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A number sign (#) is used with this entry because of the finding that somatic mutation in the gene encoding the G protein subunit alpha-i2 (GNAI1; 139360) is responsible in at least 1 case. This raises the possibility that familial cases may be caused by mutation in this or related genes. Stress-induced polymorphic ventricular tachycardia (VTSIP; 604772), also known as catecholaminergic polymorphic ventricular tachycardia, has been found to be caused by mutation in the gene encoding the cardiac ryanodine receptor gene (RYR2; 180902). Rubin et al. (1992) reported a kindred in which members in 4 successive generations suffered from paroxysmal ventricular tachycardia. They suggested that this is the first report of an autosomal dominant ventricular tachycardia not associated with cardiomyopathy, metabolic disorder, or repolarization abnormality. In generation 2, 4 of 7 sibs sustained sudden cardiac death. In generation 3, 5 of 10 sibs had documented ventricular tachycardia and 1 of the 5 had sudden cardiac death. In generation 4, 4 of 12 sibs had ventricular tachycardia and 1 of them died suddenly. All the children in generation 5, all prepubertal, were asymptomatic and had normal cardiac investigations. No systemic abnormalities were found in 2 affected fourth-generation family members studied in great detail. The ventricular tachycardia detected in these sibs on 24-hour ambulatory monitoring had a similar right bundle branch block, with left axis deviation pattern. Rubin et al. (1992) reviewed the reasons to think that reentry and triggered automaticity were not likely mechanisms, leaving abnormal automaticity as the likely cause. Familial ventricular tachycardia is usually attributable to recognized conditions such as arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, familial cardiomyopathy, or one of the long QT syndromes. There are families with ventricular tachycardia in which no recognized underlying condition has been identified. The features of the disorder are variable from family to family. Fisher et al. (1999) described a family in which members developed ventricular arrhythmias during sinus tachycardia, whether induced by exercise, isoproterenol infusion, or emotion. Their QT intervals were normal at rest and during exercise. In this family, Fisher et al. (1999) reported a 25-year period of apparently effective medical therapy. The affected members appeared to have catecholamine hypersensitivity as the basis of their ventricular arrhythmias. Guided therapy using serial exercise-pharmacologic testing provided reliable protection for this familial ventricular arrhythmia. Idiopathic ventricular tachycardia is a generic term that describes the various forms of ventricular arrhythmias that occur in patients without structural heart disease and in the absence of long QT syndrome. Many of these tachycardias are focal in origin, localize to the right ventricular outflow tract (RVOT), terminate in response to beta-blockers, verapamil, vagal maneuvers, and adenosine, and are thought to result from cAMP-mediated triggered activity. Lerman et al. (1998) studied a patient with adrenergically mediated idiopathic RVOT ventricular tachycardia that was unresponsive to adenosine and vagal maneuvers. The subject was a 58-year-old man who developed sustained monomorphic ventricular tachycardia during an intense argument. Because of insensitivity of the tachycardia to adenosine, Lerman et al. (1998) investigated the possibility that a mutation in the inhibitory branch of the cAMP signal transduction pathway could have elevated intracellular cAMP and facilitated the spontaneous initiation of ventricular tachycardia. They succeeded in identifying a point mutation in the GNAI2 gene (139360.0004) from the arrhythmogenic focus biopsied in this patient. Both stable and transient transfection of CHO-K1 cells with the mutant gene showed that this mutation increased the stimulated levels of cAMP and prevented adenosine suppression of cAMP. No mutations were detected in myocardial tissue sampled from regions remote from the origin of the tachycardia, or in peripheral lymphocytes. Cardiac \- Sudden cardiac death \- Paroxysmal ventricular tachycardia \- Right bundle branch block with left axis deviation on EKG \- No cardiomyopathy \- No repolarization abnormality Inheritance \- Autosomal dominant Metabolic \- No metabolic disorder ▲ 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-aminobutyric 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	VENTRICULAR TACHYCARDIA, FAMILIAL	c0340485	27,400	omim	https://www.omim.org/entry/192605	2019-09-22T16:32:00	{"mesh": ["C536334"], "omim": ["192605"], "synonyms": ["Alternative titles", "VENTRICULAR TACHYCARDIA, FAMILIAL POLYMORPHIC"]}
A rare cerebral malformation characterized by an almost or complete lack of cortex, specifically the cerebral hemispheres, with the cranium and meninges completely intact. In most cases, death occurs in utero or in the first weeks of life. Developmental delay, drug-resistant seizures, spastic diplegia, severe growth failure, deafness and blindness are typical. [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-aminobutyric 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	Hydranencephaly	c0020225	27,401	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2177	2021-01-23T17:23:47	{"gard": ["6681"], "mesh": ["D006832"], "umls": ["C0020225"], "icd-10": ["Q04.3"]}
Trichodiscoma SpecialtyOncology, dermatology A trichodiscoma is a cutaneous condition, a benign, usually skin-colored tumor most often affecting the face and upper trunk.[1]:674[2] ## See also[edit] * Birt–Hogg–Dubé syndrome * Fibrofolliculoma * List of cutaneous conditions * List of cutaneous neoplasms associated with systemic syndromes ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1694, 1695. ISBN 1-4160-2999-0. ## External links[edit] Classification D * ICD-10: D23.L26 (ILDS D23.L26) * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed This Epidermal nevi, neoplasms, cysts 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-aminobutyric 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	Trichodiscoma	c1704237	27,402	wikipedia	https://en.wikipedia.org/wiki/Trichodiscoma	2021-01-18T18:34:08	{"umls": ["C1704237"], "icd-10": ["L26", "D23"], "wikidata": ["Q7840764"]}
Hypothalamic disease SpecialtyNeurology, endocrinology Hypothalamic disease is a disorder presenting primarily in the hypothalamus, which may be caused by damage resulting from malnutrition, including anorexia and bulimia eating disorders,[1][2] genetic disorders, radiation, surgery, head trauma,[3] lesion,[1] tumour or other physical injury to the hypothalamus. The hypothalamus is the control center for several endocrine functions. Endocrine systems controlled by the hypothalamus are regulated by antidiuretic hormone (ADH), corticotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, oxytocin, all of which are secreted by the hypothalamus. Damage to the hypothalamus may impact any of these hormones and the related endocrine systems. Many of these hypothalamic hormones act on the pituitary gland. Hypothalamic disease therefore affects the functioning of the pituitary and the target organs controlled by the pituitary, including the adrenal glands, ovaries and testes, and the thyroid gland.[2] Numerous dysfunctions manifest as a result of hypothalamic disease. Damage to the hypothalamus may cause disruptions in body temperature regulation, growth, weight, sodium and water balance, milk production, emotions, and sleep cycles.[1][2][4] Hypopituitarism, neurogenic diabetes insipidus, tertiary hypothyroidism, and developmental disorders are examples of precipitating conditions caused by hypothalamic disease. ## Contents * 1 Hypopituitarism * 2 Neurogenic diabetes insipidus * 3 Tertiary hypothyroidism * 4 Developmental disorders * 5 Sleep disorders * 6 References * 7 External links ## Hypopituitarism[edit] The hypothalamus and pituitary gland are tightly integrated. Damage to the hypothalamus will impact the responsiveness and normal functioning of the pituitary. Hypothalamic disease may cause insufficient or inhibited signalling to the pituitary leading to deficiencies of one or more of the following hormones: thyroid-stimulating hormone, adrenocorticotropic hormone, beta-endorphin, luteinizing hormone, follicle-stimulating hormone, and melanocyte–stimulating hormones. Treatment for hypopituitarism involves hormone replacement therapy.[1] ## Neurogenic diabetes insipidus[edit] Neurogenic diabetes insipidus may occur due to low levels of ADH production from the hypothalamus.[1][5][6] Insufficient levels of ADH result in increased thirst and urine output, and prolonged excessive urine excretion increases the risk of dehydration.[6] ## Tertiary hypothyroidism[edit] The thyroid gland is an auxiliary organ to the hypothalamus-pituitary system. Thyrotropin-releasing hormone (TRH) produced by the hypothalamus signals to the pituitary to release thyroid-stimulating hormone (TSH), which then stimulates the thyroid to secrete T4 and T3 thyroid hormones.[7][8] Secondary hypothyroidism occurs when TSH secretion from the pituitary is impaired, whereas tertiary hypothyroidism is the deficiency or inhibition of TRH.[7] Thyroid hormones are responsible for metabolic activity. Insufficient production of the thyroid hormones result in suppressed metabolic activity and weight gain. Hypothalamic disease may therefore have implications for obesity.[9] ## Developmental disorders[edit] Growth hormone-releasing hormone (GHRH) is another releasing factor secreted by the hypothalamus. GHRH stimulates the pituitary gland to secrete growth hormone (GH), which has various effects on body growth and sexual development.[1][5] Insufficient GH production may cause poor somatic growth, precocious puberty or gonadotropin deficiency, failure to initiate or complete puberty, and is often associated with rapid weight gain, low T4, and low levels of sex hormones.[5] ## Sleep disorders[edit] Non-24-hour sleep-wake syndrome, a disabling condition in which one's sleep/wake cycle is longer, or rarely, shorter, than the standard 24 hours, is thought to involve or be caused by, at least in some cases, an abnormal functioning of the suprachiasmatic nucleus (SCN) in the hypothalamus.[10][11] ## References[edit] 1. ^ a b c d e f Sylvia L., A. (2004). Hypothalamic disease. In Editor-in-Chief: Luciano Martini (Ed.), Encyclopedia of endocrine diseases (pp. 678-687). New York: Elsevier. doi:10.1016/B0-12-475570-4/00714-9 2. ^ a b c MedlinePlus Encyclopedia: Hypothalamic dysfunction 3. ^ Rehan, K. (2011). An Overview of the Hypothalamus The Endocrine System’s Link to the Nervous System. Retrieved from http://www.endocrineweb.com/endocrinology/overview-hypothalamus 4. ^ Carmichael, J. D., & Braunstein, G. D. (2009). Diseases of Hypothalamic Origin. In D. W. Pfaff, A. P. Arnold, S. E. Fahrbach, A. M. Etgen & R. T. Rubin (Eds.), Hormones, Brain and Behavior (3005-3048). Los Angeles, CA: Academic Press 5. ^ a b c Rose, S. R., & Auble, B. A. (2011). Endocrine changes after pediatric traumatic brain injury. Pituitary, doi:10.1007/s11102-011-0360-x 6. ^ a b Maghnie, M., Altobelli, M., Di Iorgi, N., Genovese, E., Meloni, G., Manca-Bitti, M. L., . . . Bernasconi, S. (2004). Idiopathic central diabetes insipidus is associated with abnormal blood supply to the posterior pituitary gland caused by vascular impairment of the inferior hypophyseal artery system. The Journal of Clinical Endocrinology and Metabolism, 89(4), 1891-1896. 7. ^ a b Martin, J. B., & Riskind, P. N. (1992). Neurologic manifestations of hypothalamic disease. Progress in Brain Research, 93, 31-40; discussion 40-2. 8. ^ Chiamolera, M. I., & Wondisford, F. E. (2009). Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology, 150(3), 1091-1096. doi:10.1210/en.2008-1795 9. ^ Pinkney, J. (2000). Obesity and pituitary disease. Pituitary News, 17. Retrieved from http://www.pituitary.org.uk/content/view/166/122/ Archived 2012-01-20 at the Wayback Machine 10. ^ Stores G (2003). "Misdiagnosing sleep disorders as primary psychiatric conditions". Advances in Psychiatric Treatment. 9 (1): 69–77. doi:10.1192/apt.9.1.69. 11. ^ Stores G (2007). "Clinical diagnosis and misdiagnosis of sleep disorders". J. Neurol. Neurosurg. Psychiatry. 78 (12): 1293–7. doi:10.1136/jnnp.2006.111179. PMC 2095611. PMID 18024690. ## External links[edit] Classification D * ICD-10: E23.3 * MeSH: D007027 * v * t * e Hypothalamic disease Gonadotropin * Kallmann syndrome * Adiposogenital dystrophy CRH * Tertiary adrenal insufficiency Vasopressin * Neurogenic diabetes insipidus General * Hypothalamic hamartoma [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-aminobutyric 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	Hypothalamic disease	c0020655	27,403	wikipedia	https://en.wikipedia.org/wiki/Hypothalamic_disease	2021-01-18T18:50:21	{"mesh": ["D007027"], "umls": ["C0020655"], "wikidata": ["Q5961220"]}
A rare, potentially life-threatening, circulatory system disease characterized by variable signs and symptoms which may include headache, seizures, altered mental status, intracranial hypertension and cavernous sinus syndrome, 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-aminobutyric 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	Cerebral sinovenous thrombosis	None	27,404	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329217	2021-01-23T18:17:14	{"icd-10": ["I67.6"], "synonyms": ["CSVT"]}
Craniomandibular osteopathy, also known as lion's jaw, is a developmental disease in dogs causing extensive bony changes in the mandible and skull. In this disease, a cyclical resorption of normal bone and replacement by immature bone occurs along the inner and outer surfaces of the affected bones.[1] It usually occurs between the ages of 3 and 8 months. Breeds most commonly affected include the West Highland White Terrier, Scottish Terrier, Cairn Terrier, and Boston Terrier.[2] It is rare in large-breed dogs, but it has been reported.[3] Symptoms include firm swelling of the jaw, drooling, pain, and difficulty eating. It is an inherited disease, especially in Westies, in which it has been recognized as an autosomal recessive trait.[4] Canine distemper has also been indicated as a possible cause,[2] as has E. coli infection, which could be why it is seen occasionally in large-breed dogs.[3] Growth of lesions will usually stop around the age of one year, and possibly regress. This timing coincides with the normal completion of endochondral bone growth and ossification. If the disease is extensive, especially around the tympanic bulla (middle ear), then the prognosis is guarded. A similar disease seen in young Bullmastiffs is known as calvarial hyperostotic syndrome. It is also similar to human infantile cortical hyperostosis. It is characterized by irregular, progressive bony proliferation and thickening of the cortical bone of the calvaria, which is part of the skull. Asymmetry of the lesions may occur, which makes it different from craniomandibular osteopathy. Symptoms include painful swelling of the skull, fever, and lymph node swelling.[5] In most cases it is self-limiting.[6] ## References[edit] 1. ^ "Craniomandibular Osteopathy". The Merck Veterinary Manual. 2006. Retrieved 2007-02-04. 2. ^ a b Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3. 3. ^ a b Huchkowsky S (2002). "Craniomandibular osteopathy in a bullmastiff". Can Vet J. 43 (11): 883–5. PMC 339767. PMID 12497967. 4. ^ Hazewinkel, Herman A.W. (2004). "Hereditary Skeletal Diseases in Companion Animal Practice". Proceedings of the 29th World Congress of the World Small Animal Veterinary Association. Retrieved 2006-08-26. 5. ^ McConnell J, Hayes A, Platt S, Smith K (2006). "Calvarial hyperostosis syndrome in two bullmastiffs". Vet Radiol Ultrasound. 47 (1): 72–7. doi:10.1111/j.1740-8261.2005.00108.x. PMID 16429988. 6. ^ Pastor K, Boulay J, Schelling S, Carpenter J (2000). "Idiopathic hyperostosis of the calvaria in five young bullmastiffs". J Am Anim Hosp Assoc. 36 (5): 439–45. PMID 10997521. This veterinary medicine–related 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-aminobutyric 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	Craniomandibular osteopathy	c0264082	27,405	wikipedia	https://en.wikipedia.org/wiki/Craniomandibular_osteopathy	2021-01-18T19:09:53	{"wikidata": ["Q1786494"]}
Glycogen storage disease type 3 (GSDIII) is an inherited disorder caused by the buildup of glycogen in the body's cells. This buildup impairs the function of certain organs and tissues, especially the liver and muscles. Symptoms typically begin in infancy and may include hypoglycemia, hyperlipidemia (excess of fats in the blood), and elevated blood levels of liver enzymes; later symptoms may include hepatomegaly, chronic liver disease (cirrhosis) and liver failure later in life. Some individuals have short stature and noncancerous (benign) tumors called adenomas in the liver. GSDIII is cause by mutations in the AGL gene and is inherited in an autosomal recessive manner. Treatment typically includes a high-protein diet with cornstarch supplementation to maintain a normal level of glucose in the blood. GSDIII is divided into types IIIa, IIIb, IIIc, and IIId; types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver. [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-aminobutyric 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	Glycogen storage disease type 3	c0017922	27,406	gard	https://rarediseases.info.nih.gov/diseases/9442/glycogen-storage-disease-type-3	2021-01-18T18:00:16	{"mesh": ["D006010"], "omim": ["232400"], "orphanet": ["366"], "synonyms": ["Forbes disease", "Cori disease", "Limit dextrinosis", "Amylo-1,6-glucosidase deficiency", "Glycogen debrancher deficiency"]}
human chronic inflammatory disease Lichen planus Other namesLP Lichen planus affecting the shins Pronunciation * /ˈlaɪkən ˈpleɪnəs/ SpecialtyDermatology Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, nails, hair, and mucous membranes.[1] It is not an actual lichen, and is only named that because it looks like one.[2] It is characterized by polygonal, flat-topped, violaceous papules and plaques with overlying, reticulated, fine white scale (Wickham's striae), commonly affecting dorsal hands, flexural wrists and forearms, trunk, anterior lower legs and oral mucosa.[3] Although there is a broad clinical range of LP manifestations, the skin and oral cavity remain as the major sites of involvement.[4] The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. There is no cure, but many different medications and procedures have been used in efforts to control the symptoms. The term lichenoid reaction (lichenoid eruption or lichenoid lesion) refers to a lesion of similar or identical histopathologic and clinical appearance to lichen planus (i.e., an area which resembles lichen planus, both to the naked eye and under a microscope).[5][6] Sometimes dental materials or certain medications can cause a lichenoid reaction.[5] They can also occur in association with graft versus host disease.[5][7]:258 ## Contents * 1 Classification * 1.1 Site * 1.2 Pattern * 1.3 Overlap syndromes * 2 Signs and symptoms * 2.1 Skin * 2.2 Mucous membranes * 2.2.1 Mouth * 3 Causes * 4 Pathogenesis * 5 Diagnosis * 5.1 Skin * 5.2 Mouth * 5.3 Differential diagnosis * 5.3.1 Skin * 5.3.2 Mouth * 5.3.2.1 Oral lichenoid drug reaction * 5.3.2.2 Oral lichenoid contact reaction (allergic contact mucositis) * 5.3.2.3 Autoimmune blistering diseases * 5.3.2.4 Graft-versus-host disease (GVHD) * 5.3.2.5 Leukoplakia * 5.3.2.6 Oral squamous cell carcinoma (SCC) * 5.3.2.7 Leukoedema * 5.3.2.8 Oropharyngeal candidiasis * 5.4 Histopathology * 6 Treatment * 6.1 Skin * 6.2 Mouth * 7 Prognosis * 8 Epidemiology * 9 History * 10 Research * 11 Notes * 12 References * 13 External links ## Classification[edit] Lichen planus lesions are so called because of their "lichen-like" appearance[2] and can be classified by the site they involve, or by their morphology. ### Site[edit] Lichen planus may be categorized as affecting mucosal or cutaneous surfaces. * Cutaneous forms are those affecting the skin, scalp, and nails.[8][9][10] * Mucosal forms are those affecting the lining of the gastrointestinal tract (mouth, pharynx, esophagus, stomach, anus), larynx, and other mucosal surfaces including the genitals, peritoneum, ears, nose, bladder and conjunctiva of the eyes.[11][12][13] ### Pattern[edit] Lichen planus lesions can occur in many different forms: Lesion morphology Description[14] Papular Papular form is the classic cutaneous lichen planus (CLP) lesion characterized by shiny, red or purple-colored, flat-topped papule. Lesions may have a thin, transparent, and adherent scale. Fine whitish points or lacy lines (Wickham's striae) may be seen on the surface of well-developed papules.[1] Annular 'Ring-shaped' lesions that develop gradually from single small pigmented spots into circular groups of papules with clear, unaffected skin in the center. The ring-like lesions may very slowly enlarge, co-join and morph into larger irregular (serpentine) bands, sometimes accompanied by lines (See Linear, below). Annular CLP is uncommon and classically involves the male genitalia (glans penis and penile shaft), groin, axilla and also the extremities.[1] Linear Papules are arranged in a line (the "Blaschko line").[15] This pattern may develop secondary to trauma (koebnerization) or, uncommonly, as a spontaneous, isolated eruption, usually on the extremities, and rarely on the face.[16] Hypertrophic This pattern is characterized by hyperkeratotic thick pruritic red-brown to purple-gray plaques with follicular accentuation. Hypertrophic CLP commonly involves the extremities, especially the interphalangeal joints and the anterior legs in a symmetrical distribution.[1] This form is also known as "lichen planus verrucosus". Atrophic This morphology is characterized by the presence of a few well-demarcated, white-bluish papules or plaques with central superficial atrophy. Atrophic CLP is the clinical endpoint of chronic annular or hypertrophic LP with atrophic lesions. The use of potent topical corticosteroids for a long-term may predispose the patient to developing atrophic lesions.[1] Bullous This morphology is characterized by the development of vesicles and bullae with the skin lesions. This is a rare variant of lichen planus, and also known as "vesiculobullous lichen planus." Actinic Rare form presenting as nummular patches or plaques with a hypopigmented halo surrounding a hyperpigmented center. Actinic CLP is more prevalent in African Americans, Indians, and Middle-Eastern individuals and commonly affects the sun-exposed areas.[1] Ulcerative This morphology is characterized by chronic, painful bullae and ulceration of the feet, often with cicatricial sequelae evident. This is a rare variant of lichen planus. Pigmented This morphology is characterized by hyperpigmented, dark-brown macules in sun-exposed areas and flexural folds. This is a rare variant of lichen planus. Follicular Characterized by follicular, flat, elevated or hemispherical erythematous papules with or without keratoses presenting in groups or disseminated. The Graham‐Little‐Piccardi‐Lasseur syndrome, seen in a familial pattern and also predominantly in women, is characterized by the appearance of follicular LP on the trunk with LP follicularis decalvans on the scalp. Follicular LP on the scalp is more likely to lead to scarring alopecia.[14] Inverse Characterized by extensive erythematous lesions with poorly defined borders and in part with lichenification. Inverse LP typically affects the axillae, inguinal creases, limb flexures and submammary region. Pigmentation of the individual lesions at these inverse locations are typical. Additionally, keratotic papules and erosions with a bizarre configuration can occur.[14] ### Overlap syndromes[edit] Occasionally, lichen planus is known to occur with other conditions. For example: * Lupus erythematosus overlap syndrome. Lesions of this syndrome share features of both lupus erythematosus and lichen planus. Lesions are usually large and hypopigmented, atrophic, and with a red to blue colour and minimal scaling. Telangectasia may be present.