking, psychological stress[2] Diagnostic methodAfter other possible causes excluded[2] Differential diagnosisHyperthyroidism, hyperparathyroidism, heart disease, lung disease, drug use[2] TreatmentCounselling, medications[5] PrognosisUsually good[6] Frequency3% (EU), 11% (US)[2] Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath, numbness, or a feeling of impending doom.[1][2] The maximum degree of symptoms occurs within minutes.[2] Typically they last for about 30 minutes but the duration can vary from seconds to hours.[3] There may be a fear of losing control or chest pain.[2] Panic attacks themselves are not dangerous physically.[6][7] Panic attacks can occur due to several disorders including panic disorder, social anxiety disorder, post-traumatic stress disorder, drug use disorder, depression, and medical problems.[2][4] They can either be triggered or occur unexpectedly.[2] Smoking, caffeine, and psychological stress increase the risk of having a panic attack.[2] Before diagnosis, conditions that produce similar symptoms should be ruled out, such as hyperthyroidism, hyperparathyroidism, heart disease, lung disease, and drug use.[2] Treatment of panic attacks should be directed at the underlying cause.[6] In those with frequent attacks, counseling or medications may be used.[5] Breathing training and muscle relaxation techniques may also help.[8] Those affected are at a higher risk of suicide.[2] In Europe, about 3% of the population has a panic attack in a given year while in the United States they affect about 11%.[2] They are more common in females than in males.[2] They often begin during puberty or early adulthood.[2] Children and older people are less commonly affected.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Panic disorder * 2.2 Agoraphobia * 2.3 Experimentally induced * 2.4 Neurotransmitter imbalances * 3 Pathophysiology * 3.1 Cardiovascular disease * 4 Diagnosis * 5 Treatment * 5.1 Lifestyle changes * 5.2 Breathing exercises * 5.3 Therapy * 5.4 Medication * 6 Prognosis * 7 Epidemiology * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] People with panic attacks often report a fear of dying or heart attack, flashing vision, faintness or nausea, numbness throughout the body, heavy breathing and hyperventilation, or loss of body control. Some people also suffer from tunnel vision, mostly due to blood flow leaving the head to more critical parts of the body in defense. These feelings may provoke a strong urge to escape or flee the place where the attack began (a consequence of the "fight-or-flight response", in which the hormone causing this response is released in significant amounts). This response floods the body with hormones, particularly epinephrine (adrenaline), which aid it in defending against harm.[9] A panic attack can result when up-regulation by the sympathetic nervous system (SNS) is not moderated by the parasympathetic nervous system (PNS). The most common symptoms include trembling, dyspnea (shortness of breath), heart palpitations, chest pain (or chest tightness), hot flashes, cold flashes, burning sensations (particularly in the facial or neck area), sweating, nausea, dizziness (or slight vertigo), light-headedness, heavy-headedness, hyperventilation, paresthesias (tingling sensations), sensations of choking or smothering, difficulty moving, depersonalization and/or derealization. These physical symptoms are interpreted with alarm in people prone to panic attacks. This results in increased anxiety and forms a positive feedback loop.[10] Shortness of breath and chest pain are the predominant symptoms. People experiencing a panic attack may incorrectly attribute them to a heart attack and thus seek treatment in an emergency room. Because chest pain and shortness of breath are hallmark symptoms of cardiovascular illnesses, including unstable angina and myocardial infarction (heart attack), a diagnosis of exclusion (ruling out other conditions) must be performed before diagnosing a panic attack. It is especially important to do this for people whose mental health and heart health statuses are unknown. This can be done using an electrocardiogram and mental health assessments. Panic attacks are distinguished from other forms of anxiety by their intensity and their sudden, episodic nature.[9] They are often experienced in conjunction with anxiety disorders and other psychological conditions, although panic attacks are not generally indicative of a mental disorder. ## Causes[edit] There are long-term, biological, environmental, and social causes of panic attacks. In 1993, Fava et al. proposed a staging method of understanding the origins of disorders. The first stage in developing a disorder involves predisposing factors, such as genetics, personality, and a lack of well-being.[11] Panic disorder often occurs in early adulthood, although it may appear at any age. It occurs more frequently in women and more often in people with above-average intelligence.[citation needed] Various twin studies where one identical twin has an anxiety disorder have reported a high incidence of the other twin also having an anxiety disorder diagnosis.[12] Biological causes may include obsessive-compulsive disorder, postural orthostatic tachycardia syndrome, post-traumatic stress disorder, hypoglycemia, hyperthyroidism, Wilson's disease, mitral valve prolapse, pheochromocytoma, and inner ear disturbances (labyrinthitis). Dysregulation of the norepinephrine system in the locus coeruleus, an area of the brain stem, has been linked to panic attacks.[13] Panic attacks may also occur due to short-term stressors. Significant personal loss, including an emotional attachment to a romantic partner, life transitions, and significant life changes may all trigger a panic attack to occur. A person with an anxious temperament, excessive need for reassurance, hypochondriacal fears,[14] overcautious view of the world,[9] and cumulative stress have been correlated with panic attacks. In adolescents, social transitions may also be a cause.[15] People will often experience panic attacks as a direct result of exposure to an object/situation that they have a phobia for. Panic attacks may also become situationally-bound when certain situations are associated with panic due to previously experiencing an attack in that particular situation. People may also have a cognitive or behavioral predisposition to having panic attacks in certain situations. Some maintaining causes include avoidance of panic-provoking situations or environments, anxious/negative self-talk ("what-if" thinking), mistaken beliefs ("these symptoms are harmful and/or dangerous"), and withheld feelings. Hyperventilation syndrome may occur when a person breathes from the chest, which can lead to over-breathing (exhaling excessive carbon dioxide related to the amount of oxygen in one's bloodstream). Hyperventilation syndrome can cause respiratory alkalosis and hypocapnia. This syndrome often involves prominent mouth breathing as well. This causes a cluster of symptoms, including rapid heartbeat, dizziness, and lightheadedness, which can trigger panic attacks.[16] Panic attacks may also be caused by substances. Discontinuation or marked reduction in the dose of a substance such as a drug (drug withdrawal), for example, an antidepressant (antidepressant discontinuation syndrome), can cause a panic attack. According to the Harvard Mental Health Letter, "the most commonly reported side effects of smoking marijuana are anxiety and panic attacks. Studies report that about 20% to 30% of recreational users experience such problems after smoking marijuana."[17] Cigarette smoking is another substance that has been linked to panic attacks.[18] A common denominator of current psychiatric approaches to panic disorder is that no real danger exists, and the person's anxiety is inappropriate.[19] ### Panic disorder[edit] Main article: Panic disorder People who have repeated, persistent attacks or feel severe anxiety about having another attack are said to have panic disorder. Panic disorder is strikingly different from other types of anxiety disorders in that panic attacks are often sudden and unprovoked.[20] However, panic attacks experienced by those with panic disorder may also be linked to or heightened by certain places or situations, making daily life difficult.[21] ### Agoraphobia[edit] Main article: Agoraphobia Agoraphobia is an anxiety disorder that primarily consists of the fear of experiencing a difficult or embarrassing situation from which the sufferer cannot escape. Panic attacks are commonly linked to agoraphobia and the fear of not being able to escape a bad situation.[22] As the result, severe sufferers of agoraphobia may become confined to their homes, experiencing difficulty traveling from this "safe place".[23] The word "agoraphobia" is an English adoption of the Greek words agora (αγορά) and Phobos (φόβος). The term "agora" refers to the place where ancient Greeks used to gather and talk about issues of the city, so it applies to any or all public places; however, the essence of agoraphobia is a fear of panic attacks especially if they occur in public as the victim may feel like he or she has no escape. In the case of agoraphobia caused by a social phobia or social anxiety, sufferers may be very embarrassed by having a panic attack publicly in the first place. This translation is the reason for the common misconception that agoraphobia is a fear of open spaces, and is not clinically accurate. Agoraphobia, as described in this manner, is a symptom professionals check for when making a diagnosis of panic disorder. People who have had a panic attack in certain situations may develop irrational fears, called phobias, of these situations and begin to avoid them. Eventually, the pattern of avoidance and level of anxiety about another attack may reach the point where individuals with panic disorder are unable to drive or even step out of the house. At this stage, the person is said to have panic disorder with agoraphobia.[citation needed] ### Experimentally induced[edit] Panic attack symptoms can be experimentally induced in the laboratory by various means. Among them, for research purposes, by administering a bolus injection of the neuropeptide cholecystokinin-tetrapeptide (CCK-4).[24] Various animal models of panic attacks have been experimentally studied.[25] ### Neurotransmitter imbalances[edit] Many neurotransmitters are affected when the body is under the increased stress and anxiety that accompany a panic attack. Some include serotonin, GABA (gamma-aminobutyric acid), dopamine, norepinephrine, and glutamate. More research into how these neurotransmitters interact with one another during a panic attack is needed to make any solid conclusions, however. An increase of serotonin in certain pathways of the brain seems to be correlated with reduced anxiety. More evidence that suggests serotonin plays a role in anxiety is that people who take SSRIs tend to feel a reduction of anxiety when their brain has more serotonin available to use.[26] The main inhibitory neurotransmitter in the central nervous system (CNS) is GABA. Most of the pathways that use GABA tend to reduce anxiety immediately.[26] Dopamine's role in anxiety is not well understood. Some antipsychotic medications that affect dopamine production have been proven to treat anxiety. However, this may be attributed to dopamine's tendency to increase feelings of self-efficacy and confidence, which indirectly reduces anxiety.[26] Many physical symptoms of anxiety, such as rapid heart rate and hand tremors, are regulated by norepinephrine. Drugs that counteract norepinephrine's effect may be effective in reducing the physical symptoms of a panic attack.[26] Nevertheless, some drugs that increase 'background' norepinephrine levels such as tricyclics and SNRIs are effective for the long-term treatment of panic attacks, possibly by blunting the norepinephrine spikes associated with panic attacks.[27] Because glutamate is the primary excitatory neurotransmitter involved in the central nervous system (CNS), it can be found in almost every neural pathway in the body. Glutamate is likely involved in conditioning, which is the process by which certain fears are formed, and extinction, which is the elimination of those fears.[26] ## Pathophysiology[edit] The symptoms of a panic attack may cause the person to feel that their body is failing. The symptoms can be understood as follows. First, there is frequently the sudden onset of fear with little provoking stimulus. This leads to a release of adrenaline (epinephrine) which brings about the fight-or-flight response when the body prepares for strenuous physical activity. This leads to an increased heart rate (tachycardia), rapid breathing (hyperventilation) which may be perceived as shortness of breath (dyspnea), and sweating. Because strenuous activity rarely ensues, the hyperventilation leads to a drop in carbon dioxide levels in the lungs and then in the blood. This leads to shifts in blood pH (respiratory alkalosis or hypocapnia), causing compensatory metabolic acidosis activating chemosensing mechanisms that translate this pH shift into autonomic and respiratory responses.[28][29] Moreover, this hypocapnia and release of adrenaline during a panic attack cause vasoconstriction resulting in slightly less blood flow to the head which causes dizziness and lightheadedness.[30][31] A panic attack can cause blood sugar to be drawn away from the brain and toward the major muscles. Neuroimaging suggests heightened activity in the amygdala, thalamus, hypothalamus, and brainstem regions including the periaqueductal gray, parabrachial nucleus, and Locus coeruleus.[32] In particular, the amygdala has been suggested to have a critical role.[33] The combination of increased activity in the amygdala (fear center) and brainstem along with decreased blood flow and blood sugar in the brain can lead to decreased activity in the prefrontal cortex (PFC) region of the brain.[34] There is evidence that having an anxiety disorder increases the risk of cardiovascular disease (CVD).[35] Those affected also have a reduction in heart rate variability.[35] ### Cardiovascular disease[edit] People who have been diagnosed with panic disorder have approximately double the risk of coronary heart disease.[36] Certain stress responses to depression also have been shown to increase the risk and those diagnosed with both depression and panic disorder are nearly three times more at risk.[36] ## Diagnosis[edit] DSM-5 diagnostic criteria for a panic attack include a discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within minutes: * Palpitations, and/or accelerated heart rate * Sweating * Trembling or shaking * Sensations of shortness of breath or being smothered * Feeling of choking * Chest pain or discomfort * Nausea or abdominal distress * Feeling dizzy, unsteady, lightheaded, or faint * Derealization (feelings of unreality) or depersonalization (being detached from oneself) * Fear of losing control or going insane * Sense of impending doom * Paresthesias (numbness or tingling sensations) * Chills or hot flashes In DSM-5, culture-specific symptoms (e.g., tinnitus, neck soreness, headache, and uncontrollable screaming or crying) may be seen. Such symptoms should not count as one of the four required symptoms. Some or all of these symptoms can be found in the presence of a pheochromocytoma. Screening tools such as the Panic Disorder Severity Scale can be used to detect possible cases of disorder and suggest the need for a formal diagnostic assessment.[37][38] ## Treatment[edit] Panic disorder can be effectively treated with a variety of interventions, including psychological therapies and medication.[9] Cognitive-behavioral therapy has the most complete and longest duration of effect, followed by specific selective serotonin reuptake inhibitors.[39] A 2009 review found positive results from therapy and medication and a much better result when the two were combined.[40] ### Lifestyle changes[edit] Caffeine may cause or exacerbate panic anxiety. Anxiety can temporarily increase during withdrawal from caffeine and various other drugs.[41] Increased and regimented aerobic exercise such as running has been shown to have a positive effect on combating panic anxiety. There is evidence that suggests that this effect is correlated to the release of exercise-induced endorphins and the subsequent reduction of the stress hormone cortisol.[42] There remains a chance of panic symptoms becoming triggered or being made worse due to increased respiration rate that occurs during aerobic exercise. This increased respiration rate can lead to hyperventilation and hyperventilation syndrome, which mimics symptoms of a heart attack, thus inducing a panic attack.[43] The benefits of incorporating an exercise regimen have shown the best results when paced accordingly.[44] Muscle relaxation techniques are useful to some individuals. These can be learned using recordings, videos, or books. While muscle relaxation has proved to be less effective than cognitive-behavioral therapies in controlled trials, many people still find at least temporary relief from muscle relaxation.[14] ### Breathing exercises[edit] In the great majority of cases, hyperventilation is involved, exacerbating the effects of the panic attack. Breathing retraining exercise helps to rebalance the oxygen and CO2 levels in the blood.[45] David D. Burns recommends breathing exercises for those suffering from anxiety. One such breathing exercise is a 5-2-5 count. Using the stomach (or diaphragm)—and not the chest—inhale (feel the stomach come out, as opposed to the chest expanding) for 5 seconds. As the maximal point at inhalation is reached, hold the breath for 2 seconds. Then slowly exhale, over 5 seconds. Repeat this cycle twice and then breathe 'normally' for 5 cycles (1 cycle = 1 inhale + 1 exhale). The point is to focus on breathing and relax the heart rate. Regular diaphragmatic breathing may be achieved by extending the out-breath by counting or humming.[citation needed] Although breathing into a paper bag was a common recommendation for short-term treatment of symptoms of an acute panic attack,[46] it has been criticized as inferior to measured breathing, potentially worsening the panic attack and possibly reducing needed blood oxygen.[47][48] While the paper bag technique increases needed carbon dioxide and so reduces symptoms, it may excessively lower oxygen levels in the bloodstream. Capnometry, which provides exhaled CO2 levels, may help guide breathing.[49][50] ### Therapy[edit] According to the American Psychological Association, "most specialists agree that a combination of cognitive and behavioral therapies are the best treatment for panic disorder. Medication might also be appropriate in some cases."[51] The first part of therapy is largely informational; many people are greatly helped by simply understanding exactly what panic disorder is and how many others suffer from it. Many people who suffer from panic disorder are worried that their panic attacks mean they are "going crazy" or that the panic might induce a heart attack. Cognitive restructuring helps people replace those thoughts with more realistic, positive ways of viewing the attacks.[52] Avoidance behavior is one of the key aspects that prevent people with frequent panic attacks from functioning healthily.[14] Exposure therapy,[53] which includes repeated and prolonged confrontation with feared situations and body sensations, helps weaken anxiety responses to these external and internal stimuli and reinforce realistic ways of viewing panic symptoms. In deeper level psychoanalytic approaches, in particular object relations theory, panic attacks are frequently associated with splitting (psychology), paranoid-schizoid and depressive positions, and paranoid anxiety. They are often found comorbid with borderline personality disorder and child sexual abuse. Paranoid anxiety may reach the level of a persecutory anxiety state.[54] Meditation may also be helpful in the treatment of panic disorders.[55] There was a meta-analysis of the comorbidity of panic disorders and agoraphobia. It used exposure therapy to treat patients over a period. Hundreds of patients were used in these studies and they all met the DSM-IV criteria for both of these disorders.[56] A result was that thirty-two percent of patients had a panic episode after treatment. They concluded that the use of exposure therapy has lasting efficacy for a client who is living with a panic disorder and agoraphobia.[56] The efficacy of group therapy treatment over conventional individual therapy for people with panic disorder with or without agoraphobia appears similar.[57] ### Medication[edit] Medication options for panic attacks typically include benzodiazepines and antidepressants. Benzodiazepines are being prescribed less often because of their potential side effects, such as dependence, fatigue, slurred speech, and memory loss.[58] Antidepressant treatments for panic attacks include selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors (MAOIs). SSRIs in particular tend to be the first drug treatment used to treat panic attacks. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants appear similar for short-term efficacy.[59] SSRIs carry a relatively low risk since they are not associated with much tolerance or dependence, and are difficult to overdose with. TCAs are similar to SSRIs in their many advantages but come with more common side effects such as weight gain and cognitive disturbances. They are also easier to overdose on. MAOIs are generally suggested for patients who have not responded to other forms of treatment.[60] While the use of drugs in treating panic attacks can be very successful, it is generally recommended that people also be in some form of therapy, such as cognitive-behavioral therapy. Drug treatments are usually used throughout the duration of panic attack symptoms and discontinued after the patient has been free of symptoms for at least six months. It is usually safest to withdraw from these drugs gradually while undergoing therapy.[14] While drug treatment seems promising for children and adolescents, they are at an increased risk of suicide while taking these medications and their well-being should be monitored closely.[60] ## Prognosis[edit] Roughly one-third are treatment-resistant.[61] These people continue to have panic attacks and various other panic disorder symptoms after receiving treatment.[61] Many people being treated for panic attacks begin to experience limited symptom attacks. These panic attacks are less comprehensive, with fewer than four bodily symptoms being experienced.[9] It is not unusual to experience only one or two symptoms at a time, such as vibrations in their legs, shortness of breath, or an intense wave of heat traveling up their bodies, which is not similar to hot flashes due to estrogen shortage. Some symptoms, such as vibrations in the legs, are sufficiently different from any normal sensation that they indicate a panic disorder. Other symptoms on the list can occur in people who may or may not have panic disorder. Panic disorder does not require four or more symptoms to all be present at the same time. Causeless panic and racing heartbeat are sufficient to indicate a panic attack.[9] ## Epidemiology[edit] In Europe, about 3% of the population has a panic attack in a given year while in the United States they affect about 11%.[2] They are more common in females than in males.[2] They often begin during puberty or early adulthood.[2] Children and older people are less commonly affected.[2] A meta-analysis was conducted on data collected about twin studies and family studies on the link between genes and panic disorder. The researchers also examined the possibility of a link to phobias, obsessive-compulsive disorder (OCD), and generalized anxiety disorder. The researchers used a database called MEDLINE to accumulate their data.[62] The results concluded that the aforementioned disorders have a genetic component and are inherited or passed down through genes. For the non-phobias, the likelihood of inheriting is 30–40%, and for the phobias, it was 50–60%.[62] ## See also[edit] * Nervous breakdown * Panic ## References[edit] 1. ^ a b "Anxiety Disorders". NIMH. March 2016. Archived from the original on 29 September 2016. Retrieved 1 October 2016. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders (5th ed.), Arlington: American Psychiatric Publishing, pp. 214–217, ISBN 978-0-89042-555-8 3. ^ a b Bandelow, Borwin; Domschke, Katharina; Baldwin, David (2013). Panic Disorder and Agoraphobia. OUP Oxford. p. Chapter 1. ISBN 978-0-19-100426-1. Archived from the original on 20 December 2016. 4. ^ a b Craske, Michelle G; Stein, Murray B (December 2016). "Anxiety". The Lancet. 388 (10063): 3048–3059. doi:10.1016/S0140-6736(16)30381-6. PMID 27349358. S2CID 208789585. 5. ^ a b "Panic Disorder: When Fear Overwhelms". NIMH. 2013. Archived from the original on 4 October 2016. Retrieved 1 October 2016. 6. ^ a b c Geddes, John; Price, Jonathan; McKnight, Rebecca (2012). Psychiatry. OUP Oxford. p. 298. ISBN 978-0-19-923396-0. Archived from the original on 4 October 2016. 7. ^ Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y.-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian (7 June 2018). "International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology". European Heart Journal. 39 (22): 2032–2046. doi:10.1093/eurheartj/ehy076. PMC 5991216. PMID 29850871. 8. ^ Roth, Walton T. (January 2010). "Diversity of effective treatments of panic attacks: what do they have in common?". Depression and Anxiety. 27 (1): 5–11. doi:10.1002/da.20601. PMID 20049938. S2CID 31719106. 9. ^ a b c d e f Bourne, E. (2005). The Anxiety and Phobia Workbook, 4th Edition: New Harbinger Press.[page needed] 10. ^ Klerman, Gerald L.; Hirschfeld, Robert M. A.; Weissman, Myrna M. (1993). Panic Anxiety and Its Treatments: Report of the World Psychiatric Association Presidential Educational Program Task Force. American Psychiatric Association. p. 44. ISBN 978-0-88048-684-2. 11. ^ Cosci, Fiammetta (June 2012). "The psychological development of panic disorder: implications for neurobiology and treatment". Revista Brasileira de Psiquiatria. 34: S09–S31. doi:10.1590/s1516-44462012000500003. PMID 22729447. 12. ^ Davies, Matthew N.; Verdi, Serena; Burri, Andrea; Trzaskowski, Maciej; Lee, Minyoung; Hettema, John M.; Jansen, Rick; Boomsma, Dorret I.; Spector, Tim D. (14 August 2015). "Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression". PLOS ONE. 10 (8): e0134865. Bibcode:2015PLoSO..1034865D. doi:10.1371/journal.pone.0134865. PMC 4537268. PMID 26274327. 13. ^ Nolen-Hoeksema, Susan (2013). (Ab)normal Psychology (6th ed.). McGraw Hill. ISBN 978-0-07-803538-8.[page needed] 14. ^ a b c d Taylor, C Barr (22 April 2006). "Panic disorder". BMJ. 332 (7547): 951–955. doi:10.1136/bmj.332.7547.951. PMC 1444835. PMID 16627512. 15. ^ William T. O‘Donohue,· Lorraine T. Benuto, Lauren Woodward Tolle (eds, 2013). Handbook of Adolescent Health Psychology, Springer, New York. ISBN 978-1-4614-6632-1. Page 511 16. ^ Maddock, Richard J.; Carter, Cameron S. (May 1991). "Hyperventilation-induced panic attacks in panic disorder with agoraphobia". Biological Psychiatry. 29 (9): 843–854. doi:10.1016/0006-3223(91)90051-m. PMID 1904781. S2CID 36334143. 17. ^ "Archived copy". Archived from the original on 21 August 2016. Retrieved 2016-08-14.CS1 maint: archived copy as title (link) 18. ^ Zvolensky, Michael J.; Gonzalez, Adam; Bonn-Miller, Marcel O.; Bernstein, Amit; Goodwin, Renee D. (February 2008). "Negative reinforcement/negative affect reduction cigarette smoking outcome expectancies: Incremental validity for anxiety focused on bodily sensations and panic attack symptoms among daily smokers". Experimental and Clinical Psychopharmacology. 16 (1): 66–76. doi:10.1037/1064-1297.16.1.66. PMID 18266553. 19. ^ Gorman, JM; Kent, JM; Sullivan, GM; Coplan, JD (April 2000). "Neuroanatomical hypothesis of panic disorder, revised". The American Journal of Psychiatry. 157 (4): 493–505. doi:10.1176/appi.ajp.157.4.493. PMID 10739407. 20. ^ Panic Disorder – familydoctor.org Archived 3 February 2014 at the Wayback Machine 21. ^ "Anxiety Disorders" Archived 12 April 2014 at the Wayback Machine 22. ^ Inglis, Sally C; Clark, Robyn A; Dierckx, Riet; Prieto-Merino, David; Cleland, John GF (31 October 2015). "Structured telephone support or non-invasive telemonitoring for patients with heart failure". Cochrane Database of Systematic Reviews (10): CD007228. doi:10.1002/14651858.CD007228.pub3. hdl:2328/35732. PMID 26517969. 23. ^ "Agoraphobia". MayoClinic.com. 21 April 2011. Archived from the original on 24 June 2012. Retrieved 2012-06-15. 24. ^ Leicht, Gregor; Mulert, Christoph; Eser, Daniela; Sämann, Philipp G.; Ertl, Matthias; Laenger, Anna; Karch, Susanne; Pogarell, Oliver; Meindl, Thomas; Czisch, Michael; Rupprecht, Rainer (2013). "Benzodiazepines Counteract Rostral Anterior Cingulate Cortex Activation Induced by Cholecystokinin-Tetrapeptide in Humans". Biological Psychiatry. 73 (4): 337–44. doi:10.1016/j.biopsych.2012.09.004. PMID 23059050. S2CID 23586549. 25. ^ Moreira, Fabrício A.; Gobira, Pedro H.; Viana, Thércia G.; Vicente, Maria A.; Zangrossi, Hélio; Graeff, Frederico G. (2013). "Modeling panic disorder in rodents". Cell and Tissue Research. 354 (1): 119–25. doi:10.1007/s00441-013-1610-1. PMID 23584609. S2CID 14699738. 26. ^ a b c d e Bystritsky, Alexander; Khalsa, Sahib S.; Cameron, Michael E.; Schiffman, Jason (2013). "Current Diagnosis and Treatment of Anxiety Disorders". Pharmacy and Therapeutics. 38 (1): 30–57. PMC 3628173. PMID 23599668. 27. ^ Montoya, Alonso; Bruins, Robert; Katzman, Martin A; Blier, Pierre (1 March 2016). "The noradrenergic paradox: implications in the management of depression and anxiety". Neuropsychiatric Disease and Treatment. 12: 541–557. doi:10.2147/NDT.S91311. PMC 4780187. PMID 27042068. 28. ^ Vollmer, L L; Strawn, J R; Sah, R (May 2015). "Acid–base dysregulation and chemosensory mechanisms in panic disorder: a translational update". Translational Psychiatry. 5 (5): e572. doi:10.1038/tp.2015.67. PMC 4471296. PMID 26080089. 29. ^ Ueda, Y.; Aizawa, M.; Takahashi, A.; Fujii, M.; Isaka, Y. (8 October 2008). "Exaggerated compensatory response to acute respiratory alkalosis in panic disorder is induced by increased lactic acid production". Nephrology Dialysis Transplantation. 24 (3): 825–828. doi:10.1093/ndt/gfn585. PMID 18940883. 30. ^ Cipolla, Marilyn J. (2009). Control of Cerebral Blood Flow. Morgan & Claypool Life Sciences. 31. ^ Nardi, Antonio Egidio; Freire, Rafael Christophe R. (2016-05-25). Panic Disorder: Neurobiological and Treatment Aspects. Springer. ISBN 978-3-319-12538-1. 32. ^ Shin, Lisa M; Liberzon, Israel (January 2010). "The Neurocircuitry of Fear, Stress, and Anxiety Disorders". Neuropsychopharmacology. 35 (1): 169–191. doi:10.1038/npp.2009.83. PMC 3055419. PMID 19625997. 33. ^ Maren, Stephen (November 2009). "An Acid-Sensing Channel Sows Fear and Panic". Cell. 139 (5): 867–869. doi:10.1016/j.cell.2009.11.008. hdl:2027.42/83231. PMID 19945375. S2CID 18322284. 34. ^ PhD, Andrew M. Leeds (2016-02-03). A Guide to the Standard EMDR Therapy Protocols for Clinicians, Supervisors, and Consultants, Second Edition. Springer Publishing Company. ISBN 978-0-8261-3117-1. 35. ^ a b Chalmers, John A.; Quintana, Daniel S.; Abbott, Maree J.-Anne; Kemp, Andrew H. (11 July 2014). "Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis". Frontiers in Psychiatry. 5: 80. doi:10.3389/fpsyt.2014.00080. PMC 4092363. PMID 25071612. 36. ^ a b Soares-Filho, Gastao L. F.; Arias-Carrion, Oscar; Santulli, Gaetano; Silva, Adriana C.; Machado, Sergio; Nardi, Alexandre M. Valenca and Antonio E.; Nardi, AE (31 July 2014). "Chest Pain, Panic Disorder and Coronary Artery Disease: A Systematic Review". CNS & Neurological Disorders - Drug Targets. 13 (6): 992–1001. doi:10.2174/1871527313666140612141500. PMID 24923348. 37. ^ Houck, P. R.; Spiegel, D. A.; Shear, M. K.; Rucci, P. (2002). "Reliability of the self-report version of the Panic Disorder Severity Scale". Depression and Anxiety. 15 (4): 183–185. doi:10.1002/da.10049. PMID 12112724. S2CID 25176812. 38. ^ Shear, M. K.; Rucci, P.; Williams, J.; Frank, E.; Grochocinski, V.; Vander Bilt, J.; Houck, P.; Wang, T. (2001). "Reliability and validity of the Panic Disorder Severity Scale: Replication and extension". Journal of Psychiatric Research. 35 (5): 293–296. doi:10.1016/S0022-3956(01)00028-0. PMID 11591432. 39. ^ Generalised anxiety disorder and panic disorder in adults: management. Clinical Guideline 113. National Institute for Health and Care Excellence. 26 July 2019. ISBN 978-1-4731-2854-5. 40. ^ Bandelow, Borwin; Seidler-Brandler, Ulrich; Becker, Andreas; Wedekind, Dirk; Rüther, Eckart (January 2007). "Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders". The World Journal of Biological Psychiatry. 8 (3): 175–187. doi:10.1080/15622970601110273. PMID 17654408. S2CID 8504020. 41. ^ American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev., p. 479). Washington, D.C.: American Psychiatric Association.[page needed] 42. ^ "3 Tips for Using Exercise to Shrink Anxiety". 2013-07-17. Archived from the original on 20 April 2015. Retrieved 2015-04-14.[full citation needed] 43. ^ MedlinePlus Encyclopedia: Hyperventilation 44. ^ "Archived copy". Archived from the original on 23 April 2015. Retrieved 2015-04-14.CS1 maint: archived copy as title (link)[full citation needed] 45. ^ "Hyperventilation Syndrome]". 28 November 2016. Archived from the original on 13 July 2017. Retrieved 2017-09-18. 46. ^ Breathing in and out of a paper bag Archived 21 October 2007 at the Wayback Machine 47. ^ Bergeron, J. David; Le Baudour, Chris (2009). "Chapter 9: Caring for Medical Emergencies". First Responder (8 ed.). New Jersey: Pearson Prentice Hall. p. 262. ISBN 978-0-13-614059-7. "Do not use a paper bag in an attempt to treat hyperventilation. These patients can often be cared for with low-flow oxygen and lots of reassurance" 48. ^ Hyperventilation Syndrome – Can I treat hyperventilation syndrome by breathing into a paper bag? Archived 20 January 2013 at the Wayback Machine 49. ^ Craske, Michelle (30 September 2011). "Psychotherapy for panic disorder". Archived from the original on 14 October 2017. Retrieved 29 April 2020. 50. ^ Meuret, Alicia E.; Ritz, Thomas (October 2010). "Hyperventilation in panic disorder and asthma: Empirical evidence and clinical strategies". International Journal of Psychophysiology. 78 (1): 68–79. doi:10.1016/j.ijpsycho.2010.05.006. PMC 2937087. PMID 20685222. 51. ^ "Answers to Your Questions About Panic Disorder". American Psychological Association. 2008. 52. ^ Cramer, K., Post, T., & Behr, M. (January 1989). "Cognitive Restructuring Ability, Teacher Guidance and Perceptual Distracter Tasks: An Aptitude Treatment Interaction Study". Archived from the original on 22 December 2010. Retrieved 2010-11-19.CS1 maint: multiple names: authors list (link) 53. ^ Abramowitz, Jonathan S.; Deacon, Brett J.; Whiteside, Stephen P. H. (17 December 2012). Exposure Therapy for Anxiety: Principles and Practice. Guilford Press. ISBN 978-1-4625-0969-0. Archived from the original on 20 May 2016. 54. ^ Waska, Robert (2010). Treating Severe Depressive and Persecutory Anxiety States: To Transform the Unbearable. Karnac Books. ISBN 978-1855757202.[page needed] 55. ^ Kabat-Zinn, J; Massion, AO; Kristeller, J; Peterson, LG; Fletcher, KE; Pbert, L; Lenderking, WR; Santorelli, SF (July 1992). "Effectiveness of a meditation-based stress reduction program in the treatment of anxiety disorders". American Journal of Psychiatry. 149 (7): 936–943. CiteSeerX 10.1.1.474.4968. doi:10.1176/ajp.149.7.936. PMID 1609875. 56. ^ a b Fava, G. A.; Rafanelli, C.; Grandi, S.; Conti, S.; Ruini, C.; Mangelli, L.; Belluardo, P. (July 2001). "Long-term outcome of panic disorder with agoraphobia treated by exposure". Psychological Medicine. 31 (5): 891–898. doi:10.1017/s0033291701003592. PMID 11459386. 57. ^ Schwartze, Dominique; Barkowski, Sarah; Strauss, Bernhard; Burlingame, Gary M.; Barth, Jürgen; Rosendahl, Jenny (June 2017). "Efficacy of group psychotherapy for panic disorder: Meta-analysis of randomized, controlled trials". Group Dynamics: Theory, Research, and Practice. 21 (2): 77–93. doi:10.1037/gdn0000064. S2CID 152168481. 58. ^ Batelaan, Neeltje M.; Van Balkom, Anton J. L. M.; Stein, Dan J. (April 2012). "Evidence-based pharmacotherapy of panic disorder: an update". The International Journal of Neuropsychopharmacology. 15 (3): 403–415. doi:10.1017/S1461145711000800. PMID 21733234. 59. ^ Bakker, A.; Van Balkom, A. J. L. M.; Spinhoven, P. (2002). "SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis". Acta Psychiatrica Scandinavica. 106 (3): 163–167. doi:10.1034/j.1600-0447.2002.02255.x. PMID 12197851. S2CID 26184300. 60. ^ a b Marchesi, Carlo (March 2008). "Pharmacological management of panic disorder". Neuropsychiatric Disease and Treatment. 4 (1): 93–106. doi:10.2147/ndt.s1557. PMC 2515914. PMID 18728820. 61. ^ a b Freire, Rafael C.; Zugliani, Morena M.; Garcia, Rafael F.; Nardi, Antonio E. (22 January 2016). "Treatment–resistant panic disorder: a systematic review". Expert Opinion on Pharmacotherapy. 17 (2): 159–168. doi:10.1517/14656566.2016.1109628. PMID 26635099. S2CID 9242842. 62. ^ a b Hettema, John M.; Neale, Michael C.; Kendler, Kenneth S. (October 2001). "A Review and Meta-Analysis of the Genetic Epidemiology of Anxiety Disorders". American Journal of Psychiatry. 158 (10): 1568–1578. doi:10.1176/appi.ajp.158.10.1568. PMID 11578982. S2CID 7865025. ## External links[edit] Classification D * ICD-10: F41.0 * ICD-9-CM: 300.01 * MeSH: D016584 * DiseasesDB: 30913 * Panic attack at Curlie [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Panic attack	c0086769	29,962	wikipedia	https://en.wikipedia.org/wiki/Panic_attack	2021-01-18T18:51:26	{"mesh": ["D016584"], "icd-9": ["300.01"], "icd-10": ["F41.0"], "wikidata": ["Q696490"]}
Lymphangiosarcoma SpecialtyOncology Lymphangiosarcoma is a rare cancer which occurs in long-standing cases of primary or secondary lymphedema. It involves either the upper or lower lymphedematous extremities but is most common in upper extremities.[1] Although its name implies lymphatic origin, it is believed to arise from endothelial cells and may be more accurately referred to as angiosarcoma. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Treatment * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Lymphangiosarcoma may present as a purple discoloration or a tender skin nodule in the extremity, typically on the anterior surface. It progresses to an ulcer with crusting to an extensive necrotic focus involving the skin and subcutaneous tissue.[2] It metastasizes quickly. ## Causes[edit] It was previously a relatively common complication of the massive lymphedema of the arm which followed removal of axillary (arm pit) lymph nodes and lymphatic channels as part of the classical Halstedian radical mastectomy, as a treatment for breast cancer. The classical radical mastectomy was abandoned in most areas of the world in the late 1960s to early 1970s, being replaced by the much more conservative modified radical mastectomy and, more recently, by segmental breast tissue excision and radiation therapy. Because of this change in clinical practice lymphedema is now a rarity following breast cancer treatment—and post-mastectomy lymphangiosarcoma is now vanishingly rare. When it occurs following mastectomy it is known as Stewart-Treves syndrome. The pathogenesis of lymphangiosarcoma has not been resolved, however several vague mechanisms have been proposed. Stewart and Treves, proposed that a cancer causing agent is present in lymphedematous limbs.[3] Schreiber et al. proposed that local immunodeficiency as a result of lymphedema results in a "immunologically privileged site" in which the sarcoma is able to develop.[4][5] ## Treatment[edit] The most successful treatment for lymphangiosarcoma is amputation of the affected limb if possible. Chemotherapy may be administered if there is evidence or suspicion of metastatic disease. Evidence supporting the effectiveness of chemotherapy is, in many cases, unclear due to a wide variety of prognostic factors and small sample size. However, there is some evidence to suggest that drugs such as paclitaxel,[6] doxorubicin,[7] ifosfamide, and gemcitabine[8] exhibit antitumor activity. ## See also[edit] * Lymphangioma * Angiosarcoma * Hemangiosarcoma * Stewart-Treves Syndrome * Sarcoma ## References[edit] 1. ^ Hellman S, DeVita VT, Rosenberg S (2001). Cancer: principles & practice of oncology. Philadelphia: Lippincott-Raven. p. 1853. ISBN 0-7817-2229-2. 2. ^ LYMPHEDEMA MANAGEMENT. Academy of Lymphatic Studies 2014. 2014. pp. 26–30. ISBN 978-3131394835. Archived from the original on 26 April 2014. Retrieved 25 April 2014. 3. ^ Stewart FW, Treves N. Lymphangiosarcoma in postmastectomy lymphedema: a report of six cases in elephantiasis chirurgica. Cancer 1948;1:64–81. 4. ^ Chopra, S, Ors, F, Bergin, D MRI of angiosarcoma associated with chronic lymphoedema: Stewart Treves syndrome Br J Radiol 2007 80: e310–313 5. ^ Schreiber H, Barry FM, Russell WC, Macon IV WL, Ponsky JL, Pories WJ. Stewart–Treves Syndrome: a lethal complication of postmastectomy lymphedema and regional immune deficiency. Arch Surgery 1979;114:82–5. 6. ^ Gambini D, Visintin R, Locatelli E, Galassi B, Bareggi C, Runza L, Onida F, Tomirotti M.Tumori. 2009 Nov–Dec;95(6):828–31. Paclitaxel-dependent prolonged and persistent complete remission four years from first recurrence of secondary breast angiosarcoma. Medical Oncology Unit, IRCCS Foundation "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena", Milan, Italy. 7. ^ Verdier E, Carvalho P, Young P, Musette P, Courville P, Joly P. Lymphangiosarcoma treated with liposomal doxorubicin (Caelyx)] Ann Dermatol Venereol. 2007 Oct;134 (10 Pt 1):760–3. French. 8. ^ Sher T, Hennessy BT, Valero V, Broglio K, Woodward WA, Trent J, Hunt KK, Hortobagyi GN, Gonzalez-Angulo AM.Primary angiosarcomas of the breast. Cancer. 2007 Jul 1;110(1):173–8. ## External links[edit] Classification D * ICD-O: 9170/3 * MeSH: D008204 * DiseasesDB: 29095 * http://www.lymphedemapeople.com/thesite/lymphedema_lymphangiosarcoma.htm * v * t * e Tumours of blood vessels Blood vessel * Hemangiosarcoma * Blue rubber bleb nevus syndrome * Hemangioendothelioma * Composite * Endovascular papillary * Epithelioid * Kaposiform * Infantile * Retiform) * Spindle cell * Proliferating angioendotheliomatosis * Hemangiopericytoma * Venous lake * Kaposi's sarcoma * African cutaneous * African lymphadenopathic * AIDS-associated * Classic * Immunosuppression-associated * Hemangioblastoma * Hemangioma * Capillary * Cavernous * Glomeruloid * Microvenular * Targeted hemosiderotic * Angioma * Cherry * Seriginosum * Spider * Tufted * Universal angiomatosis * Angiokeratoma * of Mibelli * Angiolipoma * Pyogenic granuloma Lymphatic * Lymphangioma/lymphangiosarcoma * Lymphangioma circumscriptum * Acquired progressive lymphangioma * PEComa * Lymphangioleiomyomatosis * Cystic hygroma * Multifocal lymphangioendotheliomatosis * Lymphangiomatosis Either * Angioma/angiosarcoma * Angiofibroma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Lymphangiosarcoma	c0024224	29,963	wikipedia	https://en.wikipedia.org/wiki/Lymphangiosarcoma	2021-01-18T18:41:12	{"gard": ["8706"], "mesh": ["D008204"], "umls": ["C0024224"], "wikidata": ["Q3913024"]}
## Description Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006). For a discussion of genetic heterogeneity of intracranial berry aneurysms, see ANIB1 (105800). Mapping In a genomewide association study of 920 Finnish patients with intracranial aneurysm and 985 controls, Bilguvar et al. (2008) found a significant association with rs10958409 on chromosome 8q. The association was replicated in a Dutch cohort of 781 cases and 6,424 controls and a Japanese cohort of 495 cases and 676 controls. The combined p value was 1.4 x 10(-10) with an odds ratio of 1.36. Yasuno et al. (2010) performed genomewide analysis of intracranial aneurysm in an expanded cohort from the study of Bilguvar et al. (2008) with discovery and replication cohorts from Europe and Japan comprising a total of 5,891 cases and 14,181 controls. Significant association was found with rs9298506 in the 3-prime interval of SOX17 (610928) on chromosome 8q11.23-q12.1 (odds ratio of 1.28, p = 1.3 x 10(-12)). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ANEURYSM, INTRACRANIAL BERRY, 10	c1862932	29,964	omim	https://www.omim.org/entry/612587	2019-09-22T16:01:09	{"doid": ["0060228"], "mesh": ["C566284"], "omim": ["105800", "612587"], "orphanet": ["231160"], "synonyms": ["Familial berry aneurysm", "Familial intracranial saccular aneurysm"]}
A number sign (#) is used with this entry because of evidence that this form of X-linked mental retardation is caused by mutation in the BRWD3 gene (300553). Clinical Features Field et al. (2007) identified 3 families with X-linked mental retardation (XLMR) associated with macrocephaly. The first family included a nephew and an uncle with mild to moderate metal retardation and an aunt with mild cognitive difficulties during early childhood. The height, weight, and head circumference of the nephew were consistently greater than the 97th percentile. His height at age 17 years was 190 cm and head circumference was 62 cm. The right testis was undescended and was brought down by orchiopexy at age 13 months. Muscular hypotonia was noted in early life. Facial features included a long face, pointed chin, and large, prominent ears. The uncle's height was 187 cm and head circumference was 59 cm, with frontal bossing, large and prominent ears, and a pointed chin. His build was thin, with midthoracic kyphosis and minimal pectus excavatum. The second family included 2 half-brothers who shared the same mother, who was reported to have an intellectual disability and head circumference at the 97th percentile. The elder had an undescended testis; the younger had mild muscular hypotonia. Evaluated at ages 13 and 9 years, both had head circumference at greater than the 97th percentile, frontal bossing, pointed chin, and prominent ears with cupped helices. The third family was originally reported by Gedeon et al. (1994) (as family 'E') and included 3 brothers, a cousin, and an uncle, all with borderline to mild mental retardation. None of the affected males had macrocephaly or tall stature in childhood. They had large, prominent ears, triangular face, and pointed chin. Molecular Genetics In the course of systematic screening of the X-chromosome coding sequences in 250 families with nonsyndromic XLMR, Field et al. (2007) identified 2 families with truncating mutations in BRWD3. In both families, the mutation segregated with the phenotype in affected males. In a family in which an uncle and nephew had XLMR with macrocephaly, Field et al. (2007) described a splice site mutation in the BRWD3 gene (300553.0001). Three carrier females were identified and all 3 of the chromosomes carrying the mutation were preferentially inactivated. In a family in which 2 half-brothers had LXMR with macrocephaly, Field et al. (2007) identified a 1-bp insertion in the BRWD3 gene (300553.0002). In the family described by Gedeon et al. (1994), Field et al. (2007) identified a missense mutation in BRWD3 (K1596E; 300553.0003). Tarpey et al. (2009) sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation. In 2 individuals they identified nonrecurrent truncating mutations in the BRWD3 gene that segregated with mental retardation in their families. In addition to X-linked mental retardation, affected individuals had macrocephaly. INHERITANCE \- X-linked recessive HEAD & NECK Head \- Macrocephaly Face \- Prominent forehead \- Long face Ears \- Large ears \- Cupped ears GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKELETAL Feet \- Pes planus NEUROLOGIC Central Nervous System \- Mental retardation, mild-moderate \- Hypotonia \- Speech delay MOLECULAR BASIS \- Caused by mutation in the bromodomain-and WD repeat domain-containing protein 3 gene (BRWD3, 300553.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MENTAL RETARDATION, X-LINKED 93	c1970841	29,965	omim	https://www.omim.org/entry/300659	2019-09-22T16:19:51	{"mesh": ["C567066"], "omim": ["300659"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, X-LINKED, WITH MACROCEPHALY"]}
Pulmonary atresia with intact ventricular septum accounts for less than 3% of all congenital heart defects (Grossfeld et al., 1997). Chitayat et al. (1992) reported 2 sisters with hypoplastic right heart and pulmonary atresia. The first sib was found in the newborn period to have this abnormality. An attempt at surgical repair was unsuccessful. In the next pregnancy, fetal echocardiography at 22 weeks of gestation demonstrated the same cardiac abnormalities, which were confirmed at autopsy in the fetus. No other malformations were found in either case and no other relatives were affected. Grossfeld et al. (1997) reported 2 first cousins with pulmonary atresia and intact ventricular septum. The first had a severely hypoplastic right ventricle and tricuspid valve and a restrictive atrial septal defect. She died at age 12 days. The patient's maternal aunt delivered a son with congenital heart disease 23 years earlier. At that time, pulmonary atresia with intact ventricular septum, hypoplastic tricuspid valve and right ventricle, and patent ductus arteriosus were noted. That patient died at age 5 months. Grossfeld et al. (1997) suggested autosomal dominant inheritance with incomplete penetrance. De Stefano et al. (2008) reported monozygotic twin sisters with pulmonary valve atresia and intact ventricular septum. The girls died of respiratory failure at age 3 and 7 days, respectively. Echocardiography and postmortem examination of both patients showed pulmonary valve atresia with 3 fused valves and no identifiable lumen. There was generalized cardiomegaly, right atrial dilatation, right ventricular hypertrophy, and small right ventricular chambers. The tricuspid valves were dysplastic with 2 thick leaflets attached to the right ventricular endocardium. One twin also had aortic stenosis with a bicuspid aortic valve and thick, dysplastic leaflets. Molecular analysis identified a biallelic 55-kb deletion of chromosome 20q13.12 in both girls. The unaffected nonconsanguineous parents were each heterozygous for 1 of the deletions. Cardiac \- Hypoplastic right heart \- Pulmonary atresia Inheritance \- ? Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM	c0344975	29,966	omim	https://www.omim.org/entry/265150	2019-09-22T16:23:01	{"mesh": ["C562832"], "omim": ["265150"], "orphanet": ["1208"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Ankle flare" – news · newspapers · books · scholar · JSTOR (November 2014) (Learn how and when to remove this template message) Ankle flare Diagnostic methoddeep vein thrombosis A "flare" is a spreading area of redness or flush. It is the second reaction in the triple response to injury and is due to dilatation of the arteriole. When this flare occurs around the ankle, it is called an ankle flare. The condition is also known as a malleolar flare, in reference to the malleolus, the bony prominence on each side of the ankle. Ankle flares are often caused by venous ulcer, due to deep vein thrombosis or varicose veins. It is considered to be an early sign of advanced venous disease.[1] Treatment involves management of the underlying condition, along with supportive care. ## See also[edit] * Corona phlebectatica ## References[edit] 1. ^ John J. Bergan, Nisha Bunke-Paquette. The Vein Book. Oxford University Press, 2014. This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ankle flare	c2733181	29,967	wikipedia	https://en.wikipedia.org/wiki/Ankle_flare	2021-01-18T18:38:42	{"umls": ["C2733181"], "wikidata": ["Q4766081"]}
A mild to moderate form of phenylketouria (PKU), an inborn error of amino acid metabolism, characterized by blood phenylalanine concentrations of 600-1,200 micromol/L and manifests with reduced cognitive function and behavioral and developmental disorders. Dietary phenylalanine tolerance is 400-600 mg/day. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mild phenylketonuria	None	29,968	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79253	2021-01-23T17:23:49	{"gard": ["10324"], "icd-10": ["E70.1"], "synonyms": ["Mild PKU", "Variant PKU", "Variant phenylketonuria", "mPKU"]}
Mycosis fungoides is the most common form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. Although the skin is involved, the skin cells themselves are not cancerous. Mycosis fungoides usually occurs in adults over age 50, although affected children have been identified. Mycosis fungoides may progress slowly through several stages, although not all people with the condition progress through all stages. Most affected individuals initially develop skin lesions called patches, which are flat, scaly, pink or red areas on the skin that can be itchy. Cancerous T cells, which cause the formation of patches, are found in these lesions. The skin cells themselves are not cancerous; the skin problems result when cancerous T cells move from the blood into the skin. Patches are most commonly found on the lower abdomen, upper thighs, buttocks, and breasts. They can disappear and reappear or remain stable over time. In some affected individuals, patches progress to plaques, the next stage of mycosis fungoides. Plaques are raised lesions that are usually reddish, purplish, or brownish in color and itchy. Plaques commonly occur in the same body regions as patches. While some plaques arise from patches, others develop on their own, and an affected person can have both patches and plaques simultaneously. As with patches, cancerous T cells are found in plaques. Plaques can remain stable or can develop into tumors. Not everyone with patches or plaques develops tumors. The tumors in mycosis fungoides, which are composed of cancerous T cells, are raised nodules that are thicker and deeper than plaques. They can arise from patches or plaques or occur on their own. Mycosis fungoides was so named because the tumors can resemble mushrooms, a type of fungus. Common locations for tumor development include the upper thighs and groin, breasts, armpits, and the crook of the elbow. Open sores may develop on the tumors, often leading to infection. Although rare, the cancerous T cells can spread to other organs, including the lymph nodes, spleen, liver, and lungs. Spread to other organs can occur in any stage of mycosis fungoides but is most common in the tumor stage. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer. ## Frequency Mycosis fungoides occurs in about 1 in 100,000 to 350,000 individuals. It accounts for approximately 70 percent of cutaneous T-cell lymphomas. For unknown reasons, mycosis fungoides affects males nearly twice as often as females. In the United States, there are an estimated 3.6 cases per million people each year. The condition has been found in regions around the world. ## Causes The cause of mycosis fungoides is unknown. Most affected individuals have one or more chromosomal abnormalities, such as the loss or gain of genetic material. These abnormalities occur during a person's lifetime and are found only in the DNA of cancerous cells. Abnormalities have been found on most chromosomes, but some regions are more commonly affected than others. People with this condition tend to have additions of DNA in regions of chromosomes 7 and 17 or loss of DNA from regions of chromosomes 9 and 10. It is unclear whether these genetic changes play a role in mycosis fungoides, although the tendency to acquire chromosome abnormalities (chromosomal instability) is a feature of many cancers. It can lead to genetic changes that allow cells to grow and divide uncontrollably. Other research suggests that certain variants of HLA class II genes are associated with mycosis fungoides. HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. The specific variants are inherited through families. Certain variations of HLA genes may affect the risk of developing mycosis fungoides or may impact progression of the disorder. It is possible that other factors, such as environmental exposure or certain bacterial or viral infections, are involved in the development of mycosis fungoides. However, the influence of genetic and environmental factors on the development of this complex disorder remains unclear. ## Inheritance Pattern The inheritance pattern of mycosis fungoides has not been determined. Although the condition has been found in multiple members of more than a dozen families, it most often occurs in people with no history of the disorder in their family and is typically not inherited. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mycosis fungoides	c0026948	29,969	medlineplus	https://medlineplus.gov/genetics/condition/mycosis-fungoides/	2021-01-27T08:25:07	{"gard": ["3863"], "mesh": ["D009182"], "omim": ["254400"], "synonyms": []}
Medical condition Autonomic dysreflexia Other namesAutonomic hyperreflexia[1] SpecialtyNeurology Autonomic dysreflexia (AD), also previously known as mass reflex,[2] is a potential medical emergency classically characterized by uncontrolled hypertension and bradycardia, although tachycardia is known to commonly occur.[3][4] AD occurs most often in individuals with spinal cord injuries with lesions at or above the T6 spinal cord level, although it has been reported in patients with lesions as low as T10.[5] Guillain–Barré syndrome may also cause Autonomic Dysreflexia.[1] The uncontrolled hypertension in AD may result in mild symptoms, such as sweating above the lesion level, goosebumps, blurred vision, or headache; However, severe hypertension may result in potentially life-threatening complications including seizure, intracranial bleed, or retinal detachment.[3] AD is triggered by either noxious or non-noxious stimuli, resulting in sympathetic stimulation and hyperactivity.[6] The most common causes include bladder or bowel over-distension, from urinary retention and fecal compaction, respectively.[7] The resulting sympathetic surge transmits through intact peripheral nerves, resulting in systemic vasoconstriction below the level of the spinal cord lesion.[8] The peripheral arterial vasoconstriction and hypertension activates the baroreceptors, resulting in a parasympathetic surge originating in the central nervous system to inhibit the sympathetic outflow; however, the parasympathetic signal is unable to transmit below the level of the spinal cord lesion.[8] This results in bradycardia, vasodilation, flushing, pupillary constriction and nasal stuffiness above the spinal lesion, while there's piloerection, pale and cool skin below the lesion due to the prevailing sympathetic outflow.[8] Initial treatment involves sitting the patient upright, removing any constrictive clothing (including abdominal binders and support stockings), rechecking blood pressure frequently, and then checking for and removing the inciting issue, which may require urinary catheterization or bowel disimpaction.[3][2] If systolic blood pressure remains elevated (over 150 mm Hg) after initial steps, fast-acting short-duration antihypertensives are considered,[9] while other inciting causes must be investigated for the symptoms to resolve.[3] Prevention of AD involves educating the patient, family and caregivers of the precipitating cause, if known, and how to avoid it, as well as other triggers.[2] Since bladder and bowel are common causes, prevention involves routine bladder and bowel programs and urological follow-up for cystoscopy/urodynamic studies.[3] ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Causes * 2.1 Pain * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] This condition is distinct and usually episodic, with the people potentially experiencing remarkably high blood pressure, intense headaches, profuse sweating, facial erythema, goosebumps, nasal stuffiness, a "feeling of doom" or apprehension, and blurred vision.[5] An elevation of 20 mm Hg over baseline systolic blood pressure, with a potential source below the neurological level of injury, meets the current definition of dysreflexia.[10] ### Complications[edit] Autonomic dysreflexia can become chronic and recurrent, often in response to longstanding medical problems like soft tissue pressure injuries or hemorrhoids. Long term therapy may include alpha blockers or calcium channel blockers. Complications of severe acute hypertension can include seizures, pulmonary edema, myocardial infarction, or cerebral hemorrhage. Additional organs that may be affected include the kidneys and retinas of the eyes.[5] ## Causes[edit] The first episode of autonomic dysreflexia may occur weeks to years after spinal cord injury takes place, but most people at risk (80%) develop their first episode within the first year after injury. Early AD tends to be associated with less severe increases in blood pressure. One common causative factor may be an undetected urinary tract infection. The difficulty in assessing this may be complicated with the usage of indwelling or suprapubic catheters. Other causes include medication side effects and various disease processes. The use of stimulants such as cocaine and amphetamines which can result in urinary retention, and the use of CNS depressants and other psychoactive drugs can also lead to urinary retention and constipation thus leading to autonomic dysreflexia when in use over an extended period of time. ### Pain[edit] Current scientific literature suggests that noxious (painful) stimuli are the primary initiators of AD. (Note: Not all noxious stimuli will cause AD. Some otherwise severe noxious stimuli in normal people, e.g. broken bones, may not result in AD, and may in fact even go unnoticed.) However, different studies have found that activation of pain receptors in muscle and skin below the lesion in spinal cord injured individuals did not trigger AD.[11][12] These studies suggests that not all noxious stimuli are reliable triggers of AD, and because non-noxious stimuli can also trigger AD, attribution of an episode of AD to noxious stimuli may cause clinicians to overlook underlying non-noxious triggers. As a result, non-noxious trigger factors remain undetected, prolonging an episode of AD. They concluded that when deducing the potential causes of AD it is important to consider non-noxious sources of stimulation in addition to noxious triggers. Current assessment of autonomic dysreflexia in patients with known causative factors include palpation of the bladder and bowel and can also include bladder scan. ## Mechanism[edit] Supraspinal vasomotor neurons send projections to the intermediolateral cell column, which is composed of sympathetic preganglionic neurons (SPN) through the T1-L2 segments.[7] The supraspinal neurons act on the SPN and its tonic firing, modulating its action on the peripheral sympathetic chain ganglia and the adrenal medulla.[7] The sympathetic ganglia act directly on the blood vessels they innervate throughout the body, controlling vessel diameter and resistance, while the adrenal medulla indirectly controls the same action through the release of epinephrine and norepinephrine.[7] The descending autonomic pathways, which are responsible for the supraspinal communication with the SPN, are interrupted resulting in decreased sympathetic outflow below the level of the injury.[7] In this circumstance, the SPN is controlled only by spinal influences.[7] The first couple of weeks after a spinal injury, the decreased sympathetic outflow causes reduced blood pressure and sympathetic reflex.[7] Eventually, synaptic reorganization and plasticity of SPN develops into an overly sensitive state, which results in abnormal reflex activation of SPN due to afferent stimuli, such as bowel or bladder distension.[7] Reflex activation results in systemic vasoconstriction below the spinal cord disruption. The peripheral arterial vasoconstriction and hypertension activates the baroreceptors, resulting in a parasympathetic surge originating in the central nervous system, which inhibits the sympathetic outflow; however, the parasympathetic signal is unable to transmit below the level of the spinal cord lesion.[8] This results in vasodilation, flushing, pupillary constriction and nasal stuffiness above the spinal lesion, while there's piloerection, pale and cool skin below the lesion due to the prevailing sympathetic outflow.[8] Reason this issue is much more prominent for lesions at or above the T6 level is because the Splanchnic nerves emerge from the T5 level and below. Loss of brain's control over T6 and below causes splanchnic arteries to reflexively vasoconstrict and since the Splanchnic arteries are the body's largest reservoir for circulating blood, their vasocontriction dramatically effects the blood pressure of the body. ## Diagnosis[edit] The symptoms are usually not subtle, although asymptomatic events have been documented. Autonomic dysreflexia differs from autonomic instability, the various modest cardiac and neurological changes that accompany a spinal cord injury, including bradycardia, orthostatic hypotension, and ambient temperature intolerance. In autonomic dysreflexia, patients will experience hypertension, sweating, spasms (sometimes severe spasms) and erythema (more likely in upper extremities) and may suffer from headaches and blurred vision. Mortality is rare with AD, but morbidity such as stroke, retinal hemorrhage and pulmonary edema if left untreated can be quite severe. Older patients with very incomplete spinal cord injuries and systolic hypertension without symptoms are usually experiencing essential hypertension, not autonomic dysreflexia. Aggressive treatment of these elderly patients with rapidly acting antihypertensive medications can have disastrous results. ## Treatment[edit] Proper treatment of autonomic dysreflexia involves administration of anti-hypertensives along with immediate determination and removal of the triggering stimuli. Often, sitting the patient up and dangling legs over the bedside can reduce blood pressures below dangerous levels and provide partial symptom relief. Tight clothing and stockings should be removed. Straight catheterization of the bladder or relief of a blocked urinary catheter tube may resolve the problem. The rectum should be cleared of stool impaction, using anaesthetic lubricating jelly. If the noxious precipitating trigger cannot be identified, drug treatment is needed to decrease elevating intracranial pressure until further studies can identify the cause. Drug treatment includes the rapidly acting vasodilators, including sublingual or topical nitrates or oral hydralazine or clonidine. Ganglionic blockers are also used to control sympathetic nervous system outflow. Topical nitroglycerin ointment is a convenient and safe treatment—an inch or two can be applied to the chest wall or forehead, and wiped off when blood pressures begin to normalize.[13][9] Autonomic dysreflexia is abolished temporarily by spinal or general anaesthesia. These treatments are used during obstetric delivery of women with autonomic dysreflexia. ## Prognosis[edit] The cause of autonomic dysreflexia itself can be life-threatening, and must also be completely investigated and treated appropriately to prevent unnecessary morbidity and mortality. The Consortium for Spinal Cord Medicine has developed evidence-based clinical practice guidelines for the management of autonomic dysreflexia in adults, children, and pregnant women. There is also a consumer version of this guideline. ## See also[edit] * Notable individual with AD - Jeff Erlanger interviewed by Fred Rogers ## References[edit] 1. ^ a b "Autonomic dysreflexia". Medline. NIH. Retrieved 19 March 2019. 2. ^ a b c Consortium for Spinal Cord Medicine (2002). "Acute management of autonomic dysreflexia: individuals with spinal cord injury presenting to health-care facilities". The Journal of Spinal Cord Medicine. 25 Suppl 1: S67–88. PMID 12051242. 3. ^ a b c d e Daroff RB, Jankovic J, Mazziotta JC, Pomeroy SL, Bradley WG (2016). Bradley's neurology in clinical practice (Seventh ed.). London. ISBN 978-0-323-28783-8. OCLC 932031625. 4. ^ Solinsky, Ryan; Kirshblum, Steven C.; Burns, Stephen P. (2018). "Exploring Detailed Characteristics of Autonomic Dysreflexia". The Journal of Spinal Cord Medicine. 41 (5): 549–555. doi:10.1080/10790268.2017.1360434. PMC 6127514. PMID 28784041. 5. ^ a b c Vallès M, Benito J, Portell E, Vidal J (December 2005). "Cerebral hemorrhage due to autonomic dysreflexia in a spinal cord injury patient". Spinal Cord. 43 (12): 738–40. doi:10.1038/sj.sc.3101780. PMID 16010281. 6. ^ Krassioukov A, Warburton DE, Teasell R, Eng JJ (April 2009). "A systematic review of the management of autonomic dysreflexia after spinal cord injury". Archives of Physical Medicine and Rehabilitation. 90 (4): 682–95. doi:10.1016/j.apmr.2008.10.017. PMC 3108991. PMID 19345787. 7. ^ a b c d e f g h Eldahan KC, Rabchevsky AG (January 2018). "Autonomic dysreflexia after spinal cord injury: Systemic pathophysiology and methods of management". Autonomic Neuroscience. 209: 59–70. doi:10.1016/j.autneu.2017.05.002. PMC 5677594. PMID 28506502. 8. ^ a b c d e Youmans and Winn neurological surgery. Winn, H. Richard (Seventh ed.). Philadelphia, PA. 30 November 2016. ISBN 9780323287821. OCLC 963181140.CS1 maint: others (link) 9. ^ a b Solinsky, Ryan; Svircev, Jelena N.; James, Jennifer J.; Burns, Stephen P.; Bunnell, Aaron E. (2016). "A retrospective review of safety using a nursing driven protocol for autonomic dysreflexia in patients with spinal cord injuries". The Journal of Spinal Cord Medicine. 39 (6): 713–719. doi:10.1080/10790268.2015.1118186. PMC 5137561. PMID 26838482. 10. ^ Krassioukov, Andrei; Biering-Sørensen, Fin; Donovan, William; Kennelly, Michael; Kirshblum, Steven; Krogh, Klaus; Alexander, Marca Sipski; Vogel, Lawrence; Wecht, Jill (2012). "International standards to document remaining autonomic function after spinal cord injury". The Journal of Spinal Cord Medicine. 35 (4): 201–210. doi:10.1179/1079026812Z.00000000053. PMC 3425876. PMID 22925746. 11. ^ Burton AR, Brown R, Macefield VG (October 2008). "Selective activation of muscle and skin nociceptors does not trigger exaggerated sympathetic responses in spinal-injured subjects". Spinal Cord. 46 (10): 660–5. doi:10.1038/sc.2008.33. PMID 18427566. 12. ^ Marsh DR, Weaver LC (June 2004). "Autonomic dysreflexia, induced by noxious or innocuous stimulation, does not depend on changes in dorsal horn substance p". Journal of Neurotrauma. 21 (6): 817–28. doi:10.1089/0897715041269605. PMID 15253807. 13. ^ Solinsky, R.; Bunnell, A. E.; Linsenmeyer, T. A.; Svircev, J. N.; Engle, A.; Burns, S. P. (2017). "Pharmacodynamics and effectiveness of topical nitroglycerin at lowering blood pressure during autonomic dysreflexia". Spinal Cord. 55 (10): 911–914. doi:10.1038/sc.2017.58. PMID 28585557. ## Further reading[edit] * Allman KG, McIndoe A, Wilson IH (2005). Emergencies in anaesthesia. Oxford: Oxford University Press. p. 18. ISBN 978-0-19-852099-3. * Lin VWH, Cardenas DD, Cutter NC, Frost FS, Hammond MC (2010). Spinal Cord Medicine: Principles and Practice (2nd ed.). Demos Medical Publishing. ISBN 978-1-933864-19-8. * Consortium for Spinal Cord Medicine (2001). "Acute Management of Autonomic Dysreflexia: Individuals with Spinal Cord Injury Presenting to Health-Care Facilities" (PDF) (2nd ed.). Washington DC: Paralyzed Veterans of America. Archived from the original (PDF) on 2018-04-07. Retrieved 2018-04-07. * Vallès M, Benito J, Portell E, Vidal J (December 2005). "Cerebral hemorrhage due to autonomic dysreflexia in a spinal cord injury patient". Spinal Cord. 43 (12): 738–40. doi:10.1038/sj.sc.3101780. PMID 16010281. ## External links[edit] Classification D * ICD-10-CM: G90.4 * ICD-9-CM: 337.3 * MeSH: D020211 * DiseasesDB: 1155 External resources * MedlinePlus: 001431 * eMedicine: article/322809 * v * t * e Diseases of the autonomic nervous system General * Dysautonomia * Autonomic dysreflexia * Autonomic neuropathy * Pure autonomic failure Hereditary * Hereditary sensory and autonomic neuropathy * Familial dysautonomia * Congenital insensitivity to pain with anhidrosis Orthostatic intolerance * Orthostatic hypotension * Postural orthostatic tachycardia syndrome Other * Horner's syndrome * Multiple system atrophy * v * t * e Shock Distributive * Septic shock * Neurogenic shock * Anaphylactic shock * Toxic shock syndrome Obstructive * Abdominal compartment syndrome Low volume * Hemorrhage * Hypovolemia * Osmotic shock Other * Spinal shock * Cryptic shock * Vasodilatory shock [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autonomic dysreflexia	c0238015	29,970	wikipedia	https://en.wikipedia.org/wiki/Autonomic_dysreflexia	2021-01-18T18:46:06	{"mesh": ["D020211"], "icd-9": ["337.3"], "icd-10": ["G90.4"], "wikidata": ["Q4826775"]}