[17][18] * Lichen sclerosus overlap syndrome, sharing features of lichen planus and lichen sclerosus.[19] ## Signs and symptoms[edit] Lichen planus affecting the lower lip Although lichen planus can present with a variety of lesions, the most common presentation is as a well defined area of purple-coloured, itchy, flat-topped papules with interspersed lacy white lines (Wickham's striae). This description is known as the characteristic "6 Ps" of lichen planus: planar (flat-topped), purple, polygonal, pruritic, papules, and plaques.[8] This rash, after regressing, is likely to leave an area of hyperpigmentation that slowly fades. That said, a variety of other lesions can also occur.[2] ### Skin[edit] Cutaneous lichen planus on the shin Lichen planus involving the nails Variants of cutaneous lichen planus are distinguished based upon the appearance of the lesions and/or their distribution.[20] Lesions can affect the: * Extremities (face, dorsal hands, arms, and nape of neck).[a] This is more common in Middle Eastern countries in spring and summer, where sunlight appears to have a precipitating effect.[16][21][22] * Palms and soles * Intertriginous areas of the skin. This is also known as "inverse lichen planus."[16] * Nails[23] characterized by irregular longitudinal grooving and ridging of the nail plate, thinning of the nail plate, pterygium formation, shedding of the nail plate with atrophy of the nail bed, subungual keratosis, longitudinal erthronychia (red streaks), and subungual hyperpigmentation.[24] A sand-papered appearance is present in around 10% of individuals with nail lichen planus.[23] * Hair and Scalp. The scalp is rarely affected by a condition known as lichen planopilaris, acuminatus, follicular lichen planus, and peripilaris, characterised by violaceous, adherent follicular scale with progressive scarring alopecia. While lichen planus and lichen planopilaris may occur together, aside from sharing the term ‘lichen’ and revealing inflammation on skin biopsy, there is neither established data on their co-occurrence nor data to suggest a common etiology. Lichen planopilaris is considered an orphan disease with no definitive prevalence data and no proven effective treatments.[25][26] Other variants may include: * Lichen planus pemphigoides characterized by the development of tense blisters atop lesions of lichen planus or the development vesicles de novo on uninvolved skin.[27] * Keratosis lichenoides chronica (also known as "Nekam's disease") is a rare dermatosis characterized by violaceous papular and nodular lesions, often arranged in a linear or reticulate pattern on the dorsal hands and feet, extremities, and buttock, and some cases manifest by sorrheic dermatitis-like eruption on the scalp and face; also palmo plantar keratosis has been reported.[16][28][29] * Lichenoid keratoses (also known as "benign lichenoid keratosis," and "Solitary lichen planus"[16]) is a cutaneous condition characterized by brown to red scaling maculopapules, found on sun-exposed skin of extremities.[16][30] Restated, this is a cutaneous condition usually characterized by a solitary dusky-red to violaceous papular skin lesion.[31] * Lichenoid dermatitis represents a wide range of cutaneous disorders characterized by lichen planus-like skin lesions.[16][30] ### Mucous membranes[edit] Lichen planus on the lips and the lateral border of the tongue Lichen planus affecting mucosal surfaces may have one lesion or be multifocal.[32] Examples of lichen planus affecting mucosal surfaces include:[32] * Esophageal lichen planus, affecting the esophageal mucosa. This can present with difficulty or pain when swallowing due to oesophageal inflammation, or as the development of an esophageal stricture. It has also been hypothesized that it is a precursor to squamous cell carcinoma of the esophagus.[12][33] * Genital lichen planus, which may cause lesions on the glans penis or skin of the scrotum in males, and the vulva or vagina in females.[8] Symptoms may include lower urinary tract symptoms associated with stenosis of the urethra, painful sexual intercourse, and itching.[8] In females, Vulvovaginal-gingival syndrome, is severe and distinct variant affecting the vulva, vagina, and gums, with complications including scarring, vaginal stricture formation,[34] or vulva destruction.[35] The corresponding syndrome in males, affecting the glans penis and gums, is the peno-gingival syndrome.[16] It is associated with HLA-DQB1.[16][36] #### Mouth[edit] Classic white striations of non-erosive lichen planus in the left buccal mucosa (left cheek) Oral lichen planus (also termed oral mucosal lichen planus), is a form of mucosal lichen planus, where lichen planus involves the oral mucosa, the lining of the mouth.[37] This may occur in combination with other variants of lichen planus. Six clinical forms of oral lichen planus (OLP) are recognized:[38] Lesion morphology Description Reticular The most common presentation of oral lichen planus (OLP), is characterised by the net-like or spider web-like appearance of lacy white lines, oral variants of Wickham's straiae.[39] This is usually asymptomatic. Reticular OLP may eventually progress to the more severe subtypes such as the erosive form.[1] Erosive/ Ulcerative The second most common form and the most advance form of oral lichen planus,[39][1] is characterised by oral ulcers presenting with persistent, irregular areas of redness, ulcerations and erosions covered with a yellow slough. This can occur in one or more areas of the mouth. In 25% of people with erosive oral lichen planus, the gums are involved, described as desquamative gingivitis (a condition not unique to lichen planus). This may be the initial or only sign of the condition.[40] Involvement of the dorsum of the tongue might cause an altered sense of taste (dysgeusia).[1] Papular This form is characterized by small white pinpoint papules that are asymptomatic. Hence, they can be easily missed during a routine checkup. It is referred to as the initial and transient phase of OLP.[1] Plaque-like Large, homogenous white patches are characteristic of this form which may resemble leukoplakia. This form is more prevalent in tobacco smokers.[1] Atrophic This form is a common presentation that has similarities to the erosive form. It has a more prominent atrophic lesion on a background of erythema with radiating white striae at the margins.[1] Atrophic oral lichen planus may also manifest as desquamative gingivitis.[40] Bullous Rare form of OLP characterized by fluid-filled vesicles ranging in size from 1 to 2 mm to several cm in diameter. The vesicles or bullae appear white or gray-purple in color and are fluctuant. The fluid in the vesicles are usually clear but may be hemorrhagic or purulent upon secondary infection. These rupture easily and they leave an ulcerated, painful surface.[citation needed] These types often coexist in the same individual. Oral lichen planus (OLP) tends to present bilaterally as mostly white lesions on the inner cheek,[39] although any mucosal site in the mouth may be involved. Other sites, in decreasing order of frequency, may include the tongue, lips, gingivae, floor of the mouth, and very rarely, the palate.[39] Generally, oral lichen planus tends not to cause any discomfort or pain, although some people may experience soreness when eating or drinking acidic or spicy foodstuffs or beverages.[40] When symptoms arise, they are most commonly associated with the atrophic and ulcerative subtypes. These symptoms can include a burning sensation to severe pain.[39] They may also experience mucosal bleeding in response to mild trauma, such as toothbrushing. Additionally, The Koebner phenomenon (the development of new lesions at sites of trauma) is not only present in cutaneous lichen planus (CLP) but can also occur in the setting of OLP. Residual postinflammatory hyperpigmentation has been reported in association with OLP, manifesting as brown to black pigmentation on the oral mucosa and may most likely occur in dark-skinned individuals.[41] OLP may occur as a sole manifestation of the disease or in conjunction with other clinical manifestations of LP, including cutaneous LP, genital LP, nail LP, and lichen planopilaris (scalp LP).[41] ## Causes[edit] Cutaneous LP is a self-limiting condition. It usually resolves within 6 to 12 months. Oral LP is a non infectious, chronic inflammatory condition that involves the oral mucosa and may be accompanied by skin lesions. The etiology of oral LP are unknown. It is not clear whether the mechanisms causing isolated oral LP are different from those causing oral LP with cutaneous LP. An immune-mediated mechanism where basal keratinocytes are being targeted as foreign antigens by activated T cells, especially CD8+ T cells, has been proposed.[42] Upregulation of intercellular adhesion molecule-1 (ICAM-1) and cytokines associated with T-helper 1 immune response, may also pay an important role in the pathogenesis of lichen planus. Stress is thought to play a role in the pathogenesis of oral LP. Patients with anxiety and depression are reported more commonly with oral LP if compared to normal healthy individuals.[43][44] Some studies have indicated that stressful events can induce LP lesions in otherwise healthy individuals. However, a cause effect relationship between stress and the onset of oral LP has not been demonstrated. Autoimmune response to epithelial self-antigens remains a possibility. A single study of cutaneous LP reported evidence in support of autoimmunity by expanding in vitro T cells isolated from the skin lesions of two patients, followed by testing the ability of these T cells to kill autologous keratinocytes (cytotoxicity). Several potential triggers of oral LP have been proposed over the years, mainly 1. Hypersensitivity reaction * Restorative material (e.g. amalgam[45] and composite) or drugs can cause hypersensitivity reaction and lead to oral LP. * Oral LP usually resolve upon removal of the trigger, as is characteristics of oral LP 2. Viral infection ## Pathogenesis[edit] Oral LP is considered to be a T-cell mediated chronic inflammatory tissue reaction that results in a cytotoxic reaction against epithelial basal cells.[46] The inflammatory infiltrate in oral LP is primarily composed of CD8+ T cells. A potential pathway for CD8+ T cell-mediated cytotoxicity in oral LP is described as follows:[46] Antigens presented on MHC 1 molecules activates CD8+ T cells on keratinocytes or by encounters with activated CD4+ helper T cells or cytokines produced by activated CD4+ helper T cells Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF)-alpha, secretion of granzyme B, or Fas-Fas ligand interactions. Chemokines are produced by activated CD8+ T cells that attract additional inflammatory cells, thereby promoting continued inflammation. Other mechanisms that have been proposed include: * upregulation of matrix metalloproteinases that disrupt the epithelial basement membrane zone and allow entry of immune cells into the epidermis, * the release of proinflammatory mediators and proteases by mast cells, and * perturbations in the innate immune response that may involve toll-like receptors.[46][47][48][49] Oral LP may also be caused by genetic factor which influence the immune function. A separate study performed in China[50] found an association between a polymorphism in the TNF-alpha gene and risk for oral LP in a subset of patients. An Italian study found a significant increase in a genetic polymorphism of the first intron of the interferon (IFN)-gamma promoter in patients with oral LP compared with controls.[50] ## Diagnosis[edit] ### Skin[edit] Patient history and clinical presentation need to be taken to diagnose lichen planus. Patient with suspected cutaneous lichen planus needs to be evaluated clinically through patient interview and physical examination. Patients should be questioned about their medication history, any history of pruritus or genital pain and history of dysphagia or odynophagia. Examination of entire cutaneous surface including the scalp, oral cavity and external genitalia need to be included. Wickham's striae often can be seen during microscopic examination of cutaneous lesions of lichen planus.[51][52] To confirm the diagnosis of cutaneous lichen planus, a skin biopsy can be done. A punch biopsy of sufficient depth to the mid dermis is usually significant. Immunofluorescence studies are not always needed. Direct immunofluorescence (DIF) can be useful in patients with bullous lesions to differentiate the condition from an autoimmune vesiculobullous disease.[53] ### Mouth[edit] A diagnosis of oral lichen planus (LP) is confirmed through review of the patient history, physical examination, and histologic findings. The clinical evaluation should include a patient history that assesses the following: * History of LP involving other body sites or other skin disorders that may present with similar findings (e.g., autoimmune blistering diseases) * Presence of associated symptoms (e.g., pain, burning) * Medication the patients are taking within the few weeks to months after drug initiation e.g. antihypertensives, antidepressants, diuretics, antidiabetics, NSAIDS, etc. to evaluate for the possibility of an oral lichenoid drug eruption * History of dental restorations,[45] use of dental appliances, or oral exposure to substances that may cause oral lichenoid contact eruptions (e.g. dental composites, cobalt chromium based dentures etc.) A full examination that includes the evaluation of the mucosal and cutaneous surfaces, including the vulva, vagina, penis, scalp, and nails should be performed. Thorough examination may lead to the detection of extraoral manifestations of LP that provide additional support for the diagnosis or the identification of clinical findings that suggest another diagnosis. Tissue biopsies of oral LP help to confirm the diagnosis and are particularly of value for erythematous and erosive LP, which share features with multiple other mucosal disorders, including oral malignancy. Biopsies to confirm oral LP are less essential in patients who present with classic reticular LP, particularly in patients in whom a diagnosis of LP has already been confirmed through biopsy of an extraoral manifestation of this disorder.[54][55] ### Differential diagnosis[edit] #### Skin[edit] 1. Lichenoid drug eruption * The cutaneous manifestations resemble idiopathic lichen planus. 2. Chronic graft-versus-host disease * The history of preceding hematopoietic cell transplant is helpful for diagnosis 3. Psoriasis 4. Atopic dermatitis 5. Cutaneous lupus erythematosus 6. Discoid lupus erythematosus [51] #### Mouth[edit] ##### Oral lichenoid drug reaction[edit] Lichenoid drug eruptions may be caused by a variety of systemic medications and share clinical features with oral LP. Histologic findings of a deep mixed infiltrate with lymphocytes, plasma cells, and neutrophils (with or without eosinophils) and perivascular inflammation favor this diagnosis. ##### Oral lichenoid contact reaction (allergic contact mucositis)[edit] Oral lichenoid contact reactions may be caused by a variety of substances. The clinical and histologic features of oral lichenoid contact reactions are similar to oral LP. Patch testing and recognition of the proximity of an offending substance to the eruption can aid with diagnosis.[35] ##### Autoimmune blistering diseases[edit] Mucous membrane pemphigoid and other autoimmune blistering diseases may present with oral erosions and desquamative gingivitis similar to that seen in erosive LP. Biopsies for routine histologic examination and direct immunofluorescence are useful for distinguishing these disorders from oral LP. ##### Graft-versus-host disease (GVHD)[edit] Lacy, reticulated plaques or erosions that resemble oral LP may occur in GVHD. The histologic findings of these disorders are also similar. The patient history is useful for differentiating chronic GVHD from oral LP.[56] Oral involvement in acute GVHD is less well characterized than chronic GVHD, but has been associated with erythematous, erosive, ulcerative, or lichenoid oral lesions. Leukoplakia ##### Leukoplakia[edit] Leukoplakia is a manifestation of squamous epithelial hyperplasia that may be a precursor to oral squamous cell carcinoma. White patches or plaques usually appear on the oral mucosa. To rule out malignancy, a biopsy of leukoplakia is indicated.[57] ##### Oral squamous cell carcinoma (SCC)[edit] SCC can present as erythematous or white patches, ulcers, or exophytic masses. The highest risk for oral SCC may occur in patients with erythematous or erosive oral LP.[58][59][60] A biopsy is indicated. ##### Leukoedema[edit] Leukoedema is a common, benign finding in the oral cavity that presents as white-gray, somewhat translucent plaques on the mucosa. The buccal mucosa is the most common site for involvement. Symptoms are absent, and no treatment is necessary.[61][62] ##### Oropharyngeal candidiasis[edit] Oropharyngeal candidiasis (also known as thrush) is a common infection that has a predilection for infants, older adults with dentures, immunosuppressed individuals, and individuals utilizing intraoral corticosteroid therapy. Patients present with white plaques or erythematous patches on the buccal mucosa, palate, tongue, or oropharynx that may be mistaken for reticular LP.[63] ### Histopathology[edit] Further information: Histopathologic diagnosis of dermatitis Histopathology of lichen planus The histologic findings of oral LP can offer strong support for the diagnosis, but are not pathognomonic. Clinical correlation is required. Common histologic findings of oral LP include:[45] * Parakeratosis and slight acanthosis of the epithelium * Saw-toothed rete ridges * Liquefaction degeneration of the basal layer with apoptotic keratinocytes (referred to as Civatte, colloid, hyaline, or cytoid bodies) * An amorphous band of eosinophilic material at the basement membrane * A lichenoid (band-like) lymphocytic infiltrate immediately subjacent to the epithelium. ## Treatment[edit] There is no cure for lichen planus,[39] and so treatment of cutaneous and oral lichen planus is for symptomatic relief or due to cosmetic concerns.[2][39][64] When medical treatment is pursued, first-line treatment typically involves either topical or systemic corticosteroids,[2] and removal of any triggers.[65] Without treatment, most lesions will spontaneously resolve within 6–9 months for cutaneous lesions,[2] and longer for mucosal lesions.[66] ### Skin[edit] Many different treatments have been reported for cutaneous lichen planus, however there is a general lack of evidence of efficacy for any treatment.[15][67][68] Treatments tend to be prolonged, partially effective and disappointing.[15] The mainstay of localized skin lesions is topical steroids. Additional treatments include retinoids, such as acitretin, or sulfasalazine. Narrow band UVB phototherapy or systemic PUVA therapy are known treatment modalities for generalized disease.[42] ### Mouth[edit] Reassurance that the condition is benign, elimination of precipitating factors and improving oral hygiene are considered initial management for symptomatic OLP, and these measures are reported to be useful.[39] Treatment usually involves topical corticosteroids (such as betamethasone, clobetasol, dexamethasone, and triamcinolone) and analgesics, or if these are ineffective and the condition is severe, then systemic corticosteroids may be used. Calcineurin inhibitors (such as pimecrolimus, tacrolimus or cyclosporin) are sometimes used.[39] While topical steroids are widely accepted as first line treatment for mucosal lichen planus, there is only weak evidence to support their effectiveness for erosive oral lichen planus.[69] ## Prognosis[edit] Cutaneous lichen planus lesions typically resolve within 6 months to a year. However, some variant such as the hypertrophic variant might persist for years if left untreated or unmonitored.[1] It is found that cutaneous lichen planus does not carry a risk of skin cancer.[70] In contrast to cutaneous LP, which is self limited, lichen planus lesions in the mouth may persist for many years,[64] and tend to be difficult to treat, with relapses being common.[36][1] Although this condition was first described almost a century ago, it has been reported that its associated oral cancer risk has been exaggerated.[71] Overall, it is found that patients with erythematous or erosive oral lichen planus have a higher risk of oral squamous cell carcinoma compared to patients diagnosed with other variants.[72] Due to the possibility that oral LP may increase risk for oral cancer, patients with oral lichen planus are encouraged to avoid activities known to increase the risk for oral cancer, such as smoking and alcohol use.[72][70] Patients with oral lichen planus should be followed-up at least every 6 to 12 months, to assess the disease activity, changes in symptoms or even detect early signs of malignancy.[72] ## Epidemiology[edit] The overall estimated prevalence of lichen planus in worldwide population is in the range of 0.2% to 5%.[8][73][74][75][76][77] It generally occurs more commonly in females, in a ratio of 3:2, and most cases are diagnosed between the ages of 30 and 60, but it can occur at any age.[8][78][44] Lichen planus can occur in patients as diverse cutaneous manifestations alone or in combination with mucosal lichen planus and, or lichen planus of the nails. Study shows that frequency of mucosal involvement of lichen planus patients is 30- 70%.[14] Oral lichen planus is relatively common,[36] It is one of the most common mucosal diseases. The prevalence in the general population is about 1.27–2.0%,[39][64] and it occurs more commonly in middle aged people.[39] Oral lichen planus in children is rare. About 50% of females with oral lichen planus were reported to have undiagnosed vulvar lichen planus.[8] Some studies suggest that cutaneous lichen planus is more commonly found in men whilst oral lichen planus lesions are more commonly found in women.[79][80][81][82][83][84] ## History[edit] Lichen planus was first reported in 1869 by Erasmus Wilson.[66] The origin of the word is believed to be from the Greek word ‘’ Leichen’’, which means tree moss; and also from Latin word ‘’planus’’ which means flat and even surface. Dr Wilson explained the condition as an inflammatory disorder with unknown etiology. Initially, the characteristic surface markings or striae was described by Weyl in 1885. In 1895, Wickham further explained the characteristic of the lesion, now known as Wickham striae. Further on, Darier explained the presence of such characteristic markings by correlating with an increase thickness of the granular cell layer. The coexistence of oral, cervical and stomach lichen planus lesions were described by Guogerot and Burnier in 1937. A similar variant of mucosal lichen planus as the vulvovaginal-gingival syndrome with erosive lesions involving oral and vulvovaginal mucosa were introduced by Pelisse and colleagues in year 1982.[1] ## Research[edit] Apremilast is undergoing investigation as a potential treatment .[85] ## Notes[edit] 1. ^ Cutaneous lichen planus affecting the extremities is also known as "lichen planus actinicus," "Actinic lichen niditus," "Lichen planus atrophicus annularis," "Lichen planus subtropicus," "Lichen planus tropicus," "Lichenoid melanodermatitis," and "Summertime actinic lichenoid eruption" ## References[edit] 1. ^ a b c d e f g h i j k l m n o Gorouhi F, Davari P, Fazel N (2014-01-30). "Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes, risk factors, diagnosis, and prognosis". TheScientificWorldJournal. 2014: 742826. doi:10.1155/2014/742826. PMC 3929580. PMID 24672362. 2. ^ a b c d e f Limited, Therapeutic Guidelines (2009). Therapeutic guidelines (Version 3. ed.). North Melbourne, Vic.: Therapeutic Guidelines. pp. 254–55, 302. ISBN 978-0-9804764-3-9. 3. ^ "Inverse lichen planus: An unusual morphologic variant of a classic papulosquamous dermatosis". Journal of the American Academy of Dermatology. 52 (3): P64. 2005-03-01. doi:10.1016/j.jaad.2004.10.268. ISSN 1097-6787. 4. ^ Meredith A. Olson, MDa, Roy S. Rogers III, MD, Alison J. Bruce, MB, ChB (2016). "Oral lichen planus". Clinics in Dermatology.CS1 maint: multiple names: authors list (link) 5. ^ a b c Greenberg MS, Glick M, Ship JA (2008). Burket's oral medicine (11th ed.). Hamilton, Ont.: BC Decker. pp. 89–97. ISBN 9781550093452. 6. ^ Lewis MA, Jordan RC (2012). Oral medicine (2nd ed.). London: Manson Publishing. pp. 66–72. ISBN 9781840761818. 7. ^ Barnes L (editor) (2009). Surgical pathology of the head and neck (3rd ed.). New York: Informa healthcare. ISBN 9781420091632.CS1 maint: extra text: authors list (link) 8. ^ a b c d e f g Le Cleach L, Chosidow O (February 2012). "Clinical practice. Lichen planus". The New England Journal of Medicine. 366 (8): 723–32. doi:10.1056/NEJMcp1103641. PMID 22356325. 9. ^ Asch S, Goldenberg G (March 2011). "Systemic treatment of cutaneous lichen planus: an update". Cutis. 87 (3): 129–34. PMID 21488570. 10. ^ Sharma A, Białynicki-Birula R, Schwartz RA, Janniger CK (July 2012). "Lichen planus: an update and review". Cutis. 90 (1): 17–23. PMID 22908728. 11. ^ Cheng S, Kirtschig G, Cooper S, Thornhill M, Leonardi-Bee J, Murphy R (February 2012). "Interventions for erosive lichen planus affecting mucosal sites" (PDF). The Cochrane Database of Systematic Reviews. 2 (2): CD008092. doi:10.1002/14651858.CD008092.pub2. hdl:1871/48562. PMID 22336835. 12. ^ a b Yamada T, Alpers DH, et al. (2009). Textbook of gastroenterology (5th ed.). Chichester, West Sussex: Blackwell Pub. p. 3304. 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PMID 22910104. ## External links[edit] Classification D * ICD-10: L43 * ICD-9-CM: 697.0 * MeSH: D008010 * DiseasesDB: 7452 External resources * MedlinePlus: 000867 * eMedicine: derm/233 derm/663 * Patient UK: Lichen planus Wikimedia Commons has media related to Lichen planus. * Lichen planus at Curlie * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic 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-aminobutyric 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	Lichen planus	c0023646	27,407	wikipedia	https://en.wikipedia.org/wiki/Lichen_planus	2021-01-18T18:54:36	{"gard": ["12344"], "mesh": ["D008010"], "umls": ["C0023646"], "orphanet": ["254367"], "wikidata": ["Q848371"]}
Nonketotic hyperglycinemia is a disorder characterized by abnormally high levels of a molecule called glycine in the body (hyperglycinemia). The excess glycine builds up in tissues and organs, particularly the brain. Affected individuals have serious neurological problems. Nonketotic hyperglycinemia has two forms, the severe form and the attenuated form. Both forms usually begin shortly after birth, although in some cases, signs and symptoms can begin in the first few months of life. Only the attenuated form begins later in infancy. The forms are distinguished by the seriousness of the signs and symptoms. Severe nonketotic hyperglycinemia is more common. Affected babies experience extreme sleepiness (lethargy) that worsens over time and can lead to coma. They can also have weak muscle tone (hypotonia) and life-threatening breathing problems in the first days or weeks of life. Most children who survive these early signs and symptoms develop feeding difficulties, abnormal muscle stiffness (spasticity), profound intellectual disability and seizures that are difficult to control. Most affected children do not achieve normal developmental milestones, such as drinking from a bottle, sitting up, or grabbing objects, and they may lose any acquired skills over time. The signs and symptoms of the attenuated form of nonketotic hyperglycinemia are similar to, but milder than, those of the severe form of the condition. Children with attenuated nonketotic hyperglycinemia typically reach developmental milestones, although the skills they achieve vary widely. Despite delayed development, many affected children eventually learn to walk and are able to interact with others, often using sign language. Some affected children develop seizures; if present, seizures are usually mild and can be treated. Other features can include spasticity, involuntary jerking movements (chorea), or hyperactivity. Individuals with nonketotic hyperglycinemia can also have certain changes in the brain, which can be seen using magnetic resonance imaging (MRI). For example, in children with the severe form of the condition, the tissue that connects the left and right halves of the brain (the corpus callosum) is smaller than average. ## Frequency Nonketotic hyperglycinemia is estimated to affect at least 1 in 76,000 people worldwide. In Finland, the condition occurs in about 1 in 55,000 newborns, and in British Columbia, Canada, it occurs in about 1 in 63,000 newborns. ## Causes Mutations in the GLDC or AMT gene cause nonketotic hyperglycinemia. About 80 percent of cases result from mutations in the GLDC gene, while AMT gene mutations cause about 20 percent of all cases. The GLDC and AMT genes provide instructions for making enzymes that work together as a group. This group, known as the glycine cleavage system, is responsible for breaking down glycine into smaller pieces when it is no longer needed. Glycine is an amino acid, which is a building block of proteins. Glycine also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. Too much glycine can disrupt brain function. In addition, the breakdown of glycine by the glycine cleavage system produces a molecule called a methyl group. This molecule is added to and used by a vitamin called folate. Folate is required for many functions in the cell and is important for brain development. Mutations in either the GLDC or AMT gene impair the system's ability to break down glycine. Some mutations reduce the activity of the glycine cleavage system, while others completely eliminate its activity. When the function of the glycine cleavage system is disrupted, excess glycine can build up in the body's organs and tissues. In addition, the production of methyl groups for use by folate is reduced. It is unclear how these abnormalities contribute to the developmental disability, seizures, breathing difficulties, and other features characteristic of nonketotic hyperglycinemia. The activity level of the glycine cleavage system helps determine the severity of the disorder: GLDC or AMT gene mutations that completely eliminate the system's activity result in severe nonketotic hyperglycinemia, while mutations that preserve some activity cause attenuated nonketotic hyperglycinemia. ### Learn more about the genes associated with Nonketotic hyperglycinemia * AMT * GLDC ## Inheritance Pattern Nonketotic hyperglycinemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Typically, the parents of an individual with the condition each carry one copy of the mutated gene, but they usually do not show signs and symptoms of the condition. In very rare cases, one of the mutations occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or in early embryonic development. These are known as de novo mutations. [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-aminobutyric 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	Nonketotic hyperglycinemia	c0751748	27,408	medlineplus	https://medlineplus.gov/genetics/condition/nonketotic-hyperglycinemia/	2021-01-27T08:25:19	{"gard": ["7219"], "mesh": ["D020158"], "omim": ["605899"], "synonyms": []}
Pappataci fever Distribution of pappataci fever by serotype: T, Toscana, S, Sicilian; N, Naples SpecialtyInfectious disease Pappataci fever (also known as Phlebotomus fever and, somewhat confusingly, sandfly fever and three-day fever) is a vector-borne febrile arboviral infection caused by three serotypes of Phlebovirus. It occurs in subtropical regions of the Eastern Hemisphere. The name, pappataci fever, comes from the Italian word for sandfly, it is the union of the word "pappa" (food) and taci (silent) which distinguishes these insects from blood-feeding mosquitoes, which produce a typical noise while flying. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] A few days after the infective bite, a feeling of lassitude, abdominal distress and chills develop followed by fever of 39 °C to 40 °C, severe frontal headaches, muscle and joint aches, flushing of the face and a fast heart rate. After two days the fever begins to subside and the temperature returns to normal. Fatigue, a slow heart rate and low blood pressure may persist from few days to several weeks but complete recovery is the rule.[1] ## Cause[edit] Three serotypes of Phlebovirus are known as the causative agents: Naples virus, Sicilian virus and Toscana virus. ## Diagnosis[edit] Although commercial tests are not readily available, diagnosis can be confirmed by serology-based assays or quantitative PCR by laboratories that have developed assays to perform such identification. ## Prevention[edit] Prevention of sandfly bites, and control of sandflies and their breeding grounds with insecticides are the principal methods for prevention. Mosquito nets may not be sufficient to prevent sandfly bites. ## Treatment[edit] There is no specific treatment for the disease. Pain killers and fluid replacement may be useful.[2] ## Epidemiology[edit] Phlebotomus papatasi taking a bloodmeal Pappataci fever is prevalent in the subtropical zone of the Eastern Hemisphere between 20°N and 45°N,[1] particularly in Southern Europe, North Africa, the Balkans, Eastern Mediterranean, Iraq, Iran, Pakistan, Afghanistan and India.[3] The disease is transmitted by the bites of phlebotomine sandflies of the Genus Phlebotomus, in particular, Phlebotomus papatasi, Phlebotomus perniciosus and Phlebotomus perfiliewi. The sandfly becomes infected when biting an infected human in the period between 48 hours before the onset of fever and 24 hours after the end of the fever, and remains infected for its lifetime.[1] Besides this horizontal virus transmission from man to sandfly, the virus can be transmitted in insects transovarially, from an infected female sandfly to its offspring.[4] Pappataci fever is seldom recognised in endemic populations because it is mixed with other febrile illnesses of childhood, but it is more well-known among immigrants and military personnel from non-endemic regions.[5] ## References[edit] 1. ^ a b c Encyclopædia Britannica. "Pappataci fever". Retrieved 2009-07-03. 2. ^ Tavana AM. Sandfly fever in the world. Ann Trop Med Public Health 2015;8:83–7 3. ^ Gratz N.G. (2004). The vector-borne human diseases in Europe. Their distribution and burden on public health (PDF). Copenhagen, Denmark. pp. 25–6. 4. ^ Tesh, R.B. (1984). "Transovarial transmission of arboviruses in their invertebrate vectors". In K.F. Harris (ed.). Current topics in vector research. 2. pp. 57–76. ISBN 0-275-91433-X. Archived from the original on 2012-12-20. 5. ^ Sabin A.B. (1955). "Recent advances in our knowledge of dengue and sandfly fever". American Journal of Tropical Medicine and Hygiene. 4 (2): 198–207. doi:10.4269/ajtmh.1955.4.198. PMID 14361897. ## External links[edit] Classification D * ICD-10: A93.1 * ICD-9-CM: 066.0 * MeSH: D010217 * 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]: 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-aminobutyric 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	Pappataci fever	c0030372	27,409	wikipedia	https://en.wikipedia.org/wiki/Pappataci_fever	2021-01-18T19:08:26	{"mesh": ["D010217"], "umls": ["C0030372"], "icd-9": ["066.0066.0"], "icd-10": ["A93.1"], "wikidata": ["Q1813747"]}
Parotitis Parotid gland (center left) SpecialtyInfectious disease Parotitis is an inflammation of one or both parotid glands, the major salivary glands located on either side of the face, in humans. The parotid gland is the salivary gland most commonly affected by inflammation. ## Contents * 1 Etymology * 2 Causes * 2.1 Dehydration * 2.2 Infectious parotitis * 2.3 Autoimmune causes * 2.4 Blockage * 2.5 Diseases of uncertain cause * 2.6 Masseteric hypertrophy * 3 Diagnosis * 4 Treatment * 5 Notes * 6 References * 7 External links ## Etymology[edit] From Greek παρωτῖτις (νόσος), parōtĩtis (nósos) : (disease of the) parotid gland < παρωτίς (stem παρωτιδ-) : (gland) behind the ear < παρά - pará : behind, and οὖς - ous (stem ὠτ-, ōt-) : ear. ## Causes[edit] ### Dehydration[edit] Dehydration: This is a common, non-infectious cause of parotitis. It may occur in elderly or after surgery.[1] ### Infectious parotitis[edit] Acute bacterial parotitis: is most often caused by a bacterial infection of Staphylococcus aureus but may be caused by any commensal bacteria.[2] Parotitis presents as swelling at the angle of the jaw. Bacterial parotitis presents as a unilateral swelling, where the gland is swollen and tender and usually produces pus at the Stensen's duct. This pus is usually sampled and the bacteria within are identified. Common causative bacteria are Staphylococcus aureus, Streptococcus pyogenes and E coli. It is associated with poor oral hygiene; oral infections and decreased saliva production. Symptoms include fever, dehydration, chills, fast heartbeat and breathing if the infection is causing sepsis. Medications such as antihistamines and diuretics can be predisposing factors. Treatment is usually antibiotics.[3] Parotitis as extrapulmonary tuberculosis: The mycobacterium that cause tuberculosis can also cause parotid infection. Parotid swelling can be an uncommon symptom of extrapulmonary tuberculosis (TB outside of the lungs). The usual symptoms are a cough, fever, weight loss, shortness of breath, chest pain, tiredness and chills. This is caused by the bacteria Mycobacterium tuberculosis. TB can also affect the heart, thyroid and adrenal glands but the main site of infection is the lungs. Risk factors are chronic alcohol consumption, diabetes, long term steroid use, HIV infection and kidney failure.[3] Those infected tend to have enlarged, nontender, but moderately painful glands. The diagnosis is made by typical chest radiograph findings, cultures, or histologic diagnosis after the gland has been removed. When diagnosed and treated with antitubercular medications, the gland may return to normal in 1–3 months.[2] Acute viral parotitis (mumps): The most common viral cause of parotitis is mumps. Routine vaccinations have dropped the incidence of mumps to a very low level. Mumps resolves on its own in about ten days. A viral infection caused by Paramyxovirus, a single-stranded RNA virus. Common symptoms include fever, headache and bilateral or unilateral parotitis (swelling of the parotid gland on one or both sides of the face). The parotid gland is usually swollen and tender. Parotid swelling usually occurs 16–18 days after exposure to the virus. Treatment includes isolation and therefore prevention of spread of the disease and supportive measures such as hot or cold packs. Mumps usually resolves itself and can be prevented by vaccination.[4] HIV parotitis: Generalized lymphadenopathy has long been associated with HIV, but the localized enlargement of the parotid gland is less well known.[citation needed] HIV-associated salivary gland disease can involve many diseases but often presents as enlargement of the parotid gland and a dry mouth. Causes have not been specifically identified but the most likely are viral opportunists and autoimmune responses. Viruses linked to this can include; hepatitis C, cytomegalovirus, paramyxovirus, influenza A and adenovirus. Treatment is anti-retroviral therapy.[5] Disseminated Histoplasmosis: During a large urban Disseminated Histoplasmosis outbreak (est. 100,000 victims) in Indianapolis from 1978–1979, manifestations included parotitis.[6] ### Autoimmune causes[edit] These are also collectively known as chronic punctate parotitis or chronic autoimmune parotitis. Sjögren's syndrome: Chronic inflammation of the salivary glands may also be an autoimmune disease known as Sjögren's syndrome. The disease most commonly appears in people aged 40–60 years, but it may affect small children. In Sjögren syndrome, the prevalence of parotitis in women versus men is approximately 9:1. The involved parotid gland is enlarged and tender at times. The cause is unknown. The syndrome is often characterized by excessive dryness in the eyes, mouth, nose, vagina, and skin.[2] Lymphoepithelial lesion of Godwin: Most frequently associated with a circumscribed tumor with the histologic features of Sjögren syndrome. This designation has also fallen out of favour. ### Blockage[edit] Blockage of the main parotid duct, or one of its branches, is often a primary cause of acute parotitis, with further inflammation secondary to bacterial superinfection. The blockage may be from a salivary stone, a mucous plug, or, more rarely, by a tumor, usually benign. Salivary stones (also called sialolithiasis, or salivary duct calculus) are mainly made of calcium, but do not indicate any kind of calcium disorder.[7] Other causes can be duct stricture (narrowing of the duct), infection or injury. Symptoms may include recurrent swelling, pain and aggravation during eating as this is when saliva production is stimulated. Ductal obstruction may cause less saliva flow, which can result in recurrent gland infections.[8] Stones may be diagnosed via X-ray (with a success rate of about 80%[7]), a computed tomography (CT) scan or medical ultrasonography. Stones may be removed by manipulation in the doctor's office, or, in the worst cases, by surgery. Lithotripsy, also known as "shock wave" treatment, is best known for its use breaking up kidney stones. Lithotripsy can now be used on salivary stones as well. Ultrasound waves break up the stones, and the fragments flush out of the salivary duct.[7] ### Diseases of uncertain cause[edit] Chronic nonspecific parotitis: This term is generally used for patients in whom no definite cause is found. Episodes may last for several days, paralleling the time course of a bacterial or viral illness. Others may experience episodes that last only a few hours from onset to resolution. Some episodes may last for several weeks. Quiescent periods between episodes last for hours, days, or even years.[2] Recurrent parotitis of childhood: An uncommon syndrome in which recurring episodes clinically resembling mumps. Generally, episodes begin by age 5 years, and virtually all patients become asymptomatic by age 10–15 years. The duration of attacks averages 3–7 days but may last 2–3 weeks in some individuals. The spectrum varies from mild and infrequent attacks to episodes so frequent that they prevent regular school attendance. Local heat applied to the gland, massaging the gland from back to front, and taking penicillin usually cure individual episodes. Treatment of individual infections may prevent injury to the gland parenchyma. Severe disease may be treated by parotidectomy.[2] Sialadenosis (sialosis): In this disorder, both parotid glands may be diffusely enlarged with only modest symptoms. Patients are aged 20–60 years at onset, and the sexes are equally involved. The glands are soft and non-tender. Approximately half of the patients have endocrine disorders such as diabetes, nutritional disorders such as pellagra or kwashiorkor, or have taken drugs such as guanethidine, thioridazine, or isoprenaline. Sarcoidosis: The lungs, skin, and lymph nodes are most often affected, but the salivary glands are involved in approximately 10% of cases. Bilateral firm, smooth, and non-tender parotid enlargement is classic. Xerostomia occasionally occurs. The Heerfordt-Waldenstrom syndrome consists of sarcoidosis with parotid enlargement, fever, anterior uveitis, and facial nerve palsy.[2] IgG4-related sialadenitis: This term refers to IgG4-related disease (IgG4-RD) involving any of the major salivary glands, i.e. parotid or submandibular glands. This is often symmetrical and is usually associated with manifestations of IgG4-RD elsewhere in the body. IgG4-related sialadenitis is particularly associated with involvement of one or both of the lacrimal glands (referred to as IgG4-related dacryo-sialadenitis). Mikulicz's disease, now considered to be a subtype of IgG4-related disease,[9] was a term used when (i) any two of the parotid, submandibular and lacrimal glands were persistently and symmetrically enlarged and (ii) other diseases that may mimic this presentation were excluded. Pneumoparotitis: Air within the ducts of the parotid gland with or without inflammation. The duct orifice normally functions as a valve to prevent air from entering the gland from a pressurized oral cavity. Rarely, an incompetent valve allows insufflation of air into the duct system. Pneumoparotitis most commonly occurs in wind instrument players, glass blowers, and scuba divers.[2] Several lymph nodes reside within the parotid gland as a superficial and deep group of nodes. These nodes may be involved with any process that affects lymph nodes, including bacterial, fungal, viral, and neoplastic processes. Rarely, drugs such as iodides, phenylbutazone, thiouracil, isoproterenol, heavy metals, sulfisoxazole, and phenothiazines cause parotid swelling. Associated with Bulimia: Parotid gland swelling is a common feature of self-induced vomiting. This swelling usually develops 3–4 days after the stopping of chronic excessive self-induced vomiting. The swelling is bilateral, with little tenderness. Causes are not well understood. Ideal treatment should be preventative and can involve medication that increases saliva production (sialagogues), anti-inflammatory medication and the application of hot packs. Occasionally pilocarpine can be used to help resolve the swelling.[10] ### Masseteric hypertrophy[edit] Masseteric hypertrophy (enlargement of the masseter muscle’s volume) can present as facial swelling in the parotid gland area and may be confused with ‘true’ parotid gland swelling. The specific cause of masseteric hypertrophy is still unclear, but it may be related to tooth grinding or malocclusion. Treatment options can include surgical removal of some of the muscle and botulinum toxin type A injections.[11] ## Diagnosis[edit] Serum and urinary amylase rise during the first week of parotitis. ## Treatment[edit] Treatment is based on lab investigation report. ## Notes[edit] 1. ^ "UpToDate on parotitis". UpToDate. UpToDate. Retrieved 19 February 2017. 2. ^ a b c d e f g [1] Templer JW, MD, Professor of Otolaryngology, University of Missouri Medical Center at Columbia. Parotitis: Overview, Accessed 03/04/2009 3. ^ a b Henderson, S.O; Mallon, W.K (1995). "Tuberculosis as the Cause of Diffuse Parotitis". Annals of Emergency Medicine. 26 (3): 376–379. doi:10.1016/S0196-0644(95)70089-7. PMID 7661432. 4. ^ Bockelman, Chelsea; Frawley, Thomas C.; Long, Brit; Koyfman, Alex (2018). "Mumps: An Emergency Medicine-Focused Update". The Journal of Emergency Medicine. 54 (2): 207–214. doi:10.1016/j.jemermed.2017.08.037. PMID 29110978. 5. ^ Islam, Nadim M.; Bhattacharyya, Indraneel; Cohen, Donald M. (2012). "Salivary gland pathology in HIV patients". Diagnostic Histopathology. 18 (9): 366–372. doi:10.1016/j.mpdhp.2012.08.001. 6. ^ https://annals.org/aim/article-abstract/694648/large-urban-outbreak-histoplasmosis-clinical-features 7. ^ a b c Salivary Gland Stones (Salivary Calculi) Accessed March 20, 2008. 8. ^ Yu, Chuangqi; Zheng, Lingyan; Yang, Chi; Shen, Ning (2008). "Causes of chronic obstructive parotitis and management by sialoendoscopy". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 105 (3): 365–370. doi:10.1016/j.tripleo.2007.08.008. PMID 18280969. 9. ^ John H. Stone; Arezou Khosroshahi; Vikram Deshpande; John K. C. Chan; J. Godfrey Heathcote; Rob Aalberse; Atsushi Azumi; Donald B. Bloch; William R. Brugge; Mollie N. Carruthers; Wah Cheuk; Lynn Cornell; Carlos Fernandez-Del Castillo; Judith A. Ferry; David Forcione; Günter Klöppe; Daniel L. Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Yasufumi Masaki; Kenji Notohara; Kazuichi Okazaki; Ji Kon Ryu; Takako Saeki; Dushyant Sahani; Yasuharu Sato; Thomas Smyrk; James R. Stone; Masayuki Takahira; Hisanori Umehara; George Webster; Motohisa Yamamoto; Eunhee Yi; Tadashi Yoshino; Giuseppe Zamboni; Yoh Zen; Suresh Chari (October 2012). "Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations". Arthritis & Rheumatism. 64 (10): 3061–3067. doi:10.1002/art.34593. PMC 5963880. PMID 22736240. 10. ^ Westmoreland, Patricia; Krantz, Mori J.; Mehler, Philip S. (2016). "Medical Complications of Anorexia Nervosa and Bulimia". The American Journal of Medicine. 129 (1): 30–37. doi:10.1016/j.amjmed.2015.06.031. PMID 26169883. 11. ^ Pary, Augusto; Pary, Katyuscia (2011). "Masseteric Hypertrophy: Considerations Regarding Treatment Planning Decisions and Introduction of a Novel Surgical Technique". Journal of Oral and Maxillofacial Surgery. 69 (3): 944–949. doi:10.1016/j.joms.2010.06.205. PMID 21195532. ## References[edit] * Brook I. Acute bacterial suppurative parotitis: microbiology and management. [Journal Article] Journal of Craniofacial Surgery. 14(1):37–40, 2003. * Mandel L. Surattanont F. Bilateral parotid swelling: a review. [Review] [160 refs] [Journal Article. Review] Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics. 93(3):221–37, 2002. ## External links[edit] Classification D * ICD-10: B26 * ICD-9-CM: 072.9, 527.2 * MeSH: D010309 * DiseasesDB: 9670 * SNOMED CT: 14756005 * eMedicine * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic 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-aminobutyric 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	Parotitis	c0030583	27,410	wikipedia	https://en.wikipedia.org/wiki/Parotitis	2021-01-18T19:00:31	{"mesh": ["D010309"], "umls": ["C0030583"], "icd-9": ["072.9", "527.2"], "wikidata": ["Q1975850"]}