Ellis-van Creveld syndrome (EVC) is a skeletal and ectoderlam dysplasia characterized by a tetrad of short stature, postaxial polydactyly, ectodermal dysplasia, and congenital heart defects. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ellis Van Creveld syndrome	c0013903	29,971	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=289	2021-01-23T18:51:14	{"gard": ["1301"], "mesh": ["D004613"], "omim": ["225500", "617088", "618123"], "umls": ["C0013903"], "icd-10": ["Q77.6"], "synonyms": ["Chondroectodermal dysplasia", "Mesodermic dysplasia"]}
Portal hypertensive gastropathy Image of portal hypertensive gastropathy seen on endoscopy of the stomach. The normally smooth mucosa of the stomach has developed a mosaic like appearance, that resembles snake-skin. SpecialtyGastroenterology Portal hypertensive gastropathy refers to changes in the mucosa of the stomach in patients with portal hypertension; by far the most common cause of this is cirrhosis of the liver. These changes in the mucosa include friability of the mucosa and the presence of ectatic blood vessels at the surface. Patients with portal hypertensive gastropathy may experience bleeding from the stomach, which may uncommonly manifest itself in vomiting blood or melena; however, portal hypertension may cause several other more common sources of upper gastrointestinal bleeding, such as esophageal varices and gastric varices. On endoscopic evaluation of the stomach, this condition shows a characteristic mosaic or "snake-skin" appearance to the mucosa of the stomach. ## Contents * 1 Signs and symptoms * 2 Pathogenesis * 3 Treatment * 3.1 Medications * 3.2 Procedural * 4 Similar conditions * 5 References * 6 External links ## Signs and symptoms[edit] Most patients with portal hypertensive gastropathy have either a stable or improving course in the appearance of the gastropathy on endoscopy. However, according to retrospective data, roughly one in seven patients with portal hypertensive gastropathy will develop bleeding (either acute or chronic) attributable to the gastropathy.[1] Patients with chronic bleeding will usually come to the attention of the medical system because of anemia. The diagnosis of portal hypertensive gastropathy is usually made on endoscopy. The usual appearance of portal hypertensive gastropathy on endoscopy is a mosaic-like or reticular pattern in the mucosa. Red spots may or may not be present. The pattern is usually seen throughout the stomach.[2] A similar pattern can be seen with a related condition called gastric antral vascular ectasia (GAVE), or watermelon stomach. However, in GAVE, the ectatic blood vessels are more commonly found in the antrum or lower part of the stomach.[2] ## Pathogenesis[edit] Several studies have found that patients with portal hypertension develop increased blood flow to the stomach.[3] The physiological findings that correlate with worsening portal hypertensive gastropathy include an increased portal venous pressure gradient and decreased hepatic blood flow.[4] Biopsies of the stomach in patients with portal hypertensive gastropathy show ectatic (or dilated) blood vessels, evidence of bleeding by means of red blood cells in the lamina propria, and edema in the stomach wall.[2] ## Treatment[edit] Argon plasma coagulation, seen here to treat gastric antral vascular ectasia, has also been used to treat bleeding from portal hypertensive gastropathy ### Medications[edit] Several treatment options have been developed for portal hypertensive gastropathy. The first is the use of beta-blockers, which reduce portal pressures. Non-selective beta blockers (such as propranolol and nadolol) have been used to decrease the pressure of the portal vein in patients with esophageal varices, and have been shown to regress portal hypertensive gastropathy that has been worsened by medical treatment of varices.[5] Propranolol has also been evaluated in patients with chronic cirrhosis and portal hypertensive gastropathy.[6] Other medications that primarily treat bleeding, including anti-fibrinolytic medications such as tranexamic acid have also been used in case reports of patients with portal hypertensive gastropathy.[7] These medications work by stabilizing deposits of fibrin at sites that ordinarily would bleed. Finally, octreotide, an analogue of somatostatin that leads to vasoconstriction of the portal circulation, can be used for active bleeding due to portal hypertensive gastropathy.[8] Sucralfate, a coating medication has also been used, but evidence is from animal models.[9] ### Procedural[edit] Portal hypertensive gastropathy can also be treated with endoscopic treatment delivered through a fibre-optic camera into the stomach. Argon plasma coagulation and electrocautery have both been used to stop bleeding from ectatic vessels, and to attempt to obliterate the vessels, but have limited utility if the disease is diffuse.[8][10] Transjugular intrahepatic portosystemic shunt procedures, or TIPS involve decompressing the portal vein by shunting a portal venule to a lower pressure systemic venule, under guidance with fluoroscopy. Since it treats the root cause of portal hypertension gastropathy, it has been putatively used for the condition. The literature reports suggest both regression of portal hypertensive gastropathy on endoscopic images and improvement in bleeding after TIPS.[11] Finally, cryotherapy involves the use of pressurized carbon dioxide administered through the endoscope to freeze and destroy tissue in a focal area. It is being studied for the treatment of portal hypertensive gastropathy.[12] ## Similar conditions[edit] Congestion of the mucosa in other parts of the gastrointestinal tract can also be seen in portal hypertension. When the condition involves the colon, it is termed portal hypertensive colopathy.[13] ## References[edit] 1. ^ Primignani M, Carpinelli L, Preatoni P, et al. (2000). "Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC)". Gastroenterology. 119 (1): 181–7. doi:10.1053/gast.2000.8555. PMID 10889167. 2. ^ a b c Thuluvath PJ, Yoo HY (2002). "Portal Hypertensive gastropathy". Am. J. Gastroenterol. 97 (12): 2973–8. PMID 12492178. 3. ^ Iwao T, Toyonaga A, Sumino M, et al. (1992). "Portal hypertensive gastropathy in patients with cirrhosis". Gastroenterology. 102 (6): 2060–5. doi:10.1016/0016-5085(92)90332-S. PMID 1587424. 4. ^ Gupta R, Sawant P, Parameshwar RV, Lele VR, Kulhalli PM, Mahajani SS (1998). "Gastric mucosal blood flow and hepatic perfusion index in patients with portal hypertensive gastropathy". J. Gastroenterol. Hepatol. 13 (9): 921–6. doi:10.1111/j.1440-1746.1998.tb00762.x. PMID 9794191. 5. ^ Lo GH, Lai KH, Cheng JS, et al. (2001). "The effects of endoscopic variceal ligation and propranolol on portal hypertensive gastropathy: a prospective, controlled trial". Gastrointest. Endosc. 53 (6): 579–84. doi:10.1067/mge.2001.114062. PMID 11323582. 6. ^ Pérez-Ayuso RM, Piqué JM, Bosch J, et al. (1991). "Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis". Lancet. 337 (8755): 1431–4. doi:10.1016/0140-6736(91)93125-S. PMID 1675316. 7. ^ McCormick PA, Ooi H, Crosbie O (1998). "Tranexamic acid for severe bleeding gastric antral vascular ectasia in cirrhosis". Gut. 42 (5): 750–2. doi:10.1136/gut.42.5.750. PMC 1727106. PMID 9659175. 8. ^ a b Garcia N, Sanyal AJ (2001). "Portal Hypertensive Gastropathy and Gastric Antral Vascular Ectasia". Current Treatment Options in Gastroenterology. 4 (2): 163–171. doi:10.1007/s11938-001-0028-0. PMID 11469974. 9. ^ Geoffroy P, Duchateau A, Thiéfin G, Zeitoun P (1987). "Effects of propranolol and sucralfate on ethanol-induced gastric mucosal damage in chronic portal hypertensive rats". J. Hepatol. 5 (2): 162–6. doi:10.1016/S0168-8278(87)80568-8. PMID 3693860. 10. ^ Sato T, Yamazaki K, Toyota J, et al. (2005). "Efficacy of argon plasma coagulation for gastric antral vascular ectasia associated with chronic liver disease". Hepatol. Res. 32 (2): 121–6. doi:10.1016/j.hepres.2005.04.004. PMID 15967712. 11. ^ Urata J, Yamashita Y, Tsuchigame T, et al. (1998). "The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy". J. Gastroenterol. Hepatol. 13 (10): 1061–7. doi:10.1111/j.1440-1746.1998.tb00571.x. PMID 9835325. 12. ^ Clarke JO, Thuluvath PJ (2007). "Endoscopic frontiers in the field of hepatology". Minerva Gastroenterologica e Dietologica. 53 (1): 101–9. PMID 17415347. 13. ^ Bini EJ, Lascarides CE, Micale PL, Weinshel EH (2000). "Mucosal abnormalities of the colon in patients with portal hypertension: an endoscopic study". Gastrointest. Endosc. 52 (4): 511–6. doi:10.1067/mge.2000.108478. PMID 11023569. ## External links[edit] Classification D * ICD-9-CM: 537.89 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Portal hypertensive gastropathy	c0580174	29,972	wikipedia	https://en.wikipedia.org/wiki/Portal_hypertensive_gastropathy	2021-01-18T18:53:40	{"icd-9": ["537.89"], "wikidata": ["Q1495648"]}
Hughes–Stovin syndrome Deep vein thrombosis is one of the characteristics of this syndrome SpecialtyImmunology Hughes–Stovin syndrome is a rare autoimmune disorder of unknown cause that is characterized by the combination of multiple pulmonary artery aneurysms and deep vein thromboses. It is named after the two British physicians, John Patterson Hughes and Peter George Ingle Stovin, who first described it in 1959.[1] It is a rare variant of Behçet's disease, which entails more general problems with the circulatory system. Most patients are young adult males between the age of 20–40. Common clinical presentations include fever, cough, dyspnea and hemoptysis. Radiological features are similar to those of Behçet's disease.[2] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Management * 4 References * 5 External links ## Signs and symptoms[edit] * Multiple pulmonary aneurysms[3] * Peripheral venous thrombosis[3] * Recurrent fever[3] * Chills[3] * Hemoptysis[3] * Cough[3] ## Diagnosis[edit] There is no rigid set of diagnostic criteria for Hughes-Stovin. According to QJM, an international medical journal published by Oxford Press, Hughes-Stovin can be discerned from similar conditions by its resemblance to vasculitis without a presenting infection. The syndrome is also identified as being "characterized by pulmonary/bronchial artery aneurysms and thrombophlebitis, without diagnostic features of Behçet's disease (BD)."[4] ## Management[edit] There is currently no satisfactory treatment for this condition.[4] This is partly due to its rarity; the Orphanet Journal of Rare Diseases claims that fewer than forty cases of the disease have been described in English medical literature.[5] Immunosuppressive therapy is the most common treatment, involving a mix of glucocorticoids and cyclophosphamide. This is most effective in the early stages and may cause remission of the aneurysms, but is ineffective once the disease has progressed. According to the Orphanet Journal, treatments, including ventilator, surgery and transcatheter arterial embolization are also used.[5] ## References[edit] 1. ^ Hughes, JP; Stovin, PG (January 1959). "Segmental pulmonary artery aneurysms with peripheral venous thrombosis". British Journal of Diseases of the Chest. 53 (1): 19–27. doi:10.1016/S0007-0971(59)80106-6. PMID 13618502. 2. ^ "Hughes stovin syndrome". Medcyclopaedia. GE. 3. ^ a b c d e f Chalazonitis; et al. (January 29, 2009). "Hughes-Stovin Syndrome: a case report and review of the literature". Cases J. 2: 98. doi:10.1186/1757-1626-2-98. PMC 2649053. PMID 19178695. 4. ^ a b Robinson, C; Miller, D; Will, M; Dhaun, N; Walker, W (2018). "Hughes–Stovin syndrome: the diagnostic and therapeutic challenges of peripheral pulmonary artery aneurysms". QJM: An International Journal of Medicine. 111 (10): 729–730. doi:10.1093/qjmed/hcy110. ISSN 1460-2725. PMID 29860510. 5. ^ a b Khalid, Umair; Saleem, Taimur (2011). "Hughes-Stovin Syndrome". Orphanet Journal of Rare Diseases. 6 (1): 15. doi:10.1186/1750-1172-6-15. ISSN 1750-1172. PMC 3082226. PMID 21489283. ## External links[edit] Classification D * ICD-10: I28.8 External resources * Orphanet: 228116 This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hughes–Stovin syndrome	None	29,973	wikipedia	https://en.wikipedia.org/wiki/Hughes%E2%80%93Stovin_syndrome	2021-01-18T18:57:17	{"icd-9": ["279.4"], "icd-10": ["M35.9"], "orphanet": ["228116"], "synonyms": [], "wikidata": ["Q609675"]}
A number sign (#) is used with this entry because thrombocythemia-1 (THCYT1) is caused by heterozygous mutation in the thrombopoietin gene (THPO; 600044) on chromosome 3q27. Description Thrombocythemia, or thrombocytosis, is a myeloproliferative disorder characterized by excessive platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic or hemorrhagic episodes and occasional leukemic transformation (summary by Wiestner et al., 1998). ### Genetic Heterogeneity of Thrombocythemia THCYT2 (601977) is caused by germline or somatic mutation in the THPO receptor gene (MPL; 159530) on chromosome 1p34; THCYT3 (614521) is caused by germline or somatic mutation in the JAK2 gene (147796) on chromosome 9p; and a possible X-linked form (THCYTX; 300331) has been reported. Somatic mutations in the TET2 (612839), ASXL1 (612990), SH2B3 (605093), and SF3B1 (605590) genes have also been found in cases of essential thrombocythemia. Somatic mutation in the CALR gene (109091) occurs in approximately 70% of essential thrombocythemia patients who lack JAK2 and MPL mutations (Klampfl et al., 2013; Nangalia et al., 2013). Clinical Features ### Early Descriptions Fickers and Speck (1974) reported familial occurrence of thrombocythemia, with transition into blastic crisis in some patients. Slee et al. (1981) described a family in which a form of myeloproliferative disease involving the megakaryocytic cell line occurred in 3 generations, resulting in thrombocytosis in several members. Autosomal dominant transmission with incomplete penetrance was proposed. Case (1984) reported the clinical findings of 33 patients with essential thrombocythemia, all of whom met rigid criteria for diagnosis of this myeloproliferative disorder. Constitutional symptoms were present in 90%, with 25% having thrombohemorrhagic manifestations. All patients had hypercellular marrows with megakaryocytic hyperplasia and dysplasia. The median platelet count at diagnosis was 17 million with a range as high as 70 million per cu mm. Eyster et al. (1986) reported a family in which 5 members from 3 successive generations had autosomal dominant essential thrombocythemia. Age ranged from 2 to 62 years. The proposita was a 26-year-old woman with persistently elevated platelet count, mild splenomegaly, normal hemoglobin level, normal white blood cell count, and abnormal platelet aggregation. Megakaryocytes were increased in number and size. Platelet arachidonic acid metabolites and serum thrombopoietin levels were normal. Her 2 sons, aged 4 and 2 years, had platelet counts of 951,000 and 1,070,000 per cu mm. Her mother had platelet counts of about 900,000 per cu mm. Bone marrow karyotypes were normal. The proband's mother and her sister had thrombocythemia; both had had myocardial infarction at ages 52 and 57, respectively. The authors concluded that young women and children with essential thrombocythemia may have long survival without treatment. In 5 healthy members of 3 generations of a family, Cohen et al. (1997) described a benign form of familial thrombocytosis. All 5 had moderate thrombocytosis (422,000 to 662,000/mm(3); normal range 130,000-350,000/mm(3)) and low mean platelet volume (5.9-6.9 fl; normal range of 7.8-12 fl). Medical history and a 5-year follow-up of the subjects did not suggest any untoward effects. Cohen et al. (1997) suggested that abnormally elevated platelet counts can be classified into 3 groups: reactive thrombocytosis, essential thrombocytosis (a neoplastic disorder), and familial thrombocytosis. Families of the last-mentioned type were reported by Fickers and Speck (1974), Eyster et al. (1986), Fernandez-Robles et al. (1990), and Kikuchi et al. (1995). None of these families appeared to have had small platelets, suggesting that the family of Cohen et al. (1997) may have a different variant. ### Genetically Confirmed Thrombocythemia 1 Schlemper et al. (1994) reported a large 4-generation Dutch family with hereditary thrombocythemia. Of 11 affected individuals, 5 were asymptomatic, 3 had both vasoocclusive and hemorrhagic manifestations, and 3 had only vasoocclusive features. The platelet count ranged from 500 to 1,700 x 10(9)/l. Symptoms correlated with age but not with platelet count. ADP-induced platelet aggregation was the best distinguishing characteristic between patients and unaffected members of the family. No chromosome abnormalities were found. The propositus presented at the age of 32 years with recurrent transient symptoms of 'cold tip feeling,' erythromelalgia, and acrocyanosis of the toes, which eventually led to gangrene and amputation of a toe in 1968. There was 1 instance of male-to-male transmission. Van Dijken et al. (1996) observed chronic thrombocytosis in an infant from the family reported by Schlemper et al. (1994). The mother was known to have familial thrombocytosis for which she was treated with low-dose aspirin. At age 6 weeks, her son was malnourished, had enlarged liver and spleen, and marked leukocytosis with an abnormal differential white cell count. Although leukemia was suspected, the hematologic picture began to normalize about the age of 1 year and hepatosplenomegaly decreased. At the age of 5 years he was apparently well with only a just palpable spleen, like most of his family members with thrombocytosis. Kikuchi et al. (1995) observed 4 cases of thrombocytosis in 3 successive generations of a Japanese family. A high peripheral platelet count was found incidentally in the proband, with cutaneous malignant lymphoma which was thought to be coincidental. Bone marrow examinations showed megakaryocytic hyperplasia. Neither Philadelphia chromosome nor chimeric BCR/ABL junction was detected in marrow cells. Biochemical Features Kaywin et al. (1978) reported 4 male patients with essential thrombocythemia. Platelets from 2 of these patients showed dysfunction, including failure to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets of normal controls. Platelets from these 2 men contained only about half as many binding alpha-adrenergic binding sites compared to control platelets. Platelets from the other 2 patients showed normal epinephrine responses and receptor site numbers. Inheritance Dodsworth (1980) described primary thrombocytosis in monozygotic twins. Familial thrombocytosis was reported by Fernandez-Robles et al. (1990). Wiestner et al. (1998) confirmed autosomal dominant inheritance of thrombocythemia-1. Cytogenetics Sweet et al. (1979), Norrby et al. (1982), Carbonell et al. (1982), and Bernstein et al. (1982) described cases of leukemia or preleukemia associated with thrombocytosis and an insertion in chromosome 3, ins(3;3)(q26;q21q26). Bernstein et al. (1982), who referred to this as 'homologous translocation,' described 3 patients with acute nonlymphocytic leukemia (ANLL) and thrombocytosis associated with inv(3)(q21q26). Carroll et al. (1986) described sideroblastic anemia and thrombocytosis causing recurrent and ultimately fatal thromboembolism in a patient with 46,XY,ins(3;3)(q26;q21q26) in bone marrow cells. The observations suggested that a gene on 3q may regulate megakaryopoiesis. Molecular Genetics In a 4-generation Dutch kindred with essential thrombocythemia originally reported by Schlemper et al. (1994), Wiestner et al. (1998) identified a heterozygous germline mutation in the THPO gene (600044.0001). In affected members of the Japanese family reported by Kikuchi et al. (1995), Ghilardi et al. (1999) identified a heterozygous gain-of-function germline mutation in the THPO gene (600044.0003). History Early studies suggested a site for primary thrombocytosis on 21q11-qter based on several studies reporting deletion of this region in patients with the disorder (Rajendra et al., 1981). Zaccaria and Tura (1978) found partial deletion of the long arm of chromosome 21 in 5 patients with primary thrombocytosis, Petit and Van den Berghe (1979) observed a patient with an acquired deletion of 22q. However, Case (1984) could not confirm the reported association of 21q- in a study of 33 patients with essential thrombocythemia. Emilia et al. (1985) concluded that no chromosomal abnormality is consistently associated with essential thrombocytosis, and specifically noted that evidence did not indicate a clear relationship to deletion of 21q. Verhest and Monsieur (1983) found the Philadelphia chromosome (see 151410) in a patient with essential thrombocythemia with leukemic transformation. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Thrombotic episodes \- Hemorrhagic episodes HEMATOLOGY \- Thrombocythemia \- Increased bone marrow megakaryocytes LABORATORY ABNORMALITIES \- Increased serum thrombopoietin may occur MOLECULAR BASIS \- Caused by mutation in the thrombopoietin gene (THPO, 600044.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	THROMBOCYTHEMIA 1	c0040028	29,974	omim	https://www.omim.org/entry/187950	2019-09-22T16:32:40	{"doid": ["2224"], "mesh": ["D013920"], "omim": ["187950"], "orphanet": ["71493", "3318"], "synonyms": ["Alternative titles", "THROMBOCYTOSIS 1", "Hereditary thrombocythemia", "Familial thrombocythemia"]}
GRACILE syndrome is an inherited metabolic disease. GRACILE stands for growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death. Infants are very small at birth and quickly develop life-threatening complications. During the first days of life, infants will develop a buildup of lactic acid in the bloodstream (lactic acidosis) and amino acids in the urine (aminoaciduria). They will also have problems with the flow of bile from the liver (cholestasis) and too much iron in their blood. Affected individuals aren’t typically born with unique physical features. Although alkali therapy is used as treatment, about half of affected infants do not survive past the first days of life. Those that do survive this period generally do not live past 4 months despite receiving treatment. GRACILE syndrome is caused by a mutation in the BCS1L gene, and it is inherited in an autosomal recessive pattern. The BCS1L gene provides instructions needed by the mitochondria in cells to help produce energy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	GRACILE syndrome	c1864002	29,975	gard	https://rarediseases.info.nih.gov/diseases/1/gracile-syndrome	2021-01-18T18:00:13	{"mesh": ["C537934"], "omim": ["603358"], "umls": ["C1864002"], "orphanet": ["53693"], "synonyms": ["FLNMS", "Finnish lactic acidosis with hepatic hemosiderosis", "Fellman syndrome", "Growth Retardation, Aminoaciduria, Cholestasis, Iron overload, Lactic acidosis and Early death", "Finnish lethal neonatal metabolic syndrome", "Fellman disease", "Growth delay-aminoaciduria-cholestasis-iron overload-lactic acidosis-early death syndrome", "Growth restriction-aminoaciduria-cholestasis-iron overload-lactic acidosis-early death syndrome"]}
Family of genetic conditions caused by mutations affecting Ras genes The RASopathies are developmental syndromes caused by germline mutations (or in rare cases by somatic mosaicism) in genes that alter the Ras subfamily and mitogen-activated protein kinases that control signal transduction, including: * Capillary malformation-AV malformation syndrome * Autoimmune lymphoproliferative syndrome * Cardiofaciocutaneous syndrome * Hereditary gingival fibromatosis type 1 * Neurofibromatosis type 1 * Noonan syndrome * Costello syndrome, Noonan-like[1] * Legius syndrome, Noonan-like * Noonan syndrome with multiple lentigines, formerly called LEOPARD syndrome, Noonan-like ## References[edit] 1. ^ Schuhmacher AJ, Guerra C, Sauzeau V, Cañamero M, Bustelo XR, Barbacid M (June 2008). "A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition". J. Clin. Invest. 118 (6): 2169–79. doi:10.1172/JCI34385. PMC 2381749. PMID 18483625. ## External links[edit] * RASopathies Network USA, founded 2010 rasopathiesnet.org, accessed February 27, 2014 * About RAS Pathway Syndromes RASopathy Network, RAS-Pathway-syndromes.com, accessed February 27, 2014. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RASopathy	None	29,976	wikipedia	https://en.wikipedia.org/wiki/RASopathy	2021-01-18T18:29:15	{"orphanet": ["536391"], "synonyms": [], "wikidata": ["Q1029344"]}
Von Hippel-Lindau disease (VHL) is a familial cancer predisposition syndrome associated with a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), and pheochromocytoma. ## Epidemiology Prevalence is estimated at 1/53,000 and annual birth incidence at 1/36,000. Men and women are equally affected. Mean age at diagnosis is 26 years (range: infancy - 7th decade). ## Clinical description Retinal hemangioblastomas are the most common presenting feature (multiple and bilateral in about 50% of cases). They are usually asymptomatic, but they can cause retinal detachment, macular edema, glaucoma, and vision loss. Central nervous system (CNS) hemangioblastomas are the presenting feature in about 40% and occur overall in 60-80% of patients. They are most often located in the cerebellum, but also in the brainstem and spinal cord. They are benign but cause symptoms by compressing adjacent nervous tissue. In the cerebellum they are most often associated with increased intracranial pressure, headaches, vomiting, and limb or truncal ataxia. Multiple renal cysts are very common and the lifetime risk of RCC is very high (70%). Some patients have pheochromocytomas that can be asymptomatic, but may cause hypertension. Epididymal cysts and cystadenomas (60% of male patients) may occur, as well as multiple pancreatic cysts (most patients) but non-secretory pancreatic islet cell tumors only occur in a minority (about 10%). Endolymphatic sac tumors (ELST) are also been found (up to 10%) and may cause hearing loss. Head and neck paragangliomas are rare (0.5%). The mean age at diagnosis of tumors in VHL is considerably younger than in sporadic cases. Marked intrafamilial variability is reported. ## Etiology VHL is caused by highly penetrant mutations in the VHL gene (3p25.3), a classic tumor suppressor. Most cases are diagnosed via a germline mutation. ## Diagnostic methods Diagnosis can be made in the presence of a single typical tumor (e.g. retinal or CNS hemangioblastomas or RCC) and a positive family history of VHL. If there is no family history (about 20% de novo), multiple tumors (e.g. two hemangioblastomas or a hemangioblastoma and an RCC) are required for diagnosis. A complete blood count, measurement of urinary catecholamine metabolites, urinalysis, and urine cytology may be indicative of polycythemia, pheochromocytoma, renal anomalies, and RCC. Imaging studies can be used to detect CNS tumors, pheochromocytoma, endolymphatic sac tumors, renal tumors, and renal and pancreatic cysts. ## Differential diagnosis Differential diagnoses include multiple endocrine neoplasia, neurofibromatosis, polycystic kidney disease, tuberous sclerosis, Birt-Hogg-Dube syndrome, and hereditary pheochromocytoma-paraganglioma syndromes (see these terms) associated with succinate dehydrogenase subunit mutations (SDHB, SDHC and SDHD). ## Antenatal diagnosis Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villus cells if a disease-causing mutation has been identified in an affected family member. ## Genetic counseling Inheritance is autosomal dominant. Genetic counseling should be offered. ## Management and treatment Treatment requires a coordinated multidisciplinary approach. Surgery is the mainstay of treatment for tumors. Management should include lifelong surveillance (ophthalmologic, MRI brain and abdominal scans, laboratory testing). At-risk relatives should be entered into a screening program in childhood unless VHL is excluded by molecular genetic testing. ## Prognosis Prognosis depends on the occurrence of multiple tumors. RCC is the main cause of death, followed by CNS hemangioblastomas. Average life expectancy was previously estimated to be 50 years; however, regular surveillance and early detection and management of tumors have now reduced the morbidity and mortality. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Von Hippel-Lindau disease	c0019562	29,977	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=892	2021-01-23T18:59:45	{"gard": ["7855"], "mesh": ["D006623"], "omim": ["193300"], "umls": ["C0019562"], "icd-10": ["Q85.8"], "synonyms": ["Familial cerebelloretinal angiomatosis", "Lindau disease", "VHL", "Von Hippel-Lindau syndrome"]}
Aminoacylase 1 deficiency is an inherited disorder that can cause neurological problems; the pattern and severity of signs and symptoms vary widely among affected individuals. Individuals with this condition typically have delayed development of mental and motor skills (psychomotor delay). They can have movement problems, reduced muscle tone (hypotonia), mild intellectual disability, and seizures. However, some people with aminoacylase 1 deficiency have no health problems related to the condition. A key feature common to all people with aminoacylase 1 deficiency is high levels of modified protein building blocks (amino acids), called N-acetylated amino acids, in the urine. ## Frequency The prevalence of aminoacylase 1 deficiency is unknown. ## Causes Aminoacylase 1 deficiency is caused by mutations in the ACY1 gene. This gene provides instructions for making an enzyme called aminoacylase 1, which is involved in the breakdown of proteins when they are no longer needed. Many proteins in the body have an acetyl group attached to one end. This modification, called N-acetylation, helps protect and stabilize the protein. Aminoacylase 1 performs the final step in the breakdown of these proteins by removing the acetyl group from certain amino acids. The amino acids can then be recycled and used to build other proteins. Mutations in the ACY1 gene lead to an aminoacylase 1 enzyme with little or no function. Without this enzyme's function, acetyl groups are not efficiently removed from a subset of amino acids during the breakdown of proteins. The excess N-acetylated amino acids are released from the body in urine. It is not known how a reduction of aminoacylase 1 function leads to neurological problems in people with aminoacylase 1 deficiency. ### Learn more about the gene associated with Aminoacylase 1 deficiency * ACY1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Aminoacylase 1 deficiency	c1835922	29,978	medlineplus	https://medlineplus.gov/genetics/condition/aminoacylase-1-deficiency/	2021-01-27T08:25:27	{"gard": ["9741"], "mesh": ["C538246"], "omim": ["609924"], "synonyms": []}
Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome is a rare, genetic, neural tube defect malformation syndrome characterized by sacral agenesis and abnormal vertebral body ossification with normal vertebral arches associated with notochord canal persistence on ultrasonography. Additional findings include bilateral clubfoot, oligohydramnios, single umbilical artery and, in some, increased nuchal translucency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome	c3810343	29,979	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397927	2021-01-23T17:34:29	{"omim": ["615709"], "icd-10": ["Q87.5"]}