Systemic monochloroacetate poisoning is a rare, life-threatening intoxication with monochloroacetic acid (mainly through the skin, but also by inhalation or ingestion). It is characterized by vomiting, diarrhea and central nervous system (CNS)-excitability (disorientation, delirium, convulsions) as early signs of systemic poisoning, followed by CNS-depression, coma and cerebral edema. Additional signs include heart involvement (severe myocardial depression, shock, arrhythmias, nonspecific myocardial damage), severe metabolic acidosis, hypokalemia, hypocalcemia and progressive renal failure leading to anuria. Myoglobinemia and leukocytosis may occur. Manifestations may be delayed for 1-4 hours. [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-aminobutyric 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	Systemic monochloroacetate poisoning	None	27,411	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90069	2021-01-23T16:53:25	{"icd-10": ["T60.3"]}
Congenital alacrima is characterised by deficient lacrimation (ranging from a complete absence of tears to hyposecretion of tears) that is present from birth. ## Epidemiology Prevalence is unknown. ## Genetic counseling Transmission is usually autosomal recessive, but dominant transmission has also been described. ## Management and treatment Artificial tears are the first treatment option, needed to avoid corneal sequelae. [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-aminobutyric 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	Isolated congenital alacrima	c1863199	27,412	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91416	2021-01-23T17:27:25	{"mesh": ["C566307"], "omim": ["103420", "601549"], "umls": ["C1863199"], "icd-10": ["Q10.6"]}
Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome is a rare, genetic primary bone dysplasia disorder characterized by disproportionate short stature with shortening of upper and lower limbs, short and broad fingers with short hands, narrowed chest with rib abnormalities and pectus excavatum, abnormal chondral calcifications (incl. larynx, trachea and costal cartilages) and facial dysmorphism (frontal bossing, hypertelorism, prominent eyes, short flat nose, wide nostrils, high-arched palate, long philtrum). Platyspondyly (esp. of cervical spine) and abnormal epiphyses and metaphyses are observed on radiography. Atlantoaxial instability causing spinal compression and recurrent respiratory disease are potential complications that may result lethal. [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-aminobutyric 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	Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	c1849011	27,413	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93358	2021-01-23T16:58:20	{"gard": ["10616"], "mesh": ["C564794"], "omim": ["271665"], "umls": ["C1849011"], "icd-10": ["Q77.7"]}
Menometrorrhagia SpecialtyGynecology Menometrorrhagia is a condition in which prolonged or excessive uterine bleeding occurs irregularly and more frequently than normal. It is thus a combination of metrorrhagia and menorrhagia. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 See also * 6 References * 7 External links ## Causes[edit] It can occur due to any of several causes, including hormonal imbalance, endometriosis, uterine fibroids, usage of progestin-only contraception, or cancer.[1] Not least, it can be caused by deficiencies of several clotting factors. It can lead to anemia in long-standing cases.[citation needed] ## Diagnosis[edit] The initial workup includes exclusion of pregnancy and cancer, by performing a pregnancy test, a pelvic exam and a gynecologic ultrasound. Further workup depends on outcomes of the preceding tests and may include hydrosonography, hysteroscopy, endometrial biopsy, and magnetic resonance imaging.[2] ## Treatment[edit] Treatment depends on the cause. In cases where malignancy is ruled out, hormone supplementation or the therapeutic use of hormonal contraception is usually recommended to induce bleeding on a regular schedule. Selective progesterone receptor modulators (SPRMs) are sometimes used to stop uterine bleeding.[1] ## Epidemiology[edit] It occurs in up to 24% of women ages 40-55 years.[2] ## See also[edit] * Von Willebrand disease * List of hematologic conditions ## References[edit] 1. ^ a b Bouchard, Philippe (December 2011). "Current and future medical treatments for menometrorrhagia during the premenopause". Gynecological Endocrinology. 27 (Supplement 1): 1120–1125. doi:10.3109/09513590.2012.638754. ISSN 0951-3590. PMID 22182055. 2. ^ a b Donnez, J. (2011). "Menometrorrhagia during the premenopause: An overview". Gynecological Endocrinology. 27: 1114–1119. doi:10.3109/09513590.2012.637341. PMID 22182054. ## External links[edit] Classification D * ICD-10: N92.1 * ICD-9-CM: 626.2 * v * t * e Female diseases of the pelvis and genitals Internal Adnexa Ovary * Endometriosis of ovary * Female infertility * Anovulation * Poor ovarian reserve * Mittelschmerz * Oophoritis * Ovarian apoplexy * Ovarian cyst * Corpus luteum cyst * Follicular cyst of ovary * Theca lutein cyst * Ovarian hyperstimulation syndrome * Ovarian torsion Fallopian tube * Female infertility * Fallopian tube obstruction * Hematosalpinx * Hydrosalpinx * Salpingitis Uterus Endometrium * Asherman's syndrome * Dysfunctional uterine bleeding * Endometrial hyperplasia * Endometrial polyp * Endometriosis * Endometritis Menstruation * Flow * Amenorrhoea * Hypomenorrhea * Oligomenorrhea * Pain * Dysmenorrhea * PMS * Timing * Menometrorrhagia * Menorrhagia * Metrorrhagia * Female infertility * Recurrent miscarriage Myometrium * Adenomyosis Parametrium * Parametritis Cervix * Cervical dysplasia * Cervical incompetence * Cervical polyp * Cervicitis * Female infertility * Cervical stenosis * Nabothian cyst General * Hematometra / Pyometra * Retroverted uterus Vagina * Hematocolpos / Hydrocolpos * Leukorrhea / Vaginal discharge * Vaginitis * Atrophic vaginitis * Bacterial vaginosis * Candidal vulvovaginitis * Hydrocolpos Sexual dysfunction * Dyspareunia * Hypoactive sexual desire disorder * Sexual arousal disorder * Vaginismus * Urogenital fistulas * Ureterovaginal * Vesicovaginal * Obstetric fistula * Rectovaginal fistula * Prolapse * Cystocele * Enterocele * Rectocele * Sigmoidocele * Urethrocele * Vaginal bleeding * Postcoital bleeding Other / general * Pelvic congestion syndrome * Pelvic inflammatory disease External Vulva * Bartholin's cyst * Kraurosis vulvae * Vestibular papillomatosis * Vulvitis * Vulvodynia Clitoral hood or clitoris * Persistent genital arousal disorder * v * t * e Menstrual cycle Events and phases * Menstruation * Follicular phase * Ovulation * Luteal phase Life stages * Menarche * Menopause Tracking Signs * Basal body temperature * Cervical mucus * Mittelschmerz Systems * Fertility awareness * Calendar-based methods * Billings Ovulation Method * Creighton Model Suppression * Extended cycle combined hormonal contraceptive * Lactational amenorrhea Disorders * Amenorrhea * Anovulation * Dysmenorrhea * Hypomenorrhea * Irregular menstruation * Menometrorrhagia * Menorrhagia * Metrorrhagia * Oligomenorrhea Related events * Folliculogenesis * Menstrual synchrony * Premenstrual syndrome / Premenstrual dysphoric disorder / Menstrual psychosis * Sexual activity In culture and religion * Chhaupadi * Feminine hygiene * Sanitary napkin * Tampon * Menstrual cup * Menstrual Hygiene Day * Menstrual taboo * Menstruation hut * Niddah [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-aminobutyric 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	Menometrorrhagia	c0232943	27,414	wikipedia	https://en.wikipedia.org/wiki/Menometrorrhagia	2021-01-18T18:53:58	{"icd-9": ["626.2"], "icd-10": ["N92.1"], "wikidata": ["Q3333223"]}
Although Gibbs and Gibbs (1952) described the electroencephalographic features in 1952, it was Gastaut (1982) who 30 years later recognized 'benign occipital epilepsy' as a form of partial epilepsy in children. Kuzniecky and Rosenblatt (1987) studied a family in which 3 sibs had benign occipital epilepsy and a fourth had the EEG findings. Typical EEG abnormality was found in other relatives. These EEG changes were evident particularly in younger members. BOE is characterized by motor seizures, preceded in some cases by visual symptoms, and a relatively benign course. Kuzniecky and Rosenblatt (1987) cited several other workers who found families with a frequent history of epilepsy. Neuro \- Benign occipital epilepsy Lab \- Typical EEG abnormality 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-aminobutyric 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	EPILEPSY, BENIGN OCCIPITAL	c1851549	27,415	omim	https://www.omim.org/entry/132090	2019-09-22T16:41:31	{"mesh": ["D004828"], "omim": ["132090"], "orphanet": ["25968"]}
Congenital bile acid synthesis defect type 3 (BAS defect type 3) is a severe anomaly of bile acid synthesis (see this term) characterized by severe neonatal cholestatic liver disease. ## Epidemiology To date, only 2 cases of this disorder have been reported. ## Clinical description The index case was a 10-week-old infant with severe progressive cholestasis, hepatosplenomegaly, coagulopathy, cirrhosis and liver synthetic failure from early infancy. Serum transaminases (AST, ALT) were markedly elevated and gamma-GT was normal. Liver histology showed cholestasis, extensive portal fibrosis, inflammation and giant cell transformation, as well as bile duct proliferation. ## Etiology BAS defect type 3 is caused by mutations in the 7-alpha hydroxylase gene (CYP7B1, 8q21.3). The deficiency in oxysterol 7alpha-hydroxylation leads to the accumulation of hepatotoxic unsaturated monohydroxy bile acids. The mode of transmission is presumed to be autosomal recessive. ## Diagnostic methods Diagnosis, based on analysis of urine using liquid secondary ionization mass spectrometry (LSIMS) shows sulfate and glycosulfate conjugates of unsaturated monohydroxy-cholenoic acids (3beta-hydroxy-5-cholenoic and 3beta-hydroxy-5-cholestenoic acids) and an absence of primary bile acids. ## Management and treatment This anomaly of bile acid synthesis is particularly severe and is not treatable by primary bile acid therapy. [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-aminobutyric 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	Congenital bile acid synthesis defect type 3	c3151147	27,416	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79302	2021-01-23T19:07:45	{"mesh": ["C566340"], "omim": ["613812"], "umls": ["C3151147"], "icd-10": ["K76.8"], "synonyms": ["BASD3", "Oxysterol 7-alpha-hydroxylase deficiency"]}
Duane syndrome affects the ability of the eye to move from side to side. Symptoms include restricted movement of eye outward and/or inward and the eyeball may be pulled back into the socket. In addition, the opening of the eye may be narrow. Some people with Duane syndrome develop "lazy eye" (amblyopia), a condition that may cause vision loss in the affected eye. Duane syndrome usually only occurs in one eye, and is not associated with other signs or symptoms. There are three types of Duane syndrome, which vary by which eye movements are most severely restricted. The exact cause of Duane syndrome is unknown. About 10% of cases are inherited in families in an autosomal dominant pattern. Diagnosis of Duane syndrome is based on the symptoms, an eye exam, and imaging studies. Treatment is focused on managing the symptoms, and includes corrective eye glasses and contact lens, and sometimes 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-aminobutyric 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	Duane syndrome	c0013261	27,417	gard	https://rarediseases.info.nih.gov/diseases/6288/duane-syndrome	2021-01-18T18:00:48	{"mesh": ["D004370"], "orphanet": ["233"], "synonyms": ["Duane anomaly", "Duane retraction syndrome", "DRS", "Stilling-Turk-Duane syndrome"]}
Benign familial mesial temporal lobe epilepsy is a rare epilepsy characterized by seizures with viscerosensory or experential auras, onset in adolescence or early adulthood and good prognosis. It is defined as at least 24 months of seizure freedom with or without antiepileptic medication. [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-aminobutyric 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	Benign familial mesial temporal lobe epilepsy	c1968848	27,418	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163717	2021-01-23T19:02:12	{"mesh": ["C566903"], "omim": ["611630", "614417", "615697"], "synonyms": ["Benign FMTLE"]}
Cap myopathy is a very rare congenital myopathy presenting a weakness of facial and respiratory muscles associated with craniofacial and thoracic deformities, as well as weakness of limb proximal and distal muscles. Onset is at birth or in childhood, weakness progression is slow but may lead to a severe and even fatal 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-aminobutyric 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	Cap myopathy	c3710589	27,419	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171881	2021-01-23T18:56:11	{"gard": ["11915"], "mesh": ["C579969"], "omim": ["609284", "609285"], "umls": ["C3710589"], "icd-10": ["G71.2"], "synonyms": ["Cap disease"]}
Muscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males. Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate. Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in most cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond. A related condition called X-linked dilated cardiomyopathy is a form of heart disease caused by mutations in the same gene as Duchenne and Becker muscular dystrophy, and it is sometimes classified as subclinical Becker muscular dystrophy. People with X-linked dilated cardiomyopathy typically do not have any skeletal muscle weakness or wasting, although they may have subtle changes in their skeletal muscle cells that are detectable through laboratory testing. ## Frequency Duchenne and Becker muscular dystrophies together affect 1 in 3,500 to 5,000 newborn males worldwide. Between 400 and 600 boys in the United States are born with these conditions each year. ## Causes Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells. Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy. Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies. ### Learn more about the gene associated with Duchenne and Becker muscular dystrophy * DMD ## Inheritance Pattern This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In many cases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene. The remainder of cases probably result from new mutations in the gene in affected males and are not inherited. In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry a DMD gene mutation may have muscle weakness and cramping. These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males. Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including cardiomyopathy. [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-aminobutyric 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	Duchenne and Becker muscular dystrophy	c0917713	27,420	medlineplus	https://medlineplus.gov/genetics/condition/duchenne-and-becker-muscular-dystrophy/	2021-01-27T08:25:38	{"gard": ["5900", "6291"], "mesh": ["D020388"], "omim": ["300376", "310200"], "synonyms": []}
Molybdenum cofactor deficiency is a rare condition characterized by brain dysfunction (encephalopathy) that worsens over time. Babies with this condition appear normal at birth, but within a week they have difficulty feeding and develop seizures that do not improve with treatment (intractable seizures). Brain abnormalities, including deterioration (atrophy) of brain tissue, lead to severe developmental delay; affected individuals usually do not learn to sit unassisted or to speak. A small percentage of affected individuals have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises. Other features of molybdenum cofactor deficiency can include a small head size (microcephaly) and facial features that are described as "coarse." Tests reveal that affected individuals have high levels of chemicals called sulfite, S-sulfocysteine, xanthine, and hypoxanthine in the urine and low levels of a chemical called uric acid in the blood. Because of the serious health problems caused by molybdenum cofactor deficiency, affected individuals usually do not survive past early childhood. ## Frequency Molybdenum cofactor deficiency is a rare condition that is estimated to occur in 1 in 100,000 to 200,000 newborns worldwide. More than 100 cases have been reported in the medical literature, although it is thought that the condition is underdiagnosed, so the number of affected individuals may be higher. ## Causes Molybdenum cofactor deficiency is caused by mutations in the MOCS1, MOCS2, or GPHN gene. There are three forms of the disorder, named types A, B, and C (or complementation groups A, B, and C). The forms have the same signs and symptoms but are distinguished by their genetic cause: MOCS1 gene mutations cause type A, MOCS2 gene mutations cause type B, and GPHN gene mutations cause type C. The proteins produced from each of these genes are involved in the formation (biosynthesis) of a molecule called molybdenum cofactor. Molybdenum cofactor, which contains the element molybdenum, is essential to the function of several enzymes. These enzymes help break down (metabolize) different substances in the body, some of which are toxic if not metabolized. Mutations in the MOCS1, MOCS2, or GPHN gene reduce or eliminate the function of the associated protein, which impairs molybdenum cofactor biosynthesis. Without the cofactor, the metabolic enzymes that rely on it cannot function. The resulting loss of enzyme activity leads to buildup of certain chemicals, including sulfite, S-sulfocysteine, xanthine, and hypoxanthine (which can be identified in urine), and low levels of uric acid in the blood. Sulfite, which is normally broken down by one of the molybdenum cofactor-dependent enzymes, is toxic, especially to the brain. Researchers suggest that damage caused by the abnormally high levels of sulfite (and possibly other chemicals) leads to encephalopathy, seizures, and the other features of molybdenum cofactor deficiency. ### Learn more about the genes associated with Molybdenum cofactor deficiency * GPHN * MOCS1 * MOCS2 ## Inheritance Pattern Molybdenum cofactor deficiency has an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. An affected individual usually inherits one altered copy of the gene from each parent. Parents of an individual with an autosomal recessive condition typically do not show signs and symptoms of the condition. At least one individual with molybdenum cofactor deficiency inherited two mutated copies of the MOCS1 gene through a mechanism called uniparental isodisomy. In this case, an error occurred during the formation of egg or sperm cells, and the child received two copies of the mutated gene from one parent instead of one copy from each parent. [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-aminobutyric 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	Molybdenum cofactor deficiency	c1854988	27,421	medlineplus	https://medlineplus.gov/genetics/condition/molybdenum-cofactor-deficiency/	2021-01-27T08:25:27	{"gard": ["3705"], "mesh": ["C565372"], "omim": ["252150", "252160", "615501"], "synonyms": []}
## Clinical Features Lowry and Wood (1975) described epiphyseal dysplasia, microcephaly, and nystagmus in 2 brothers. The radiologic finding consisted of small and irregular epiphyses, square iliac bones, and flattened acetabula. The brothers were both 'small-for-date' babies. The older brother was mildly retarded. Lowry et al. (1989) presented follow-up information on these brothers. They were reexamined at the ages of 17.75 and 15.75 years. Both had restricted elbow extension and the younger brother had bilateral dislocated radial heads. The older brother had developed typical changes of retinitis pigmentosa. The younger brother also had retinitis pigmentosa, although he was not studied as fully as was the older brother (Lowry, 1993). Nevin et al. (1986) described affected brother and sister with short stature, microcephaly, mental retardation, and multiple epiphyseal dysplasia. They did not have nystagmus. Nevin et al. (1986) concluded that autosomal recessive inheritance was likely. Hankenson et al. (1989) described a brother and sister with epiphyseal dysplasia and microcephaly. They did not have mental retardation or nystagmus. Brunetti-Pierri et al. (2003) described a patient with microcephaly and multiple epiphyseal dysplasia, but no additional features, suggesting a mild form of Lowry-Wood syndrome. No mutations were found on molecular analysis of the cartilage oligomeric matrix protein gene (600310). Magnani et al. (2009) described a 17-year-old boy who displayed clinical features consistent with Lowry-Wood syndrome, including microcephaly, short stature, multiple epiphyseal dysplasia, tapetoretinal degeneration, and mental retardation. Bilateral restricted elbow extension, knock knees, and hip dislocation were also present. Radiographs showed evidence of radial dislocation due to absence of radial heads, lateral dislocation of both patellae, multiple epiphyseal dysplasia that was more severe at the proximal femoral epiphyses, and dislocation of both hips with severe dysplasia. Conventional karyotyping was normal; molecular karyotyping by array-based competitive genomic hybridization showed copy number variants that were probably benign. Magnani et al. (2009) suggested that severe hypoplasia or agenesis of the radial heads and multiple joint dislocations (elbows, hips, and knees, including the patellae) might be additional signs of Lowry-Wood syndrome. Skel \- Small epiphyses \- Irregular epiphyses \- Square iliac bones \- Flattened acetabulae Growth \- Small for gestational age \- Short stature Neuro \- Mild mental retardation Inheritance \- Autosomal recessive HEENT \- Microcephaly \- Nystagmus ▲ 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-aminobutyric 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	EPIPHYSEAL DYSPLASIA, MICROCEPHALY, AND NYSTAGMUS	c0796021	27,422	omim	https://www.omim.org/entry/226960	2019-09-22T16:28:09	{"mesh": ["C537038"], "omim": ["226960"], "orphanet": ["1824"], "synonyms": ["Alternative titles", "LOWRY-WOOD SYNDROME"]}
"Deep bite" redirects here. For the village, see Deep Bight, Newfoundland and Labrador. Malocclusion Malocclusion in 10-year-old girl SpecialtyDentistry A malocclusion is a misalignment or incorrect relation between the teeth of the two dental arches when they approach each other as the jaws close. The term was coined by Edward Angle, the "father of modern orthodontics",[1][2] as a derivative of occlusion. This refers to the manner in which opposing teeth meet (mal- \+ occlusion = "incorrect occlusion"). The malocclusion classification is based on the relationship of the Mesiobuccal cusp of the maxillary first molar and the buccal groove of the mandibular first molar. If this molar relationship exists, then the teeth can align into normal occlusion. According to Angle, malocclusion is any deviation of the occlusion from the ideal.[3] However the assessment for malocclusion should also take into account aesthetics and the impact on functionality. If these aspects are acceptable to the patient despite meeting the formal definition of malocclusion, then treatment may not be necessary. ## Contents * 1 Causes * 1.1 Behavioral and dental factors * 1.2 Primary vs. secondary dentition * 2 Signs and symptoms * 3 Classification * 3.1 Overbites * 3.2 Angle's classification method * 3.3 Review of Angle's system of classes and alternative systems * 3.4 Incisor classification * 3.5 Canine relationship * 4 Crowding of teeth * 4.1 Causes * 4.2 Treatment * 5 Treatment * 5.1 Crowding * 5.2 Class I * 5.3 Class II * 5.3.1 Class II Division 1 * 5.3.2 Class II Division 2 * 5.4 Class III * 5.5 Deep bite * 5.6 Open Bite * 6 Tooth size discrepancy * 7 Other conditions * 8 See also * 9 References * 10 Further reading * 11 External links ## Causes[edit] The aetiology of malocclusion is somewhat contentious, however, simply put it is multifactorial, with influences being both genetic[4] and environmental.[5] Malocclusion is already present in one of the Skhul and Qafzeh hominin fossils and other prehistoric human skulls.[6][7] There are 3 generally accepted causative factors of malocclusion: * Skeletal factors – the size, shape and relative positions of the upper and lower jaws. Variations can be caused by environmental or behavioral factors such as masticatory muscles, nocturnal mouth breathing, and cleft lip and palate * Muscle factors – the form and function of the muscles that surround the teeth. This could be impacted by habits such as digit sucking, nail biting, pacifier and tongue thrusting[8] * Dental factors – size of the teeth in relation to the jaw, early loss of teeth could result in spacing or mesial migration causing crowding, abnormal eruption path or timings, extra teeth (supernumeraries), too few teeth (hypodontia) There is not one cause of malocclusion, and when planning orthodontic treatment it is often helpful to consider the above factors and the impact they have played on malocclusion. These can also be influenced by oral habits and pressure resulting in malocclusion.[9][10] ### Behavioral and dental factors[edit] In the active skeletal growth,[11] mouthbreathing, finger sucking, thumb sucking, pacifier sucking, onychophagia (nail biting), dermatophagia, pen biting, pencil biting, abnormal posture, deglutition disorders and other habits greatly influence the development of the face and dental arches.[12][13][14][15][16] Pacifier sucking habits are also correlated with otitis media.[17][18] Dental caries, periapical inflammation and tooth loss in the deciduous teeth can alter the correct permanent teeth eruptions. ### Primary vs. secondary dentition[edit] Malocclusion can occur in primary and secondary dentition. In primary dentition malocclusion is caused by: * Underdevelopment of the dentoalvelor tissue. * Over development of bones around the mouth. * Cleft lip and palate. * Overcrowding of teeth. * Abnormal development and growth of teeth. In secondary dentition malocclusion is caused by: * Periodontal disease. * Overeruption of teeth.[19] * Premature and congenital loss of missing teeth. ## Signs and symptoms[edit] Malocclusion is a common finding,[20][21] although it is not usually serious enough to require treatment. Those who have more severe malocclusions, which present as a part of craniofacial anomalies, may require orthodontic and sometimes surgical treatment (orthognathic surgery) to correct the problem. The ultimate goal of orthodontic treatment is to achieve a stable, functional and aesthetic alignment of teeth which serves to better the patients dental and total health.[22] The symptoms which arise as a result of malocclusion derive from a deficiency in one or more of these categories.[23] The symptoms are as follows: * Tooth decay (caries): misaligned teeth will make it more difficult to maintain oral hygiene. Children with poor oral hygiene and diet will be at an increased risk. * Periodontal disease: irregular teeth would hinder the ability to clean teeth meaning poor plaque control. Additionally, if teeth are crowded, some may be more buccally or lingually placed, there will be reduced bone and periodontal support. Furthermore, in Class III malocclusions, mandibular anterior teeth are pushed labially which contributes to gingival recession and weakens periodontal support. * Trauma to anterior teeth: Those with an increased overjet are at an increased risk of trauma. A systematic review found that an overjet of greater than 3mm will double the risk of trauma. * Masticatory function: people with anterior open bites, large increased & reverse overjet and hypodontia will find it more difficult to chew food. * Speech impairment: a lisp is when the incisors cannot make contact, orthodontics can treat this. However, other forms of misaligned teeth will have little impact on speech and orthodontic treatment has little effect on fixing any problems. * Tooth impaction: these can cause resorption of adjacent teeth and other pathologies for example a dentigerous cyst formation. * Psychosocial wellbeing: malocclusions of teeth with perceived poor aesthetics can have a significant effect on self-esteem. This is subjective in nature and will vary widely, being subject cultural and racial influences.[23][24] Malocclusions may be coupled with skeletal disharmony of the face, where the relations between the upper and lower jaws are not appropriate. Such skeletal disharmonies often distort sufferer's face shape, severely affect aesthetics of the face, and may be coupled with mastication or speech problems. Most skeletal malocclusions can only be treated by orthognathic surgery.[citation needed] ## Classification[edit] Depending on the sagittal relations of teeth and jaws, malocclusions can be divided mainly into three types according to Angle's classification system published 1899. However, there are also other conditions, e.g. crowding of teeth, not directly fitting into this classification. Many authors have tried to modify or replace Angle's classification. This has resulted in many subtypes and new systems (see section below: Review of Angle's system of classes). A deep bite (also known as a Type II Malocclusion) is a condition in which the upper teeth overlap the lower teeth, which can result in hard and soft tissue trauma, in addition to an effect on appearance.[25] It has been found to occur in 15-20% of the US population.[26] An open bite is a condition characterised by a complete lack of overlap and occlusion between the upper and lower incisors.[27] In children, open bite can be caused by prolonged thumb sucking.[28] Patients often present with impaired speech and mastication.[29] ### Overbites[edit] This is a vertical measurement of the degree of overlap between the maxillary incisors and the mandibular incisors. There are three features that are analysed in the classification of an overbite: * Degree of overlap: edge to edge, reduced, average, increased * Complete or incomplete: whether there is contact between the lower teeth the opposing teeth/tissue (hard palate or gingivae) or not. * Whether contact is traumatic or atraumatic An average overbite is when the upper anterior teeth cover a third of the lower teeth. Covering less than this is described as ‘reduced’ and more than this is an ‘increased’ overbite. No overlap or contact is considered an ‘anterior open bite’.[23][24][30] ### Angle's classification method[edit] Class I with severe crowding and labially erupted canines Class II molar relationship Edward Angle, who is considered the father of modern orthodontics, was the first to classify malocclusion. He based his classifications on the relative position of the maxillary first molar.[31] According to Angle, the mesiobuccal cusp of the upper first molar should align with the buccal groove of the mandibular first molar. The teeth should all fit on a line of occlusion which, in the upper arch, is a smooth curve through the central fossae of the posterior teeth and cingulum of the canines and incisors, and in the lower arch, is a smooth curve through the buccal cusps of the posterior teeth and incisal edges of the anterior teeth. Any variations from this resulted in malocclusion types. It is also possible to have different classes of malocclusion on left and right sides. * Class I: Neutrocclusion Here the molar relationship of the occlusion is normal but the incorrect line of occlusion or as described for the maxillary first molar, but the other teeth have problems like spacing, crowding, over or under eruption, etc. * Class II: Distocclusion (retrognathism, overjet, overbite) In this situation, the mesiobuccal cusp of the upper first molar is not aligned with the mesiobuccal groove of the lower first molar. Instead it is anterior to it. Usually the mesiobuccal cusp rests in between the first mandibular molars and second premolars. There are two subtypes: * Class II Division 1: The molar relationships are like that of Class II and the anterior teeth are protruded. * Class II Division 2: The molar relationships are Class II but the central are retroclined and the lateral teeth are seen overlapping the centrals. * Class III: Mesiocclusion (prognathism, Anterior crossbite, negative overjet, underbite) In this case the upper molars are placed not in the mesiobuccal groove but posteriorly to it. The mesiobuccal cusp of the maxillary first molar lies posteriorly to the mesiobuccal groove of the mandibular first molar. Usually seen as when the lower front teeth are more prominent than the upper front teeth. In this case the patient very often has a large mandible or a short maxillary bone. ### Review of Angle's system of classes and alternative systems[edit] A major disadvantage of classifying malocclusions according to Angle's system is that it only takes into consideration the two-dimensional viewing along a spatial axis in the sagittal plane in the terminal occlusion, even though occlusion problems are, in principle, three-dimensional. Deviations in other spatial axes, asymmetric deviations, functional faults and other therapy-related features are not recognised. Another shortcoming is the lack of a theoretical basis of this purely descriptive classification system. Among the much discussed weaknesses of the system is the fact that it only considers the static occlusion, that it does not take into account the development and causes (aetiology) of occlusion problems and it disregards the proportions (or relationships in general) of teeth and face.[32] Thus, numerous attempts have been made to modify the Angle system or to replace it completely with a more efficient one,[33] but Angle's classification continues to prevail mainly because of its simplicity and clarity.[citation needed] Well-known modifications to Angle's classification date back to Martin Dewey (1915) and Benno Lischer (1912, 1933). Alternative systems have been suggested by, among others, Simon (1930, the first three-dimensional classification system), Jacob A. Salzmann (1950, with a classification system based on skeletal structures) and James L. Ackerman and William R. Proffit (1969).[34] ### Incisor classification[edit] Besides the molar relationship, the British Standards Institute Classification also classifies malocclusion into incisor relationship and canine relationship. Class I: The lower incisor edges occlude with or lie immediately below the cingulum plateau of the upper central incisors Class II: The lower incisor edges lie posterior to the cingulum plateau of the upper incisors Division 1 – the upper central incisors are proclined or of average inclination and there is an increase in overjet Division 2 – The upper central incisors are retroclined. The overjet is usually minimal or may be increased. Class III: The lower incisor edges lie anterior to the cingulum plateau of the upper incisors. The overjet is reduced or reversed. ### Canine relationship[edit] Class I: Mesial slope of upper canine coincides with distal slope of lower canine Class II: Mesial slope of upper canine is ahead of distal slope of lower canine Class III: Mesial slope of upper canine is behind to distal slope of lower canine ## Crowding of teeth[edit] Crowding is defined by the amount of space that would be required for the teeth to be in correct alignment. It is obtained in two ways. 1) by measuring the amount of space required and reducing this from calculating the space available via the width of the teeth. Or 2) by measuring the degree of overlap of the teeth. The following criteria is used:[23] 0-4mm = Mild crowding 4-8mm = Moderate crowding >8mm = Severe crowding ### Causes[edit] Genetic (inheritance) factors, extra teeth, lost teeth, impacted teeth, or abnormally shaped teeth have been cited as causes of crowding. Ill-fitting dental fillings, crowns, appliances, retainers, or braces as well as misalignment of jaw fractures after a severe injury are also known to cause crowding.[25] Tumors of the mouth and jaw, thumb sucking, tongue thrusting, pacifier use beyond age three, and prolonged use of a bottle have also been identified.[25] Lack of masticatory stress during development can cause tooth overcrowding.[35][36] Children who chewed a hard resinous gum for two hours a day, showed increased facial growth.[35] Experiments in animals have shown similar results. In an experiment on two groups of rock hyraxes fed hardened or softened versions of the same foods, the animals fed softer food had significantly narrower and shorter faces and thinner and shorter mandibles than animals fed hard food.[37] A 2016 review found that breastfeeding lowers the incidence of malocclusions developing later on in developing infants. [38] During the transition to agriculture, the shape of the human mandible went through a series of changes. The mandible underwent a complex shape changes not matched by the teeth, leading to incongruity between the dental and mandibular form. These changes in human skulls may have been "driven by the decreasing bite forces required to chew the processed foods eaten once humans switched to growing different types of cereals, milking and herding animals about 10,000 years ago."[36][39] ### Treatment[edit] Orthodontic management of the condition includes dental braces, lingual braces, clear aligners or palatal expanders.[40] To mask mild cases, veneers can be used. ## Treatment[edit] Malocclusion is often treated with orthodontics,[40] such as tooth extraction, clear aligners, or dental braces, followed by growth modification in children or jaw surgery (orthognathic surgery) in adults. Surgical intervention is used only in rare occasions. This may include surgical reshaping to lengthen or shorten the jaw. Wires, plates, or screws may be used to secure the jaw bone, in a manner like the surgical stabilization of jaw fractures. Very few people have "perfect" alignment of their teeth with most problems being minor that do not require treatment.[35] ### Crowding[edit] Crowding of the teeth is treated with orthodontics, often with tooth extraction, clear aligners, or dental braces, followed by growth modification in children or jaw surgery (orthognathic surgery) in adults. Surgery may be required on rare occasions. This may include surgical reshaping to lengthen or shorten the jaw (orthognathic surgery). Wires, plates, or screws may be used to secure the jaw bone, in a manner similar to the surgical stabilization of jaw fractures. Very few people have "perfect" alignment of their teeth. However, most problems are very minor and do not require treatment.[37] ### Class I[edit] While treatment is not crucial in class I malocclusions, in severe cases of crowding can be an indication for intervention. Studies indicate that tooth extraction can have benefits to correcting malocclusion in individuals.[41][42] Further research is needed as reoccurring crowding has been examined in other clinical trials.[41][43] ### Class II[edit] A few treatment options for class II malocclusions include: 1. Functional appliance which maintains the mandible in a postured position to influence both the orofacial musculature and dentoalveolar development prior to fixed appliance therapy. This is ideally done through pubertal growth in pre-adolescent children and the fixed appliance during permanent dentition .[44] Different types of removable appliances include Activator, Bionatar, Medium opening activator, Herbst, Frankel and twin block appliance with the twin block being the most widely used one. [45] 2. Growth modification through headgear to redirect maxillary growth 3. Orthodontic camouflage so that jaw discrepancy no longer apparent 4. Orthonagthic surgery – sagittal split osteotomy mandibular advancement carried out when growth is complete where skeletal discrepancy is severe in anterior-posterior relationship or in vertical direction. Fixed appliance is required before, during and after surgery. 5. Upper Removable Appliance – limited role in contemporary treatment of increased overjets. Mostly used for very mild Class II, overjet due to incisor proclination, favourable overbite. #### Class II Division 1[edit] Low- to moderate- quality evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth (class II division 1) is more effective for reducing the incidence of incisal trauma than providing one course of orthodontic treatment in adolescence.[46] There do not appear to be any other advantages of providing early treatment when compared to late treatment.[46] Low-quality evidence suggests that, compared to no treatment, late treatment in adolescence with functional appliances is effective for reducing the prominence of upper front teeth.[46] #### Class II Division 2[edit] Treatment can be undertaken using orthodontic treatments using dental braces.[47] While treatment is carried out, there is no evidence from clinical trials to recommend or discourage any type of orthodontic treatment in children.[47] A 2018 Cochrane systematic review anticipated that the evidence base supporting treatment approaches is not likely to improve occlusion due to the low prevalence of the condition and the ethical difficulties in recruiting people to participate in a randomized controlled trials for treating this condition.[47] ### Class III[edit] The British Standard Institute (BSI) classify class III incisor relationship as the lower incisor edge lies anterior to the cingulum plateau of the upper incisors, with reduced or reversed over jet.[48] The skeletal facial deformity is characterized by mandibular prognathism, maxillary retrognathism or a combination of the two. This effects 3-8% of UK population with a higher incidence seen in Asia.[49] One of the main reasons for correcting Class III malocclusion is aesthetics and function. This can have a psychological impact on the person with malocclusion resulting in speech and mastication problems as well. In mild class III cases, the patient is quite accepting of the aesthetics and the situation is monitored to observe the progression of skeletal growth.[50] Maxillary and mandibular skeletal changes during prepubertal, pubertal and post pubertal stages show that class III malocclusion is established before the prepubertal stage.[51] One treatment option is the use of growth modification appliances such as the Chin Cap which has greatly improved the skeletal framework in the initial stages. However, majority of cases are shown to relapse into inherited class III malocclusion during the pubertal growth stage and when the appliance is removed after treatment.[51] Another approach is to carry out orthognathic surgery, such as a bilateral sagittal split osteotomy (BSSO) which is indicated by horizontal mandibular excess. This involves surgically cutting through the mandible and moving the fragment forward or backwards for desired function and is supplemented with pre and post surgical orthodontics to ensure correct tooth relationship. Although the most common surgery of the mandible, it comes with several complications including: bleeding from inferior alveolar artery, unfavorable splits, condylar resorption, avascular necrosis and worsening of temporomandibular joint.[52] Orthodontic camouflage can also be used in patients with mild skeletal discrepancies. This is a less invasive approach that uses orthodontic brackets to correct malocclusion and try to hide the skeletal discrepancy. Due to limitations of orthodontics, this option is more viable for patients who are not as concerned about the aesthetics of their facial appearance and are happy to address the malocclusion only, as well as avoiding the risks which come with orthognathic surgery.[53] ### Deep bite[edit] The most common corrective treatments available are fixed or removal appliances (such as dental braces), which may or may not require surgical intervention. At this time there is no robust evidence that treatment will be successful.[47] ### Open Bite[edit] An open bite malocclusion is when the upper teeth don't overlap the lower teeth. When this malocclusion occurs at the front teeth it is known as anterior open bite. An open bite is difficult to treat due to multifactorial causes, with relapse being a major concern. This is particularly so for an anterior open bite.[54] Therefore, it is important to carry out a thorough initial assessment in order to obtain a diagnosis to tailor a suitable treatment plan.[54] It is important to take into consideration any habitual risk factors, as this is crucial for a successful outcome without relapse. Treatment approach includes behavior changes, appliances and surgery. Treatment for adults include a combination of extractions, fixed appliances, intermaxillary elastics and orthognathic surgery.[29] For children, orthodontics is usually used to compensate for continued growth. With children with mixed dentition, the malocclusion may resolve on its own as the permanent teeth erupt. Furthermore, should the malocclusion be caused by childhood habits such as digit, thumb or pacifier sucking, it may result in resolution as the habit is stopped. Habit deterrent appliances may be used to help in breaking digit and thumb sucking habits. Other treatment options for patients who are still growing include functional appliances and headgear appliances. ## Tooth size discrepancy[edit] Identifying the presence of tooth size discrepancies between the maxillary and mandibular arches is an important component of correct orthodontic diagnosis and treatment planning. To establish appropriate alignment and occlusion, the size of upper and lower front teeth, or upper and lower teeth in general, needs to be proportional. Inter-arch tooth size discrepancy (ITSD) is defined as a disproportion in the mesio-distal dimensions of teeth of opposing dental arches. The prevalence is clinically significant among orthodontic patients and has been reported to range from 17% to 30%.[55] Identifying inter-arch tooth size discrepancy (ITSD) before treatment begins allows the practitioner to develop the treatment plan in a way that will take ITSD into account. ITSD corrective treatment may entail demanding reduction (interproximal wear), increase (crowns and resins), or elimination (extractions) of dental mass prior to treatment finalization.