Not to be confused with environmental burden of disease. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Environmental disease" – news · newspapers · books · scholar · JSTOR (June 2009) (Learn how and when to remove this template message) In epidemiology, environmental diseases are diseases that can be directly attributed to environmental factors (as distinct from genetic factors or infection). Apart from the true monogenic genetic disorders, environmental diseases may determine the development of disease in those genetically predisposed to a particular condition. Stress, physical and mental abuse, diet, exposure to toxins, pathogens, radiation, and chemicals found in almost all personal care products and household cleaners are possible causes of a large segment of non-hereditary disease. If a disease process is concluded to be the result of a combination of genetic and environmental factor influences, its etiological origin can be referred to as having a multifactorial pattern. There are many different types of environmental disease including:[1] * Lifestyle disease such as cardiovascular disease, diseases caused by substance abuse such as alcoholism, and smoking-related disease * Disease caused by physical factors in the environment, such as skin cancer caused by excessive exposure to ultraviolet radiation in sunlight * Disease caused by exposure to toxic or irritant chemicals in the environment such as toxic metals ## Contents * 1 Environmental Diseases vs. Pollution-Related Diseases * 2 Urban Associated Diseases * 3 Chemicals * 3.1 Metals * 3.2 Halogens * 3.3 Organic compounds * 3.4 Noxious gases * 4 Categorization and surveillance * 5 See also * 6 References * 7 Notes ## Environmental Diseases vs. Pollution-Related Diseases[edit] Environmental diseases are a direct result from the environment. Meanwhile, pollution-related diseases are attributed to exposure to toxins in the air, water, and soil. Therefore all pollution-related disease are environmental diseases, but not all environmental diseases are pollution-related diseases. ## Urban Associated Diseases[edit] Urban areas are highly dense regions that currently hold ~50% of the global population, a number expected to grow to 70% by 2050,[2] and produce over 80% of the global GDP.[3] These areas are known to have a higher incidence of certain diseases, which is of particular concern given their rapid growth. The urban environment includes many risk factors for a variety of different environmental diseases. Some of these risk factors, for instance, air-pollution, are well known, while others such as altered microbial exposure are less familiar to the general public. For instance, asthma can be induced and exacerbated by combustion related pollution, which is more prevalent in urban areas.[4] On the other hand, urban areas, compared to their rural counterparts, lack diverse microbial communities, which can help prevent the development of asthma.[5] Both of these effects lead to a higher incidence of asthma in cities. Infectious diseases are also often more common in cities, as transfer between hosts is facilitated by high population densities. However, recent research shows that increased access to healthcare weakens the urban association with these diseases,[6] and the net effect is still unclear. Interestingly, many mental health disorders have also been associated with urban areas, especially in low socioeconomic areas.[7] Increased levels of stress, air & light & noise pollution, and reduced "green" space are all urban-associated environmental effects that are adversely linked to mental health.[2] Though urban areas are often correlated with dirtiness and disease, they are likely to have more access to higher quality health care which can lead to more positive health outcomes. This benefit will continue to grow as innovation in health technologies steadily rises. Taking this into account, while overall trends do exist, it is important to note that urban risk factors are nuanced and often city and context dependent.[2] ## Chemicals[edit] Further information: Pollution; Hazardous waste; Toxicity class; Volatile organic compound; Plastic pollution; Organic dust toxic syndrome; Persistent, bioaccumulative and toxic substances; and Persistent organic pollutant ### Metals[edit] Further information: heavy metals, metal toxicity, Toxic heavy metal, Lead poisoning, Mercury poisoning, Zinc toxicity, Chromium toxicity, and cadmium poisoning Poisoning by lead and mercury has been known since antiquity. Other toxic metals or metals that are known to evoke adverse immune reactions are arsenic, phosphorus, zinc, beryllium, cadmium, chromium, manganese, nickel, cobalt, osmium, platinum,[8] selenium, tellurium, thallium, uranium, and vanadium. ### Halogens[edit] There are many other diseases likely to have been caused by common anions found in natural drinking water. Fluoride is one of the most common found in drier climates where the geology favors release of fluoride ions to soil as the rocks decompose. In Sri Lanka, 90% of the country is underlain by crystalline metamorphic rocks of which most carry mica as a major mineral. Mica carries fluoride in their structure and releases to soil when decomposes. In the dry and arid climates, fluoride concentrates on top soil and slowly dissolves in shallow groundwater. This has been the cause of high fluoride levels in drinking water where the majority of the rural Sri Lankans obtain their drinking water from backyard wells. High fluoride in drinking water has caused a high incidence of fluorosis among dry zone population in Sri Lanka. However, in the wet zone, high rainfall effectively removes fluoride from soils where no fluorosis is evident. In some parts of Sri Lanka iodine deficiency has also been noted which has been identified as a result of iodine fixation by hydrated iron oxide found in lateritic soils in wet coastal lowlands. See also: Pool chlorine hypothesis ### Organic compounds[edit] Additionally, there are environmental diseases caused by the aromatic carbon compounds including : benzene, hexachlorocyclohexane, toluene diisocyanate, phenol, pentachlorophenol, quinone and hydroquinone. Also included are the aromatic nitro-, amino-, and pyridilium-deratives: nitrobenzene, dinitrobenzene, trinitrotoluene, paramethylaminophenol sulfate (Metol), dinitro-ortho-cresol, aniline, trinitrophenylmethylnitramine (tetryl), hexanitrodiphenylamine (aurantia), phenylenediamines, and paraquat. The aliphatic carbon compounds can also cause environmental disease. Included in these are methanol, nitroglycerine, nitrocellulose, dimethylnitrosamine, and the halogenated hydrocarbons: methyl chloride, methyl bromide, trichloroethylene, carbon tetrachloride, and the chlorinated naphthalenes. Also included are glycols: ethylene chlorhydrin and diethylene dioxide as well as carbon disulfide, acrylonitrile, acrylamide, and vinyl chloride. ### Noxious gases[edit] See also: passive smoking Noxious gases can be categorized as : Simple asphyxiants, chemical asphyxiants, and irritant gases. The simple asphixiants are nitrogen, methane, and carbon dioxide. The chemical asphyxiants are carbon monoxide, sulfuretted hydrogen and hydrogen cyanide. The irritant gases are sulfur dioxide, ammonia, nitrogen dioxide, chlorine, phosgene, and fluorine and its compounds, which include luroine and hydrofluoric acid, fluorspar, fluorapatite, cryolite, and organic fluorine compounds. ## Categorization and surveillance[edit] The U.S. Coast Guard has developed a Coast Guard-wide comprehensive system for surveillance of workplace diseases. The American Medical Association's fifth edition of the Current Medical Information and Terminology (CMIT) was used as a reference to expand the basic list of 50 Sentinel Health Events (Occupational) [SHE(O)] published by the National Institute for Occupational Health and Safety (NIOSH), September, 1983. ## See also[edit] * Effects of deforestation on public health * Environmental factor * Environmental health * Environmental medicine * Occupational disease * Phenocopy * Risk factor * Microplastics ## References[edit] 1. ^ Miller, Joe; Levine, Joe (2010-02-01). Biology. Pearson Prentice Hall. ISBN 9780133685190. 2. ^ a b c Flies, Emily J.; Mavoa, Suzanne; Zosky, Graeme R.; Mantzioris, Evangeline; Williams, Craig; Eri, Rajaraman; Brook, Barry W.; Buettel, Jessie C. (2019-12-01). "Urban-associated diseases: Candidate diseases, environmental risk factors, and a path forward". Environment International. 133 (Pt A): 105187. doi:10.1016/j.envint.2019.105187. ISSN 0160-4120. PMID 31648161. 3. ^ "Overview". World Bank. Retrieved 2020-11-26. 4. ^ Guarnieri, Michael; Balmes, John R (2014-05-03). "Outdoor air pollution and asthma". The Lancet. 383 (9928): 1581–1592. doi:10.1016/S0140-6736(14)60617-6. ISSN 0140-6736. PMC 4465283. PMID 24792855. 5. ^ Stein, Michelle M.; Hrusch, Cara L.; Gozdz, Justyna; Igartua, Catherine; Pivniouk, Vadim; Murray, Sean E.; Ledford, Julie G.; Marques dos Santos, Mauricius; Anderson, Rebecca L.; Metwali, Nervana; Neilson, Julia W. (2016-08-04). "Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children". New England Journal of Medicine. 375 (5): 411–421. doi:10.1056/NEJMoa1508749. ISSN 0028-4793. PMC 5137793. PMID 27518660. 6. ^ Cooke, Graham S; Andrieux-Meyer, Isabelle; Applegate, Tanya L; Atun, Rifat; Burry, Jessica R; Cheinquer, Hugo; Dusheiko, Geoff; Feld, Jordan J; Gore, Charles; Griswold, Max G; Hamid, Saeed (2019-02-01). "Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission". The Lancet Gastroenterology & Hepatology. 4 (2): 135–184. doi:10.1016/S2468-1253(18)30270-X. ISSN 2468-1253. PMID 30647010. 7. ^ Peen, J.; Schoevers, R. A.; Beekman, A. T.; Dekker, J. (2010). "The current status of urban-rural differences in psychiatric disorders". Acta Psychiatrica Scandinavica. 121 (2): 84–93. doi:10.1111/j.1600-0447.2009.01438.x. ISSN 1600-0447. PMID 19624573. S2CID 15917409. 8. ^ McWhinney, S. R.; Goldberg, R. M.; McLeod, H. L. (2009). "Platinum Neurotoxicity Pharmacogenetics". Molecular Cancer Therapeutics. 8 (1): 10–16. doi:10.1158/1535-7163.MCT-08-0840. PMC 2651829. PMID 19139108. ## Notes[edit] * The Diseases of Occupations, Sixth Edition, Donald Hunter, C.B.E., D.Sc., M.D., F.R.C.P., Hodder and Stoughton, London. ISBN 0-340-22084-8, 1978. * Aviat Space Environ Med. 1991 Aug;62(8):795-7. * Use of sentinel health events (occupational) in computer assisted occupational health surveillance. Stockwell JR, Adess ML, Titlow TB, Zaharias GR. U.S. Coast Guard Office of Health Services, Washington, D.C. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Environmental disease	c0021508	29,980	wikipedia	https://en.wikipedia.org/wiki/Environmental_disease	2021-01-18T18:57:23	{"mesh": ["D007280"], "wikidata": ["Q3751709"]}
Persistent generalized lymphadenopathy (PGL) is enlarged, painless, non-tender lymph nodes occurring in a couple of different areas for more than three to six months for which no other reason can be found.[1] This condition occurs frequently in people in the latency period of HIV/AIDS.[1] The lymphatic system is part of the immune surveillance system. Blood contains fluid and blood cells. The fluid, which may contain suspended foreign material such as bacteria and viruses, seeps through blood vessel walls into the tissues, where it bathes the body cells and exchanges substances with them. Some of this lymph fluid is then taken up by lymphatic vessels and passed back to the heart, where it is again mixed with the blood. On its way, the fluid passes through the lymph nodes, small nodular organs located throughout the body but concentrated in certain areas such as the armpits or groin. These lymph nodes are also known as glands or lymphoid tissue. If they detect something foreign passing through them, they enlarge. This is called lymphadenopathy or swollen glands. Usually this is localized (for example, an infected spot on the scalp will cause lymph nodes in the neck on that same side to swell). However, when two or more lymph node groups are involved, it is called generalized lymphadenopathy. Usually this is in response to a significant systemic disease and will subside once the person has recovered. Sometimes it can persist long-term, even when no explanation for the lymphadenopathy can be found. PGL is often found in cases of autoimmune disease (where the body is attacking itself). These include diseases such as rheumatoid arthritis, lupus and sarcoidosis. Some forms of cancer will also cause PGL. Sometimes, despite exhaustive investigation, no cause for PGL is found. For the patient and the physician, this can continue to be a source of concern, but many adults have had PGL all their lives and suffered no ill effects. In others, the PGL may persist for a decade or more and then mysteriously subside. Children often have generalized lymphadenopathy of the head and neck, or even PGL, without the finding of a sinister cause. At puberty this usually disappears. The immune system of some people may be sensitized by exposure to a living exogenous irritant such as a bacterial or viral infection, which then results in PGL after the organism has been cleared from the body. In some cases the sensitization is caused by non-living exogenous irritants such as cyclic hydrocarbons (for example, resinous vapours) or pesticides and herbicides. ## References[edit] 1. ^ a b Dolin, [edited by] Gerald L. Mandell, John E. Bennett, Raphael (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). Philadelphia, PA: Churchill Livingstone/Elsevier. pp. Chapter 121. ISBN 978-0-443-06839-3.CS1 maint: extra text: authors list (link) * v * t * e Lymphatic disease: organ and vessel diseases Thymus * Abscess * Hyperplasia * Hypoplasia * DiGeorge syndrome * Ectopic thymus * Thymoma * Thymic carcinoma Spleen * Asplenia * Asplenia with cardiovascular anomalies * Accessory spleen * Polysplenia * Wandering spleen * Splenomegaly * Banti's syndrome * Splenic infarction * Splenic tumor Lymph node * Lymphadenopathy * Generalized lymphadenopathy * Castleman's disease * Intranodal palisaded myofibroblastoma * Kikuchi disease * Tonsils * see Template:Respiratory pathology Lymphatic vessels * Lymphangitis * Lymphangiectasia * Lymphedema * Primary lymphedema * Congenital lymphedema * Lymphedema praecox * Lymphedema tarda * Lymphedema–distichiasis syndrome * Milroy's disease * Secondary lymphedema * Bullous lymphedema * Factitial lymphedema * Postinflammatory lymphedema * Postmastectomy lymphangiosarcoma * Waldmann disease This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Persistent generalized lymphadenopathy	c0476486	29,981	wikipedia	https://en.wikipedia.org/wiki/Persistent_generalized_lymphadenopathy	2021-01-18T18:56:22	{"umls": ["C0476486"], "wikidata": ["Q7170411"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2018) An innate immune defect is a defect in the innate immune response that blunts the response to infection. These defects may occur in monocytes, neutrophils, natural killer cells, basophils, mast cells or complement proteins.[1] ## Contents * 1 Types * 1.1 Toll-like Receptor (TLR) immunodeficiencies * 1.1.1 MyD88 deficiency * 1.1.2 IRAK4 deficiency * 1.1.3 UNC93B and TLR3 deficiency * 1.2 Defects in IFN-γ/IL-12 signaling * 2 Diagnosis * 3 Treatment * 4 References ## Types[edit] ### Toll-like Receptor (TLR) immunodeficiencies[edit] Several TLR immunodeficiencies have been described in which cellular proteins that should transmit the message from the TLRs to the nucleus are abnormal. These signaling defects result in a failure of cytokines to be produced in response to bacterial infection. Disorders of this type include MyD88 deficiency, IRAK-4 deficiency other UNC93B deficiency and TLR3 mutations.[2] #### MyD88 deficiency[edit] Myeloid differentiation primary response gene 88 deficiency (MyD88) is a disorder of the innate immune system. It belongs to rare primary immunodeficiency characterized by an increased susceptibility to certain types of bacterial infections. Patients suffer from abnormally frequent and severe infections by a subset of bacteria known as pyogenic bacteria such as Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa. However, affected individuals have normal resistance to other common bacteria, virusesfungi, and parasites.[3] MYD88 deficiency is caused by mutations in the MYD88 gene and is inherited in an autosomal recessive manner. MYD88 gene provides instructions for making a protein that plays an important role in stimulating the immune system to respond to bacterial infection.[4] The MyD88 protein is part of a signaling pathway that is involved in early recognition of pathogens and the initiation of inflammation to fight infection. This signaling pathway is part of the innate immune response. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent by about age 10.[5] #### IRAK4 deficiency[edit] Interleukin-1 receptor-associated kinase deficiency is an inherited disorder of the immune system.[6] This immunodeficiency leads to recurrent infections caused by the pyogenic bacteria, for example Streptococcus pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa, but not by other infectious agents. Most patients with IRAK-4 deficiency suffer from invasive bacterial infections, which can cause sepsis, meningitis or they affect the joints that can lead to inflammation and arthritis.[7] These invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, patients are characterized by infections of the upper respiratory tract, eyes or skin. Although fever is a common reaction to bacterial infections, many people with IRAK-4 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe. Most patients have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent with age.[8] #### UNC93B and TLR3 deficiency[edit] UNC93B1 is very important signaling molecule involved in the production of interferon which plays a key role in the killing of viruses. Signaling through TLRs 3, 7, 8, and 9 normally induces production of interferons that are binding to viral RNA and destroy the virus. Deficiency of UNC93B1 or TLR3 leads for example to susceptibility to encephalitis caused by herpes simplex virus (HSV-1) due to decreased production of interferons in the central nervous system.[5] ### Defects in IFN-γ/IL-12 signaling[edit] Interferon-γ (IFN-γ)/interleukin-12 (IL-12) pathway deficiencies belongs to rare innate immune defects. They are characterized by susceptibility to salmonella infections and also mycobacteria. Mycobacteria is the family of bacteria which cause tuberculosis and other related infections.[9] This deficiency usually occurs in children's after tuberculosis vaccination. The other typical symptoms may be different skin infections, swollen lymph nodes or blood stream infections with an enlarged liver and spleen.[10] ## Diagnosis[edit] Patients with innate immune defects have generally intact adaptive immune systems with normal antibodies and T-cells. The main symptom is increased level of eosinophils in the blood, but elevated immunoglobulin E (IgE) levels may also be present. The diagnosis is made in suspected patients by measuring cytokine production by white blood cells, after stimulation by bacterial products. Testing of TLR function is becoming available through commercial reference laboratories. By abnormal tests is usually made repeat testing and also genetic testing.[11] ## Treatment[edit] The common treatment for these defects usually involves antibiotic therapy to treat acute infections. Prophylactic antibiotic therapy is also used. Some patients require immunoglobulin treatment.[11] ## References[edit] 1. ^ Allenspach E, Torgerson TR (May 2016). "Autoimmunity and Primary Immunodeficiency Disorders". Journal of Clinical Immunology. 36 Suppl 1 (1): 57–67. doi:10.1007/s10875-016-0294-1. PMID 27210535. 2. ^ Maglione PJ, Simchoni N, Cunningham-Rundles C (November 2015). "Toll-like receptor signaling in primary immune deficiencies". Annals of the New York Academy of Sciences. 1356 (1): 1–21. doi:10.1111/nyas.12763. PMC 4629506. PMID 25930993. 3. ^ von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, et al. (August 2008). "Pyogenic bacterial infections in humans with MyD88 deficiency". Science. 321 (5889): 691–6. doi:10.1126/science.1158298. PMC 2688396. PMID 18669862. 4. ^ Yamamoto T, Tsutsumi N, Tochio H, Ohnishi H, Kubota K, Kato Z, Shirakawa M, Kondo N (March 2014). "Functional assessment of the mutational effects of human IRAK4 and MyD88 genes". Molecular Immunology. 58 (1): 66–76. doi:10.1016/j.molimm.2013.11.008. PMID 24316379. 5. ^ a b Picard C, Casanova JL, Puel A (July 2011). "Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IκBα deficiency". Clinical Microbiology Reviews. 24 (3): 490–7. doi:10.1128/CMR.00001-11. PMC 3131061. PMID 21734245. 6. ^ Brietzke A, Goldammer T, Rebl H, Korytář T, Köllner B, Yang W, Rebl A, Seyfert HM (January 2014). "Characterization of the interleukin 1 receptor-associated kinase 4 (IRAK4)-encoding gene in salmonid fish: the functional copy is rearranged in Oncorhynchus mykiss and that factor can impair TLR signaling in mammalian cells". Fish & Shellfish Immunology. 36 (1): 206–14. doi:10.1016/j.fsi.2013.11.005. PMID 24239597. 7. ^ Maglione PJ, Simchoni N, Black S, Radigan L, Overbey JR, Bagiella E, et al. (December 2014). "IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens". Blood. 124 (24): 3561–71. doi:10.1182/blood-2014-07-587824. PMC 4256908. PMID 25320238. 8. ^ Picard C, von Bernuth H, Ghandil P, Chrabieh M, Levy O, Arkwright PD, et al. (November 2010). "Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency". Medicine. 89 (6): 403–25. doi:10.1097/MD.0b013e3181fd8ec3. PMC 3103888. PMID 21057262. 9. ^ Rosenzweig SD, Holland SM (February 2005). "Defects in the interferon-gamma and interleukin-12 pathways". Immunological Reviews. 203 (1): 38–47. doi:10.1111/j.0105-2896.2005.00227.x. PMID 15661020. 10. ^ Dorman SE, Holland SM (2000). "Interferon-gamma and interleukin-12 pathway defects and human disease" (PDF). Cytokine & Growth Factor Reviews. 11 (4): 321–33. doi:10.1016/S1359-6101(00)00010-1. PMID 10959079. 11. ^ a b Raje N, Dinakar C (November 2015). "Overview of Immunodeficiency Disorders". Immunology and Allergy Clinics of North America. 35 (4): 599–623. doi:10.1016/j.iac.2015.07.001. PMC 4600970. PMID 26454309. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Innate immune defect	None	29,982	wikipedia	https://en.wikipedia.org/wiki/Innate_immune_defect	2021-01-18T18:32:13	{"wikidata": ["Q48933598"]}
A number sign (#) is used with this entry because hereditary neuropathy with liability to pressure palsies (HNPP) can be caused by deletion of the gene encoding peripheral myelin protein-22 (PMP22; 601097); duplication of PMP22 causes Charcot-Marie-Tooth disease type 1A (CMT1A; 118220). Point mutation in PMP22 may result in HNPP or CMT1A. Clinical Features This disorder may have been described first by De Jong (1947) who reported a family in which 1 man and 4 women in 3 generations had recurrent peroneal neuropathy after digging potatoes in a kneeling position. Families were reported by Davies (1954) and by Earl et al. (1964). The latter group found that motor nerve conduction velocity (NCV) was reduced in some clinically normal family members. Staal et al. (1965) studied a family in which members in 4 generations showed transient unilateral peroneal palsies. The neuropathy manifested itself especially after prolonged work in a kneeling position. The family, living in Holland, knew the disease as 'bulb diggers' palsy. Other nerve palsies, such as ulna, occur as well (Davies, 1954). Females are less severely affected. In a Danish family, Roos and Thygesen (1972) observed 19 cases in 5 generations. The usual age of onset was between ages 15 and 20 years. The course of the disorder and the episodic nature of the neuropathy, which often was of mechanical provocation, suggested that it was the same disorder as that reported by Davies (1954), Wahle and Tonnis (1958), Earl et al. (1964), and others. Gabreels-Festen et al. (1992) called attention to atypical presentation of this disorder. Manifestations included pes cavus, scoliosis, and deafness. Madrid and Bradley (1975) reviewed the pathology, which is distinguished by the presence of sausage-shaped swellings of the myelin sheath, from which the term tomaculous neuropathy (Latin: tomaculum = sausage) was derived. Oda et al. (1990) demonstrated that the tomacula occur not only in sensory nerves but also in motor nerves. Fewings et al. (1985) reported a family. Sellman and Mayer (1987) reported conduction block in 5 nerves of 4 patients from 2 families with hereditary neuropathy with susceptibility to pressure palsies. Pathologic changes included segmental demyelination and tomaculous swellings. Barisic et al. (1990) described this disorder in monozygotic twin sisters and their father. Only 1 of the twins was clinically affected. She developed unilateral peroneal palsy 20 minutes following local pressure. A 25 to 70% reduction of motor and sensory conduction velocity was recorded in the clinically unaffected twin sister and in the father. Sural nerve biopsy showed 'sausage-like' formations. Cortisone was thought to be beneficial. Gouider et al. (1995) found mild electrophysiologic abnormalities in all symptomatic and asymptomatic deletion carriers, even in childhood. The most consistent findings were mild increase in the distal motor latency of the median nerve at the wrist, reduced sensory velocity in the palm, and delayed distal motor latency or reduced motor velocity in the peroneal nerve. The authors found that 37.5% of the subjects had absent ankle jerks and 12.5% had global areflexia. However, even these affected subjects did not have the severe slowing or motor nerve conduction velocities that could cause confusion with Charcot-Marie-Tooth disease type 1A. Sessa et al. (1997) described a father and son with a clinical presentation suggestive of HNPP but without typical tomacula on sural nerve biopsy. Molecular analysis confirmed a deletion at 17p11.2 in both patients. The father, a 45-year-old man, had acute onset of weakness and paresthesia in the right hand after sustained pressure. On examination 3 months later, motor deficit was present in the distribution of the right ulnar and median nerves as well as the right peroneal nerves. Pes cavus and hammertoes were present. The son, an 18-year-old parachutist, reported acute onset of weakness in his left shoulder after parachuting. Sessa et al. (1997) concluded that their observations supported the relevance of DNA analysis for the diagnosis of HNPP. Stogbauer et al. (1998) described a 29-year-old man who had had 3 episodes of painless palsy of the brachial plexus on either the right or the left side over a period of 6 years. These episodes were not preceded by strenuous use of the affected arm or by infections. Recovery had generally been excellent. Clinical examination showed no signs of generalized neuropathy. There was no pes cavus, and deep tendon reflexes were normal. Nerve conduction velocity studies showed prolonged distal motor latencies as well as prolonged motor nerve conduction velocities of the median and peroneal nerves. Sural nerve biopsy showed demyelination and remyelination, as well as focal myelin thickening (i.e., tomacula). Using intragenic polymorphisms of the PMP22 gene, Stogbauer et al. (1998) demonstrated that the maternal allele was lost, indicating deletion. It appeared to be a de novo deletion. There are conditions that mimic the symptoms of carpal tunnel syndrome (CTS; 115430) or predispose people to develop it. One such condition is HNNP, which most frequently manifests initially as a peripheral nerve entrapment, including median nerve compression at the carpal canal with delayed nerve conduction velocities. Potocki et al. (1999) described a family with dominantly inherited CTS that was associated with the chromosome deletion in 17p12 that causes HNPP. The authors suggested that HNPP is probably underdiagnosed because it typically has episodic and transient clinical manifestations. Stockton et al. (2001) evaluated 50 patients diagnosed with idiopathic CTS and found no instance of the chromosome 17 microdeletion that causes HNPP. Cruz-Martinez et al. (1997) reported 2 young females who developed unilateral peroneal nerve palsy after a diet for fashion reasons. Both patients had no previous history of palsies. In both, the palsy developed after nocturnal sleeping. A deletion of the PMP22 gene was demonstrated. Nerve conduction studies showed abnormalities in several relatives, some of whom had had palsies. Conduction block at the fibular head was in agreement with the hypothesis that the peroneal nerve becomes more susceptible to minor injuries, perhaps as a result of the loss of subcutaneous tissue. 'Slimmer paralysis' can occur in persons with HNPP and no history of previous palsy and probably can occur occasionally in individuals without the genetic defect. Weight loss must be added to trivial trauma of attraction or pressure as a precipitating factor in the genetic disorder. Shaibani et al. (1997) reported the case of a 22-year-old male who awoke with right foot drop and numbness found to be due to HNPP by nerve conduction studies, sural nerve biopsy, and molecular genetic analysis. Two months later he developed involuntary flexion/extension movements of the right toes with associated intermittent dystonic flexion of the right foot. Over the next 2 months these movements spread to the left foot and hand, and myoclonus of the left trapezius and rhomboid muscles appeared. This was thought to be the first case report of moving toes syndrome and segmental myoclonus in association with HNPP. Shaibani et al. (1997) concluded that the temporal and topographic patterns of spread of the abnormal movements suggested a central mechanism probably induced by peripheral pathology. Felice et al. (1999) described the cases of 2 children with liability to pressure palsies: a 13-year-old girl with a droopy left shoulder that was initially attributed to scoliosis; and a 16-year-old male who presented with right biceps brachii atrophy that was first observed by his pediatrician during a routine physical examination. Nerve conduction studies in both children showed evidence of superimposed diffuse demyelinating polyneuropathy. The girl had frequently carried a heavy backpack on both shoulders. Ohkoshi et al. (2001) reported a 19-year-old woman who presented with 2 episodes of hand drop and a subsequent episode of aphonia and hoarseness after sleeping in the prone position. Molecular analysis showed a common deletion on 17p11.2, confirming a diagnosis of HNPP. Laryngoscopic findings showed right vocal cord paresis which resolved after 6 weeks. The authors noted that vocal cord paralysis had not previously been reported in patients with HNPP. Korn-Lubetzki et al. (2002) described a Jewish Kurdish family in which a father and 2 daughters were diagnosed with inflammatory demyelinating polyneuropathy (139393) within a period of 10 years. DNA analysis identified the deletion on chromosome 17 that is typical of HNPP. The authors suggested that screening for the HNPP deletion in patients with atypical, recurrent, or familial inflammatory demyelinating polyneuropathy may be warranted. Hardon et al. (2002) described a previously healthy 2-year-old boy who presented with radial nerve palsy due to HNPP. He had developed acute severe weakness of his right hand, with no other symptoms. He had the habit of sleeping with his right arm hanging through the bars of his bed. Neurologic examination revealed a paralysis of the wrist and digit extensors and of the abductor pollicis longus muscle on the right. Neurophysiologic study showed a lower right radial nerve compound motor action potential with a normal nerve conduction velocity. The mother experienced numbness in digits I through III of her left hand and was found to have prolonged motor and sensory distal latencies and moderate slowing of the NCVs of the left median nerve compatible with carpal tunnel syndrome. Both mother and son were shown to have the same deletion in the 17p11.2 region. The boy's radial nerve palsy completely recovered in 2 months. Hardon et al. (2002) concluded that even in very young children with a negative family history but otherwise typical compressive nerve palsy, the possibility of HNPP needs to be considered. Kalfakis et al. (2002) reported a 37-year-old patient with non-Hodgkin lymphoma who was treated with a total of 4 mg vincristine and developed a tetraparesis, inability to walk, and areflexia. Genetic analysis identified the characteristic deletion of the PMP22 gene found in HNPP. Kalfakis et al. (2002) suggested that diagnostic investigations for hereditary neuropathies, including HNPP, should be performed before administration of vincristine. Studies of patients with HNPP show accentuated distal slowing along with nonuniform conduction abnormalities at segments liable to compression, suggesting a distal myelinopathy as an underlying pathophysiologic mechanism. Li et al. (2002) evaluated 12 patients with HNPP by standard nerve conduction studies and by conduction to more proximal muscles in the arm and leg. Three CMT1A patients and 6 healthy subjects were also evaluated as controls. Li et al. (2002) found accentuated distal slowing primarily in median and peroneal nerve segments liable to pressure palsies or repetitive trauma. However, the ulnar and tibial nerves, which are less liable to compression, had minimal changes. In addition, distal latencies to more proximal muscles in the arm and leg did not have distal slowing. Li et al. (2002) concluded that their findings did not support a distal myelinopathy as a determinant of the conduction abnormalities in HNPP. Li et al. (2007) reported clinical features of an Australian family with HNPP due to a frameshift mutation in the PMP22 gene (601097.0009); the family had previously been reported by Nicholson et al. (1994). The mean age at onset was 15 years, and all patients reported transient episodes of focal weakness or sensory loss. Nine of 11 patients had mild neurologic abnormalities and mild sensory abnormalities specifically in the feet. Electrophysiologic studies showed a pattern similar to HNPP resulting from the classic PMP22 deletion, with accentuated distal slowing occurring at sites subject to nerve compression. Three patients older than age 65 years had clinical and electrophysiologic evidence of length-dependent axonal loss. Further studies showed a 24% reduction of PMP22 levels in myelinated axons from dermal biopsies. Li et al. (2007) concluded that the phenotype of HNPP due to a PMP22 truncating mutation is indistinguishable from that due to the PMP22 1.5-Mb deletion. The findings indicated that a reduction in PMP22 is sufficient to induce the HNPP phenotype independent of effects from other genes. Diagnosis Aarskog and Vedeler (2000) described a quantitative PCR method for detecting both duplication and deletion of the PMP22 gene in CMT1A and HNPP, respectively. Their method of real-time quantitative PCR is a sensitive, specific, and reproducible method allowing 13 patients to be diagnosed in 2 hours. It involves no radioisotopes and requires no post-PCR handling. ### Differential Diagnosis Although HNPP shares clinical features with neuritis with brachial predilection (NAPB; 162100), they are considered distinct disorders (Gouider et al., 1994). Martinelli et al. (1989) described a family in which multiple members had intermittent brachial plexus palsy with the histologic findings of tomaculous neuropathy. Patients showed reduced interpupillary distance (hypotelorism), a finding that has been reported in neuritis with brachial predilection (Airaksinen et al., 1985; Jacob et al., 1961; Gardner and Maloney, 1968). Stogbauer et al. (1997) found linkage of neuritis with brachial predilection to 17q24-q25 in a region distinct from the 17p location of PMP22. Inheritance Roos and Thygesen (1972) thought X-linked dominant inheritance could not be excluded; autosomal dominant inheritance is proved, however, by the reports of father-to-son transmission by Davies (1954), Lhermitte et al. (1973), Cruz Martinez et al. (1977), Dubi et al. (1979), and Hinault et al. (1981). Subclinical electrophysiologic abnormalities permit demonstration of autosomal dominant inheritance (Staal et al., 1965; Debruyne et al., 1980). Molecular Genetics Using DNA markers, Chance et al. (1993) demonstrated a large interstitial deletion in distal 17p11.2 in persons with HNPP from 3 unrelated pedigrees (601097.0004). In 1 pedigree, de novo genesis of the deletion was documented. The deletion spanned approximately 1.5 Mb and included all markers that were known to be duplicated in CMT1A. The deleted region appeared uniform in all pedigrees and included the gene for peripheral myelin protein-22 (PMP22), the gene that is duplicated or the site of point mutation in CMT1A. Since the breakpoints in HNPP and CMT1A map to the same intervals in 17p11.2, these genetic disorders may be the result of reciprocal products of unequal crossover. The relationship of HNPP to the PMP22 gene was further supported by the demonstration by Mariman et al. (1993) of close linkage to DNA markers in the same region as that to which CMT1A had been mapped. In keeping with this possibility was the finding that D17S122, another marker from the CMT1A region, displayed apparent loss of heterozygosity in the large Dutch family they studied. Le Guern et al. (1994) found deletion of the D17S122 locus in all affected members of 7 French families with HNPP. In none was an allele contributed to the affected offspring by the affected parent, indicating an interstitial deletion within the 17p11.2 region. Thus, they confirmed the 'mirror image' deletion/duplication relationship of HNPP and CMT1A (see 601097.0004). Reisecker et al. (1994) described an apparently new mutation case due to deletion of the PMP22 gene inherited from the mother, who did not show the mutation. In 3 families with HNPP, Verhalle et al. (1994) confirmed the presence of a deletion on 17p11.2, which included all the markers known to be duplicated in CMT1A. Silander et al. (1994) found deletions in 17p11.2 in all affected patients in 13 Finnish families with HNPP. Mariman et al. (1994) found the 17p deletion in 15 of 22 Dutch families with HNPP diagnosed clinically, electrophysiologically, and, in all cases but 1, demonstration of tomacula on sural nerve biopsies. Single-strand conformation analysis of the protein coding regions of the PMP22 gene did not reveal mutations in patients from the 7 families without the 17p deletion. Umehara et al. (1995) found deletions in 17p11.2 in 2 unrelated Japanese families with HNPP. Gonnaud et al. (1995) found interstitial deletions of the 17p11.2 region in affected and unaffected members of 4 unrelated families, including an affected woman who did not receive the paternal allele for PMP22. Most de novo CMT1A duplications and HNPP deletions have been of paternal origin. LeGuern et al. (1996) investigated a rare case of de novo HNPP of maternal origin. Affected individuals in the family carried a deletion corresponding to the CMT1A/HNPP monomer unit. Segregation analysis of 17p12-p11 markers in the family indicated that the deletion was not generated by unequal crossing over between homologous chromosomes 17, as in de novo cases of paternal origin, but rather by an intrachromosomal rearrangement. The authors concluded that 2 distinct mechanisms can, therefore, lead to the same 17p11.2 deletion. Intrachromosomal rearrangement may be specific to maternal transmission. Lopes et al. (1999) sequenced the crossover hotspot in 28 patients with CMT1A or HNPP. Rearrangements in 3 of 4 HNPP patients were of maternal origin, and 2 of 4 were intrachromosomal in nature. Some patients exhibited chimeric sequences between proximal and distal repeat sequences in the region (CMT1A-REPs), suggesting conversion of DNA segments associated with the crossing-over. The finding of rearrangements supported a double-strand break repair model, which was first described in yeast (Szostak et al., 1983). Successive steps of this model are heteroduplex DNA formation, mismatch correction, and gene conversion. The authors hypothesized that the double-strand break repair model of DNA exchange may apply universally from yeasts to humans. Kleopa et al. (2004) reported a family from Cyprus in which 4 affected individuals had features of HNPP and/or CMT1A. One patient presented with typical HNPP, which later progressed to severe CMT1, 2 patients had HNPP with features of CMT1, and 1 patient had a chronic asymptomatic CMT1 phenotype. All 4 patients had the same heterozygous point mutation in the PMP22 gene (601457.0019). Kleopa et al. (2004) emphasized the broad phenotypic spectrum resulting from mutations in the PMP22 gene, as well as the phenotypic overlap of HNPP and CMT1A. Population Genetics In southwestern Finland, with a population of 435,000, Meretoja et al. (1997) established a diagnosis of HNPP in 69 patients from 23 unrelated families through family and medical history, clinical, neurologic, and neurophysiologic examinations, and demonstration of deletion at 17p11.2 in at least one member of each family. This gave a prevalence of at least 16/100,000, which is remarkably high. However, due to the insidious nature of HNPP, this is still probably an underestimation. The prevalence of HNPP was somewhat lower than that for CMT in this population, which agreed with the proposal that HNPP and CMT1A are reciprocal products of the same unequal crossing-over. Animal Model Maycox et al. (1997) found that transgenic mice expressing antisense PMP22 RNA exhibited modestly reduced levels of PMP22 together with a phenotype reminiscent of HNPP. Transgenic antisense homozygotes displayed a striking movement disorder and a slowing of nerve conduction that worsened with age. The authors found that a subset of axons had thickened myelin sheaths and tomacula in young adults, with significant myelin degeneration detected in older animals. History De Jong (1947) was the first to describe HNPP in a large family; Koehler (2003) reviewed important features of the article and provided a biographic sketch of de Jong (1909-1998). INHERITANCE \- Autosomal dominant NEUROLOGIC Peripheral Nervous System \- Peroneal muscle weakness, transient, recurrent due to peripheral neuropathy \- Radial, ulnar, and median nerve muscles may be affected \- Vocal cord paralysis has been reported \- Hyporeflexia \- Tomacula (sausage-shaped swellings of the myelin sheath) on nerve biopsy \- Segmental demyelination/remyelination on nerve biopsy \- Decreased motor nerve conduction velocities (NCV) MISCELLANEOUS \- Onset in first and second decades \- Precipitated by mechanical compression or pressure on nerve \- Allelic disorder to Charcot-Marie-Tooth disease type 1A ( 118220 ) MOLECULAR BASIS \- Caused by mutation in the gene encoding peripheral myelin protein-22 (PMP22, 601097.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	NEUROPATHY, HEREDITARY, WITH LIABILITY TO PRESSURE PALSIES	c0393814	29,983	omim	https://www.omim.org/entry/162500	2019-09-22T16:37:25	{"doid": ["0060843"], "mesh": ["C536965"], "omim": ["162500"], "orphanet": ["640"], "synonyms": ["Alternative titles", "POLYNEUROPATHY, FAMILIAL RECURRENT", "TOMACULOUS NEUROPATHY"], "genereviews": ["NBK1392"]}