[56] Several methods have been used to determine ITSD. Of these methods the one most commonly used is the Bolton analysis. Bolton developed a method to calculate the ratio between the mesiodistal width of maxillary and mandibular teeth and stated that a correct and harmonious occlusion is possible only with adequate proportionality of tooth sizes.[56] Bolton's formula concludes that if in the anterior portion the ratio is less than 77.2% the lower teeth are too narrow, the upper teeth are too wide or there is a combination of both. If the ratio is higher than 77.2% either the lower teeth are too wide, the upper teeth are too narrow or there is a combination of both.[55] ## Other conditions[edit] Further information: Open bite malocclusion Open bite treatment after eight months of braces. Other kinds of malocclusions can be due to or horizontal, vertical, or transverse skeletal discrepancies, including skeletal asymmetries. Increased vertical growth causes a long facial profile and commonly leads to an open bite malocclusion, while decreased vertical facial growth causes a short facial profile and is commonly associated with a deep bite malocclusion. However, there are many other more common causes for open bites (such as tongue thrusting and thumb sucking) and likewise for deep bites.[57][58][59] The upper or lower jaw can be overgrown (macrognathia) or undergrown (micrognathia).[58][57][59] It has been reported that patients with micrognathia are also affected by retrognathia (abnormal posterior positioning of the mandible or maxilla relative to the facial structure).[58] These patients are majorly predisposed to a class II malocclusion. Mandibular macrognathia results in prognathism and predisposes patients to a class III malocclusion. [60] Most malocclusion studies to date have focused on Class III malocclusions. Genetic studies for Class II and Class I malocclusion are more rare. An example of hereditary mandibular prognathism can be seen amongst the Hapsburg Royal family where one third of the affected individuals with severe class III malocclusion had one parent with a similar phenotype [61] The frequent presentation of dental malocclusions in patients with craniofacial birth defects also supports a strong genetic aetiology. About 150 genes are associated with craniofacial conditions presenting with malocclusions. [62] Micrognathia is a commonly recurring craniofacial birth defect appearing among multiple syndromes. 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"Orthodontics-surgical combination therapy for Class III skeletal malocclusion". Contemporary Clinical Dentistry. 3 (1): 78–82. doi:10.4103/0976-237X.94552. PMC 3341765. PMID 22557903. 53. ^ Zere E, Chaudhari PK, Sharan J, Dhingra K, Tiwari N (2018-06-22). "Developing Class III malocclusions: challenges and solutions". Clinical, Cosmetic and Investigational Dentistry. 10: 99–116. doi:10.2147/ccide.s134303. PMC 6016584. PMID 29950903. 54. ^ a b Atsawasuwan P, Hohlt W, Evans CA (April 2015). "Nonsurgical approach to Class I open-bite malocclusion with extrusion mechanics: a 3-year retention case report". American Journal of Orthodontics and Dentofacial Orthopedics. 147 (4): 499–508. doi:10.1016/j.ajodo.2014.04.024. PMID 25836010. 55. ^ a b Grauer D, Heymann GC, Swift EJ (June 2012). "Clinical management of tooth size discrepancies". Journal of Esthetic and Restorative Dentistry. 24 (3): 155–9. doi:10.1111/j.1708-8240.2012.00520.x. PMID 22691075. 56. ^ a b Cançado RH, Gonçalves Júnior W, Valarelli FP, Freitas KM, Crêspo JA (2015). "Association between Bolton discrepancy and Angle malocclusions". Brazilian Oral Research. 29: 1–6. doi:10.1590/1807-3107BOR-2015.vol29.0116. PMID 26486769. 57. ^ a b c Harrington C, Gallagher JR, Borzabadi-Farahani A (July 2015). "A retrospective analysis of dentofacial deformities and orthognathic surgeries using the index of orthognathic functional treatment need (IOFTN)". International Journal of Pediatric Otorhinolaryngology. 79 (7): 1063–6. doi:10.1016/j.ijporl.2015.04.027. PMID 25957779. 58. ^ a b c d Posnick JC (September 2013). "Definition and Prevalence of Dentofacial Deformities". Orthognatic Surgery: Principles and Practice. Amsterdam: Elsevier. pp. 61–68. doi:10.1016/B978-1-4557-2698-1.00003-4. ISBN 978-145572698-1. 59. ^ a b c Borzabadi-Farahani A, Eslamipour F, Shahmoradi M (June 2016). "Functional needs of subjects with dentofacial deformities: A study using the index of orthognathic functional treatment need (IOFTN)". Journal of Plastic, Reconstructive & Aesthetic Surgery. 69 (6): 796–801. doi:10.1016/j.bjps.2016.03.008. PMID 27068664. 60. ^ Purkait, S (2011). Essentials of Oral Pathology 4th Edition. 61. ^ Joshi N, Hamdan AM, Fakhouri WD (December 2014). "Skeletal malocclusion: a developmental disorder with a life-long morbidity". Journal of Clinical Medicine Research. 6 (6): 399–408. doi:10.14740/jocmr1905w. PMC 4169080. PMID 25247012. 62. ^ Moreno Uribe LM, Miller SF (April 2015). "Genetics of the dentofacial variation in human malocclusion". Orthodontics & Craniofacial Research. 18 Suppl 1 (S1): 91–9. doi:10.1111/ocr.12083. PMC 4418210. PMID 25865537. ## Further reading[edit] * Peter S. Ungar, "The Trouble with Teeth: Our teeth are crowded, crooked and riddled with cavities. It hasn't always been this way", Scientific American, vol. 322, no. 4 (April 2020), pp. 44–49. "Our teeth [...] evolved over hundreds of millions of years to be incredibly strong and to align precisely for efficient chewing. [...] Our dental disorders largely stem from a shift in the oral environment caused by the introduction of softer, more sugary foods than the ones our ancestors typically ate." ## External links[edit] Classification D * ICD-10: K07.3, K07.4, K07.5, K07.6 * ICD-9-CM: 524.4 * MeSH: D008310 Wikimedia Commons has media related to Malocclusion. * v * t * e Orthodontics Diagnosis * Bolton analysis * Cephalometric analysis * Cephalometry * Dentition analysis * Failure of eruption of teeth * Little's Irregularity Index * Malocclusion * Scissor bite * Standard anatomical position * Tooth ankylosis * Tongue thrust Conditions * Overbite * Open bite * Crossbite * Prognathism * Retrognathism * Maxillary hypoplasia * Condylar hyperplasia * Overeruption * Mouth breathing Appliances * ACCO appliance * Archwire * Activator appliance * Braces * Damon system * Elastics * Frankel appliance * Invisalign * Lingual arch * Lip bumper * List of orthodontic functional appliances * List of palatal expanders * Lingual braces * Headgear * Orthodontic technology * Orthodontic spacer * Palatal lift prosthesis * Palatal expander * Quad helix * Retainer * SureSmile * Self-ligating braces * Splint activator * Twin Block Appliance Procedures * Anchorage (orthodontics) * Cantilever mechanics * Fiberotomy * Interproximal reduction * Intrusion (orthodontics) * Molar distalization * SARPE * Serial extraction Materials * Beta-titanium * Nickel titanium * Stainless steel * TiMolium * Elgiloy * Ceramic * Composite Notable contributors * Edward Angle * Spencer Atkinson * Clifford Ballard * Raymond Begg * Hans Peter Bimler * Samir Bishara * Arne Björk * Charles B. Bolton * Holly Broadbent Sr. * Allan G. Brodie * Charles J. Burstone * Peter Buschang * Calvin Case * Harold Chapman (Orthodontist) * David Di Biase * Jean Delaire * Terry Dischinger * William B. Downs * John Nutting Farrar * Rolf Frankel * Sheldon Friel * Thomas M. Graber * Charles A. Hawley * Reed Holdaway * John Hooper (Orthodontist) * Joseph Jarabak * Harold Kesling * Albert Ketcham * Juri Kurol * Craven Kurz * Benno Lischer * James A. McNamara * Birte Melsen * Robert Moyers * Hayes Nance * Ravindra Nanda * George Northcroft * Dean Harold Noyes * Frederick Bogue Noyes * Albin Oppenheim * Herbert A. Pullen * Earl W. Renfroe * Robert M. Ricketts * Alfred Paul Rogers * Ronald Roth * Everett Shapiro * Frederick Lester Stanton * Earl Emanuel Shepard * Cecil C. Steiner * David L. Turpin * Charles H. Tweed * Katherine Vig * Edmund H. Wuerpel * Won-Sik Yang Organizations * American Association of Orthodontists * American Board of Orthodontics * British Orthodontic Society * Canadian Association of Orthodontists * Indian Orthodontic Society * Italian Academy of Orthodontic Technology * Society for Orthodontic Dental Technology (Germany) Journals * American Journal of Orthodontics and Dentofacial Orthopedics * The Angle Orthodontist * Journal of Orthodontics Institution * Angle School of Orthodontia * v * t * e Dental disease involving the jaw General * Jaw abnormality * malocclusion * Orthodontics * Gnathitis Size * Micrognathism * Maxillary hypoplasia Maxilla and Mandible * Cherubism * Congenital epulis * Torus mandibularis * Torus palatinus Other * Jaw and base of cranium * Prognathism * Retrognathism * Dental arch * Crossbite * Overbite * Temporomandibular joint 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-aminobutyric 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	Malocclusion	c1317785	27,423	wikipedia	https://en.wikipedia.org/wiki/Malocclusion	2021-01-18T19:02:51	{"mesh": ["D008310"], "umls": ["C1317785", "C4280618", "C4280617", "C0040433"], "icd-9": ["524.4"], "icd-10": ["K07.4"], "wikidata": ["Q1320428"]}
Inborn errors of metabolism SpecialtyMedical genetics Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of metabolism.[1] The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic disorders.[2] The term inborn errors of metabolism was coined by a British physician, Archibald Garrod (1857–1936), in 1908. He is known for work that prefigured the "one gene-one enzyme" hypothesis, based on his studies on the nature and inheritance of alkaptonuria. His seminal text, Inborn Errors of Metabolism was published in 1923.[3] ## Contents * 1 Classification * 2 Signs and symptoms * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References * 7 External links ## Classification[edit] Traditionally the inherited metabolic diseases were classified as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases. In recent decades, hundreds of new inherited disorders of metabolism have been discovered and the categories have proliferated. Following are some of the major classes of congenital metabolic diseases, with prominent examples of each class. Many others do not fall into these categories.[citation needed] * Disorders of carbohydrate metabolism * glycogen storage disease * G6PD deficiency[4] * Disorders of amino acid metabolism[5] * phenylketonuria * maple syrup urine disease * glutaric acidemia type 1 * Urea Cycle Disorder or Urea Cycle Defects * Carbamoyl phosphate synthetase I deficiency * Disorders of organic acid metabolism (organic acidurias) * alkaptonuria * 2-hydroxyglutaric acidurias * Disorders of fatty acid oxidation and mitochondrial metabolism * Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) * Disorders of porphyrin metabolism * acute intermittent porphyria * Disorders of purine or pyrimidine metabolism * Lesch–Nyhan syndrome * Disorders of steroid metabolism * lipoid congenital adrenal hyperplasia * congenital adrenal hyperplasia * Disorders of mitochondrial function * Kearns–Sayre syndrome * Disorders of peroxisomal function * Zellweger syndrome * Lysosomal storage disorders[6] * Gaucher's disease * Niemann–Pick disease ## Signs and symptoms[edit] Because of the enormous number of these diseases the wide range of systems affected badly, nearly every "presenting complaint" to a healthcare provider may have a congenital metabolic disease as a possible cause, especially in childhood and adolescence. The following are examples of potential manifestations affecting each of the major organ systems. * Growth failure, failure to grow, loss of weight * Ambiguous genitalia, delayed puberty, precocious puberty * Developmental delay, seizures, dementia, encephalopathy, stroke * Deafness, blindness, pain agnosia * Skin rash, abnormal pigmentation, lacking of pigmentation, excessive hair growth, lumps and bumps * Dental abnormalities * Immunodeficiency, low platelet count, low red blood cell count, enlarged spleen, enlarged lymph nodes * Many forms of cancer * Recurrent vomiting, diarrhea, abdominal pain * Excessive urination, kidney failure, dehydration, edema * Low blood pressure, heart failure, enlarged heart, hypertension, myocardial infarction * Liver enlargement, jaundice, liver failure * Unusual facial features, congenital malformations * Excessive breathing (hyperventilation), respiratory failure * Abnormal behavior, depression, psychosis * Joint pain, muscle weakness, cramps * Hypothyroidism, adrenal insufficiency, hypogonadism, diabetes mellitus ## Diagnosis[edit] Dozens of congenital metabolic diseases are now detectable by newborn screening tests, especially expanded testing using mass spectrometry. This is an increasingly common way for the diagnosis to be made and sometimes results in earlier treatment and a better outcome. There is a revolutionary gas chromatography–mass spectrometry-based technology with an integrated analytics system, which has now made it possible to test a newborn for over 100 mm genetic metabolic disorders. Because of the multiplicity of conditions, many different diagnostic tests are used for screening. An abnormal result is often followed by a subsequent "definitive test" to confirm the suspected diagnosis. Gas chromatography–mass spectrometry (GCMS) Common screening tests used in the last sixty years: * Ferric chloride test (detects abnormal metabolites in urine) * Ninhydrin paper chromatography (detects abnormal amino acid patterns) * Guthrie test (detects excessive amounts of specific amino acids in blood) The dried blood spot can be used for multianalyte testing using Tandem Mass Spectrometry (MS/MS). This given an indication for a disorder. The same has to be further confirmed by enzyme assays, IEX-Ninhydrin, GC/MS or DNA Testing. * Quantitative measurement of amino acids in plasma and urine * IEX-Ninhydrin post-column derivitization liquid ion chromatography (detects abnormal amino acid patterns and quantitative analysis) * Urine organic acid analysis by gas chromatography–mass spectrometry * Plasma acylcarnitine analysis by mass spectrometry * Urine purine and pyrimidine analysis by gas chromatography-mass spectrometry Specific diagnostic tests (or focused screening for a small set of disorders): * Tissue biopsy: liver, muscle, brain, bone marrow * Skin biopsy and fibroblast cultivation for specific enzyme testing * Specific DNA testing A 2015 review reported that even with all these diagnostic tests, there are cases when "biochemical testing, gene sequencing, and enzymatic testing can neither confirm nor rule out an IEM, resulting in the need to rely on the patient's clinical course".[7] ## Treatment[edit] In the middle of the 20th century the principal treatment for some of the amino acid disorders was restriction of dietary protein and all other care was simply management of complications. In the past twenty years, enzyme replacement, gene therapy, and organ transplantation have become available and beneficial for many previously untreatable disorders. Some of the more common or promising therapies are listed: * Dietary restriction * E.g., reduction of dietary protein remains a mainstay of treatment for phenylketonuria and other amino acid disorders * Dietary supplementation or replacement * E.g., oral ingestion of cornstarch several times a day helps prevent people with glycogen storage diseases from becoming seriously hypoglycemic. * Vitamins * E.g., thiamine supplementation benefits several types of disorders that cause lactic acidosis. * Intermediary metabolites, compounds, or drugs that facilitate or retard specific metabolic pathways * Dialysis * Enzyme replacement E.g. Acid-alpha glucosidase for Pompe disease * Gene therapy * Bone marrow or organ transplantation * Treatment of symptoms and complications * Prenatal diagnosis ## Epidemiology[edit] In a study in British Columbia, the overall incidence of the inborn errors of metabolism were estimated to be 40 per 100,000 live births or 1 in 2,500 births,[8] overall representing more than approximately 15% of single gene disorders in the population.[8] While a Mexican study established an overall incidence of 3.4: 1000 live newborns and a carrier detection of 6.8:1000 NBS [6] Type of inborn error Incidence Disease involving amino acids (e.g. PKU), organic acids, primary lactic acidosis, galactosemia, or a urea cycle disease 24 per 100 000 births[8] 1 in 4,200[8] Lysosomal storage disease 8 per 100 000 births[8] 1 in 12,500[8] Peroxisomal disorder ~3 to 4 per 100 000 of births[8] ~1 in 30,000[8] Respiratory chain-based mitochondrial disease ~3 per 100 000 births[8] 1 in 33,000[8] Glycogen storage disease 2.3 per 100 000 births[8] 1 in 43,000[8] ## References[edit] 1. ^ "Inborn errors of metabolism: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2017-02-27. 2. ^ "Inherited metabolic disorders - Symptoms and causes". Mayo Clinic. 3. ^ Archibald Garrod. 1923. Inborn Errors of Metabolism at Electronic Scholarly Publishing site 4. ^ Cantú-Reyna, C.; Santos-Guzmán, J.; Cruz-Camino, H.; Vazquez Cantu, D.L.; Góngora-Cortéz, J.J.; Gutiérrez-Castillo, A. (4 February 2019). "Glucose-6-Phosphate dehydrogenase deficiency incidence in a Hispanic population". Journal of Neonatal-Perinatal Medicine. 12 (2): 203–207. doi:10.3233/NPM-1831. PMID 30741698. 5. ^ Zea-Rey, Alexandra V.; Cruz-Camino, Héctor; Vazquez-Cantu, Diana L.; Gutiérrez-García, Valeria M.; Santos-Guzmán, Jesús; Cantú-Reyna, Consuelo (27 November 2017). "The Incidence of Transient Neonatal Tyrosinemia Within a Mexican Population". Journal of Inborn Errors of Metabolism and Screening. 5: 232640981774423. doi:10.1177/2326409817744230. 6. ^ a b Navarrete-Martínez, Juana Inés; Limón-Rojas, Ana Elena; Gaytán-García, Maria de Jesús; Reyna-Figueroa, Jesús; Wakida-Kusunoki, Guillermo; Delgado-Calvillo, Ma. del Rocío; Cantú-Reyna, Consuelo; Cruz-Camino, Héctor; Cervantes-Barragán, David Eduardo (May 2017). "Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: Three-year findings from a screening program in a closed Mexican health system". Molecular Genetics and Metabolism. 121 (1): 16–21. doi:10.1016/j.ymgme.2017.03.001. PMID 28302345. 7. ^ Vernon, Hilary (Jun 2015). "Inborn Errors of Metabolism: Advances in Diagnosis and Therapy". JAMA Pediatrics. 169 (8): 778–82. doi:10.1001/jamapediatrics.2015.0754. PMID 26075348. 8. ^ a b c d e f g h i j k l Applegarth DA, Toone JR, Lowry RB (January 2000). "Incidence of inborn errors of metabolism in British Columbia, 1969-1996". Pediatrics. 105 (1): e10. doi:10.1542/peds.105.1.e10. PMID 10617747. ## External links[edit] Classification D * ICD-10: E70-E90 * ICD-9-CM: 270-279 * MeSH: D008661 External resources * MedlinePlus: 002438 * eMedicine: emerg/768 article/804757 * National Institutes of Health offers the office of rare diseases, home reference, medlineplus and health information. * v * t * e Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders Including glycogen storage diseases (GSD) Sucrose, transport (extracellular) Disaccharide catabolism * Congenital alactasia * Sucrose intolerance Monosaccharide transport * Glucose-galactose malabsorption * Inborn errors of renal tubular transport (Renal glycosuria) * Fructose malabsorption Hexose → glucose Monosaccharide catabolism Fructose: * Essential fructosuria * Fructose intolerance Galactose / galactosemia: * GALK deficiency * GALT deficiency/GALE deficiency Glucose ⇄ glycogen Glycogenesis * GSD type 0 (glycogen synthase deficiency) * GSD type IV (Andersen's disease, branching enzyme deficiency) * Adult polyglucosan body disease (APBD) Glycogenolysis Extralysosomal: * GSD type III (Cori's disease, debranching enzyme deficiency) * GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency) * GSD type V (McArdle's disease, myophosphorylase deficiency) * GSD type IX (phosphorylase kinase deficiency) Lysosomal (LSD): * GSD type II (Pompe's disease, glucosidase deficiency) Glucose ⇄ CAC Glycolysis * MODY 2/HHF3 * GSD type VII (Tarui's disease, phosphofructokinase deficiency) * Triosephosphate isomerase deficiency * Pyruvate kinase deficiency Gluconeogenesis * PCD * Fructose bisphosphatase deficiency * GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency) Pentose phosphate pathway * Glucose-6-phosphate dehydrogenase deficiency * Transaldolase deficiency * 6-phosphogluconate dehydrogenase deficiency Other * Hyperoxaluria * Primary hyperoxaluria * Pentosuria * Aldolase A deficiency * 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 Inborn error of lipid metabolism: fatty-acid metabolism disorders Synthesis * Biotinidase deficiency (BTD) Degradation Acyl transport * Carnitine * CPT1 * CPT2 * CDSP * CACTD * Adrenoleukodystrophy (ALD) Beta oxidation General * Acyl CoA dehydrogenase * Short-chain SCADD * Medium-chain MCADD * Long-chain 3-hydroxy LCHAD * Very long-chain VLCADD * Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy Unsaturated * 2,4 Dienoyl-CoA reductase deficiency (DECRD) Odd chain * Propionic acidemia (PCC deficiency) Other * 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD) * Glutaric acidemia type 2 (MADD) To acetyl-CoA * Malonic aciduria (MCD) Aldehyde * Sjögren–Larsson syndrome (SLS) * v * t * e Inborn error of lipid metabolism: dyslipidemia Hyperlipidemia * Hypercholesterolemia/Hypertriglyceridemia * Lipoprotein lipase deficiency/Type Ia * Familial apoprotein CII deficiency/Type Ib * Familial hypercholesterolemia/Type IIa * Combined hyperlipidemia/Type IIb * Familial dysbetalipoproteinemia/Type III * Familial hypertriglyceridemia/Type IV * Xanthoma/Xanthomatosis Hypolipoproteinemia Hypoalphalipoproteinemia/HDL * Lecithin cholesterol acyltransferase deficiency * Tangier disease Hypobetalipoproteinemia/LDL * Abetalipoproteinemia * Apolipoprotein B deficiency * Chylomicron retention disease Lipodystrophy * Barraquer–Simons syndrome Other * Lipomatosis * Adiposis dolorosa * Lipoid proteinosis * APOA1 familial renal amyloidosis * v * t * e Heme metabolism disorders Porphyria, hepatic and erythropoietic (porphyrin) early mitochondrial: * ALAD porphyria * Acute intermittent porphyria cytoplasmic: * Gunther disease/congenital erythropoietic porphyria * Porphyria cutanea tarda/Hepatoerythropoietic porphyria late mitochondrial: * Hereditary coproporphyria * Harderoporphyria * Variegate porphyria * Erythropoietic protoporphyria Hereditary hyperbilirubinemia (bilirubin) unconjugated: * Gilbert's syndrome * Crigler–Najjar syndrome * Lucey–Driscoll syndrome conjugated: * Dubin–Johnson syndrome nd sheet * Rotor syndrome * v * t * e Inborn error of purine–pyrimidine metabolism Purine metabolism Anabolism * Adenylosuccinate lyase deficiency * Adenosine Monophosphate Deaminase Deficiency type 1 Nucleotide salvage * Lesch–Nyhan syndrome/Hyperuricemia * Adenine phosphoribosyltransferase deficiency Catabolism * Adenosine deaminase deficiency * Purine nucleoside phosphorylase deficiency * Xanthinuria * Gout * Mitochondrial neurogastrointestinal encephalopathy syndrome Pyrimidine metabolism Anabolism * Orotic aciduria * Miller syndrome Catabolism * Dihydropyrimidine dehydrogenase deficiency * v * t * e Inborn errors of steroid metabolism Mevalonate pathway * HMG-CoA lyase deficiency * Hyper-IgD syndrome * Mevalonate kinase deficiency To cholesterol * 7-Dehydrocholesterol path: Hydrops-ectopic calcification-moth-eaten skeletal dysplasia * CHILD syndrome * Conradi-Hünermann syndrome * Lathosterolosis * Smith–Lemli–Opitz syndrome * desmosterol path: Desmosterolosis Steroids Corticosteroid (including CAH) * aldosterone: Glucocorticoid remediable aldosteronism * cortisol/cortisone: CAH 17α-hydroxylase * CAH 11β-hydroxylase * both: CAH 3β-dehydrogenase * CAH 21-hydroxylase * Apparent mineralocorticoid excess syndrome/11β-dehydrogenase Sex steroid To androgens * 17α-Hydroxylase deficiency * 17,20-Lyase deficiency * Cytochrome b5 deficiency * 3β-Hydroxysteroid dehydrogenase deficiency * 17β-Hydroxysteroid dehydrogenase deficiency * 5α-Reductase deficiency * Pseudovaginal perineoscrotal hypospadias To estrogens * Aromatase deficiency * Aromatase excess syndrome Other * X-linked ichthyosis * Antley–Bixler syndrome * v * t * e Metabolic disorders of vitamins, coenzymes, and cofactors B7 Biotin/MCD * Biotinidase deficiency * Holocarboxylase synthetase deficiency Other B * B5 (Pantothenate kinase-associated neurodegeneration) * B12 (Methylmalonic acidemia) Other vitamin * Familial isolated vitamin E deficiency Nonvitamin cofactor * Tetrahydrobiopterin deficiency * Molybdenum cofactor deficiency * Metabolism portal [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-aminobutyric 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	Inborn errors of metabolism	c0025521	27,424	wikipedia	https://en.wikipedia.org/wiki/Inborn_errors_of_metabolism	2021-01-18T18:29:57	{"mesh": ["D008661"], "umls": ["C0025521"], "icd-9": ["279", "270"], "icd-10": ["E70", "E90"], "orphanet": ["68367"], "wikidata": ["Q1758393"]}