A number sign (#) is used with this entry because of evidence that Alkuraya-Kucinskas syndrome (ALKKUCS) is caused by homozygous or compound heterozygous mutation in the KIAA1109 gene (611565) on chromosome 4q27. Description ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures (summary by Gueneau et al., 2018). Clinical Features Alazami et al. (2015) reported a fetus (family 13DG1900) with hydrocephalus, micrognathia, club feet, arthrogryposis with flexion deformity, pleural effusion, and Dandy-Walker malformation who died 1 hour after birth. Gueneau et al. (2018) reported 13 individuals from 10 unrelated families with a severe neurodevelopmental disorder, including the fetus reported by Alazami et al. (2015), who was born of consanguineous Saudi parents. Among the 13 patients reported by Gueneau et al. (2018), only 3 patients from 2 families were alive at 7, 11, and 13 years of age. Seven patients died between birth and the first months of life, and 3 affected pregnancies were terminated due to detection of the condition on prenatal ultrasound. In addition, 3 families had a history of recurrent miscarriages. The 3 living children (2 Lithuanian sibs and a girl from the UK) had global developmental delay from infancy and variable intellectual disability. The least severely affected patient was an 11-year-old girl from the UK with behavioral problems and learning disabilities who was able to walk and attend school. Prenatal ultrasound showed severe microcephaly (-5 SD) and reduced white matter volume. She had dysmorphic features, including hypertelorism, upslanting palpebral fissures, and high-arched palate, as well as a complex congenital heart disorder with tetralogy of Fallot. The 2 Lithuanian sibs had severe intellectual disability with absent language and hypotonia resulting in inability to stand without support, as well as early-onset epilepsy, plagiocephaly, and cerebral parenchymal rarefaction and ventriculomegaly on brain imaging. These 3 children had eye movement abnormalities, including oculomotor apraxia, hypermetropia, and strabismus, as well as mild joint contractures and foot deformities. The more severely affected 10 deceased infants and fetuses showed abnormalities on prenatal ultrasound, mainly arthrogryposis with flexion deformities, edema, and abnormal brain imaging. The patients had joint contractures, adducted thumbs, camptodactyly, clinodactyly, clenched hands, club foot, and overlapping fingers and toes. There were variable dysmorphic features, including macrocephaly, hydrocephalus, hypotelorism, hypertelorism, small eyes, low-set ears, posteriorly rotated ears, short nose, flattened nasal bridge, anteverted nares, retrognathia, cataracts, cystic hygroma, and webbed neck. Pre- and postnatal brain imaging showed multiple variable severe abnormalities in all patients. Abnormalities included enlarged ventricles, hypoplasia or absence of the corpus callosum, cortical lamination or migration defects, thin parenchymal mantle, gyral abnormalities, lissencephaly, neuronal heterotopia, prominent germinal matrix, and brainstem and cerebellar hypoplasia or dysplasia, often with a kinked brainstem. Additional congenital abnormalities were variable, but included pericardial or pleural effusions, heart or kidney abnormalities, and scrotum or penis hypoplasia. The infants that were born had hypotonia and breathing difficulties. Inheritance The transmission pattern of ALKKUCS in the families reported by Gueneau et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In a female infant, born of consanguineous Saudi parents, with ALKKUCS, Alazami et al. (2015) identified a homozygous nonsense mutation in the KIAA1109 gene (Y519X; 611565.0001). The patient was part of a large cohort of 143 multiplex consanguineous families with various neurodevelopmental disorders who underwent whole-exome sequencing. Functional studies of the variant were not performed. In 12 patients from 9 unrelated families with ALKKUCS, Gueneau et al. (2018) identified homozygous or compound heterozygous mutations in the KIAA1109 gene (see, e.g., 611565.0002-611565.0006). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families from whom parental DNA was available. Functional studies of the KIAA1109 variants and studies of patient cells were not performed, but Gueneau et al. (2018) noted that the only individuals who survived beyond infancy had biallelic missense mutations. Knockdown of the gene in zebrafish resulted in head defects and abnormal body curvature (see ANIMAL MODEL). Animal Model Verstreken et al. (2009) found that deletion of the KIAA1109 ortholog 'tweek' in Drosophila resulted in larval lethality. Rare homozygous flies that survived to adulthood were unable to walk or stand upright for long periods and exhibited seizures. The authors named the gene tweek after the cartoon character 'Tweek' from the television series 'South Park,' because the behavior of the adult mutant flies reminded them of the character. Tweek mutation resulted in NMJ synaptic vesicles that were reduced in number, but increased in size, with increased neurotransmitter release during spontaneous vesicle fusion events. The basal content of PI(4,5)P2 was reduced at tweek mutant NMJs, with altered PI(4,5)P2 distribution during neuronal activity and altered synaptic vesicle recycling. Gueneau et al. (2018) noted that Kiaa1109-null mice show embryonic lethality, but that some Drosophila with complete loss of Kiaa1109 can survive; the surviving animals present with severe neurologic defects, such as seizures and inability to stand or walk (tweek phenotype). Gueneau et al. (2018) found that morpholino knockdown of the kiaa1109 gene in zebrafish resulted in increased frequency of hydrocephalus or other head defects and increased body curvature compared to controls. However, unlike in mice, homozygosity for disruption of the kiaa1109 gene did not appear to result in lethality. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly Face \- Retrognathism Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Small eyes \- Hypotelorism \- Hypertelorism \- Upslanting palpebral fissures \- Cataracts \- Eye movement abnormalities \- Oculomotor apraxia \- Hypermetropia \- Strabismus Nose \- Short nose \- Flattened nasal bridge \- Anteverted nares Mouth \- High-arched palate Neck \- Webbed neck \- Cystic hygroma CARDIOVASCULAR Heart \- Cardiac defects (in some patients) \- Pericardial effusions (in some patients) RESPIRATORY \- Breathing difficulties, neonatal Lung \- Pleural effusions (in some patients) GENITOURINARY External Genitalia (Male) \- Hypoplastic scrotum \- Small penis Kidneys \- Renal defects (in some patients) SKELETAL \- Arthrogryposis Skull \- Plagiocephaly Limbs \- Flexion deformities Hands \- Overlapping fingers \- Camptodactyly \- Clenched hands \- Adducted thumbs \- Clinodactyly Feet \- Club feet \- Foot deformities \- Overlapping toes \- Cutaneous syndactyly MUSCLE, SOFT TISSUES \- Hypotonia \- Edema NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Poor or absent speech \- Inability to stand or walk (most patients) \- Seizures (in some patients) \- Lack of development \- Hydrocephalus \- Enlarged ventricles \- Cerebral parenchymal rarefaction \- Underdevelopment of the cerebral parenchyma \- Hypoplasia or absence of the corpus callosum \- Cortical lamination defects \- Neuronal migration defects \- Thin parenchymal mantle \- Gyral abnormalities \- Lissencephaly \- Neuronal heterotopia \- Prominent germinal matrix \- Brainstem hypoplasia \- Cerebellar hypoplasia \- Cerebellar dysplasia \- Kinked brainstem Behavioral Psychiatric Manifestations \- Behavioral problems MISCELLANEOUS \- Onset in utero \- Most affected individuals die in utero or soon after birth MOLECULAR BASIS \- Caused by mutation in the KIAA1109 gene (KIAA1109, 611565.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ALKURAYA-KUCINSKAS SYNDROME	c4693347	29,984	omim	https://www.omim.org/entry/617822	2019-09-22T15:45:01	{"omim": ["617822"]}
Tietze syndrome is an inflammatory condition characterized by chest pain and swelling of the cartilage around the ribs. Specifically, people with Tietze syndrome have swelling of the cartilage that joins the upper ribs to the breastbone. This is called the costochondral junction. Signs and symptoms of this condition usually develop in people who are under the age of 40. Symptoms include mild to severe chest pain that may extend into the arms and shoulders. The chest, shoulders, and arms may also have redness and warmth. In some cases, Tietze syndrome may resolve on its own without treatment, while other people experience patterns of pain followed by some relief of pain. Management for pain includes options such as minimizing physical activity, applying heat or ice as directed by your doctor, and taking pain medications and/or nonsteroidal anti-inflammatory drugs. Your doctor may also recommend seeing a chiropractor. Of note, this syndrome is different from Tietz syndrome, which is characterized by profound hearing loss from birth, fair skin, and light-colored hair. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tietze syndrome	c0040213	29,985	gard	https://rarediseases.info.nih.gov/diseases/10100/tietze-syndrome	2021-01-18T17:57:21	{"mesh": ["D013991"], "umls": ["C0040213"], "synonyms": ["Tietze's syndrome", "Chondropathia tuberosa", "Costochondral junction syndrome"]}
Pseudopseudohypoparathyroidism (PPHP) is an inherited condition that causes short stature, round face, and short hand bones. PPHP causes joints and other soft tissues in the body to harden. It also affects how bones are formed. As a result, PPHP can cause bone, joint, and nerve damage, and this damage can cause lasting pain. Some people with PPHP (10%) also have learning disability. PHPP is caused by mutations in the GNAS gene and is inherited in an autosomal dominant fashion. This condition is usually inherited from the father (genomic imprinting). PPHP is genetically related to pseudohypoparathyroidism type Ia (PHP-1a). Signs and symptoms are similar, however people with PPHP do not show resistance to parathyroid hormone while people with PHP-1a do. Obesity is characteristic for PHP-1a and may be severe, while obesity is less prominent and may be absent among people with PPHP. Both PHP-1a and PPHP are caused by mutations that affect the function of the GNAS gene. But people who inherit the mutation from their mother develop PHP-1a; whereas those who inherit the mutation from their father develop PPHP. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pseudopseudohypoparathyroidism	c0033835	29,986	gard	https://rarediseases.info.nih.gov/diseases/7860/pseudopseudohypoparathyroidism	2021-01-18T17:58:04	{"mesh": ["D011556"], "omim": ["612463"], "umls": ["C0033835"], "orphanet": ["79445"], "synonyms": ["PPHP", "Albright hereditary osteodystrophy without multiple hormone resistance", "Pseudopseudo-Hypoparathyroidism", "Pseudo-Pseudohypoparathyroidism"]}
Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of systemic scleroderma (systemic sclerosis) characterized by skin hardening (fibrosis) and problems in many organs of the body. The disease can occur at any age but mainly affects people between 40 and 50 years of age. Symptoms include Raynaud’s phenomenon; skin fibrosis beginning on the fingers and face that rapidly becomes generalized; "spider veins" (telangiectasias) on the thorax, face, lips, tongue, and fingers; gastroesophageal reflux; and difficulty eating (dysphagia) along with weight loss, vomiting, diarrhea or constipation. Dry mouth and dental involvement can occur. Joint pain (arthralgias), muscular pain, weakness, cramps, and destruction of the tips of the fingers or toes (acroosteolysis) are frequent. Severe problems involving the lung (fibrosis or pulmonary hypertension) and kidney problems may also occur. The exact cause of the condition is unknown. There is currently no cure. Treatment depends of the symptoms, but may include medication and surgery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Diffuse cutaneous systemic sclerosis	c1258104	29,987	gard	https://rarediseases.info.nih.gov/diseases/9751/diffuse-cutaneous-systemic-sclerosis	2021-01-18T18:00:52	{"mesh": ["D045743"], "umls": ["C1258104"], "orphanet": ["220393"], "synonyms": ["Diffuse cutaneous systemic sclerosis", "DcSSc", "Progressive cutaneous systemic scleroderma", "Progressive cutaneous systemic sclerosis", "Diffuse cutaneous systemic scleroderma"]}
## Summary ### Clinical characteristics. Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD. ### Diagnosis/testing. The diagnosis of IBMPFD is established in a proband with typical clinical findings and a heterozygous pathogenic variant in HNRNPA1, HNRNPA2B1, or VCP identified by molecular genetic testing. ### Management. Treatment of manifestations: Weight control to avoid obesity; physical therapy and stretching exercises to promote mobility and prevent contractures; mechanical aids (canes, walkers, orthotics, wheelchairs) for ambulation/mobility; surgical intervention for foot deformity and scoliosis; respiratory aids when indicated; social and emotional support; assisted living arrangements for muscle weakness and/or dementia; bisphosphonates to relieve pain and disability from PDB. Surveillance: At periodic intervals: echocardiogram and ECG to monitor for evidence of cardiomyopathy; pulmonary function studies; sleep study; alkaline phosphatase, skeletal x-rays and bone scans to monitor for PDB onset and effectiveness of therapy; assessment of behavior and mental status. ### Genetic counseling. IBMPFD is inherited in an autosomal dominant manner. An estimated 80% of affected individuals have an affected parent; approximately 20% have the disorder as a result of a de novo pathogenic variant. Each child of an individual with IBMPFD has a 50% chance of inheriting the pathogenic variant. Once the IBMPFD-causing pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings Inclusion body or nonspecific myopathy associated with Paget disease of bone with or without frontotemporal dementia (IBMPFD) should be suspected in individuals with a combination of the following findings. Myopathy that is usually proximal, progressive, and adult-onset: * Serum CK concentration is normal to mildly elevated (mean: 195 U/L; range: 40-1145 U/L; normal range: 20-222 U/L). * EMG (electromyogram) shows myopathic changes, and neuropathic changes including acute and chronic denervation. Skeletal muscle pathology is typically nonspecific (both light microscopy and electron microscopy). On light microscopy, findings characteristic of inclusion body myopathy consisting of rimmed vacuoles and cytoplasmic TAR DNA-binding protein 43 (TDP-43) and ubiquitin-positive inclusions may be visible in some fibers; the inclusions appear with time and can be observed at a later stage of the disease in some individuals. Paget disease of bone (PDB), suspected in individuals with spine or hip pain, bony tenderness, reduced height, pathologic fractures, long-bone or cranial-bone deformity, or hearing loss resulting from eighth-nerve compression by calvarial bony overgrowth. The diagnosis of PDB can be established with the following findings: * Elevated serum alkaline phosphatase concentration (mean: 359 U/L; range: 58-1724 U/L; normal range: 30-130 U/L) * Elevated urine concentrations of pyridinoline (PYD) and deoxypyridinoline (DPD): * Mean PYD: 153 IU/L (normal: 31.1 IU/L) * Mean DPD: 40 IU/L (normal: 6.8 IU/L) Note: The DPD/PYD ratio is not significantly different between affected persons (0.291) and normal controls (0.214). * Bone findings – either of the following: * Skeletal radiographs reveal diagnostic changes of coarse trabeculation; cortical thickening; and spotty sclerosis in the skull, pelvis, spine, and scapula that later becomes widespread. Radiographic findings of PDB are typically present ten to 15 years before the diagnosis of PDB can be made based on clinical findings. * Radionuclide scan shows focally increased bony uptake (a more sensitive indicator of PDB than skeletal radiographs). Frontotemporal dementia (FTD), diagnosed by comprehensive neuropsychological assessment that reveals behavioral alteration (e.g., lack of personal/social awareness, perseveration, disinhibition), early expressive or receptive language dysfunction, and relative preservation of memory, orientation, and praxis [Miller et al 1997]. Brain MRI studies reveal atrophy of anterior temporal and frontal lobes. ### Establishing the Diagnosis The diagnosis of IBMPFD is established in a proband with typical clinical findings and a heterozygous pathogenic variant in HNRNPA1, HNRNPA2B1, or VCP identified by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel, single-gene testing) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of IBMPFD is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of IBMPFD has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of IBMPFD molecular genetic testing approaches can include use of a multigene panel or single-gene testing: * A multigene panel that includes HNRNPA1, HNRNPA2B1, VCP and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Single-gene testing. If a multigene panel is not available, single-gene testing could be performed starting with VCP, pathogenic variants in which cause the vast majority of IBMPFD. Sequence analysis of VCP detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, gene-targeted deletion/duplication analysis can be considered; however, to date no large deletions or complex rearrangements involving VCP have been reported. If no pathogenic variant is found in VCP, sequence analysis of HNRNPA1 and HNRNPA2B1 can be performed. #### Option 2 When the diagnosis of IBMPFD is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia (IBMPFD) View in own window Gene 1, 2Proportion of IBMPFD Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 HNRNPA1<1%1 family 6Unknown 7 HNRNPA2B1<1%1 family 6Unknown 7 VCP>99%~100% 8Unknown 7 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Kim et al [2013] 7\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 8\. Al-Obeidi et al [2018] ## Clinical Characteristics ### Clinical Description Inclusion body myopathy associated with Paget disease of bone and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset Paget disease of bone (PDB), and premature frontotemporal dementia (FTD). Death typically occurs in the sixth or seventh decade from progressive respiratory failure. Recently Al-Obeidi et al [2018] studied 231 individuals (118 males and 113 females) from 36 families and found that myopathy, PDB, and FTD were present in 90%, 42%, and 30% of the individuals, respectively, beginning at an average age of 43, 41, and 56 years, respectively. Intra- and interfamilial variability is observed in this disorder. Myopathy. In families studied thus far, 90% of affected individuals had proximal limb-girdle weakness. * Diagnosis was at a mean age of 43 years (range: 3-61 years; typically 20s-40s). * Muscle weakness is usually proximal, involving the hip and shoulder girdle muscles; however, several individuals have had initial weakness of the muscles of the hands and feet. * Affected individuals experience difficulty walking upstairs and raising the arms above the shoulders. * The gait is typically waddling and the stance lordotic. * Weakness progresses and other limb and respiratory muscle groups become involved over time. Many affected individuals become wheelchair bound. * Muscle biopsy findings: * Light microscopy of muscle biopsy reveals nonspecific changes: variability in fiber size, type I fiber predominance, and atrophic and hypertrophic fibers. Fibers may contain single or multiple vacuoles. Rimmed vacuoles and cytoplasmic ubiquitin and TAR DNA-binding protein 43 (TDP-43) positive inclusions visible in some fibers are characteristic of inclusion body myopathy [Weihl et al 2008]. The inclusions appear with time and can be observed at a later stage of the disease in some individuals. In advanced cases, severe degenerative muscle changes and fatty replacement of muscle fibers may be noted. Inflammatory cells are absent. * Electron microscopy may show nonspecific cytoplasmic changes. The characteristic inclusions, composed of randomly oriented tubulofilaments roughly 15-21 nm in diameter, are seen in muscle nuclei and in cytoplasm. In one family, atrophic and vacuolated muscle fibers containing abundant cytoplasmic-paired helical filaments with epitopes of phosphorylated tau, congophilia, abnormal accumulation of β-amyloid precursor protein (βAPP) epitopes, and accumulation of apolipoprotein E (ApoE) were observed [Alvarez et al 1998]. Paget disease of bone (PDB). In families studied by Al-Obeidi et al [2018], 42% of affected individuals had PDB. The mean age at diagnosis was 41 years (range: 31-61 years). PDB was often asymptomatic, but was diagnosed based on the serum concentration of alkaline phosphatase and bone scans; therefore, it may be underdiagnosed. PDB involves focal areas of increased bone turnover that lead to complications such as bone pain, localized painful enlargement and deformity of the long bones, pathologic fractures (rare), and deafness. PDB typically manifests as spine and/or hip pain. Frontotemporal dementia (FTD). FTD is a degenerative condition of the frontal and anterior temporal lobes that differs from the dementia seen in disorders such as Alzheimer disease (see Alzheimer Disease Overview), Pick disease, and Creutzfeldt-Jakob disease (see Genetic Prion Disease). The areas of the brain affected by FTD control reasoning, personality, movement, speech, social graces, and language; memory is preserved. Among those studied, features were consistent with frontotemporal dementia. In the early stages, dysnomia, dyscalculia, comprehension deficits, and paraphasic errors were evident. Adjusting for aphasia, episodic memory is minimally impaired in the early stages. Progressive aphasia with inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia are noted. In families studied by Al-Obeidi et al [2018], approximately 30% of affected individuals had dementia. Mean age at diagnosis of dementia was 56 years (range: 30-86 years). This was a cross-sectional study and several individuals were not old enough to have developed FTD. Several individuals were in advanced stages of dementia when diagnosed with IBMPFD and detailed evaluation of the FTD was not possible in them. Dilated cardiomyopathy. In several individuals in the first family originally reported by Kimonis et al [2000] with limb-girdle myopathy and Paget disease of bone, cardiac failure and cardiomyopathy were noted in the later stages of the disease. Hübbers et al [2007] reported dilated cardiomyopathy characterized by ubiquitin-positive cytoplasmic aggregates and nuclear inclusions in an affected woman. This relatively uncommon finding was most recently reported in four of 18 affected individuals in a large family [Miller et al 2009]. See Dilated Cardiomyopathy Overview. Amyotrophic lateral sclerosis (ALS). Al-Obeidi et al [2018] reported that approximately 10% of individuals with IBMPFD had a previous diagnosis of ALS. Benatar et al [2013] conducted a systematic EMG characterization of 17 individuals with a diagnosis of IBMPFD from eight families and found that the EMG was abnormal in all individuals. The abnormality was purely neurogenic in four and mixed neurogenic/myopathic in seven individuals; thus, motor neuron involvement as characteristic of ALS was identified in 11/17 (65%) of the participants. An earlier study by Johnson et al [2010] identified a pathogenic variant in VCP in five of 289 (1%-2%) cases of familial ALS. The parent of one proband died at age 58 years with dementia, parkinsonism, Paget disease, and upper-limb muscle weakness, findings that strongly suggested IBMPFD. In another individual with a pathogenic variant in VCP and diagnosis of ALS, neuropsychological testing performed within one year of symptom onset suggested mild frontal lobe dysfunction. The study findings widened the spectrum of clinical findings associated with IBMPFD to include ALS. See Amyotrophic Lateral Sclerosis Overview. Parkinson disease (PD). PD is now known to be a feature of IBMPFD. Spina et al [2013] reported affected individuals with PD, but complete details were lacking. Al-Obeidi et al [2018] reported an incidence of 3.8% of Parkinson disease in a cohort of 231 individuals. Individuals with PD in IBMPFD tend to have classic symptoms and respond well to standard treatment [Chan et al 2012]. More recently, Regensburger et al [2017] reported an individual with VCP-related multisystem proteinopathy presenting as early-onset PD. Other phenotypic features including hepatic steatosis, cataracts, sensorimotor axonal neuropathy, pyramidal tract dysfunction, sphincter disturbance, and sensorineural hearing loss have been reported [Haubenberger et al 2005, Guyant-Maréchal et al 2006, Hübbers et al 2007, Djamshidian et al 2009, Miller et al 2009, Kumar et al 2010]. Neuropathology. VCP-related IBMPFD represents a novel class of neurodegenerative diseases called TDP-43 proteinopathies. Neuropathologic findings associated with IBMPFD include ubiquitin-positive neuronal intranuclear inclusions, dystrophic neuritis, and rare intracytoplasmic inclusions. These findings are abundant in the neocortex, less robust in limbic and subcortical nuclei, and absent in the dentate gyrus [Forman et al 2006, Neumann et al 2007, van der Zee et al 2009]. IBMPFD associated with pathogenic variants in either HNRNPA2B1 or HNRNPA1 has similar neuropathologic findings. ### Genotype-Phenotype Correlations Al-Obeidi et al [2018] analyzed clinical, radiologic, biochemical, and pathogenic variant data in 231 individuals from 36 families with 15 different pathogenic variants in VCP. Inter- and intrafamilial variability made establishing correlations difficult. No significant genotype-phenotype correlations were identified. No major differences are noted in the IBMPFD phenotype associated with pathogenic variants in either HNRNPA or HNRNPA2B1 except that the Paget disease of the bone seen with a pathogenic variant in HNRNPA2B1 is much more severe and involves the extremities – unlike the distribution in VCP-related disease, in which the sites of predilection are the spine, hip, pelvis, skull, and scapulae with relative sparing of the extremities [Waggoner et al 2002, Kim et al 2013] ### Penetrance Penetrance is almost complete; however, it is age related. Penetrance by phenotype (see Figure 1).There is marked intra- and interfamilial variability in severity, age of onset, distribution of weakness, and presence or absence of Paget disease, myopathy, and cognitive impairment [Al-Obeidi et al 2018]: #### Figure 1. IBMPFD phenotypes FTD = frontotemporal dementia; IBM = inclusion body myopathy; IBMPFD = inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia; PDB = Paget disease of bone * Presence of all three major manifestations: 10% of affected individuals * Presence of only two major manifestations in any combination: 50% of affected individuals * Each of the three major manifestations as an apparently isolated finding: * Inclusion body myopathy: 37% * Paget disease of bone: 5% * Frontotemporal dementia: 3% ### Prevalence IBMPFD is rare; the true prevalence is unknown. A study from the UK estimated a prevalence of approximately 1:300,000, although this was not a population ascertainment and the true incidence may be higher. Because previous studies have shown that individuals receive a diagnosis after a diagnostic odyssey of several years and are typically seen by numerous specialists in a number of disciplines (neurology, rheumatology, endocrinology, pain management, genetics), this disorder is considered to be significantly underdiagnosed. As the spectrum of disorders associated with pathogenic variants in VCP expands (as indicated by the number of worldwide publications) it is anticipated that the disorder will be increasingly recognized. Very few families have been reported with IBMPFD associated with a pathogenic variant in either HNRNPA1 or HNRNPA2B1; thus no estimates of prevalence are available. ## Differential Diagnosis The differential diagnosis of inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD) includes the following disorders. Limb-girdle muscular dystrophy (LGMD). Because the muscle biopsy is nonspecific in the majority of individuals with IBMPFD, the disorder has been labeled as an LGMD. GNE-related myopathy is characterized by adult-onset, slowly progressive distal muscle weakness that begins with gait disturbance and foot drop secondary to anterior tibialis muscle weakness. Weakness eventually includes the hand and thigh muscles, but commonly spares the quadriceps muscles, even in advanced disease. Affected individuals are usually wheelchair bound approximately 20 years after onset. If quadriceps sparing is incomplete, loss of ambulation tends to occur earlier. Muscle histopathology typically shows rimmed vacuoles and characteristic filamentous inclusions. GNE-related myopathy is inherited in an autosomal recessive manner. Sporadic inclusion-body myositis (sIBM) (OMIM 147421) is the most common acquired muscle disease in individuals of European heritage older than age 50 years. Pathologically it is characterized by inflammatory, degenerative, and mitochondrial changes that interact in an as-yet-unknown manner to cause progressive muscle degeneration and weakness. The cause is unknown, but it is thought to involve a complex interplay between environmental factors, genetic susceptibility, and aging [Askanas & Engel 2002]. Facioscapulohumeral muscular dystrophy (FSHD). FSHD typically presents before age 20 years with weakness of the facial muscles and the stabilizers of the scapula or the dorsiflexors of the foot. Severity is variable. Weakness is slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened. Although some controversy remains, FSHD is likely caused by inappropriate expression of the double homeobox-containing gene DUX4 in muscle cells. Inheritance of FSHD1 is autosomal dominant; inheritance of FSHD2 is digenic. Scapuloperoneal myopathy (SPM). Scapuloperoneal syndromes are heterogeneous (see OMIM 616852,181430, and 300695). They are characterized by weakness in the distribution of the shoulder girdle and peroneal muscles. Scapuloperoneal myopathy can resemble FSHD clinically. Amyotrophic lateral sclerosis (ALS). Because of asymmetric involvement and association of both distal and proximal muscle groups, individuals with IBMPFD have been misdiagnosed as having ALS. Published data indicate that up to 10% of individuals with VCP-confirmed IBMPFD had a previous diagnosis of ALS [Kimonis et al 2008]. Furthermore, studies indicate that pathogenic variants in VCP cause ALS, broadening the phenotype of IBMPFD to include motor neuron degeneration [Johnson et al 2010]. More than 30 genes are known to be associated with ALS. Paget disease of bone (PDB) (OMIM PS167250). Pathogenic variants in SQSTM1, ZNF687, TNFRSF11A, and TNFRSF11A have been associated with PDB. The SQSTM1 p.Pro392Leu pathogenic variant accounts for 16% of simplex cases (i.e., a single occurrence in a family) and 46% of familial cases in the French Canadian population. Frontotemporal dementia (FTD) causes a substantial proportion of primary degenerative dementia occurring before age 65 years. (See Chromosome 3-Linked Frontotemporal Dementia, GRN-Related Frontotemporal Dementia.) Frontotemporal dementia with parkinsonism-17 (FTDP-17) (OMIM 600274) is a presenile dementia affecting the frontal and temporal cortex and some subcortical nuclei. Clinical presentation is variable. Individuals may present with slowly progressive behavioral changes, language disturbances, and/or extrapyramidal signs. Some present with rigidity, bradykinesia, supranuclear palsy, and saccadic eye movement disorders. Symptoms usually start between ages 40 and 60 years, but may occur earlier or later. Disease duration is usually between five and ten years, but occasionally may be up to 20 to 30 years. The disease progresses over a few years into a profound dementia with mutism. FTDP-17 is caused by pathogenic variants in MAPT and inherited in an autosomal dominant manner. Alzheimer disease. Imaging studies in IBMPFD reveal atrophy of anterior temporal and frontal lobes. By contrast, more widespread atrophy or perfusion deficits – for example, involving parietal lobes – are more compatible with Alzheimer disease. Other disorders * Limb-girdle myopathy with bone fragility (also referred to as diaphyseal medullary stenosis with malignant fibrous histiocytoma [DMSMFH]) (OMIM 112250), associated with progressive myopathy of a limb-girdle distribution, bone fragility, poor healing of long bones, premature graying with thin hair, thin skin, hernias, and clotting disorders that may resemble IBMPFD. Skeletal radiographs demonstrate coarse trabeculation, patchy sclerosis, cortical thickening, and narrowing of medullary cavities. DMSMFH is caused by pathogenic variants in MTAP and inherited in an autosomal dominant manner. * Nasu Hakola disease (also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, or PLOSL) is a presenile dementia associated with loss of myelin, basal ganglia calcification, and bone cysts caused by pathogenic variants in TYROBP or TREM2 and inherited in an autosomal recessive manner. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD), the evaluations summarized in Table 2 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 2. Recommended Evaluations Following Initial Diagnosis in Individuals with IBMPFD View in own window System/ConcernEvaluation MuscleAssessment of muscle strength, muscle wasting, & tendon reflexes. EMG &/or muscle biopsy may be necessary, CardiacBaseline echocardiogram & ECG LungsBaseline pulmonary function studies BoneBlood alkaline phosphatase, urine pyridinoline studies, & bone scan studies followed by skeletal x-ray to evaluate distribution & severity of Paget disease of bone NeurologicBaseline neuropsychological studies of behavior & mental status OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations Individuals benefit from care by a multidisciplinary team including: a neuromuscular specialist, endocrinologist with expertise in Paget disease, specially trained nurses, pulmonologist, speech therapist, physical therapist, occupational therapist, respiratory therapist, nutritionist, psychologist, social worker, and medical geneticist/genetic counselor. ### Table 3. Treatment of Manifestations in Individuals with IBMPFD View in own window Manifestation/ConcernTreatmentConsiderations/Other MyopathyWeight controlTo avoid obesity Physical therapy & stretching exercisesTo promote mobility & prevent contractures Occupational therapy & use of mechanical aids (e.g., canes, walkers, orthotics, wheelchairs)As needed for ambulation & mobility Surgical intervention as needed for orthopedic complications (e.g., foot deformity, scoliosis) Use of respiratory aids if indicated Social & emotional support & stimulationTo maximize sense of social involvement & productivity & ↓ social isolation Assisted living arrangements as necessitated by muscle weakness &/or dementia Paget disease of boneTreatment w/potent bisphosphonatesCan ↓ alkaline phosphatase concentration & relieve pain & disability ### Surveillance ### Table 4. Recommended Surveillance for Individuals with IBMFD View in own window System/ConcernEvaluationFrequency CardiacEchocardiogram & ECG to monitor for evidence of cardiomyopathy * Obtain baseline studies. * If normal, reevaluate at 2-3-yr intervals or if symptomatic. LungsPulmonary function studiesAnnual Sleep studyAs needed BoneAlkaline phosphatase, skeletal x-rays, &/or bone scans to monitor therapy & (if symptomatic) PDB * Annual alkaline phosphatase * Bone scan only when alkaline phosphatase ↑ or symptoms of pain or bony deformity observed NeurologicAssessment of behavior & mental statusAt baseline & every 2-3 yrs ### Agents/Circumstances to Avoid Individuals and their families should be educated about safety precautions and environmental modification in the home and at work. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia	c1833662	29,988	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1476/	2021-01-18T21:17:55	{"mesh": ["C563476"], "synonyms": ["IBMPFD", "Inclusion Body Myopathy with Early-Onset Paget Disease of Bone and/or Frontotemporal Dementia", "Multisystem Proteinopathy"]}
A number sign (#) is used with this entry because of evidence that pulmonary surfactant metabolism dysfunction-4 (SMDP4) is caused by mutation in the CSF2RA gene (306250) on chromosome Xp22. Description Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. Three forms of PAP have been described: hereditary (usually congenital), secondary, and acquired. Hereditary PAP is associated with mutations in the CSF2RA gene or in genes encoding surfactant proteins. Secondary PAP develops in conditions in which there are reduced numbers or functional impairment of alveolar macrophages and is associated with inhalation of inorganic dust (silica) or toxic fumes, hematologic malignancies, pharmacologic immunosuppression, infections, and impaired CSF2RB (138960) expression. Acquired PAP (610910), the most common form, usually occurs in adults and is caused by neutralizing autoantibodies to CSF2 (138960) (Martinez-Moczygemba et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of congenital pulmonary surfactant metabolism dysfunction, see SMDP1 (265120). Clinical Features Martinez-Moczygemba et al. (2008) reported a 4-year-old female with symptoms associated with Turner syndrome and respiratory insufficiency who had been diagnosed with PAP at age 3 years. She had exhibited respiratory failure caused by respiratory syncytial virus pneumonia in the first month of life, with a diagnosis of reactive airways disease. The patient presented with respiratory distress and hypoxemia, with a 'crazy paving' pattern on chest imaging. Open lung biopsy revealed alveolar proteinaceous material without alveolar epithelial hyperplasia or chronic interstitial changes, and bronchoalveolar lavage revealed proteinaceous material and foamy macrophages. ELISA showed no anti-CSF2 antibodies and elevated baseline CSF2 serum levels. Exogenous CSF2 administration, which may be efficacious in some patients with acquired PAP, resulted in no clinical improvement. Suzuki et al. (2008) reported 2 sisters with PAP. The index patient presented at age 6 years with a 2-year history of progressive tachypnea and failure to thrive. Both parents were well developed and healthy with no history of lung disease. Examination of the patient revealed moderate tachypnea, mild tachycardia, and inspiratory crackles. Pulmonary function testing showed severe restrictive impairment. Oxygen saturation was 88% while breathing room air and decreased while talking or walking a short distance. PAP diagnosis was suspected based on chest radiography and confirmed by histopathologic examination of lung tissue. CSF2 autoantibodies were absent. Serum SPD (SFTPD; 178635) was increased in the patient compared with her parents and controls. The patient's 8-year-old sister, who was thought to be healthy, also had increased serum SPD. Subsequent clinical evaluation revealed that the sister had poor growth, a diffusion capacity for carbon dioxide of 57% that predicted, and mild patchy ground glass opacities throughout both lungs, consistent with a diagnosis of PAP. Molecular Genetics Using flow cytometry, Martinez-Moczygemba et al. (2008) found that CSF2RA was absent on monocytes from the patient they reported with PAP. The patient's mother expressed CSF2RA on all monocytes, whereas the patient's father and sister expressed CSF2RA only on a subpopulation of monocytes. Stimulation of granulocytes with CSF2 induced upregulation of CD11B (ITGAM; 120980) in the mother, but not the patient. Karyotypic analysis showed that the patient had 1 X chromosome of apparently normal length and 1 X chromosome with a truncated Xp arm that did not hybridize with a PAR1 probe. RT-PCR analysis detected expression of CSF2RA and IL3RA (308385), which are located in PAR1, in leukocytes from the patient's family members, but not in those from the patient. PCR analysis of the 11 coding exons of the CSF2RA gene detected a deletion of exons 5 through 13 (306250.0001), providing a genetic basis for the absence of CSF2RA mRNA and protein. The authors noted that the deletion affecting CSF2RA likely extends to IL3RA, but that impaired IL3 (147740) responses do not result in PAP in mice and have not been associated with PAP in humans. Using flow cytometry, Suzuki et al. (2008) found that both CSF2RA and CSF2RB were present on leukocytes from the 2 sisters they reported with PAP, as well as all family members tested. However, Western blot analysis showed that the affected sisters expressed only a truncated form of CSF2RA, whereas their father was heterozygous for the normal and truncated forms, and their mother expressed only normal CSF2RA. CSF2 binding and CSF2-dependent signaling were severely reduced, but not abolished, in the sisters, and their CD11B stimulation test was abnormal. Suzuki et al. (2008) identified a mutation in the CSF2RA gene in the affected sisters that resulted in a gly174-to-arg (G174R; 306250.0002) substitution that altered 1 of 11 predicted N-glycosylation sites. The father was heterozygous for the G174R mutation, but the mother had only wildtype CSF2RA, suggesting a deletion of 1 maternal CSF2RA allele. PCR analysis showed that CSF2RA copy number was reduced in the sisters and their mother, but not in the father. FISH analysis demonstrated a 1.6-Mb deletion of PAR1, including the CSF2RA gene, in 1 X chromosome of the sisters and mother. Transfection of CSF2RA with the G174R mutation into 293 cells faithfully reproduced the CSF2 signaling defect at physiologic CSF2 concentrations. At high CSF2 concentrations, similar to those observed in the index patient, signaling was partially rescued, thereby providing a molecular explanation for the slow disease progression in the 2 sisters. Suzuki et al. (2008) concluded that PAP may be caused by compound heterozygous abnormalities affecting the CSF2RA gene, and that CSF2 signaling is critical for surfactant homeostasis in humans. Clinical Management Martinez-Moczygemba et al. (2008) noted that diagnosing PAP due to CSF2RA deficiency has important therapeutic implications, since bone marrow transplantation from a healthy donor should result in CSF2RA expression on leukocytes and thereby cure the impaired surfactant homeostasis that underlies PAP. The patient they reported with PAP due to CSF2RA deficiency underwent bone marrow transplantation, but she died of an infectious respiratory complication 4 weeks after transplantation, before the establishment of immune competency. Animal Model Using Csf2rb (138981)-null mice, which develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (HPAP) in children with CSF2RA or CSF2RB mutations, Suzuki et al. (2014) showed that pulmonary macrophage transplantation (PMT) of either wildtype or Csf2rb gene-corrected macrophages without myeloablation was safe and well tolerated. One administration corrected lung disease and secondary systemic manifestations, normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least 1 year, as did therapeutic effects. Suzuki et al. (2014) concluded that their findings identified mechanisms regulating alveolar macrophage population size in health and disease, indicated that GMCSF (138960) is required for phenotypic determination of alveolar macrophages, and supported translation of PMT as the first specific therapy for children with hereditary pulmonary alveolar proteinosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SURFACTANT METABOLISM DYSFUNCTION, PULMONARY, 4	c2931035	29,989	omim	https://www.omim.org/entry/300770	2019-09-22T16:19:36	{"doid": ["12120"], "mesh": ["C535832"], "omim": ["300770"], "orphanet": ["264675"], "synonyms": ["Alternative titles", "PULMONARY ALVEOLAR PROTEINOSIS, CONGENITAL, 4", "PAP DUE TO CSF2RA DEFICIENCY", "CSF2RA DEFICIENCY"]}
A number sign (#) is used with this entry because Griscelli syndrome type 3 (GS3), which is characterized by hypomelanosis with no immunologic or neurologic manifestations, can be caused by mutation in the melanophilin (MLPH; 606526) or MYO5A (160777) genes. For a discussion of phenotypic and genetic heterogeneity in Griscelli syndrome, see the entry for GS1 (214450). Clinical Features Sanal et al. (2002) reported 2 patients with silver-gray hair, eyebrows, and eyelashes who had large clumps of pigment, typical of Griscelli syndrome, on microscopic analysis of their hair shafts. The patients developed no other manifestations over 6 and 8 years of follow-up, respectively. Molecular Genetics In the 2 patients reported by Sanal et al. (2002) with hypopigmentation without any immunologic or neurologic manifestations, Menasche et al. (2003) identified a homozygous mutation in the MLPH gene (606526.0001) in 1 patient and homozygous deletion of the F-exon of the MYO5A gene (160777.0004) in the other. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Silver-gray eyelashes \- Silver-gray eyebrows SKIN, NAILS, & HAIR Hair \- Silver-gray hair \- Silver-gray eyelashes \- Silver-gray eyebrows \- Large clumps of pigment irregularly distributed along hair shaft (light microscopy) NEUROLOGIC \- No neurologic abnormalities IMMUNOLOGY \- No immunologic abnormalities MISCELLANEOUS \- Genetic heterogeneity \- See also Griscelli syndrome, type 1 ( 214450 ) for a similar disorder with characteristic neurologic disease and Griscelli syndrome, type 2 ( 607624 ) for a similar disorder with characteristic immunodeficiency/hemophagocytic syndrome. MOLECULAR BASIS \- Caused by mutation in the myosin 5a gene (MYO5A, 160777.0004 ) \- Caused by mutation in the melanophilin gene (MLPH, 606526.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	GRISCELLI SYNDROME, TYPE 3	c1836573	29,990	omim	https://www.omim.org/entry/609227	2019-09-22T16:06:28	{"doid": ["0060834"], "mesh": ["C537303"], "omim": ["609227"], "orphanet": ["381", "79478"], "synonyms": ["Chédiak-Higashi-like syndrome", "Griscelli-Pruniéras syndrome", "Partial albinism-immunodeficiency syndrome"]}
Odontogenic cyst are a group of jaw cysts that are formed from tissues involved in odontogenesis (tooth development). Odontogenic cysts are closed sacs, and have a distinct membrane derived from rests of odontogenic epithelium. It may contain air, fluids, or semi-solid material. Intra-bony cysts are most common in the jaws, because the mandible and maxilla are the only bones with epithelial components. That odontogenic epithelium is critical in normal tooth development. However, epithelial rests may be the origin for the cyst lining later. Not all oral cysts are odontogenic cyst. For example, mucous cyst of the oral mucosa and nasolabial duct cyst are not of odontogenic origin. In addition, there are several conditions with so-called (radiographic) 'pseudocystic appearance' in jaws; ranging from anatomic variants such as Stafne static bone cyst, to the aggressive aneurysmal bone cyst.[1] ## Contents * 1 Classification[2] * 2 Cystic neoplasm * 3 Diagnosis * 4 Treatment * 5 See also * 6 References ## Classification[2][edit] Relative incidence of odontogenic cysts.[3] * I. Cysts of the jaws * A. Epithelial-lined cysts * 1\. Developmental origin * (a) Odontogenic * i. Gingival cyst of infants * ii. Odontogenic keratocyst * iii. Dentigerous cyst * iv. Eruption cyst * v. Gingival cyst of adults * vi. Developmental lateral periodontal cyst * vii. Botryoid odontogenic cyst * viii. Glandular odontogenic cyst * ix. Calcifying odontogenic cyst * (b) Non-odontogenic * i. Midpalatal raphé cyst of infants * ii. Nasopalatine duct cyst * iii. Nasolabial cyst * 2\. Inflammatory origin * i. Radicular cyst, apical and lateral * ii. Residual cyst * iii. Paradental cyst and juvenile paradental cyst * iv. Inflammatory collateral cyst * B. Non-epithelial-lined cysts * 1\. Solitary bone cyst * 2\. Aneurysmal bone cyst * II. Cysts associated with the maxillary antrum * 1\. Mucocele * 2\. Retention cyst * 3\. Pseudocyst * 4\. Postoperative maxillary cyst * III. Cysts of the soft tissues of the mouth, face and neck * 1\. Dermoid and epidermoid cysts * 2\. Lymphoepithelial (branchial) cyst * 3\. Thyroglossal duct cyst * 4\. Anterior median lingual cyst (intralingual cyst of foregut origin) * 5\. Oral cysts with gastric or intestinal epithelium (oral alimentary tract cyst) * 6\. Cystic hygroma * 7\. Nasopharyngeal cyst * 8\. Thymic cyst * 9\. Cysts of the salivary glands: mucous extravasation cyst; mucous retention cyst; ranula; polycystic (dysgenetic) disease of the parotid * 10\. Parasitic cysts: hydatid cyst; Cysticercus cellulosae; trichinosis * Buccal bifurcation cyst * Calcifying odontogenic cyst * Dentigerous cyst (associated with the crowns of non-erupted teeth) * Glandular odontogenic cyst * Keratocyst (in the jaws, these can appear solitary or associated with the Gorlin-Goltz or Nevoid basal cell carcinoma syndrome. * Paradental cyst * Periapical cyst (The periapical cyst, otherwise known as radicular cyst, is the most common odontogenic cyst.) * Radicular cyst (associated with the roots of non-vital teeth, also known as Periapical cyst) * Residual cyst ## Cystic neoplasm[edit] Most cysts in the body are benign (dysfunctional) tumors, the result of plugged ducts or other natural body outlets for secretions. However, sometimes these masses are considered neoplasm: * Keratocyst * Calcifying odotogenic cyst * According to the current (2005) classification of the World Health Organization, both (parakeratizied) odontogenic keratocyst and calcifying odotogenic cyst have neoplastic characteristics, thus renamed as Keratocystic odontogenic tumor and Calcifying odotogenic tumor, respectively. * Cystic ameloblastoma * Long standing dentigerous cyst, odontogenic keratocyst, and residual cyst may have neoplastic potential converting into the locally aggressive ameloblastoma, or the malignant squamous cell carcinoma and mucoepidermoid carcinoma. ## Diagnosis[edit] Cholesterol clefts in a periapical (radicular) cyst. On histopathology, cholesterol clefts indicate mainly a periapical (radicular) cyst[4] or an inflamed dentigerous cyst.[5] ## Treatment[edit] Treatment ranges from simple enucleation of the cyst to curettage to resection. For example, small radicular cyst may resolved after successful endodontic ("root-canal") treatment. Because of high recurrence potential and aggressive behaviour, curettage is recommended for keratocyst. However, the conservative enucleation is the treatment of choice for most odontogenic cysts. The removed cyst must be evaluated by pathologist to confirm the diagnosis, and to rule out other neoplastic lesions with similar clinical or radiographic features (e.g., cystic or solid ameloblastoma, central mucoepidermoid carcinoma).[6] There are cysts, e.g. buccal bifurcation cyst with self-resolation nature, in which close observation can be employed unless the cyst is infected and symptomatic.[7] ## See also[edit] * Cyst * Mucous cyst of the oral mucosa ## References[edit] 1. ^ Zadik, Yehuda; Aktaş Alper; Drucker Scott; Nitzan W Dorrit (2012). "Aneurysmal bone cyst of mandibular condyle: A case report and review of the literature". J Craniomaxillofac Surg. 40 (8): e243–8. doi:10.1016/j.jcms.2011.10.026. PMID 22118925. 2. ^ Shear, Mervyn; Speight, Paul (2007). Cysts of the oral and maxillofacial regions (4th ed.). Oxford: Blackwell Munksgaard. ISBN 978-14051-4937-2. 3. ^ Leandro Bezerra Borges; Francisco Vagnaldo Fechine; Mário Rogério Lima Mota; Fabrício Bitu Sousa; Ana Paula Negreiros Nunes Alves (2012). "Odontogenic lesions of the jaw: a clinical-pathological study of 461 cases". Revista Gaúcha de Odontologia. 60 (1). 4. ^ Annie S. Morrison; Kelly Magliocca. "Mandible & maxilla - Odontogenic cysts - Periapical (radicular) cyst". Pathology Outlines. Topic Completed: 1 March 2014. Revised: 13 December 2019 5. ^ Kelly Magliocca; Annie S. Morrison. "Mandible & maxilla - Odontogenic cysts - Dentigerous". Pathology Outlines. Topic Completed: 1 October 2013. Revised: 2 December 2019 6. ^ Pou, Anna. "Odontogenic cysts and tumors". UTMB Department of otolaryngology. Archived from the original on 23 August 2012. Retrieved 11 September 2012. 7. ^ Zadik Y, Yitschaky O, Neuman T, Nitzan DW (May 2011). "On the Self-Resolution Nature of the Buccal Bifurcation Cyst". J Oral Maxillofac Surg. 69 (7): e282–e284. doi:10.1016/j.joms.2011.02.124. PMID 21571416.[dead link] * v * t * e Acquired tooth disease Hard tissues * Caries (tooth decay) * Attrition * Abrasion * Erosion * Hypercementosis * tooth resorption (External resorption, Internal resorption, Root resorption) Pulp/periapical (Endodontal) Pulpal * External resorption * Internal resorption * Irreversible pulpitis * Reversible pulpitis * Pulp necrosis * Pink tooth of Mummery Periapical * Acute apical periodontitis * Chronic apical periodontitis * Combined periodontic-endodontic lesions * Fistula * Periapical abscess * Phoenix abscess * Vertical root fracture Ungrouped * Pulpitis * Radicular cyst * Periapical abscess Gingiva/periodontal (Periodontal) * Gingivitis * Periodontitis (Chronic periodontitis) * Periodontal disease Bone cyst * Dentigerous cyst * Calcifying odontogenic cyst * Glandular odontogenic cyst Other * Cracked tooth syndrome To be grouped from periodontology Diagnoses * Chronic periodontitis * Localized aggressive periodontitis * Generalized aggressive periodontitis * Periodontitis as a manifestation of systemic disease * Necrotizing periodontal diseases * Abscesses of the periodontium * Combined periodontic-endodontic lesions Pathogenesis * A. actinomycetemcomitans * Capnocytophaga sp. * F. nucleatum * P. gingivalis * P. intermedia * T. forsythia * T. denticola Pathologic entities * Calculus * Edentulism * Fremitus * Furcation defect * Gingival enlargement * Gingival pocket * Gingivitis * Horizontal bony defect * Linear gingival erythema * Occlusal trauma * Periodontal pocket * Periodontal disease * Periodontitis * Plaque * Recession * Vertical bony defect * v * t * e Cystic diseases Respiratory system * Langerhans cell histiocytosis * Lymphangioleiomyomatosis * Cystic bronchiectasis Skin * stratified squamous: follicular infundibulum * Epidermoid cyst and Proliferating epidermoid cyst * Milia * Eruptive vellus hair cyst * outer root sheath * Trichilemmal cyst and Pilar cyst and Proliferating trichilemmal cyst and Malignant trichilemmal cyst * sebaceous duct * Steatocystoma multiplex and Steatocystoma simplex * Keratocyst * nonstratified squamous: Cutaneous ciliated cyst * Hidrocystoma * no epithelium: Pseudocyst of the auricle * Mucocele * other and ungrouped: Cutaneous columnar cyst * Keratin implantation cyst * Verrucous cyst * Adenoid cystic carcinoma * Breast cyst Human musculoskeletal system * Cystic hygroma Human digestive system * oral cavity: Cysts of the jaws * Odontogenic cyst * Periapical cyst * Dentigerous cyst * Odontogenic keratocyst * Nasopalatine duct cyst * liver: Polycystic liver disease * Congenital hepatic fibrosis * Peliosis hepatis * bile duct: Biliary hamartomas * Caroli disease * Choledochal cysts * Bile duct hamartoma Nervous system * Cystic leukoencephalopathy Genitourinary system * Polycystic kidney disease * Autosomal dominant polycystic kidney * Autosomal recessive polycystic kidney * Medullary cystic kidney disease * Nephronophthisis * Congenital cystic dysplasia Other conditions * Hydatid cyst * Von Hippel–Lindau disease * Tuberous sclerosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Odontogenic cyst	c0028879	29,991	wikipedia	https://en.wikipedia.org/wiki/Odontogenic_cyst	2021-01-18T19:04:09	{"mesh": ["D009807"], "umls": ["C0028879"], "wikidata": ["Q7077950"]}
Glassy cell carcinoma of the cervix uteri is a rare cancer of the uterine cervix, composed of nests of large neoplastic cells with 'ground glass' cytoplasm, surrounded by a stroma with prominent eosinophilic infiltrates. It is a poorly differentiated, aggressive variant of adenosquamous carcinoma that usually affects young women and presents with dysfunctional vaginal bleeding and lower abdominal pain. Distant metastases to the lungs, liver spleen or bones are often present at the time of diagnosis. It is often associated with high-risk HPV-infection (types 18, 16 and 32). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Glassy cell carcinoma of the cervix uteri	None	29,992	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=213833	2021-01-23T18:38:54	{"icd-10": ["C53.0", "C53.1", "C53.8"]}
A number sign (#) is used with this entry because of evidence that boomerang dysplasia (BOOMD) is caused by heterozygous mutation in the FLNB gene (603381) on chromosome 3p14. Clinical Features Kozlowski et al. (1981), Tenconi et al. (1983), and Kozlowski et al. (1985) each described 1 patient with a disorder termed boomerang dysplasia because of the unusual shape of the long bones of the legs. All 3 patients died in the neonatal period. They had dwarfism with short, bowed, rigid limbs and characteristic facies. In particular, the nose had a broad root and severe hypoplasia of the nares and septum. Radiographically, the radii and fibulae were absent, while the remaining long bones had the boomerang configuration. The iliac bodies were small and ossification in the lower spine and digits was retarded. All 3 patients were males, from Japan, Italy, and Australia. Winship et al. (1990) described a fourth patient, again a male infant. Shortened boomerang-shaped radii, femora, and tibias were noted. The vertebral borders showed coronal clefts. Hunter and Carpenter (1991) described a patient with apparent manifestations of both type I atelosteogenesis (108720) and boomerang dysplasia and concluded that these disorders are 'part of a spectrum, probably reflecting a common etiology.' Greally et al. (1993) presented a case that supported the hypothesis of Hunter and Carpenter (1991). Urioste et al. (1997) reported a possible case of boomerang dysplasia in the offspring of healthy, nonconsanguineous parents. Delivery was induced at 27 weeks of gestation. He was markedly disproportionate with a large head, very short and flipper-like limbs, numerous malformations, and generalized alopecia. Radiologic skeletal examination showed generalized underossification. The pubic bones were absent. Only one well-ossified and bowed bone was observed in the legs, which had the appearance of a boomerang. Histologic studies showed multinucleated giant chondrocytes in the cartilage. The karyotype was apparently normal. Odent et al. (1999) reported a female fetus of 24 weeks' gestation with clinical and radiologic features compatible with boomerang dysplasia. Histopathology, however, showed unusual lateral fan-shaped diaphyseal ossification. Odent et al. (1999) concluded that these features represented a variant of boomerang dysplasia with clinical characteristics of both atelosteogenesis type I and boomerang dysplasia. Wessels et al. (2003) reported a male fetus with boomerang dysplasia that was diagnosed by ultrasound at 16 weeks of gestation. Delivery was induced at 17 weeks of gestation; postdelivery examination revealed dwarfism and micromelia of the 4 limbs. In each limb only 1 of the 3 long tubular bones was ossified; the presumed radius had a boomerang shape and the presumed tibia had a segment shape. The hands and feet were very short and broad with severe brachydactyly. The ossification centers of all vertebrae except for T11-12 and L1-3 were absent. The thorax was small and bell-shaped with short ribs. The skull showed micrognathia. Molecular Genetics In a 22-week male fetus previously studied by Krakow et al. (2004) and a 17-week male fetus previously described by Wessels et al. (2003), both diagnosed with boomerang dysplasia, Bicknell et al. (2005) identified heterozygosity for mutations in the FLNB gene, leu171 to arg (L171R; 603381.0009) and ser235 to pro (S235P; 603381.0010), respectively. Limbs \- Short, bowed, rigid limbs Radiology \- Absent radii and fibulae with boomerang shaped remaining long bones \- Small iliac bodies \- Retarded ossification of lower spine and digits Inheritance \- Autosomal dominant Misc \- Neonatal death Growth \- Congential dwarfism Nose \- Broad nasal root \- Hypoplastic nares and septum ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BOOMERANG DYSPLASIA	c0432201	29,993	omim	https://www.omim.org/entry/112310	2019-09-22T16:44:10	{"doid": ["0050680"], "mesh": ["C536573"], "omim": ["112310"], "orphanet": ["1263"], "genereviews": ["NBK2534"]}
Denys-Drash syndrome is a condition that affects the kidneys and genitalia. Kidney disease typically begins in the first few months of life, often leading to kidney failure in childhood. In addition, up to 90 percent of people with this condition develop a rare form of kidney cancer known as Wilms tumor. Males with Denys-Drash syndrome have gonadal dysgenesis, a condition in which the external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear to be completely female. The testes are also undescended, meaning that they remain in the pelvis, abdomen, or groin. Affected females usually have normal genitalia. For this reason, females with this condition may be diagnosed with isolated nephrotic syndrome. Denys-Drash syndrome is caused by mutations in the WT1 gene. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Denys-Drash syndrome	c0950121	29,994	gard	https://rarediseases.info.nih.gov/diseases/5576/denys-drash-syndrome	2021-01-18T18:00:55	{"mesh": ["D030321"], "omim": ["194080"], "umls": ["C0950121"], "orphanet": ["220"], "synonyms": ["Drash syndrome", "Wilms tumor and pseudohermaphroditism", "Nephropathy, wilms tumor, and genital anomalies", "Pseudohermaphroditism, nephron disorder and Wilms' tumor", "Nephropathy associated with male pseudohermaphroditism and Wilms' tumor"]}
A rare hereditary angioedema characterized by potentially life-threatening episodes of subcutaneous and/or submucosal edema without urticaria, associated with C1 esterase inhibitor (C1-INH) deficiency. Hereditary angioedema (HAE) type 1 is caused by quantitative, HAE type 2 by qualitative defects of C1-INH. The two subtypes are clinically indistinguishable. Patients may present at any age (but most commonly in childhood) with recurrent attacks of nonpitting edema of the skin, severe abdominal symptoms such as pain and swelling, and/or respiratory distress due to upper respiratory airways involvement. Genital, bladder, muscle, or joint swelling may occur in some cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hereditary angioedema with C1Inh deficiency	None	29,995	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=528623	2021-01-23T18:35:24	{"synonyms": ["HAE with C1 inhibitor deficiency", "HAE with C1Inh deficiency", "Hereditary angioneurotic edema with C1 inhibitor deficiency", "Hereditary angioneurotic edema with C1Inh deficiency"]}