A number sign (#) is used with this entry because pseudohypoaldosteronism type IIE (PHA2E) is caused by heterozygous mutation in the CUL3 gene (603136) on chromosome 2q36. For a phenotypic description and a discussion of genetic heterogeneity of pseudohypoaldosteronism type II, see PHA2A (145260). Clinical Features Boyden et al. (2012) studied a cohort of 52 PHAII kindreds, including 126 affected subjects with renal hyperkalemia and otherwise normal renal function; hypertension and acidosis were present in 71% and 82%, respectively. They detected 21 affected individuals from 17 kindreds with mutation in the CUL3 gene. The mean age at diagnosis or referral was 9 +/- 6 years, mean potassium was 7.5 +/- 0.9, and mean bicarbonate was 15.5 +/- 2.0. Hypertension was present in 94% of patients at or before 18 years of age. The CUL3 mutation patients had by far the most severe manifestations of PHAII compared to patients with other mutations. Clinical Management Thiazide diuretics correct abnormalities in virtually all PHAII subjects (Boyden et al., 2012). Molecular Genetics After identifying mutations in the KLHL3 gene (605775) in kindreds with PHAII (see 614495), Boyden et al. (2012) considered CUL3, the presumed functional partner of KLHL3, as a candidate. Sequencing CUL3 in 21 index patients revealed 17 with novel heterozygous CUL3 mutations. Eight of the 17 were de novo mutations. Boyden et al. (2012) observed that the CUL3 mutations identified in their cohort all clustered in sites implicated in splicing of exon 9, including the intron 8 splice acceptor (n = 4), the intron 9 splice donor (n = 5), the putative intron 8 splice branch site (n = 5), and a putative splice enhancer in exon 9 (n = 3, within a TTGGA(T/A)) splice enhancer consensus sequence. Genotype/Phenotype Correlations Boyden et al. (2012) observed that families with PHAII due to mutation in the WNK1 gene (PHA2C; 614492) are significantly less severely affected than those with mutation in the WNK4 gene (PHA2B; 614491) or dominant or recessive mutation in the KLHL3 gene (605775; PHA2D, 614495), and all are less severely affected than those with dominant mutation in the CUL3 gene (PHA2E). INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Hypertension METABOLIC FEATURES \- Hyperchloremic metabolic acidosis (HCO3 15.5 +/- 2.0 mM) LABORATORY ABNORMALITIES \- Hyperkalemia (7.5 +/- 0.9 mM) \- Hyperchloremia (mean 114 mM) MISCELLANEOUS \- 21 patients from 17 kindreds reported (as of February 2012) \- Age at diagnosis 9 +/- 6 years \- 94% develop hypertension at 18 years of age or less \- Responsive to thiazide diuretics MOLECULAR BASIS \- Caused by mutation in the cullin 3 gene (CUL3, 603136.0001 ) ▲ 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-aminobutyric 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	PSEUDOHYPOALDOSTERONISM, TYPE IIE	c1449844	27,425	omim	https://www.omim.org/entry/614496	2019-09-22T15:55:04	{"mesh": ["D011546"], "omim": ["614496"], "orphanet": ["300530", "757"], "synonyms": ["PHA2E"], "genereviews": ["NBK65707"]}
A rare autoimmune bullous skin disease characterized by mucocutaneous bullae with subsequent erosion and formation of vegetative plaques, predominantly affecting intertriginous areas and the oral mucosa. Two clinical forms of the disease are recognized: the Hallopeau type, which presents an indolent course with pustules healing as vegetative plaques and frequent lack of involvement of the oral mucosa, and the Neumann type, which takes a more severe, refractory course with vegetations developing during an eruption of vesiculobullous lesions and involvement of the oral mucosa. Serum analysis reveals antibodies against desmoglein 1 and 3. [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-aminobutyric 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	Pemphigus vegetans	c0263316	27,426	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79479	2021-01-23T17:17:49	{"umls": ["C0263316", "C0406647"], "icd-10": ["L10.1"]}
This article is about a group of muscle wasting disorders. For the disease amyotrophic lateral sclerosis, also known as motor neurone disease, see Amyotrophic lateral sclerosis. Group of neurological disorders affecting motor neurons Motor neuron disease spinal diagram SpecialtyNeurology Motor neuron diseases or motor neurone diseases (MNDs) are a group of rare neurodegenerative disorders that selectively affect motor neurons, the cells which control voluntary muscles of the body.[1][2] They include amyotrophic lateral sclerosis (ALS),[3][4] progressive bulbar palsy (PBP), pseudobulbar palsy, progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), and monomelic amyotrophy (MMA), as well as some rarer variants resembling ALS. Motor neuron diseases affect both children and adults.[5] While each motor neuron disease affects patients differently, they all cause movement-related symptoms, mainly muscle weakness.[6] Most of these diseases seem to occur randomly without known causes, but some forms are inherited.[2] Studies into these inherited forms have led to discoveries of various genes (e.g. SOD1) that are thought to be important in understanding how the disease occurs.[7] Symptoms of motor neuron diseases can be first seen at birth or can come on slowly later in life. Most of these diseases worsen over time; while some, such as ALS, shorten one's life expectancy, others do not.[2] Currently, there are no approved treatments for the majority of motor neuron disorders, and care is mostly symptomatic.[2] ## Contents * 1 Signs and symptoms * 1.1 Patterns of weakness * 1.2 Lower and upper motor neuron findings * 2 Causes * 2.1 DNA damage * 2.2 Associated risk factors * 3 Diagnosis * 3.1 Classification * 3.2 Tests * 4 Treatment * 5 Prognosis * 6 Terminology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] A man with amyotrophic lateral sclerosis (ALS). (A) He needs assistance to stand. (B) Advanced atrophy of the tongue. (C) There is upper limb and truncal muscle atrophy with a positive Babinski sign. (D) Advanced thenar muscle atrophy.[8] Signs and symptoms depend on the specific disease, but motor neuron diseases typically manifest as a group of movement-related symptoms.[6] They come on slowly, and worsen over the course of more than three months. Various patterns of muscle weakness are seen, and muscle cramps and spasms may occur. One can have difficulty breathing with climbing stairs (exertion), difficulty breathing when lying down (orthopnea), or even respiratory failure if breathing muscles become involved. Bulbar symptoms, including difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and excessive saliva production (sialorrhea), can also occur. Sensation, or the ability to feel, is typically not affected. Emotional disturbance (e.g. pseudobulbar affect) and cognitive and behavioural changes (e.g. problems in word fluency, decision-making, and memory) are also seen.[2][6] There can be lower motor neuron findings (e.g. muscle wasting, muscle twitching), upper motor neuron findings (e.g. brisk reflexes, Babinski reflex, Hoffman's reflex, increased muscle tone), or both.[6] Motor neuron diseases are seen both in children and in adults.[2] Those that affect children tend to be inherited or familial, and their symptoms are either present at birth or appear before learning to walk. Those that affect adults tend to appear after age 40.[2] The clinical course depends on the specific disease, but most progress or worsen over the course of months.[6] Some are fatal (e.g. ALS), while others are not (e.g. PLS).[2] ### Patterns of weakness[edit] Various patterns of muscle weakness occur in different motor neuron diseases.[6] Weakness can be symmetric or asymmetric, and it can occur in body parts that are distal, proximal, or both... According to Statland et al., there are three main weakness patterns that are seen in motor neuron diseases, which are:[6][9] 1. Asymmetric distal weakness without sensory loss (e.g. ALS, PLS, PMA, MMA) 2. Symmetric weakness without sensory loss (e.g. PMA, PLS) 3. Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement; e.g. ALS, PBP, PLS) ### Lower and upper motor neuron findings[edit] Motor neuron diseases are on a spectrum in terms of upper and lower motor neuron involvement.[6] Some have just lower or upper motor neuron findings, while others have a mix of both. Lower motor neuron (LMN) findings include muscle atrophy and fasciculations, and upper motor neuron (UMN) findings include hyperreflexia, spasticity, muscle spasm, and abnormal reflexes.[2][6] Pure upper motor neuron diseases, or those with just UMN findings, include PLS. Pure lower motor neuron diseases, or those with just LMN findings, include PMA. Motor neuron diseases with both UMN and LMN findings include both familial and sporadic ALS. ## Causes[edit] Most cases are sporadic and their causes are usually not known.[2] It is thought that environmental, toxic, viral, or genetic factors may be involved.[2] ### DNA damage[edit] TARDBP (TAR DNA-binding protein 43), also referred to as TDP-43, is a critical component of the non-homologous end joining (NHEJ) enzymatic pathway that repairs DNA double-strand breaks in pluripotent stem cell-derived motor neurons.[10] TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the XRCC4-DNA ligase protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ALS patients’ spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ.[10] ### Associated risk factors[edit] In adults, men are more commonly affected than women.[2] ## Diagnosis[edit] Differential diagnosis can be challenging due to the number of overlapping symptoms, shared between several motor neuron diseases. Frequently, the diagnosis is based on clinical findings (i.e. LMN vs. UMN signs and symptoms, patterns of weakness), family history of MND, and a variation of tests, many of which are used to rule out disease mimics, which can manifest with identical symptoms.[citation needed] ### Classification[edit] Corticospinal tract. Upper motor neurons originating in the primary motor cortex synapse to either lower motor neurons in the anterior horn of the central gray matter of the spinal cord (insert) or brainstem motor neurons (not shown). Motor neuron disease can affect either upper motor neurons (UMNs) or lower motor neurons (LMNs). Motor neuron disease describes a collection of clinical disorders, characterized by progressive muscle weakness and the degeneration of the motor neuron on electrophysiological testing. As discussed above, the term "motor neuron disease" has varying meanings in different countries. Similarly, the literature inconsistently classifies which degenerative motor neuron disorders can be included under the umbrella term "motor neuron disease". The four main types of MND are marked () in the table below.[11] All types of MND can be differentiated by two defining characteristics:[6] 1. Is the disease sporadic or inherited? 2. Is there involvement of the upper motor neurons (UMN), the lower motor neurons (LMN), or both? Sporadic or acquired MNDs occur in patients with no family history of degenerative motor neuron disease. Inherited or genetic MNDs adhere to one of the following inheritance patterns: autosomal dominant, autosomal recessive, or X-linked. Some disorders, like ALS, can occur sporadically (85%) or can have a genetic cause (15%) with the same clinical symptoms and progression of disease.[6] UMNs are motor neurons that project from the cortex down to the brainstem or spinal cord.[12] LMNs originate in the anterior horns of the spinal cord and synapse on peripheral muscles.[12] Both motor neurons are necessary for the strong contraction of a muscle, but damage to an UMN can be distinguished from damage to a LMN by physical exam. Type UMN degeneration LMN degeneration Sporadic MNDs Sporadic amyotrophic lateral sclerosis (ALS) Yes[6] Yes[6] Primary lateral sclerosis (PLS)* Yes[6] No[6] Progressive muscular atrophy (PMA)* No[6] Yes[6] Progressive bulbar palsy (PBP)* Yes[11] Yes, bulbar region[11] Pseudobulbar palsy Yes, bulbar region[6] No[6] Monomelic amyotrophy (MMA) No Yes Inherited MNDs Familial amyotrophic lateral sclerosis (ALS)* Yes[6] Yes[6] ### Tests[edit] * Cerebrospinal fluid (CSF) tests: Analysis of the fluid from around the brain and spinal cord could reveal signs of an infection or inflammation.[13] * Magnetic resonance imaging (MRI): An MRI of the brain and spinal cord is recommended in patients with UMN signs and symptoms to explore other causes, such as a tumor, inflammation, or lack of blood supply (stroke).[13] * Electromyogram (EMG) & nerve conduction study (NCS): The EMG, which evaluates muscle function, and NCS, which evaluates nerve function, are performed together in patients with LMN signs. * For patients with MND affecting the LMNs, the EMG will show evidence of: (1) acute denervation, which is ongoing as motor neurons degenerate, and (2) chronic denervation and reinnervation of the muscle, as the remaining motor neurons attempt to fill in for lost motor neurons.[13] * By contrast, the NCS in these patients is usually normal. It can show a low compound muscle action potential (CMAP), which results from the loss of motor neurons, but the sensory neurons should remain unaffected.[14] * Tissue biopsy: Taking a small sample of a muscle or nerve may be necessary if the EMG/NCS is not specific enough to rule out other causes of progressive muscle weakness, but it is rarely used. ## Treatment[edit] There are no known curative treatments for the majority of motor neuron disorders. Please refer to the articles on individual disorders for more details.[15] ## Prognosis[edit] The table below lists life expectancy for patients who are diagnosed with MND. Type Median survival time from start of symptoms Amyotrophic lateral sclerosis (ALS) 2–5 years[13][16] Primary lateral sclerosis (PLS) 8–10 years[13] Progressive muscular atrophy (PMA) 2–4 years[13] Progressive bulbar palsy (PBP) 6 months – 3 years[16] Pseudobulbar palsy No change in survival ## Terminology[edit] In the United States and Canada, the term motor neuron disease usually refers to the group of disorders while amyotrophic lateral sclerosis is frequently called Lou Gehrig's disease.[2][5][17] In the United Kingdom and Australia, the term motor neuron(e) disease is used for amyotrophic lateral sclerosis,[3][4]although is not uncommon to refer to the entire group.[18][19] While MND refers to a specific subset of similar diseases, there are numerous other diseases of motor neurons that are referred to collectively as "motor neuron disorders", for instance the diseases belonging to the spinal muscular atrophies group.[1] However, they are not classified as "motor neuron diseases" by the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11),[20] which is the definition followed in this article. ## See also[edit] * Spinal muscular atrophies * Hereditary motor and sensory neuropathies ## References[edit] 1. ^ a b Ince PG, Clark B, Holton J, Revesz T, Wharton SB (2008). "Chapter 13: Diseases of movement and system degenerations". In Greenfield JG, Love S, Louis DN, Ellison DW (eds.). Greenfield's neuropathology. 1 (8th ed.). London: Hodder Arnold. p. 947. ISBN 978-0-340-90681-1. 2. ^ a b c d e f g h i j k l m "Motor Neuron Diseases Fact Sheet: National Institute of Neurological Disorders and Stroke (NINDS)". www.ninds.nih.gov. Archived from the original on 13 April 2014. Retrieved 7 November 2010. 3. ^ a b "Motor neurone disease – NHS". nhs.uk. 15 January 2018. Retrieved 24 October 2020. 4. ^ a b Australia, Healthdirect (17 April 2020). "Motor neurone disease (MND)". www.healthdirect.gov.au. Retrieved 24 October 2020. 5. ^ a b Cooper-Knock J, Jenkins T, Shaw PJ (1 September 2013). Clinical and molecular aspects of motor neuron disease. San Rafael, California. ISBN 978-1-61504-429-0. OCLC 860981760. 6. ^ a b c d e f g h i j k l m n o p q r s t u Statland, Jeffrey M.; Barohn, Richard J.; McVey, April L.; Katz, Jonathan S.; Dimachkie, Mazen M. (1 November 2015). "Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis". Neurologic Clinics. 33 (4): 735–748. doi:10.1016/j.ncl.2015.07.006. ISSN 0733-8619. PMC 4629510. PMID 26515618. 7. ^ Cooper-Knock J, Jenkins T, Shaw PJ (1 September 2013). Clinical and molecular aspects of motor neuron disease. San Rafael, California (1537 Fourth Street, San Rafael, CA 94901 USA). ISBN 9781615044290. OCLC 860981760.CS1 maint: location (link) 8. ^ "Patient with amyotrophic lateral sclerosis (ALS) (case \| Open-i". openi.nlm.nih.gov. Archived from the original on 15 December 2018. Retrieved 12 December 2018. 9. ^ Barohn RJ, Amato AA (May 2013). "Pattern-recognition approach to neuropathy and neuronopathy". Neurologic Clinics. 31 (2): 343–61. doi:10.1016/j.ncl.2013.02.001. PMC 3922643. PMID 23642713. 10. ^ a b Mitra J, Guerrero EN, Hegde PM, Liachko NF, Wang H, Vasquez V, Gao J, Pandey A, Taylor JP, Kraemer BC, Wu P, Boldogh I, Garruto RM, Mitra S, Rao KS, Hegde ML (2019). "Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects". Proc Natl Acad Sci U S A. 116 (10): 4696–4705. doi:10.1073/pnas.1818415116. PMC 6410842. PMID 30770445.CS1 maint: multiple names: authors list (link) 11. ^ a b c "What forms does MND take?". www.mndnsw.asn.au. Retrieved 11 December 2018. 12. ^ a b Blumenfeld H (2002). Neuroanatomy through clinical cases. Sunderland, Mass.: Sinauer. ISBN 087893060-4. OCLC 44628054. 13. ^ a b c d e f Foster LA, Salajegheh MK (August 2018). "Motor Neuron Disease: Pathophysiology, Diagnosis, and Management". The American Journal of Medicine. 0 (1): 32–37. doi:10.1016/j.amjmed.2018.07.012. PMID 30075105. 14. ^ Duleep, Anuradha; Shefner, Jeremy (1 February 2013). "Electrodiagnosis of Motor Neuron Disease". Physical Medicine and Rehabilitation Clinics of North America. 24 (1): 139–151. doi:10.1016/j.pmr.2012.08.022. ISSN 1047-9651. PMID 23177036. 15. ^ "NIH: ninds: Motor Neuron Diseases Information Page". 27 March 2019. Retrieved 18 November 2019. 16. ^ a b "Different types of MND". Irish Motor Neurone Disease Association. Retrieved 12 December 2018. 17. ^ Shaw PJ (August 2005). "Molecular and cellular pathways of neurodegeneration in motor neurone disease". Journal of Neurology, Neurosurgery, and Psychiatry. 76 (8): 1046–57. doi:10.1136/jnnp.2004.048652. PMC 1739758. PMID 16024877. "Many doctors use the terms motor neuron disease and ALS interchangeably." 18. ^ "An introduction to motor neurone disease (MND)" (PDF). motor neurone disease association. 2015. 19. ^ Schapira AH, Wszolek ZK, Dawson TM, Wood NW (13 February 2017). Neurodegeneration. Chichester, West Sussex. ISBN 978-1-118-66191-8. OCLC 958876527. 20. ^ "8B60 Motor neuron disease". ICD-11 for Mortality and Morbidity Statistics. World Health Organisation. ## External links[edit] * Motor neuron diseases at NINDS Classification D * ICD-10: G12.2 * ICD-9-CM: 335.2 * MeSH: D016472 * DiseasesDB: 8358 Wikimedia Commons has media related to Motor neuron diseases. * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral 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-aminobutyric 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	Motor neuron disease	c0085084	27,427	wikipedia	https://en.wikipedia.org/wiki/Motor_neuron_disease	2021-01-18T19:00:43	{"mesh": ["D016472"], "umls": ["C0085084"], "orphanet": ["98503"], "wikidata": ["Q3221083"]}
Hemoglobin E - beta-thalassemia (HbE - BT) is a form of beta-thalassemia (see this term) that results in a mild to severe clinical presentation ranging from a condition indistinguishable from beta-thalassemia major to a mild form of beta-thalassemia intermedia (see these terms). ## Epidemiology Prevalence of this form is not known but HbE - beta-thalassemia is predominant in Southeast Asia. ## Clinical description Mild HbE - BT (about 15% of cases) is characterized by normal Hb levels (9-12 g/dl) and patients usually do not develop clinically significant symptoms. No treatment is required. Moderately severe forms (most cases) are characterized by decreased Hb levels (6-8 g/dl) and the clinical manifestations are similar to those of beta-thalassemia intermedia. Transfusions are not required unless infections precipitate further anemia. Iron overload may occur. Severe forms are characterized by very low Hb levels (4-5 g/dl) and patients present with manifestations similar to beta-thalassemia major and are treated as thalassemia major patients. HbE - BT patients are compound heterozygotes for hemoglobin E and beta-thalassemia. [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-aminobutyric 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	Hemoglobin E-beta-thalassemia syndrome	c0472777	27,428	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231249	2021-01-23T19:03:06	{"umls": ["C0472777"], "icd-10": ["D58.2"], "synonyms": ["E-beta-thalassemia", "HbE-beta-thalassemia syndrome"]}