Disease that can be transmitted from other species to humans "Zoonotic" redirects here. For the television episode, see Zoonotic (Law & Order: Criminal Intent). Zoonosis Other namesZoönosis A dog with rabies. Pronunciation * /zoʊˈɒnəsɪs, ˌzoʊəˈnoʊsɪs/[1] SpecialtyInfectious disease A zoonosis (plural zoonoses, or zoonotic diseases) is an infectious disease caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human animal (usually a vertebrate) to a human.[1][2][3] Typically, the first infected human transmits the infectious agent to at least one other human, who, in turn, infects others. Major modern diseases such as Ebola virus disease and salmonellosis are zoonoses. HIV was a zoonotic disease transmitted to humans in the early part of the 20th century, though it has now mutated to a separate human-only disease. Most strains of influenza that infect humans are human diseases, although many strains of bird flu and swine flu are zoonoses; these viruses occasionally recombine with human strains of the flu and can cause pandemics such as the 1918 Spanish flu or the 2009 swine flu.[4] Taenia solium infection is one of the neglected tropical diseases with public health and veterinary concern in endemic regions.[5] Zoonoses can be caused by a range of disease pathogens such as emergent viruses, bacteria, fungi and parasites; of 1,415 pathogens known to infect humans, 61% were zoonotic.[6] Most human diseases originated in other animals; however, only diseases that routinely involve non-human to human transmission, such as rabies, are considered direct zoonosis.[7] Zoonoses have different modes of transmission. In direct zoonosis the disease is directly transmitted from other animals to humans through media such as air (influenza) or through bites and saliva (rabies).[8] In contrast, transmission can also occur via an intermediate species (referred to as a vector), which carry the disease pathogen without getting sick. When humans infect other animals, it is called reverse zoonosis or anthroponosis.[9] The term is from Greek: ζῷον zoon "animal" and νόσος nosos "sickness". Host genetics plays an important role in determining which animal viruses will be able to make copies of themselves in the human body. Dangerous animal viruses are those that require few mutations to begin replicating themselves in human cells. These viruses are dangerous since the required combinations of mutations might randomly arise in the natural reservoir.[10] Recently, there has been a rise in frequency of appearance of new zoonotic diseases. According to a report from the United Nations Environment Programme and International Livestock Research Institute named: "Preventing the next pandemic – Zoonotic diseases and how to break the chain of transmission" the causes are mostly environmental.[11][12] ## Contents * 1 Causes * 1.1 Contamination of food or water supply * 1.2 Farming, ranching and animal husbandry * 1.3 Wild animal attacks * 1.4 Insect vectors * 1.5 Pets * 1.6 Exhibition * 1.7 Hunting and bushmeat * 1.8 Deforestation, biodiversity loss and environmental degradation * 1.9 Climate change * 1.10 Secondary transmission * 2 Lists of diseases * 3 History * 4 Use in vaccines * 5 See also * 6 References * 7 Bibliography * 8 External links ## Causes[edit] Zoonotic transmission can occur in any context in which there is contact with or consumption of animals, animal products, or animal derivatives. This can occur in a companionistic (pets), economic (farming, trade, butchering, etc.), predatory (hunting, butchering or consuming wild game) or research context. ### Contamination of food or water supply[edit] The most significant zoonotic pathogens causing foodborne diseases are Escherichia coli O157:H7, Campylobacter, Caliciviridae, and Salmonella.[13][14][15] In 2006 a conference held in Berlin focused on the issue of zoonotic pathogen effects on food safety, urging government intervention and public vigilance against the risks of catching food-borne diseases from farm-to-table dining.[16] Many food outbreaks can be linked to zoonotic pathogens. Many different types of food that have an animal origin can become contaminated. Some common foods linked to zoonotic contaminations include eggs, seafood, meat, dairy, and even some vegetables.[17] Outbreaks involving contaminated food should be handled in preparedness plans to prevent widespread outbreaks and to efficiently and effectively contain outbreaks.[citation needed] ### Farming, ranching and animal husbandry[edit] See also: Intensive animal farming § Human health impact Contact with farm animals can lead to disease in farmers or others that come into contact with infected farm animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses, tanneries and wool mills.[18] Close contact with sheep who have recently given birth can lead to clamydiosis, or enzootic abortion, in pregnant women, as well as an increased risk of Q fever, toxoplasmosis, and listeriosis in pregnant or the otherwise immunocompromised. Echinococcosis is caused by a tapeworm which can be spread from infected sheep by food or water contaminated with feces or wool. Bird flu is common in chickens. While rare in humans, the main public health worry is that a strain of bird flu will recombine with a human flu virus and cause a pandemic like the 1918 Spanish flu. In 2017, free range chickens in the UK were temporarily ordered to remain inside due to the threat of bird flu.[19] Cattle are an important reservoir of cryptosporidiosis[20] and mainly affects the immunocompromised. Recent reports have shown Minks can also get infected.[21] Veterinarians are exposed to unique occupational hazards and zoonotic diseases. In the US, studies have highlighted an increased risk to injuries and a lack of veterinary awareness for these hazards. Research has proved the importance for continued clinical veterinarian education on occupational risks associated with musculoskeletal injuries, animal bites, needle-sticks, and cuts.[22] A July 2020 report by the United Nations Environment Programme stated that the increase in zoonotic pandemics is directly attributable to anthropogenic destruction of nature and the increased global demand for meat, and that the industrial farming of pigs and chickens in particular will be a primary risk factor for the spillover of zoonotic diseases in the future.[23] ### Wild animal attacks[edit] * Rabies ### Insect vectors[edit] * African sleeping sickness * Dirofilariasis * Eastern equine encephalitis * Japanese encephalitis * Saint Louis encephalitis * Scrub typhus * Tularemia * Venezuelan equine encephalitis * West Nile fever * Western equine encephalitis * Zika fever ### Pets[edit] Further information: Feline zoonosis Pets can transmit a number of diseases. Dogs and cats are routinely vaccinated against rabies. Pets can also transmit ringworm and Giardia, which are endemic in both animal and human populations. Toxoplasmosis is a common infection of cats; in humans it is a mild disease although it can be dangerous to pregnant women.[24] Dirofilariasis is caused by Dirofilaria immitis through mosquitoes infected by mammals like dogs and cats. Cat-scratch disease is caused by Bartonella henselae and Bartonella quintana from fleas which are endemic in cats. Toxocariasis is infection of humans of any of species of roundworm, including species specific to the dog (Toxocara canis) or the cat (Toxocara cati). Cryptosporidiosis can be spread to humans from pet lizards, such as the leopard gecko. Encephalitozoon cuniculi is a microsporidial parasite carried by many mammals, including rabbits, and is an important opportunistic pathogen in people immunocompromised by HIV/AIDS, organ transplantation, or CD4+ T-lymphocyte deficiency.[25] ### Exhibition[edit] Outbreaks of zoonoses have been traced to human interaction with and exposure to other animals at fairs, live animal markets,[26] petting zoos, and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings.[27] The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians,[28] include educational responsibilities of venue operators, limiting public animal contact, and animal care and management. ### Hunting and bushmeat[edit] Main articles: Hunting and Bushmeat * COVID-19 * HIV * SARS ### Deforestation, biodiversity loss and environmental degradation[edit] Main articles: Deforestation, Biodiversity loss, and Environmental degradation Kate Jones, chair of ecology and biodiversity at University College London, says zoonotic diseases are increasingly linked to environmental change and human behaviour. The disruption of pristine forests driven by logging, mining, road building through remote places, rapid urbanisation and population growth is bringing people into closer contact with animal species they may never have been near before. The resulting transmission of disease from wildlife to humans, she says, is now "a hidden cost of human economic development".[29] In a guest article published by IPBES, Peter Daszak and three co-chairs of the 2019 Global Assessment Report on Biodiversity and Ecosystem Services, Josef Settele, Sandra Díaz and Eduardo Brondizio, write that "rampant deforestation, uncontrolled expansion of agriculture, intensive farming, mining and infrastructure development, as well as the exploitation of wild species have created a ‘perfect storm’ for the spillover of diseases from wildlife to people."[30] An April 2020 study published in the Proceedings of the Royal Society Part B found that increased virus spillover events from animals to humans can be linked to biodiversity loss and environmental degradation, as humans further encroach on wildlands to engage in agriculture, hunting and resource extraction they become exposed to pathogens which normally would remain in these areas. Such spillover events have been tripling every decade since 1980.[31] An August 2020 study published in Nature concludes that the anthropogenic destruction of ecosystems for the purpose of expanding agriculture and human settlements reduces biodiversity and allows for smaller animals such as bats and rats, who are more adaptable to human pressures and also carry the most zoonotic diseases, to proliferate. This in turn can result in more pandemics.[32] In October 2020, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services published its report on the 'era of pandemics' by 22 experts in a variety of fields, and concluded that anthropogenic destruction of biodiversity is paving the way to the pandemic era, and could result in as many as 850,000 viruses being transmitted from animals – in particular birds and mammals – to humans. The increased pressure on ecosystems is being driven by the "exponential rise" in consumption and trade of commodities such as meat, palm oil, and metals, largely facilitated by developed nations, and by a growing human population. According to Peter Daszak, the chair of the group who produced the report, "there is no great mystery about the cause of the Covid-19 pandemic, or of any modern pandemic. The same human activities that drive climate change and biodiversity loss also drive pandemic risk through their impacts on our environment."[33][34][35] ### Climate change[edit] Further information: Effects of global warming on human health § Coronavirus According to a report from the United Nations Environment Programme and International Livestock Research Institute named: "Preventing the next pandemic – Zoonotic diseases and how to break the chain of transmission" climate change is one of the 7 human – related causes of increase in the number of zoonotic diseases.[11][12] ### Secondary transmission[edit] This section needs expansion. You can help by adding to it. (August 2020) * Ebola and Marburg ## Lists of diseases[edit] Disease[36] Pathogen(s) Animals involved Mode of transmission Emergence African sleeping sickness Trypanosoma brucei rhodesiense range of wild animals and domestic livestock transmitted by the bite of the tsetse fly 'present in Africa for thousands of years' – major outbreak 1900–1920, cases continue (sub-Saharan Africa, 2020) Angiostrongyliasis Angiostrongylus cantonensis, Angiostrongylus costaricensis rats, cotton rats consuming raw or undercooked snails, slugs, other mollusks, crustaceans, contaminated water, and unwashed vegetables contaminated with larvae Anisakiasis Anisakis whales, dolphins, seals, sea lions, other marine animals eating raw or undercooked fish and squid contaminated with eggs Anthrax Bacillus anthracis commonly – grazing herbivores such as cattle, sheep, goats, camels, horses, and pigs by ingestion, inhalation or skin contact of spores Babesiosis Babesia spp. mice, other animals tick bite Baylisascariasis Baylisascaris procyonis raccoons ingestion of eggs in feces Barmah Forest fever Barmah Forest virus kangaroos, wallabies, opossums mosquito bite Bird flu Influenza A virus subtype H5N1 wild birds, domesticated birds such as chickens[citation needed] close contact 2003–19 Avian Influenza in Southeast Asia and Egypt Bovine spongiform encephalopathy Prions cattle eating infected meat isolated similar cases reported in ancient history; in recent UK history probable start in the 1970s[37] Brucellosis Brucella spp. cattle, goats, pigs, sheep infected milk or meat historically widespread in Mediterranean region; identified early 20th century Bubonic plague, Pneumonic plague, Septicemic plague, Sylvatic plague Yersinia pestis rabbits, hares, rodents, ferrets, goats, sheep, camels flea bite Epidemics like Black Death in Europe around 1347–53 during the Late Middle Age, Third Plague Pandemic in China-Qing dynasty and India alone Capillariasis Capillaria spp. rodents, birds, foxes eating raw or undercooked fish, ingesting embryonated eggs in fecal-contaminated food, water, or soil Cat-scratch disease Bartonella henselae cats bites or scratches from infected cats Chagas disease Trypanosoma cruzi armadillos, Triatominae (kissing bug) Contact of mucosae or wounds with feces of kissing bugs. Accidental ingestion of parasites in food contaminated by bugs or infected mammal excretae. Clamydiosis / Enzootic abortion Chlamydophila abortus domestic livestock, particularly sheep close contact with postpartum ewes COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suspected: bats, pangolins, felines, minks respiratory transmission COVID-19 pandemic; 2019–present; Ongoing pandemic Creutzfeldt-Jacob disease PrPvCJD cattle eating meat from animals with Bovine spongiform encephalopathy (BSE) 1996–2001: United Kingdom Crimean–Congo hemorrhagic fever Crimean-Congo hemorrhagic fever orthonairovirus cattle, goats, sheep, birds, multimammate rats, hares tick bite, contact with bodily fluids Cryptococcosis Cryptococcus neoformans commonly – birds like pigeons inhaling fungi Cryptosporidiosis Cryptosporidium spp. cattle, dogs, cats, mice, pigs, horses, deer, sheep, goats, rabbits, leopard geckos, birds ingesting cysts from water contaminated with feces Cysticercosis and taeniasis Taenia solium, Taenia asiatica, Taenia saginata commonly – pigs and cattle consuming water, soil or food contaminated with the tapeworm eggs (cysticercosis) or raw or undercooked pork contaminated with the cysticerci (taeniasis) Dirofilariasis Dirofilaria spp. dogs, wolves, coyotes, foxes, jackals, cats, monkeys, raccoons, bears, muskrats, rabbits, leopards, seals, sea lions, beavers, ferrets, reptiles mosquito bite Eastern equine encephalitis, Venezuelan equine encephalitis, Western equine encephalitis Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, Western equine encephalitis virus horses, donkeys, zebras, birds mosquito bite Ebola virus disease (a haemorrhagic fever) Ebolavirus spp. chimpanzees, gorillas, orangutans, fruit bats, monkeys, shrews, forest antelope and porcupines through body fluids and organs 2013–16; possible in Africa Other haemorrhagic fevers (Crimean-Congo haemorrhagic fever, Dengue fever, Lassa fever, Marburg viral haemorrhagic fever, Rift Valley fever[38]) Varies – commonly viruses varies (sometimes unknown) – commonly camels, rabbits, hares, hedgehogs, cattle, sheep, goats, horses and swine infection usually occurs through direct contact with infected animals 2019–20 dengue fever (Ongoing epidemic). Echinococcosis Echinococcus spp. commonly – dogs, foxes, jackals, wolves, coyotes, sheep, pigs, rodents ingestion of infective eggs from contaminated food or water with feces of an infected, definitive host or fur Fasciolosis Fasciola hepatica, Fasciola gigantica sheep, cattle, buffaloes ingesting contaminated plants Foodborne illnesses (commonly diarrheal diseases) Campylobacter spp., Escherichia coli, Salmonella spp., Listeria spp., Shigella spp. and Trichinella spp. animals domesticated for food production (cattle, poultry) raw or undercooked food made from animals and unwashed vegetables contaminated with feces Giardiasis Giardia lamblia beavers, other rodents, raccoons, deer, cattle, goats, sheep, dogs, cats ingesting spores and cysts in food and water contaminated with feces Glanders Burkholderia mallei. horses, donkeys direct contact Gnathostomiasis Gnathostoma spp. dogs, minks, opossums, cats, lions, tigers, leopards, raccoons, poultry, other birds, frogs raw or undercooked fish or meat Hantavirus Hantavirus spp. deer mice, cotton rats and other rodents exposure to feces, urine, saliva or bodily fluids Henipavirus Henipavirus spp. horses, bats exposure to feces, urine, saliva or contact with sick horses Histoplasmosis Histoplasma capsulatum birds, bats inhaling fungi in guano HIV SIV Simian immunodeficiency virus Non-human primates Blood SIV Monkeys Immunodeficiency resembling human AIDS was reported in captive monkeys in the United States beginning in 1983.[39][40][41] SIV was isolated in 1985 from some of these animals, captive rhesus macaques suffering from simian AIDS (SAIDS).[40] The discovery of SIV was made shortly after HIV-1 had been isolated as the cause of AIDS and led to the discovery of HIV-2 strains in West Africa. HIV-2 was more similar to the then-known SIV strains than to HIV-1, suggesting for the first time the simian origin of HIV. Further studies indicated that HIV-2 is derived from the SIVsmm strain found in sooty mangabeys, whereas HIV-1, the predominant virus found in humans, is derived from SIV strains infecting chimpanzees (SIVcpz) Japanese encephalitis Japanese encephalitis virus pigs, water birds mosquito bite Kyasanur Forest disease Kyasanur Forest disease virus rodents, shrews, bats, monkeys tick bite La Crosse encephalitis La Crosse virus chipmunks, tree squirrels mosquito bite Leishmaniasis Leishmania spp. dogs, rodents, other animals[42][43] sandfly bite 2004 Afghanistan Leprosy Mycobacterium leprae, Mycobacterium lepromatosis armadillos, monkeys, rabbits, mice[44] direct contact, including meat consumption. However, scientists believe most infections are spread human to human.[44][45] Leptospirosis Leptospira interrogans rats, mice, pigs, horses, goats, sheep, cattle, buffaloes, opossums, raccoons, mongooses, foxes, dogs direct or indirect contact with urine of infected animals 1616–20 New England infection: Present day in the United States–Native Americans; Killed around 90–95% of (Native America) Lassa fever Lassa fever virus rodents exposure to rodents Lyme disease Borrelia burgdorferi deer, wolves, dogs, birds, rodents, rabbits, hares, reptiles tick bite Lymphocytic choriomeningitis Lymphocytic choriomeningitis virus rodents exposure to urine, feces, or saliva Melioidosis Burkholderia pseudomallei various animals direct contact with contaminated soil and surface water Microsporidiosis Encephalitozoon cuniculi Rabbits, dogs, mice, and other mammals ingestion of spores Middle East respiratory syndrome MERS coronavirus bats, camels close contact 2012–present: Saudi Arabia Monkeypox Monkeypox virus rodents, primates contact with infected rodents, primates, or contaminated materials Nipah virus infection Nipah virus (NiV) bats, pigs direct contact with infected bats, infected pigs Orf Orf virus goats, sheep close contact Psittacosis Chlamydophila psittaci macaws, cockatiels, budgerigars, pigeons, sparrows, ducks, hens, gulls and many other bird species contact with bird droplets Q fever Coxiella burnetii livestock and other domestic animals such as dogs and cats inhalation of spores, contact with bodily fluid or faeces Rabies Rabies virus commonly – dogs, bats, monkeys, raccoons, foxes, skunks, cattle, goats, sheep, wolves, coyotes, groundhogs, horses, mongooses and cats through saliva by biting, or through scratches from an infected animal Variety of places like Oceanic, South America, Europe; Year is unknown Rat-bite fever Streptobacillus moniliformis, Spirillum minus rats, mice bites of rats but also urine and mucus secretions Rift Valley fever Phlebovirus livestock, buffaloes, camels mosquito bite, contact with bodily fluids, blood, tissues, breathing around butchered animals or raw milk 2006–07 East Africa outbreak Rocky Mountain spotted fever Rickettsia rickettsii dogs, rodents tick bite Ross River fever Ross River virus kangaroos, wallabies, horses, opossums, birds, flying foxes mosquito bite Saint Louis encephalitis Saint Louis encephalitis virus birds mosquito bite Severe acute respiratory syndrome SARS coronavirus bats, civets close contact, respiratory droplets 2002–04 SARS outbreak; started in China Smallpox Variola virus Possible Monkeys or horses Spread to person to person quickly The last cases was in 1977; WHO certified to Eraticated (for the world) in December 1979 or 1980. Swine influenza A new strain of the influenza virus endemic in pigs (excludes H1N1 swine flu, which is a human virus). pigs close contact 2009–10; 2009 swine flu pandemic; The outbreak began in Mexico. Taenia crassiceps infection Taenia crassiceps wolves, coyotes, jackals, foxes contact with soil contaminated with feces Toxocariasis Toxocara canis, Toxocara cati dogs, foxes, cats ingestion of eggs in soil, fresh or unwashed vegetables or undercooked meat Toxoplasmosis Toxoplasma gondii cats, livestock, poultry exposure to cat feces, organ transplantation, blood transfusion, contaminated soil, water, grass, unwashed vegetables, unpasteurized dairy products and undercooked meat Trichinosis Trichinella spp. rodents, pigs, horses, bears, walruses, dogs, foxes, crocodiles, birds eating undercooked meat Tuberculosis Mycobacterium bovis infected cattle, deer, llamas, pigs, domestic cats, wild carnivores (foxes, coyotes) and omnivores (possums, mustelids and rodents) milk, exhaled air, sputum, urine, faeces and pus from infected animals Tularemia Francisella tularensis lagomorphs (type A), rodents (type B), birds ticks, deer flies, and other insects including mosquitoes West Nile fever Flavivirus birds, horses mosquito bite Zika fever Zika virus chimpanzees, gorillas, orangutans, monkeys, baboons mosquito bite, sexual intercourse, blood transfusion and sometimes bites of monkeys 2015–16 epidemic in the Americas and Oceanic ## History[edit] During most of human prehistory groups of hunter-gatherers were probably very small. Such groups probably made contact with other such bands only rarely. Such isolation would have caused epidemic diseases to be restricted to any given local population, because propagation and expansion of epidemics depend on frequent contact with other individuals who have not yet developed an adequate immune response. To persist in such a population, a pathogen either had to be a chronic infection, staying present and potentially infectious in the infected host for long periods, or it had to have other additional species as reservoir where it can maintain itself until further susceptible hosts are contacted and infected. In fact, for many 'human' diseases, the human is actually better viewed as an accidental or incidental victim and a dead-end host. Examples include rabies, anthrax, tularemia and West Nile virus. Thus, much of human exposure to infectious disease has been zoonotic. Possibilities for zoonotic disease transmissions Through religious scripture, different civilizations as early as 500 years B.C.E had dietary laws that prohibit or allow the consumption of certain animals. Christian and Hebrew religions have reflected these traditions in the Book of Leviticus,[46] while Islamic religions spread the laws throughout the Quran, referring to these rules as Haram and Halal.[citation needed]. Some consider these dietary rules evolved, among other reasons, to reduce the risk of contracting diseases from animals.[citation needed] Many modern diseases, even epidemic diseases, started out as zoonotic diseases. It is hard to establish with certainty which diseases jumped from other animals to humans, but there is increasing evidence from DNA and RNA sequencing, that measles, smallpox, influenza, HIV, and diphtheria came to humans this way. Various forms of the common cold and tuberculosis also are adaptations of strains originating in other species. Some experts have suggested that all human viral infections were originally zoonotic.[47] Zoonoses are of interest because they are often previously unrecognized diseases or have increased virulence in populations lacking immunity. The West Nile virus appeared in the United States in 1999 in the New York City area, and moved through the country in the summer of 2002, causing much distress. Bubonic plague is a zoonotic disease,[48] as are salmonellosis, Rocky Mountain spotted fever, and Lyme disease. A major factor contributing to the appearance of new zoonotic pathogens in human populations is increased contact between humans and wildlife.[49] This can be caused either by encroachment of human activity into wilderness areas or by movement of wild animals into areas of human activity. An example of this is the outbreak of Nipah virus in peninsular Malaysia in 1999, when intensive pig farming began on the habitat of infected fruit bats. Unidentified infection of the pigs amplified the force of infection, eventually transmitting the virus to farmers and causing 105 human deaths.[50] Similarly, in recent times avian influenza and West Nile virus have spilled over into human populations probably due to interactions between the carrier host and domestic animals. Highly mobile animals such as bats and birds may present a greater risk of zoonotic transmission than other animals due to the ease with which they can move into areas of human habitation. Because they depend on the human host for part of their life-cycle, diseases such as African schistosomiasis, river blindness, and elephantiasis are not defined as zoonotic, even though they may depend on transmission by insects or other vectors. ## Use in vaccines[edit] The first vaccine against smallpox by Edward Jenner in 1800 was by infection of a zoonotic bovine virus which caused a disease called cowpox. Jenner had noticed that milkmaids were resistant to smallpox. Milkmaids contracted a milder version of the disease from infected cows that conferred cross immunity to the human disease. Jenner abstracted an infectious preparation of 'cowpox' and subsequently used it to inoculate persons against smallpox. As a result, smallpox has been eradicated globally, and mass vaccination against this disease ceased in 1981. ## See also[edit] * Animal welfare#Animal welfare organizations – The well-being of (non-human) animals * Conservation medicine * Cross-species transmission – Transmission of a pathogen between different species * Emerging infectious disease – Infectious disease of emerging pathogen, often novel in its outbreak range or transmission mode * Foodborne illness – Illness resulting from food that is spoiled or contaminated by pathogenic bacteria, viruses, parasites, or toxins * Spillover infection – Occurs when a reservoir population causes an epidemic in a novel host population * Wildlife disease * Veterinary medicine – Deals with the diseases of animals, animal welfare, etc. * Wildlife smuggling and zoonoses – Health risks associated with the trade in exotic wildlife * List of zoonotic primate viruses – Wikipedia list article ## References[edit] 1. ^ a b "zoonosis". Merriam-Webster Dictionary. Retrieved 29 March 2019. 2. ^ WHO. "Zoonoses". Archived from the original on 3 January 2015. Retrieved 18 December 2014. 3. ^ "A glimpse into Canada's highest containment laboratory for animal health: The National Centre for Foreign Animal Diseases". science.gc.ca. Government of Canada. 22 October 2018. Archived from the original on 20 June 2019. Retrieved 16 August 2019. "Zoonoses are infectious diseases which jump from an animal host or reservoir into humans." 4. ^ Scotch, M.; Brownstein, J. S.; Vegso, S.; Galusha, D.; Rabinowitz, P. (2011). "Human vs. Animal Outbreaks of the 2009 swine-origin H1N1 influenza A epidemic". Ecohealth. 8 (3): 376–80. doi:10.1007/s10393-011-0706-x. PMC 3246131. PMID 21912985. 5. ^ Coral-Almeida, Marco; Gabriël, Sarah; Abatih, Emmanuel Nji; Praet, Nicolas; Benitez, Washington; Dorny, Pierre (6 July 2015). "'Taenia solium' Human Cysticercosis: A Systematic Review of Sero-epidemiological Data from Endemic Zones around the World". PLOS Neglected Tropical Diseases. 9 (7): e0003919. doi:10.1371/journal.pntd.0003919. ISSN 1935-2735. PMC 4493064. PMID 26147942. 6. ^ Taylor LH, Latham SM, Woolhouse ME (2001). "Risk factors for human disease emergence". Philosophical Transactions of the Royal Society B: Biological Sciences. 356 (1411): 983–89. doi:10.1098/rstb.2001.0888. PMC 1088493. PMID 11516376. 7. ^ Marx PA, Apetrei C, Drucker E (October 2004). "AIDS as a zoonosis? Confusion over the origin of the virus and the origin of the epidemics". Journal of Medical Primatology. 33 (5–6): 220–26. doi:10.1111/j.1600-0684.2004.00078.x. PMID 15525322. 8. ^ "Zoonosis". Medical Dictionary. Archived from the original on 28 June 2013. Retrieved 30 January 2013. 9. ^ Messenger AM, Barnes AN, Gray GC (2014). "Reverse zoonotic disease transmission (zooanthroponosis): a systematic review of seldom-documented human biological threats to animals". PLOS ONE. 9 (2): e89055. Bibcode:2014PLoSO...989055M. doi:10.1371/journal.pone.0089055. PMC 3938448. PMID 24586500. 10. ^ Warren, Cody J.; Sawyer, Sara L. (19 April 2019). "How host genetics dictates successful viral zoonosis". PLOS Biology. 17 (4): e3000217. doi:10.1371/journal.pbio.3000217. ISSN 1545-7885. PMC 6474636. PMID 31002666. 11. ^ a b "Coronavirus: Fear over rise in animal-to-human diseases". BBC. 6 July 2020. Retrieved 7 July 2020. 12. ^ a b "Preventing the next pandemic – Zoonotic diseases and how to break the chain of transmission". United Nations Environmental Programm. United Nations. Retrieved 7 July 2020. 13. ^ Humphrey T, O'Brien S, Madsen M (2007). "Campylobacters as zoonotic pathogens: A food production perspective". International Journal of Food Microbiology. 117 (3): 237–57. doi:10.1016/j.ijfoodmicro.2007.01.006. PMID 17368847. 14. ^ Cloeckaert A (2006). "Introduction: emerging antimicrobial resistance mechanisms in the zoonotic foodborne pathogens Salmonella and Campylobacter". Microbes and Infection. 8 (7): 1889–90. doi:10.1016/j.micinf.2005.12.024. PMID 16714136. 15. ^ Frederick, A. Murphy (1999). "The Threat Posed by the Global Emergence of Livestock, Food-borne, and Zoonotic Pathogens". Annals of the New York Academy of Sciences. 894 (1): 20–27. Bibcode:1999NYASA.894...20M. doi:10.1111/j.1749-6632.1999.tb08039.x. PMID 10681965. S2CID 13384121. 16. ^ Med-Vet-Net. "Priority Setting for Foodborne and Zoonotic Pathogens" (PDF). Archived (PDF) from the original on 25 June 2008. Retrieved 5 April 2008. 17. ^ "Investigating Foodborne Outbreaks". Centers for Disease Control and Prevention. 15 September 2011. Archived from the original on 28 June 2013. Retrieved 5 June 2013. 18. ^ "Inhalation Anthrax". cdc.gov. Archived from the original on 26 March 2017. Retrieved 26 March 2017. 19. ^ "Avian flu: Poultry to be allowed outside under new rules". BBC News. 28 February 2017. Archived from the original on 7 March 2017. Retrieved 26 March 2017. 20. ^ Lassen, Brian; Ståhl, Marie; Enemark, Heidi L (5 June 2014). "Cryptosporidiosis – an occupational risk and a disregarded disease in Estonia". Acta Veterinaria Scandinavica. 56 (1): 36. doi:10.1186/1751-0147-56-36. ISSN 0044-605X. PMC 4089559. PMID 24902957. 21. ^ "Mink found to have coronavirus on two Dutch farms – ministry". Reuters. 26 April 2020. Archived from the original on 27 April 2020. Retrieved 27 April 2020. 22. ^ Rood, Kerry A.; Pate, Michael L. (2 January 2019). "Assessment of Musculoskeletal Injuries Associated with Palpation, Infection Control Practices, and Zoonotic Disease Risks among Utah Clinical Veterinarians". Journal of Agromedicine. 24 (1): 35–45. doi:10.1080/1059924X.2018.1536574. ISSN 1059-924X. PMID 30362924. S2CID 53092026. 23. ^ Carrington, Damian (6 July 2020). "Coronavirus: world treating symptoms, not cause of pandemics, says UN". The Guardian. Retrieved 7 July 2020. 24. ^ Prevention, CDC – Centers for Disease Control and. "Toxoplasmosis – General Information – Pregnant Women". cdc.gov. Archived from the original on 18 November 2015. Retrieved 1 April 2017. 25. ^ Weese, J. Scott (2011). Companion animal zoonoses. Wiley-Blackwell. pp. 282–84. ISBN 978-0813819648. 26. ^ Wildlife, Exotic Pets, and Emerging Zoonoses 27. ^ Centers for Disease Control and Prevention (2005). "Compendium of Measures To Prevent Disease Associated with Animals in Public Settings, 2005: National Association of State Public Health Veterinarians, Inc. (NASPHV)" (PDF). MMWR. 54 (RR–4): inclusive page numbers. Archived (PDF) from the original on 17 December 2008. Retrieved 28 December 2008. 28. ^ http://www.nasphv.org/ 29. ^ Vidal, John (18 March 2020). "'Tip of the iceberg': is our destruction of nature responsible for Covid-19?". The Guardian. ISSN 0261-3077. Retrieved 18 March 2020. 30. ^ Carrington, Damian (27 April 2020). "Halt destruction of nature or suffer even worse pandemics, say world's top scientists". The Guardian. Retrieved 27 April 2020. 31. ^ Shield, Charli (16 April 2020). "Coronavirus Pandemic Linked to Destruction of Wildlife and World's Ecosystems". Deutsche Welle. Retrieved 16 April 2020. 32. ^ Carrington, Damian (5 August 2020). "Deadly diseases from wildlife thrive when nature is destroyed, study finds". The Guardian. Retrieved 7 August 2020. 33. ^ Woolaston, Katie; Fisher, Judith Lorraine (29 October 2020). "UN report says up to 850,000 animal viruses could be caught by humans, unless we protect nature". The Conversation. Retrieved 29 October 2020. 34. ^ Carrington, Damian (29 October 2020). "Protecting nature is vital to escape 'era of pandemics' – report". The Guardian. Retrieved 29 October 2020. 35. ^ "Escaping the 'Era of Pandemics': experts warn worse crises to come; offer options to reduce risk". EurekAlert!. 29 October 2020. Retrieved 29 October 2020. 36. ^ Information in this table is largely compiled from: World Health Organization. "Zoonoses and the Human-Animal-Ecosystems Interface". Archived from the original on 6 December 2014. Retrieved 21 December 2014. 37. ^ Prusiner SB (May 2001). "Shattuck lecture—neurodegenerative diseases and prions". The New England Journal of Medicine. 344 (20): 1516–26. doi:10.1056/NEJM200105173442006. PMID 11357156. 38. ^ "Haemorrhagic fevers, Viral". World Health Organization. Archived from the original on 27 July 2019. Retrieved 19 June 2019. 39. ^ Letvin NL, Eaton KA, Aldrich WR, Sehgal PK, Blake BJ, Schlossman SF, et al. (May 1983). "Acquired immunodeficiency syndrome in a colony of macaque monkeys". Proceedings of the National Academy of Sciences of the United States of America. 80 (9): 2718–22. Bibcode:1983PNAS...80.2718L. doi:10.1073/pnas.80.9.2718. PMC 393899. PMID 6221343. 40. ^ a b Daniel MD, Letvin NL, King NW, Kannagi M, Sehgal PK, Hunt RD, et al. (June 1985). "Isolation of T-cell tropic HTLV-III-like retrovirus from macaques". Science. 228 (4704): 1201–4. Bibcode:1985Sci...228.1201D. doi:10.1126/science.3159089. PMID 3159089. 41. ^ King NW, Hunt RD, Letvin NL (December 1983). "Histopathologic changes in macaques with an acquired immunodeficiency syndrome (AIDS)". The American Journal of Pathology. 113 (3): 382–8. PMC 1916356. PMID 6316791. 42. ^ "Parasites – Leishmaniasis". CDC. 27 February 2019. Archived from the original on 15 June 2019. Retrieved 19 June 2019. 43. ^ "Leishmaniasis". World Health Organization. Archived from the original on 26 July 2019. Retrieved 19 June 2019. 44. ^ a b Clark, Laura. "How Armadillos Can Spread Leprosy". Smithsonianmag.com. Smithsonian.com. Archived from the original on 28 March 2017. Retrieved 16 April 2017. 45. ^ Shute, Nancy. "Leprosy From An Armadillo? That's An Unlikely Peccadillo". NPR.org. National Public Radio. Archived from the original on 17 April 2017. Retrieved 16 April 2017. 46. ^ Book of Leviticus Chapter 11 "From among all the land animals, these are the creatures that you may eat. Any animal that has divided hoofs and is cleft-footed and chews the cud—such you may eat. But among those that chew the cud or have divided hoofs, you shall not eat the following: the camel ... ". Online version available: Leviticus 11 47. ^ Benatar, David (1 September 2007). "The Chickens Come Home to Roost". American Journal of Public Health. 97 (9): 1545–46. doi:10.2105/AJPH.2006.090431. PMC 1963309. PMID 17666704. 48. ^ Meerburg BG, Singleton GR, Kijlstra A (2009). "Rodent-borne diseases and their risks for public health". Crit Rev Microbiol. 35 (3): 221–70. doi:10.1080/10408410902989837. PMID 19548807. S2CID 205694138. 49. ^ Daszak P, Cunningham AA, Hyatt AD (2001). "Anthropogenic environmental change and the emergence of infectious diseases in wildlife". Acta Tropica. 78 (2): 103–16. doi:10.1016/S0001-706X(00)00179-0. PMID 11230820. 50. ^ Field H, Young P, Yob JM, Mills J, Hall L, Mackenzie J (2001). "The natural history of Hendra and Nipah viruses". Microbes and Infection / Institut Pasteur. 3 (4): 307–14. doi:10.1016/S1286-4579(01)01384-3. PMID 11334748. ## Bibliography[edit] * Bardosh, K. One Health: Science, Politics and Zoonotic Disease in Africa. 2016. Routledge; London. ISBN 978-1-138-96148-7. * Crawford, Dorothy (2018). Deadly Companions: How Microbes Shaped our History. Oxford University Press. ISBN 978-0198815440. * Greger, Michael (2007). "The Human/Animal Interface: Emergence and resurgence of infectious diseases". Critical Reviews in Microbiology. 33 (4): 243–99. doi:10.1080/10408410701647594. PMID 18033595. S2CID 8940310. * H. Krauss, A. Weber, M. Appel, B. Enders, A. v. Graevenitz, H. D. Isenberg, H. G. Schiefer, W. Slenczka, H. Zahner: Zoonoses. Infectious Diseases Transmissible from Animals to Humans. 3rd Edition, 456 pages. ASM Press. American Society for Microbiology, Washington, D.C., 2003. ISBN 1-55581-236-8. * Jorge Guerra González (2010), Infection Risk and Limitation of Fundamental Rights by Animal-To-Human Transplantations. EU, Spanish and German Law with Special Consideration of English Law (in German), Hamburg: Verlag Dr. Kovac, ISBN 978-3-8300-4712-4 * David Quammen (2013). Spillover: Animal Infections and the Next Human Pandemic. ISBN 978-0-393-34661-9. ## External links[edit] Classification D * MeSH: D015047 * DiseasesDB: 28555 Wikimedia Commons has media related to Zoonoses. Look up zoonosis in Wiktionary, the free dictionary. Scholia has a topic profile for Zoonosis. * AVMA Collections: Zoonosis Updates * WHO tropical diseases and zoonoses * Detection and Forensic Analysis of Wildlife and Zoonotic Disease * Publications in Zoonotics and Wildlife Disease * A message from nature: coronavirus. United Nations Environment Programme * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox * v * t * e Tick-borne diseases and infestations Diseases Bacterial infections Rickettsiales * Anaplasmosis * Boutonneuse fever * Ehrlichiosis (Human granulocytic, Human monocytotropic, Human E. ewingii infection) * Scrub typhus * Spotted fever rickettsiosis * Pacific Coast tick fever * American tick bite fever * rickettsialpox * Rocky Mountain spotted fever) Spirochaete * Baggio–Yoshinari syndrome * Lyme disease * Relapsing fever borreliosis Thiotrichales * Tularemia Viral infections * Bhanja virus * Bourbon virus * Colorado tick fever * Crimean–Congo hemorrhagic fever * Heartland bandavirus * Kemerovo tickborne viral fever * Kyasanur Forest disease * Omsk hemorrhagic fever * Powassan encephalitis * Severe fever with thrombocytopenia syndrome * Tete orthobunyavirus * Tick-borne encephalitis Protozoan infections * Babesiosis Other diseases * Tick paralysis * Alpha-gal allergy * Southern tick-associated rash illness Infestations * Tick infestation Species and bites Amblyomma * Amblyomma americanum * Amblyomma cajennense * Amblyomma triguttatum Dermacentor * Dermacentor andersoni * Dermacentor variabilis Ixodes * Ixodes cornuatus * Ixodes holocyclus * Ixodes pacificus * Ixodes ricinus * Ixodes scapularis Ornithodoros * Ornithodoros gurneyi * Ornithodoros hermsi * Ornithodoros moubata Other * Rhipicephalus sanguineus * v * t * e Concepts in infectious disease Transmission Basic concepts * Asymptomatic carrier * Host * Incubation period * Index case * Infectious period * Latent period * Natural reservoir * Subclinical infection * Super-spreader Modes * Human-to-human transmission * Horizontal * Vertical * Cross-species transmission * Spillover infection * Vector * Zoonosis * Reverse zoonosis Routes * Airborne disease * Blood-borne disease * Foodborne illness * Waterborne disease * Hospital-acquired infection * Fomite * Fecal-oral route * Sexual Modelling * Attack rate * Basic reproduction number * Compartmental models in epidemiology * Critical community size * Herd immunity * Infection rate * Serial interval * Transmission risks and rates Medication * Antimicrobial * Antibiotic * Antiviral drug * Antimicrobial resistance * Immunotherapy * Phage therapy * Vaccination Emerging infections * Disease X * Emergent virus Other * Discovery of disease-causing pathogens * Eradication of infectious diseases * Pandemic Authority control * BNE: XX528485 * BNF: cb119626189 (data) * GND: 4121949-1 * LCCN: sh85150001 * NDL: 00971020 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Zoonosis	c0043528	29,996	wikipedia	https://en.wikipedia.org/wiki/Zoonosis	2021-01-18T18:48:32	{"mesh": ["D015047"], "wikidata": ["Q182672"]}
Tumor-like disorders of the lung pleura are a group of conditions that on initial radiological studies might be confused with malignant lesions. Radiologists must be aware of these conditions in order to avoid misdiagnosing patients. Examples of such lesions are: pleural plaques, thoracic splenosis, catamenial pneumothorax, pleural pseudotumor, diffuse pleural thickening, diffuse pulmonary lymphangiomatosis and Erdheim–Chester disease.[1] ## Contents * 1 Pleural Plaque * 1.1 Pathophysiology * 1.2 Symptoms * 1.3 Diagnosis * 1.4 Treatment * 2 Thoracic Splenosis * 2.1 Pathophysiology * 2.2 Symptoms * 2.3 Diagnosis * 2.4 Treatment * 3 Catamenial pneumothorax * 3.1 Pathophysiology * 3.2 Symptoms * 3.3 Diagnosis * 3.4 Treatment * 4 Pleural Pseudotumor * 4.1 Pathophysiology * 4.2 Symptoms * 4.3 Diagnosis * 4.4 Treatment * 5 Diffuse Pleural Thickening * 5.1 Pathophysiology * 5.2 Symptoms * 5.3 Diagnosis * 5.4 Treatment * 6 Diffuse Pulmonary Lymphangiomatosis * 6.1 Pathophysiology * 6.2 Symptoms * 6.3 Diagnosis * 6.4 Treatment * 7 Erdheim–Chester Disease * 8 Notes ## Pleural Plaque[edit] ### Pathophysiology[edit] Exposure to asbestos fibers reach the pleura of the lungs through the lymphatic channels or blood stream. Historically, ship builders and insulation workers are at greater risk.[2] ### Symptoms[edit] Affected persons are usually asymptomatic.[3] ### Diagnosis[edit] On radiological studies, pleural plaques are visualized using conventional chest x-rays and computed tomography scans (CT scans). The locations of the lesions are mostly in the parietal pleura of the lungs, especially in the posterior/lateral regions of the thorax, diaphragmatic domes, and lung fissures. In some cases, calcifications are also evident, especially with CT scans.[1] ### Treatment[edit] No treatment is required since pleural plaques are benign. However, studies have demonstrated that pleural plaques are an independent risk factor for developing bronchogenic carcinoma and/or mesothelioma.[3] ## Thoracic Splenosis[edit] Thoracic splenosis is splenosis that migrated to the thoracic cavity. ### Pathophysiology[edit] Following thoracoabdominal trauma, most commonly a penetrating injury, laceration of the diaphragm, and spleen allows ectopic splenic tissue to reach the pleural space of the lung.[4] ### Symptoms[edit] Affected persons are usually asymptomatic. However, on rare occasions, thoracic splenosis can present with chest pain and/or hemoptysis.[5] ### Diagnosis[edit] On radiological studies, thoracic splenic lesions are visualized using CT scans. Visualized lesions can be described as solitary or multiple nodules. The locations of the lesions are mostly in the lower left pleural space and/or splenic bed. Confirmation can be done using scintigraphy with 99mTc tagged heat-damaged red blood cells.[6] ### Treatment[edit] No treatment is required since thoracic splenosis is a benign condition.[7] ## Catamenial pneumothorax[edit] ### Pathophysiology[edit] Ectopic endometrial tissue reaches the pleural space of the lung or the right hemi-diaphragmatic region and erodes the visceral pleura, causing the formation of a spontaneous pneumothorax. The condition is often cyclical, due to its associations with the beginning of the menstrual cycle.[8] ### Symptoms[edit] Affected persons usually present with recurrent spontaneous pneumothorax associated with the onset of the menstrual cycle. Additionally, chest/scapular pain and/or evidence of endometriosis in the abdominopelvic cavity are other manifestations.[8] ### Diagnosis[edit] On radiological studies, pneumothorax is visualized using conventional chest x-rays and CT scans. In 90% of the cases, the pneumothorax is located on the right side. In some cases, small nodules can be seen in the pleura using CT scans. Confirmation can be done using video assisted thoracoscopic surgery (VATS).[8] ### Treatment[edit] Treatment for the pneumothorax is with chest tube placement. As for the ectopic endometrial tissue, therapy with gonadotropin-releasing–hormone or resection of the lesions can improve symptoms.[8] ## Pleural Pseudotumor[edit] ### Pathophysiology[edit] Initial formation of a pleural effusion causes retraction of the lung lobules and widening of the fissures. This widening of the fissures allows the accumulation of liquid and the formation of a well-defined lenticular lesion.[9] ### Symptoms[edit] Affected persons usually present with signs of systemic fluid overload due to conditions such as congestive heart failure (CHF), cirrhosis or chronic kidney disease.[9] ### Diagnosis[edit] On radiological studies, a pleural pseudotumor is visualized as a biconcave or lenticular lesion using conventional chest x-rays and CT scans. The lesion is most commonly located in the minor (horizontal) fissure of the lung. A pleural pseudotumor is also associated with the presence of dependent pleural effusions.[9] ### Treatment[edit] Diuretics causes regression of the lesion.[9] ## Diffuse Pleural Thickening[edit] ### Pathophysiology[edit] Inflammatory pleuritis causes fusion of the parietal and visceral pleura of the lungs. In most cases, initial formation of empyema or hemothorax is the triggering factor for this inflammatory reaction. However, it can also be associated with connective tissue disorders and exposure to asbestos.[10] ### Symptoms[edit] Affected persons usually present with dyspnea.[11] ### Diagnosis[edit] On radiological studies, thickening of the pleura can be visualized extending along various rib levels using conventional chest x-rays and CT scans. The lesion usually has calcification, poorly defined and irregular borders, and associated blunting of the costophrenic angles.[11] ### Treatment[edit] No treatment is available. ## Diffuse Pulmonary Lymphangiomatosis[edit] ### Pathophysiology[edit] Congenital anomaly causes abnormal proliferation and dilation of lymphatic channels.[12] ### Symptoms[edit] Affected persons are usually young adults that present with progressive dyspnea.[12] ### Diagnosis[edit] On radiological studies, diffuse lesions are visualized throughout the thoracic cavity using CT scans. The location of the lesions is mostly in the upper lobes of the lungs, usually in a lymphatic distribution. Thickening of the pleura and interlobular septal is also evident. In addition, pleural/pericardial effusions and mediastinal fat infiltration is appreciated. Definitive diagnosis is achieved through tissue biopsy.[1] ### Treatment[edit] Thoracentesis and pericardiocentesis are procedures performed to remove excess fluid in the pleural and pericardial spaces, respectively. There is evidence in the literature that chemotherapy and radiation therapy helps to improve symptoms.[13] ## Erdheim–Chester Disease[edit] See Erdheim–Chester disease ## Notes[edit] 1. ^ a b c Walker, Christopher et al. “Tumorlike conditions of the pleura.” RadioGraphics 32 (2012): 971-985. 2. ^ Fletcher DE. "A mortality study of shipyard workers with pleural plaques." Br J Ind Med 1972; 29(2): 142–145. 3. ^ a b Milano, Michael. “Pleural Plaque and Asbestos Exposure.” Asbestos.net. 2012. <http://www.asbestos.net/diseases/pleural-disease/pleural-plaque-and-asbestos-exposure> 4. ^ Backhus, Leah et al. “Intrathoracic Splenosis after Remote Trauma.” N Engl J Med 355 (2006): 1811. 5. ^ O’Connor, JV et al. “Thoracic splenosis.” Ann Thorac Surg 66. 2 (1998): 552-553. 6. ^ Naylor, Margaret et al. “Noninvasive methods of diagnosing thoracic splenosis.” Ann Thorac Surg 68 (1999): 243-244. 7. ^ Itinteang, Tinte et al. “Thoracic splenosis: a treatment approach.” Med J Aust 184. 8 (2006): 416. 8. ^ a b c d Catamenial pneumothorax Kronauer, Christoph. “Catamenial Pneumothorax.” N Engl J Med (2006); 355:e9 9. ^ a b c d Haus, Brian et al. “Pseudotumor/Vanishing Tumor of the Lung.”Learning Radiology. 2005. <http://www.learningradiology.com/archives05/COW%20159-Pseudotumor/pseudotumorcorrect.htm> 10. ^ Miles, Susan et al. “Diffuse Pleural Thickening.” Mesothelioma Resource Online. 2008. <http://www.mesotheliomasymptoms.com/diffuse-pleural-thickening> 11. ^ a b McLoud, Theresa et al. “Diffuse Pleural Thickening in an Asbestos-Exposed Population: Prevalence and Causes.” AJR 144 (1985): 9-18. 12. ^ a b Tazelaar, Henry et al. “Diffuse pulmonary lymphangiomatosis.” Human Pathology 24. 12 (1993): 1313-1322. 13. ^ Rostom AY. “Treatment of thoracic lymphangiomatosis.” Arch Dis Child 2000; 83(2):138–139. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tumor-like disorders of the lung pleura	None	29,997	wikipedia	https://en.wikipedia.org/wiki/Tumor-like_disorders_of_the_lung_pleura	2021-01-18T19:00:29	{"wikidata": ["Q7852669"]}
Cortical deafness Location of the primary auditory cortex in the brain SpecialtyNeurology, otorhinolaryngology Cortical deafness is a rare form of sensorineural hearing loss caused by damage to the primary auditory cortex. Cortical deafness is an auditory disorder where the patient is unable to hear sounds but has no apparent damage to the anatomy of the ear (see auditory system), which can be thought of as the combination of auditory verbal agnosia and auditory agnosia. Patients with cortical deafness cannot hear any sounds, that is, they are not aware of sounds including non-speech, voices, and speech sounds.[1] Although patients appear and feel completely deaf, they can still exhibit some reflex responses such as turning their head towards a loud sound.[2] ## Contents * 1 Cause * 2 Diagnosis * 2.1 Case examples * 3 Treatment * 4 History * 5 References * 6 Further reading * 7 External links ## Cause[edit] Cortical deafness is caused by bilateral cortical lesions in the primary auditory cortex located in the temporal lobes of the brain.[3] The ascending auditory pathways are damaged, causing a loss of perception of sound. Inner ear functions, however, remains intact. Cortical deafness is most often cause by stroke, but can also result from brain injury or birth defects.[4] More specifically, a common cause is bilateral embolic stroke to the area of Heschl's gyri.[5] Cortical deafness is extremely rare, with only twelve reported cases. Each case has a distinct context and different rates of recovery. It is thought that cortical deafness could be a part of a spectrum of an overall cortical hearing disorder.[3] In some cases, patients with cortical deafness have had recovery of some hearing function, resulting in partial auditory deficits such as auditory verbal agnosia.[3][6] This syndrome might be difficult to distinguish from a bilateral temporal lesion such as described above. ## Diagnosis[edit] Since cortical deafness and auditory agnosia have many similarities, diagnosing the disorder proves to be difficult. Bilateral lesions near the primary auditory cortex in the temporal lobe are important criteria. Cortical deafness requires demonstration that brainstem auditory responses are normal, but cortical evoked potentials are impaired. Brainstem auditory evoked potentials (BAEP), also referred to as brainstem auditory evoked responses (BAER) show the neuronal activity in the auditory nerve, cochlear nucleus, superior olive, and inferior colliculus of the brainstem. They typically have a response latency of no more than six milliseconds with an amplitude of approximately one microvolt. The latency of the responses gives critical information: if cortical deafness is applicable, LLR (long-latency responses) are completely abolished and MLR (middle latency responses) are either abolished or significantly impaired.[2] In auditory agnosia, LLRs and MLRs are preserved. Another important aspect of cortical deafness that is often overlooked is that patients feel deaf. They are aware of their inability to hear environmental sounds, non-speech and speech sounds. Patients with auditory agnosia can be unaware of their deficit, and insist that they are not deaf.[7] Verbal deafness and auditory agnosia are disorders of a selective, perceptive and associative nature whereas cortical deafness relies on the anatomic and functional disconnection of the auditory cortex from acoustic impulses. ### Case examples[edit] Although cortical deafness has very specific parameters of diagnosis, its causes on the other hand can vary tremendously. The following are three case studies with different reasons for cortical deafness. 1. A case published in 2001 describes the patient as 20-year-old man referred for cochlear implants because of bilateral deafness following a motorcycle accident two years earlier.[2] His CT shows hemorrhagic lesions involving both internal capsules. He was comatose for several weeks and awoke quadriparetic, cognitively impaired and completely deaf. He exhibited a response towards the occasional sudden, loud sound, however, by turning his head. Reading and writing capabilities were maintained, and he was able to communicate by lip-reading. His own speech was dysarthric, but comprehensible. Normal tympanograms and stapedial reflexes imply that the middle and inner ear remained functioning and the auditory nerve was intact. His auditory nerve was tested by evoking responses with normal auditory nerve potentials at 10 dB bilaterally. The results of the BAER waves were normal, but an abnormal complex IV-V suggested that the pathways were functioning through the brainstem, but there was a lesion present in the mid-brain. With these findings, it was determined the patient had cortical deafness due to bilateral interruption of the ascending auditory pathway associated with hemorrhagic lesions of both internal capsules. Therefore, cochlear implantation was not performed.[2] 2. Published in 1994, this patient was monitored over the course of almost 20 years after exhibiting signs of hearing impairment as an infant.[4] Audiologic and related test results in concurrence with MRI confirmed bilateral absence of considerable portions of her temporal lobes resulting in cortical deafness. Although physiologic measures demonstrate normal peripheral hearing sensitivity, this patient's speech has the inflection and prosodic characteristics associated with profound peripheral hearing loss, and she is unable to understand spoken communication. Behaviorally obtained pure-tone thresholds were variable, ranging from normal to moderate hearing loss with normal middle ear muscle reflexes and normal ABRs to high- and low-intensity stimuli. Auditory middle latency and cortical evoked potentials were grossly abnormal, consistent with the central nature of cortical deafness. Because of her inability to communicate auditorily, this patient was ultimately taught American Sign Language and educated at the Louisiana School for the Deaf. At the completion of the case study, the patient was married and expecting a child.[4] 3. A more recent study, published in 2013 the patient described is a 56-year-old woman a history of hypertension, hypercholesterolemia, and multiple cerebrovascular accident (CVA) who presented in March 2009 with a complaint of complete bilateral hearing loss. In March 2009, she experienced an acute right-sided insulotemporal intracerebral hemorrhage. Immediately after this event, the patient complained of hearing loss with the inability to hear all sounds except for severe bilateral tinnitus. Imaging revealed sequelae in the left cerebral cortex from her previous CVA. The new right-sided hemorrhage was centered on the posterior putamen with surrounding edema involving the posterior portion of the posterior limbs of the internal, external, and extreme capsules. Signal abnormalities extended into the right temporal lobe. The patient had no other neurologic deficits and spoke fluently, although with poor internal volume control of her voice. Otoscopic examination revealed normal-appearing external auditory canals, intact tympanic membranes bilaterally, and normal middle ear anatomy. Audiogram at that time showed bilateral profound hearing loss with no responses to pure-tone or speech testing. ## Treatment[edit] Auditory perception can improve with time. There seems to be a level of neuroplasticity that allows patients to recover the ability to perceive environmental and certain musical sounds.[8] Patients presenting with cortical hearing loss and no other associated symptoms recover to a variable degree, depending on the size and type of the cerebral lesion. Patients whose symptoms include both motor deficits and aphasias often have larger lesions with an associated poorer prognosis in regard to functional status and recovery.[8] Cochlear or auditory brainstem implantation could also be treatment options. Electrical stimulation of the peripheral auditory system may result in improved sound perception or cortical remapping in patients with cortical deafness.[3] However, hearing aids are an inappropriate answer for cases like these. Any auditory signal, regardless if has been amplified to normal or high intensities, is useless to a system unable to complete its processing.[4] Ideally, patients should be directed toward resources to aid them in lip-reading, learning American Sign Language, as well as speech and occupational therapy. Patients should follow-up regularly to evaluate for any long-term recovery.[8] ## History[edit] Early reports, published in the late 19th century, describe patients with acute onset of deafness after experiencing symptoms described as apoplexy. The only means of definitive diagnosis in these reports were postmortem dissections.[8] Subsequent cases throughout the 20th century reflect advancements in diagnoses of both hearing loss and stroke. With the advent of audiometric and electrophysiologic studies, investigators could diagnose cortical deafness with increasing precision. Advances in imaging techniques, such as MRI, greatly improved the diagnosis and localization of cerebral infarcts that coincide with primary or secondary auditory centers.[8] Neurological and cognitive testing help to distinguish between total cortical deafness and auditory agnosia, resulting in the inability to perceive words, music, or specific environmental sounds. ## References[edit] 1. ^ Ingram, John Henry (2007). Neurolinguistics: an introduction to spoken language processing and its disorders. Cambridge, UK: Cambridge University Press. pp. 160–171. ISBN 978-0-521-79190-8. OCLC 297335127. 2. ^ a b c d Bogousslavsky, Julien (2001). Stroke Syndromes. Cambridge: Cambridge UP. pp. 153. 3. ^ a b c d Graham J, Greenwood R, Lecky B (October 1980). "Cortical deafness—a case report and review of the literature". J. Neurol. Sci. 48 (1): 35–49. doi:10.1016/0022-510X(80)90148-3. PMID 7420124. 4. ^ a b c d Hood, Linda (1999). "Cortical Deafness: A longitudinal study" (PDF). The American Journal of Nursing. 5. ^ citation needed 6. ^ Cavinato M, Rigon J, Volpato C, Semenza C, Piccione F (2012). "Preservation of auditory P300-like potentials in cortical deafness". PLoS ONE. 7 (1): e29909. doi:10.1371/journal.pone.0029909. PMC 3260175. PMID 22272260. 7. ^ Denes, G., and Luigi Pizzamiglio. "Comprehension Disorders." Handbook of Clinical and Experimental Neuropsychology. Hove, East Sussex, UK: Psychology, 1999. 210. Print. 8. ^ a b c d e Brody, Robert M., Brian D. Nicholas, Michael J. Wolf, Paula B. Marcinkevich, and Gregory J. Artz. "Cortical Deafness: A Case Report and Review of the Literature." Otology and Neurology 34.7 (2013): 1226–229. Ovid. Web. ## Further reading[edit] * Hood L, Berlin C, Allen P (1994). "Cortical deafness: a longitudinal study". J Am Acad Audiol. 5 (5): 330–42. PMID 7987023. ## External links[edit] Classification D * MeSH: D006313 * v * t * e Disorders of hearing and balance Hearing Symptoms * Hearing loss * Excessive response * Tinnitus * Hyperacusis * Phonophobia Disease Loss * Conductive hearing loss * Otosclerosis * Superior canal dehiscence * Sensorineural hearing loss * Presbycusis * Cortical deafness * Nonsyndromic deafness Other * Deafblindness * Wolfram syndrome * Usher syndrome * Auditory processing disorder * Spatial hearing loss Tests * Hearing test * Rinne test * Tone decay test * Weber test * Audiometry * pure tone * visual reinforcement Balance Symptoms * Vertigo * nystagmus Disease * Balance disorder * Peripheral * Ménière's disease * Benign paroxysmal positional vertigo * Labyrinthitis * Labyrinthine fistula Tests * Dix–Hallpike test * Unterberger test * Romberg's test * Vestibulo–ocular reflex * v * t * e Symptoms, signs and syndromes associated with lesions of the brain and brainstem Brainstem Medulla (CN 8, 9, 10, 12) * Lateral medullary syndrome/Wallenberg * PICA * Medial medullary syndrome/Dejerine * ASA Pons (CN 5, 6, 7, 8) * Upper dorsal pontine syndrome/Raymond-Céstan syndrome * Lateral pontine syndrome (AICA) (lateral) * Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar) * Locked-in syndrome * Internuclear ophthalmoplegia * One and a half syndrome Midbrain (CN 3, 4) * Weber's syndrome * ventral peduncle, PCA * Benedikt syndrome * ventral tegmentum, PCA * Parinaud's syndrome * dorsal, tumor * Claude's syndrome Other * Alternating hemiplegia Cerebellum * Latearl * Dysmetria * Dysdiadochokinesia * Intention tremor) * Medial * Cerebellar ataxia Basal ganglia * Chorea * Dystonia * Parkinson's disease Cortex * ACA syndrome * MCA syndrome * PCA syndrome * Frontal lobe * Expressive aphasia * Abulia * Parietal lobe * Receptive aphasia * Hemispatial neglect * Gerstmann syndrome * Astereognosis * Occipital lobe * Bálint's syndrome * Cortical blindness * Pure alexia * Temporal lobe * Cortical deafness * Prosopagnosia Thalamus * Thalamic syndrome Other * Upper motor neuron lesion * Aphasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cortical deafness	c0392704	29,998	wikipedia	https://en.wikipedia.org/wiki/Cortical_deafness	2021-01-18T19:08:16	{"mesh": ["D006313"], "wikidata": ["Q5173263"]}
Orbital cellulitis Orbital Cellulitis SpecialtyOphthalmology Orbital cellulitis is inflammation of eye tissues behind the orbital septum. It is most commonly caused by an acute spread of infection into the eye socket from either the adjacent sinuses or through the blood. It may also occur after trauma. When it affects the rear of the eye, it is known as retro-orbital cellulitis. It should not be confused with periorbital cellulitis, which refers to cellulitis anterior to the septum. Without proper treatment, orbital cellulitis may lead to serious consequences, including permanent loss of vision or even death. ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Causes * 3 Risk Factors * 4 Diagnosis * 4.1 Differential Diagnosis * 5 Treatment * 6 Prognosis * 6.1 Death and blindness rates without treatment * 7 Epidemiology * 8 References * 9 External links ## Signs and symptoms[edit] Orbital cellulitis commonly presents with painful eye movement, sudden vision loss, chemosis, bulging of the infected eye, and limited eye movement. Along with these symptoms, patients typically have redness and swelling of the eyelid, pain, discharge, inability to open the eye, occasional fever and lethargy. ### Complications[edit] Complications include hearing loss, blood infection, meningitis, cavernous sinus thrombosis, cerebral abscess, and blindness.[1][2] It is possible that children experience more severe complications due to their immature immune system and because they have thinner orbital bones, which makes the infection easier to spread.[3][4] ## Causes[edit] Gram-positive stain, possibly showing staphylococcus aureus, which is one of the primary causes of orbital cellulitis. Orbital cellulitis occurs commonly from bacterial infection spread via the paranasal sinuses, usually from a previous sinus infection. Other ways in which orbital cellulitis may occur are from blood stream infections or from eyelid skin infections. Upper respiratory infection, sinus infection, trauma to the eye, ocular or periocular infection, and systemic infection all increase one's risk of orbital cellulitis. Staphylococcus aureus, Haemophilus influenzae B, Moraxella catarrhalis, Streptococcus pneumoniae, and beta-hemolytic streptococci are bacteria that can be responsible for orbital cellulitis.[5][4] * Staphylococcus aureus is a gram-positive bacterium, which is the most common cause of staphylococcal infections. Staphylococcus aureus infection can spread from the skin to the orbit. This organism is able to produce toxins which promotes its virulence, leading to the inflammatory response seen in orbital cellulitis. Staphylococcus infections are identified by a cluster arrangement on gram stain. Staphylococcus aureus forms large yellow colonies when cultured (which is distinct from other Staph infections such as Staphylococcus epidermidis, which forms white colonies). * Streptococcus pneumoniae is also a gram-positive bacterium responsible for orbital cellulitis due to its ability to infect the sinuses. Streptococcal bacteria can invade surrounding tissues, causing the inflammatory response seen in orbital cellulitis (similar to Staphyloccoccus aureus). Streptococcal infections are identified on culture by their formation of pairs or chains. Streptococcus pneumoniae produce green (alpha) hemolysis, or partial reduction of red blood cell hemoglobin. ## Risk Factors[edit] Risk factors for the development of orbital cellulitis include, but are not limited to:[6][7] * Recent upper respiratory illness * Sinus infection * Younger age * Retained foreign bodies within the orbit * Trauma * Immunosuppression * Systemic infection * Dental infection ## Diagnosis[edit] Early diagnosis of orbital cellulitis is urgent, and it involves a complete and thorough physical examination. Common presenting signs include: a protruding eye (proptosis), eyelid edema (swelling), eye pain, vision loss, inability to move the eye completely (ophthalmoplegia), and fever. It is important to correlate physical findings with patient history and reported symptoms.[8] CT scan and MRI of the orbits are two imaging modalities that are commonly used to aid in the diagnosis and monitoring of orbital cellulitis, as they can provide detailed images that can show the extent of inflammation along with possible abscess location, size, and involvement of surrounding structures.[3] Ultrasound has also been used as an imaging modality in the past, but it cannot provide the same level of detail as CT or MRI.[3] Blood cultures, electrolytes, and a complete blood count (CBC) with differential showing elevated white blood cell count is a useful laboratory test that may aid in diagnosis.[8][5] ### Differential Diagnosis[edit] A variety of pathologies and diseases can present similarly to orbital cellulitis, including:[9] * Inflammatory causes (thyroid eye disease, idiopathic orbital inflammatory syndrome, sarcoidosis, granulomatosis with polyangiitis) * Infectious causes (subperiosteal abscess) * Neoplastic, benign and malignant (dermoid cyst, capillary hemangioma, rhabdomyosarcoma, optic nerve glioma, lymphangioma, neurofibroma, leukemia) * Trauma (orbital fracture, retrobulbar hemorrhage, orbital foreign body, carotid cavernous fistula) * Malformation (congenital, vascular) ## Treatment[edit] Immediate treatment is very important, and it typically involves intravenous (IV) antibiotics in the hospital and frequent observation (every 4–6 hours).[2][10] Several lab tests should be ordered, including a complete blood count, differential, and blood culture. * Antibiotic therapy – Since orbital cellulitis is commonly caused by Staphylococcus and Streptococcus species, both penicillins and cephalosporins are typically the best choices for IV antibiotics. However, due to the increasing rise of MRSA (methicillin-resistant Staphylococcus aureus) orbital cellulitis can also be treated with Vancomycin, Clindamycin, or Doxycycline. If improvement is noted after 48 hours of IV antibiotics, healthcare professionals can then consider switching a patient to oral antibiotics (which must be used for 2–3 weeks). * Surgical intervention – An abscess can threaten the vision or neurological status of a patient with orbital cellulitis, therefore sometimes surgical intervention is necessary. Surgery typically requires drainage of the sinuses and if a subperiosteal abscess is present in the medial orbit, drainage can be performed endoscopically. Post-operatively, patients must follow up regularly with their surgeon and remain under close observation. ## Prognosis[edit] Although orbital cellulitis is considered an ophthalmic emergency, the prognosis is good if prompt medical treatment is received. ### Death and blindness rates without treatment[edit] Bacterial infections of the orbit have long been associated with a risk of devastating outcomes and intracranial spread. The natural course of the disease, as documented by Gamble (1933), in the pre-antibiotic era, resulted in death in 17% of patients and permanent blindness in 20%.[11] ## Epidemiology[edit] Orbital cellulitis is an uncommon medical condition, with the reported rates being much higher among the pediatric population compared to the adult population.[3] One study reported that children are approximately 16 times more likely to suffer from orbital cellulitis compared to adults.[12] It is twice as common among male children compared to female children.[1] Some studies reported that orbital cellulitis follows a seasonal pattern, with the highest rates occurring during the fall and winter, which coincides with the higher rates of sinus infection during the colder months.[13] ## References[edit] 1. ^ a b Nageswaran, Savithri; Woods, Charles R.; Benjamin, Daniel K.; Givner, Laurence B.; Shetty, Avinash K. (2006). "Orbital Cellulitis in Children". The Pediatric Infectious Disease Journal. 25 (8): 695–699. doi:10.1097/01.inf.0000227820.36036.f1. ISSN 0891-3668. PMID 16874168. S2CID 23453070. 2. ^ a b Garcia, G (2000-08-01). "Criteria for nonsurgical management of subperiosteal abscess of the orbit Analysis of outcomes 1988–1998". Ophthalmology. 107 (8): 1454–1456. doi:10.1016/s0161-6420(00)00242-6. ISSN 0161-6420. PMID 10919887. 3. ^ a b c d Tsirouki, Theodora; Dastiridou, Anna I.; Ibánez flores, Nuria; Cerpa, Johnny Castellar; Moschos, Marilita M.; Brazitikos, Periklis; Androudi, Sofia (2018). "Orbital cellulitis". Survey of Ophthalmology. 63 (4): 534–553. doi:10.1016/j.survophthal.2017.12.001. ISSN 0039-6257. PMID 29248536. 4. ^ a b Ruiz Carrillo, José Daniel; Vázquez Guerrero, Edwin; Mercado Uribe, Mónica Cecilia (2017-03-01). "Orbital cellulitis complicated by subperiosteal abscess due to Streptococcus pyogenes infection". Boletín Médico del Hospital Infantil de México (English Edition). 74 (2): 134–140. doi:10.1016/j.bmhime.2017.11.020. ISSN 2444-3409. 5. ^ a b Howe, L.; Jones, N. S. (2004-12-01). "Guidelines for the management of periorbital cellulitis/abscess". Clinical Otolaryngology and Allied Sciences. 29 (6): 725–728. doi:10.1111/j.1365-2273.2004.00889.x. ISSN 1365-2273. PMID 15533168. 6. ^ Branson, Sara V.; McClintic, Elysa; Yeatts, R. Patrick (2018). "Septic Cavernous Sinus Thrombosis Associated With Orbital Cellulitis". Ophthalmic Plastic and Reconstructive Surgery. 35 (3): 272–280. doi:10.1097/iop.0000000000001231. ISSN 0740-9303. PMID 30320718. 7. ^ O., Chaudhry, Imtiaz A. Al-Rashed, Waleed Arat, Yonca (2012). "The Hot Orbit: Orbital Cellulitis". Middle East African Journal of Ophthalmology. Medknow Publications & Media Pvt Ltd. 19 (1): 34–42. doi:10.4103/0974-9233.92114. OCLC 806537339. PMC 3277022. PMID 22346113. 8. ^ a b Mejia, Ernesto; Braiman, Melvyn (2018), "Ocular Cellulitis", StatPearls, StatPearls Publishing, PMID 30020691, retrieved 2018-11-25 9. ^ Hood, C T (2009-07-24). "The Wills eye manual: office and emergency room diagnosis and treatment of eye disease". British Journal of Ophthalmology. 93 (8): 1127–1128. doi:10.1136/bjo.2008.152355. ISSN 0007-1161. S2CID 72653095. 10. ^ Mbbs, M P Ferguson; Fraco, A A McNab (1999). "Current treatment and outcome in orbital cellulitis". Australian and New Zealand Journal of Ophthalmology. 27 (6): 375–379. doi:10.1046/j.1440-1606.1999.00242.x. ISSN 0814-9763. PMID 10641894. 11. ^ GAMBLE, R. C. (1933-10-01). "Acute Inflammations of the Orbit in Children". Archives of Ophthalmology. 10 (4): 483–497. doi:10.1001/archopht.1933.00830050059008. ISSN 0003-9950. 12. ^ Murphy, C; Livingstone, I; Foot, B; Murgatroyd, H; MacEwen, C J (2014-06-17). "Orbital cellulitis in Scotland: current incidence, aetiology, management and outcomes: Table 1". British Journal of Ophthalmology. 98 (11): 1575–1578. doi:10.1136/bjophthalmol-2014-305222. ISSN 0007-1161. PMID 24939424. S2CID 206873221. 13. ^ Ivanišević, Milan; Ivanišević, Petar; Lešin, Mladen (2018-10-29). "Epidemiological characteristics of orbital cellulitis among adult population in the Split region, Croatia". Wiener Klinische Wochenschrift. 131 (9–10): 205–208. doi:10.1007/s00508-018-1402-4. ISSN 0043-5325. PMID 30374774. S2CID 53102990. * * * * * Noel LP, Clarke WN, MacDonald N (1990). "Clinical management of orbital cellulitis in children". Canadian Journal of Ophthalmology. 25 (1): 11–16. PMID 2328431. * Shapiro E, Wald E, Brozanski B (1982). "Periorbital cellulitis and paranasal sinusitis: a reappraisal". Pediatric Infectious Disease. 1 (2): 91–94. doi:10.1097/00006454-198203000-00005. PMID 7177909. S2CID 24237202. ## External links[edit] Classification D * ICD-10: H05.0 * ICD-9-CM: 376.01 * MeSH: D054517 * DiseasesDB: 9249 External resources * MedlinePlus: 001012 * eMedicine: article/1217858 * MedlinePlus. * Death Rates for Orbital Cellulitis * Pub Med Health - Orbital Cellulitis * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Orbital cellulitis	c0149507	29,999	wikipedia	https://en.wikipedia.org/wiki/Orbital_cellulitis	2021-01-18T19:10:14	{"mesh": ["D054517"], "umls": ["C0149507"], "wikidata": ["Q622969"]}

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.