Succinic semialdehyde dehydrogenase deficiency Other names4-hydroxybutyric aciduria or Gamma-hydroxybutyric aciduria, Gamma-Hydroxybutyric acid Succinic semialdehyde dehydrogenase deficiency (SSADHD), is a rare autosomal recessive disorder[1] of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families.[2] The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.[3] SSADH deficiency is caused by an enzyme deficiency in GABA degradation. Under normal conditions, SSADH works with the enzyme GABA transaminase to convert GABA to succinic acid. Succinic acid can then be utilized for energy production via the Krebs cycle. However, because of the deficiency, the final intermediate of the GABA degradation pathway, succinic semialdehyde, accumulates and cannot be oxidized to succinic acid and is therefore reduced to gamma-hydroxybutyric acid (GHB) by gamma-hydroxybutyric dehydrogenase. This causes elevations in GHB and is believed to be the trademark of this disorder and cause for the neurological manifestations seen.[2] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Mechanism * 4 Diagnosis * 4.1 Neuroimaging * 4.2 Laboratory * 5 Treatments * 5.1 Vigabatrin * 5.2 Sodium valproate * 5.3 GABAB receptor antagonist: CGP-35348 * 5.4 GABAB agonist: baclofen * 5.5 Taurine * 5.6 Ketogenic diet * 5.7 Other interventions * 6 Research * 6.1 Animal models * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] The symptoms of SSADH deficiency fall into three primary categories: neurological, psychiatric, and ocular. The most constant features seen are developmental delay, hypotonia and intellectual disability. Nearly half of patients seen manifest ataxia, behavior problems, seizures, and hyporeflexia.[2] The age of onset ranges from newborn period to 25 years. Problems unique to neonates can include prematurity, lethargy, decreased sucking, respiratory difficulty and hypoglycemia. Gastrointestinal symptoms have been seen primarily in this population and are usually related to increased feeding. Ocular problems related to the disorder include strabismus, nystagmus, retinitis, disc pallor, and oculomotor apraxia.[4] Over half of the patients with SSADH deficiency have seizures. These include absence, tonic clonic, and convulsive status epilepticus. It is unclear whether decreased levels of GABA or elevated levels of GHB are responsible for these seizures but alterations in these neurotransmitters and their receptor binding or neurotransmitter transport is hypothesized to play a role in the pathogenesis of the seizures in this population.[5] Symptoms associated with SSADH may be mild, moderate or severe and often vary greatly from case to case. The symptoms of SSADH are caused by the accumulation of GHB in the brain and include the following manifestations (Defined as: common, > 70% of patients; frequent 30-70% of patients;unusual, < 30% of patients): Common manifestations include: * Delayed gross motor development * Delayed mental development * Delayed fine motor skill development * Delayed speech and language development * Hypotonia Frequent manifestations include: * Seizures * Hyporeflexia * Ataxia * Behavioral problems * Hyperkinesis Unusual manifestations include: * Neonatal problems * EEG abnormalities * Psychoses * MRI or X-ray computed tomography abnormalities * Oculomotor apraxia * Microcephaly * Macrocephaly * Hyperreflexia * Somnolence * Choreoathetosis * Myopathy ## Genetics[edit] Succinic semialdehyde dehydrogenase deficiency has an autosomal recessive pattern of inheritance. SSADH deficiency is inherited in an autosomal recessive fashion. Such diseases are caused by an error in a single DNA gene. Because the disease is autosomal, the defective gene is found on an autosome (chromosome 6), rather than the sex-linked 23rd chromosome. Being a recessive disorder, the disease can only be inherited from both parents since the disorder can only occur when a person has two copies of the gene.[citation needed] It is believed that the genetic basis for SSADH deficiency resides in the SSADH human ALDH5A1 gene which maps to chromosome 6p22. More than 47 disease-causing mutations have been identified for the disorder, all of which lead to absence of functional proteins through missense, nonsense, or splicing errors; no hotspots have been identified. Consanguinity is frequent; this suggests the occurrence of rare disease causing alleles in the general population.[6] ## Mechanism[edit] GABA is a major inhibitory neurotransmitter in the central nervous system. It modulates the activity of several neurotransmitters including dopamine, serotonin, and norepinephrine. GABA is synthesized in a single step from its precursor glutamate by glutamic acid decarboxylase. GABA is metabolized by successive transamination and oxidation to yield succinic semialdehyde and succinic acid respectively via the catalyzing effects of GABA transaminase. The succinic semialdehyde can be converted into either succinic acid by SSADH or to GHB by the enzyme succinic semialdehyde reductase.[7] The absence of SSADH leads to a 30-fold increase of GHB and a 2-4 fold increase of GABA in the brains of patients with SSADH deficiency as compared to normal brain concentrations of the compounds. Elevations of GHB have been shown to induce spike and wave activity similar to that seen in generalized absence epilepsy in animal models as well, which has motivated researchers to increase their knowledge on the relationship between GHB and the neurological manifestations seen in SSADH deficiency.[8] GABA acts via binding to its receptors which include the ligand gated ion channels, GABAA and GABAC and the G-protein couple receptors GABAB. The GABAB receptor has been found to be the most important of the three receptors for this disorder as it is vital in both GABA and GHB release. This receptor mediates the release through presynaptic effects through a voltage dependent inhibition of high voltage activation of calcium channels. Many experiments have been able to show that it is the increased levels of both GABA and GHB that seem to alter the function of GABAB receptor, which may further play a role in the tonic-clonic seizures that are often seen in patients with the disorder.[9] In terms of intracellular signaling, GHB inhibits mitogen activated protein (MAP) kinase action via the GABAB receptor mechanism. MAP kinase is imperative for numerous physiological changes including regulation of cell division and differentiation, thus, down-regulation of this pathway may occur during the presence of too much GHB as found in SSADH deficiency.[9] In 2003, Ren and Mody et al. proved that repeated exposure of GHB to MAP kinase affected myelin expression. This is a critical finding since myelin is the electrical and insulating phospholipid layer that surrounds the axons of many neurons in the brain. Proper myelination is critical for carrying electrical signals, or data, from one nerve cell to the next. When myelin becomes damaged, it can cause numerous neurological problems, many of which are seen in patients with SSADH deficiency. Thus, Ren and Mody's work in the relationship between increased levels of GHB and myelin expression may further show the significance of this pathway in terms of the neurological deficits seen in SSADH deficiency.[10] Glutamine metabolism may also play a role in the pathophysiology of SSADH deficiency. The major ionotropic glutamine receptors include the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainite receptor. High levels of GHB have been shown to depress both the NMDA and AMPA/kainite receptor mediated functions and may also alter glutamatergic excitatory synaptic transmission as well. Decreased glutamine, coupled with elevated GABA, has also suggested disruption of the glutamine–glutamate shuttle which ultimately provides for astrocytic glutamine as a precursor for neuronal glutamate and GABA. This disruption has the potential to impair glutamate homeostasis and may lead to uncoupling of the normal balance between glutamatergic excitatory activity and GABAergic inhibition, and may be responsible for the convulsive seizures that are observed in this disorder.[11] Finally, additional mitochondrial processes may also be affected by SSADH deficiency. Succinate semialdehyde is considered a reactive carbonyl and may lead to increased oxidative stress. This stress is believed to contribute to the formation of free radicals in the brain tissue of animal models induced with SSADH deficiency, which further leads to secondary cell damage and death. Additionally, oxidative stress may be responsible for loss of striatal dopamine which may contribute to pathophysiology of the disease.[9] ## Diagnosis[edit] ### Neuroimaging[edit] Cranial computed topography, magnetic resonance imaging, and flurodeoxyglucose positron emission topography are just some of the neuroimaging modalities that have been used to diagnose patients with SSADH deficiency. On the basis of 29 previously published cases that had imaging results available, there were some common abnormalities found. These included increased T2-weighted signal abnormalities involving the globus pallidi bilaterally and symmetrically as well as the presence of subcortical white matter. Similar abnormalities have been identified in the brainstem and cerebellar dentate nucleus.[2] Signal intensity on a T2 image may be a result of edema or an inflammatory response. Because this type of imaging is a water detecting sequence, any form of calcification or mineralization would also appear dark, thus explaining why accumulation of extra blood or fluid would appear bright on a T2 image. Another explanation for signal intensity may be demyelination since the globus pallidi are traversed by a number of myelinated axons, thus confirming Ren and Mody's 2003 work proving that repeated exposure of GHB to MAP kinase affected myelin expression, thus causing the numerous neurological dysfunctions seen in SSADH deficiency patients. Ultimately, because the globus pallidus is intimately linked with the basal ganglia and thalamus, it would be expected that some of the motor dysfunctions seen in SSADH patients such as ataxia and hyporeflexia would be common.[12] ### Laboratory[edit] Detection of the disorder is possible with an organic acid analysis of the urine. Patients with SSADH deficiency will excrete high levels of GHB but this can be difficult to measure since GHB has high volatility and may be obscured on gas chromatography or mass spectrometry studies by a high urea peak. Other GABA metabolites can also be identified in urine such as glycine. Finally, succinic semialdehyde dehydrogenase levels can be measured in cultured leukocytes of the patient. This occurs due to the accumulation of 4,5-dihydroxyhexanoic acid which is normally undetectable in mammalian tissues but is characteristic of SSADH deficiency. This agent can eventually compromise the pathways of fatty acid, glycine, and pyruvate metabolism, and then become detectable in patients' leukocytes. Such enzyme levels can also be compared to non-affected parents and siblings.[2] ## Treatments[edit] A number of pharmacological treatments have been suggested or tested for efficacy on Aldh5a1-/- mice and/or humans. Below is a small sampling of the most common treatments though to be therapeutic to patients with SSADH deficiency. Unfortunately, there is very little data to support the benefit of the following treatments since few controlled studies have been conducted in patients. Two hallmarks of SSADH disorder are the increased levels of both GHB and GABA. Potential treatment modalities into biochemical and neurological correction should aim to reduce one or both while not exacerbating the other.[13] ### Vigabatrin[edit] The most common therapeutic agent available for SSADH deficiency is one that reduces the levels of GHB via inhibition of GABA transaminase. Vigabatrin is an irreversible inhibitor of GABA transaminases which leads to decreased levels of GHB and elevation of GABA. Clinical results after use are diverse, ranging from improved ataxia and speech in some patients to worsening of symptoms in others. Lower doses (30–50 mg/kg per day) is associated with fewer side effects and greater improvement of clinical features at high doses of the therapeutic. Although vigabatrin has not been consistently successful in patients with SSADH deficiency, it has shown enhanced survival of Aldh5a1-/- mice at very high doses.[9] ### Sodium valproate[edit] Sodium valproate has been used for the treatment of generalized and partial seizures in humans for both epilepsy and bipolar disorder. Valproate enhances GABA synthesis and release leading to augmented GABAergic functions in some areas of the brain. Successful interventions with valproate have been noted, but no clinical trials have been conducted thus far.[9] However, Valproate is usually contraindicated as it may inhibit residual SSADH enzyme activity.[14] ### GABAB receptor antagonist: CGP-35348[edit] The GABAB antagonist CGP-35348 (3-amino-propyl-(diethoxymethyl) phosphinic acid) has been used in Aldh5a1-/- mice with strong results. It has shown to reduce the frequency of absence seizures, though there have been some cases in which it worsened convulsive seizures.[9] ### GABAB agonist: baclofen[edit] Baclofen (β-p-chlorophenyl-GABA) has some analgesic properties and has been traditionally used for spasticity. Its pharmacological effects primarily take place via presynaptic GABAB receptors in the spinal cord, simultaneously releasing excitatory neurotransmitters onto motor neurons. Because the number and function of GABAB receptors has been shown to progressively diminish in Aldh5a1-/- mice, such a therapy may prove to be useful. However, no data on the efficacy of baclofen on Aldh5a1-/- mice or human patients has been reported.[9] ### Taurine[edit] Taurine is a non-protein sulfur amino acid that is found in high concentrations in human milk. It has been shown to have neuroprotective and neuromodulating properties. While it is an inhibitory neurotransmitter, its ability to cross the blood brain barrier is limited. There is a lot of literature that indicates that taurine acts as antagonist at GABAA and GABAB receptors which may further enhance its ability to treat patients with SSADH deficiency, but further pharmacological studies are yet to be conducted to see if taurine could serve a therapeutic purpose.[9] Taurine has been successfully used in a single case open study in a child with SSADH deficiency; with resolving of brain lesions, and improvement in coordination and gait.[15] ### Ketogenic diet[edit] During prolonged periods of fasting, ketone bodies serve as the primary energy source for the brain. In 2006, Henderson et al. showed that there is a therapeutic effect of maintaining a ketogenic diet – a diet consisting of high fat/low carbohydrate meals – in children with epilepsy. Ketogenic diets have also been shown to have some neuroprotective effects in models of Parkinson's disease and hypoxia as well.[16] In a recent study conducted at the Hospital for Sick Children in Canada in 2007, researchers found that a ketogenic diet prolonged the lifespan of Aldh5a1-/- mice by greater than 300%, along with the normalization of ataxia and some improvement in various seizure types seen in SSADH deficient murine models.[17] These effects were in conjunction with "...a significant restoration of GABAergic synaptic activity and region-specific restoration of GABAA receptor associated chloride channel binding."[17] Ultimately, the data seen in the study indicated that a ketogenic diet may work in its ability to restore GABAergic inhibition. But further studies on murine models need to be conducted, ultimately leading to the possibility of conducting a controlled study on humans afflicted with the disorder. There is speculation that a ketogenic diet may be harmful for humans with SSADH deficiency as it may cause elevated levels of GHB in the bloodstream. ### Other interventions[edit] Other therapeutic interventions[9] include: * ethosuximide and other anticonvulsant drugs * GHB receptor antagonist NCS-382 * GABAA receptor modulators * uridine * acamprosate * dopaminergic agents * dextromethorphan * glutamine * antioxidants * Lamotrigine[18] The GABA(B) receptor antagonist, SGS-742, is currently being tested as a potential therapeutic in an NIH phase II clinical trial (NCT02019667).[19] ## Research[edit] While SSADH deficiency has been studied for nearly 30 years, knowledge of the disorder and its pathophysiology remains unclear. However, the progress that has been made with both murine and human models of the disorder have provided a lot of insights into how the disease manifests itself and what more can be done in terms of therapeutic interventions. Much of the current research into SSADH has been led by a dedicated team of physicians and scientists, including Phillip L. Pearl, MD of the Boston Children's Hospital at Harvard Medical School and K. Michael Gibson, PhD of Washington State University College of Pharmacy. Both have contributed significant efforts to finding appropriate therapies for SSADH deficiency and have specifically spent most of their recent efforts into understanding the efficacy of the ketogenic diet for patients with SSADH deficiency. In addition, a lot of the research that was published in 2007 examined the pathogenesis for the disorder by examining the role of oxidative stress on tissues in various cerebral structures of Aldh5a1-/- mice.[citation needed] Ultimately, the metabolic pathway of SSADH deficiency is known, but how the enzyme deficiency and accumulation of GABA and GHB contribute to the clinical phenotype is not. For the future however, treatment strategies should focus on both decreasing the total production of GHB and increasing the total concentration of GABA and further assessing whether the effects of these changes influences the neurological manifestations seen in patients afflicted with SSADH deficiency. Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).[20] ### Animal models[edit] Several scientists have developed murine models of SSADH (Aldh5a1-/-) by typical gene methodology to create a uniform absence of the SSADH enzyme activity as well as accumulations of GHB and GABA in tissues and physiological fluids. The mice are born at the expected Mendelian frequencies for an autosomal recessive disorder. Most of the models include distinctive neurological phenotypes and exhibit hypotonia, truncal ataxia, generalized tonic-clonic seizures associated with 100% mortality. The mice uniformly die at 3-4 postnatal weeks. While this model is considered to be more severe than the phenotypes seen in humans, currently, it is the most highly regarded, valid, metabolic model to study potential therapeutic interventions for the disorder.[21] Studies have shown that alterations of both the GABAA receptor and the GABAB receptor early in the life of the Aldh5a1-/- mice can increase levels of GHB and enhance GABA release. Besides these effects, it has also been shown that "...a developmental down-regulation of GABAA receptor mediated neurotransmission in Aldh5a1-/- mice likely contributes to the progression of generalized convulsive seizures seen in mutant animals."[9] Other studies have confirmed the relationship between elevated levels of GHB and MAP kinase in mutant animals contribute to profound myelin abnormalities. ## See also[edit] * Inborn errors of metabolism ## References[edit] 1. ^ Chambliss, K. L.; Hinson, D. D.; Trettel, F.; Malaspina, P.; Novelletto, A.; Jakobs, C.; Gibson, K. M. (1998). "Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria)". American Journal of Human Genetics. 63 (2): 399–408. doi:10.1086/301964. PMC 1377305. PMID 9683595. 2. ^ a b c d e Pearl, P. L.; Novotny, E. J.; Acosta, M. T.; Jakobs, C.; Gibson, K. M. (2003). "Succinic semialdehyde dehydrogenase deficiency in children and adults". Annals of Neurology. 54 Suppl 6: S73–80. doi:10.1002/ana.10629. PMID 12891657. S2CID 34085564. 3. ^ Jakobs, C.; Jaeken, J.; Gibson, K. M. (1993). "Inherited disorders of GABA metabolism". Journal of Inherited Metabolic Disease. 16 (4): 704–715. doi:10.1007/BF00711902. PMC 3675887. PMID 8412016. 4. ^ Pearl, P. L.; Gibson, K. M. (Apr 2004). "Clinical aspects of the disorders of GABA metabolism in children". Current Opinion in Neurology. 17 (2): 107–113. doi:10.1097/00019052-200404000-00005. ISSN 1350-7540. PMID 15021235. S2CID 24090637. 5. ^ Gibson, K. M.; Schor, D. S.; Gupta, M.; Guerand, W. S.; Senephansiri, H.; Burlingame, T. G.; Bartels, H.; Hogema, B. M.; et al. (2002). "Focal neurometabolic alterations in mice deficient for succinate semialdehyde dehydrogenase". Journal of Neurochemistry. 81 (1): 71–79. doi:10.1046/j.1471-4159.2002.00784.x. PMID 12067239. S2CID 27277845. 6. ^ Trettel, F.; Malaspina, P.; Jodice, C.; Novelletto, A.; Slaughter, C. A.; Caudle, D. L.; Hinson, D. D.; Chambliss, K. L.; Gibson, K. M. (1997). "Human succinic semialdehyde dehydrogenase. Molecular cloning and chromosomal localization". Advances in Experimental Medicine and Biology. 414: 253–260. doi:10.1007/978-1-4615-5871-2_29. ISSN 0065-2598. PMID 9059628. 7. ^ Nelson, D. L.; Cox M. M. (2004). Lehninger Principles of Biochemistry (4th ed.). W. H. Freeman. ISBN 978-0-7167-4339-2. 8. ^ Buzzi, A.; Wu, Y.; Frantseva, M. V.; Perez Velazquez, J. L.; Cortez, M. A.; Liu, C. C.; Shen, L. Q.; Gibson, K. M.; Snead, O. C. III (May 2006). "Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function". Brain Research. 1090 (1): 15–22. doi:10.1016/j.brainres.2006.02.131. PMID 16647690. S2CID 10173411. 9. ^ a b c d e f g h i j Knerr, I.; Pearl, P. L.; Bottiglieri, T.; Snead, O. C.; Jakobs, C.; Gibson, K. M. (2007). "Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (γ-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies in Aldh5a1-/- mice and characterization of γ-hyrodxybutyric acid pharmacology". Journal of Inherited Metabolic Disease. 30 (3): 279–294. doi:10.1007/s10545-007-0574-2. PMID 17457693. S2CID 20004337. 10. ^ Ren, X.; Mody, I. (2003). "Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABAB receptor activation in mouse frontal cortex and hippocampus". Journal of Biological Chemistry. 278 (43): 42006–42011. doi:10.1074/jbc.M304238200. PMID 12923192. S2CID 53646170. 11. ^ Berton, F.; Brancucci, A.; Beghè, F.; Cammalleri, M.; Demuro, A.; Francesconi, W.; Gessa G. L. (1999). "Gamma-Hydroxybutyrate inhibits excitatory postsynaptic potentials in rat hippocampal slices". European Journal of Pharmacology. 380 (2–3): 109–116. doi:10.1016/S0014-2999(99)00515-4. PMID 10513569. 12. ^ Licht, Daniel MD; Stefanie Mason (2008). "Email Interview". Cite journal requires `\|journal=` (help) 13. ^ Pearl Phillip L.; Shukla Lovy; Theodore William H.; Jakobs Cornelis; Gibson K. Michael (2011). "Epilepsy in Succinic Semialdehyde Dehydrogenase Deficiency, a Disorder of GABA Metabolism". Brain and Development. 33 (9): 796–805. doi:10.1016/j.braindev.2011.04.013. PMC 4385391. PMID 21664777. 14. ^ Shinka, T.; Ohfu, M.; Hirose, S.; Kuhara, T. (Jul 2003). "Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency". Journal of Chromatography B. 792 (1): 99–106. doi:10.1016/S1570-0232(03)00276-9. ISSN 1570-0232. PMID 12829002. 15. ^ Saronwala, A.; Tournay, A.; Gargus, J. J. "Genetic inborn error of metabolism provides a unique window into molecular mechanisms underlying taurine therapy". Taurine in health and Disease. ISBN 978-81-7895-520-9. 16. ^ Henderson, C. B.; Filloux, F. M.; Alder, S. C.; Lyon, J. L.; Caplin, D. A. (2006). "Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis". Journal of Child Neurology. 21 (3): 193–198. doi:10.2310/7010.2006.00044. PMID 16901419. S2CID 4504870. 17. ^ a b Nylen, K.; Velazquez, J. L.; Likhodii, S. S.; Cortez, M. A.; Shen, L.; Leshchenko, Y.; Adeli, K.; Gibson, K. M.; Burnham, W. M.; Snead, O. C. III (2007). "A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype". Experimental Neurology. 210 (2): 449–457. doi:10.1016/j.expneurol.2007.11.015. PMC 2362105. PMID 18199435. 18. ^ Gibson, K. M.; Hoffmann, G. F.; Hodson, A. K.; Bottiglieri, T.; Jakobs, C. (1998). "4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism". Neuropediatrics. 29 (1): 14–22. doi:10.1055/s-2007-973527. PMID 9553943. 19. ^ Parviz, M.; Vogel, K.; Gibson, K.M.; Pearl, P.L. (2014). "Disorders of GABA Metabolism: SSADH and GABA-transaminase Deficiencies". Journal of Pediatric Epilepsy. 3 (4): 217–227. doi:10.3233/PEP-14097. PMC 4256671. PMID 25485164. 20. ^ "Patient registry". 21. ^ Gropman, A. (2003). "Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency". Annals of Neurology. 54: S66–S72. doi:10.1002/ana.10626. PMID 12891656. S2CID 22632304. ## Further reading[edit] * GeneReviews/NCBI/NIH/UW entry on Succinic Semialdehyde Dehydrogenase Deficiency * Ricci L, Frosini M, Gaggelli N, Valensin G, Machetti F, Sgaragli G, Valoti M (2006). "Inhibition of rabbit brain 4-aminobutyrate transaminase by some taurine analogues: A kinetic analysis". Biochemical Pharmacology. 71 (10): 1510–1519. doi:10.1016/j.bcp.2006.02.007. PMID 16540097. * NINDS - National Institute of Neurological Disorders and Stroke ## External links[edit] Classification D * ICD-10: E72.8 * OMIM: 271980 * MeSH: C535803 C535803, C535803 * DiseasesDB: 29825 External resources * Orphanet: 22 * 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]: 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-aminobutyric 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	Succinic semialdehyde dehydrogenase deficiency	c0268631	27,429	wikipedia	https://en.wikipedia.org/wiki/Succinic_semialdehyde_dehydrogenase_deficiency	2021-01-18T18:28:10	{"gard": ["7695"], "mesh": ["C535803"], "umls": ["C0268631"], "orphanet": ["22"], "wikidata": ["Q2823333"]}
Appendix cancer Other namesAppendiceal cancer SpecialtyOncology, general surgery SymptomsBloating, discomfort in lower right abdomen, shortness of breath, loss of appetite [1] Usual onset~50-55 years old [2] TypesColonic-Type Adenocarcinoma, Non-carcinoid Appendix Tumors, Signet-Ring Cell Adenocarcinoma [3] Risk factorsSmoking, family history, Multiple endocrine neoplasia type 1 [4] Diagnostic methodBiopsy, CT Scan, MRI[5] Differential diagnosisAcid reflux, Irritable bowel syndrome, Lactose intolerance, Stomach cancer[6] TreatmentAppendectomy, chemotherapy, radiation therapy [7] PrognosisFive-year survival rate 25-88% (U.S.) [8] Frequency~1,000 cases per year (U.S.)[9] DeathsUnknown Appendix cancer are very rare cancers of the vermiform appendix. Gastrointestinal stromal tumors are rare tumors with malignant potential. Primary lymphomas can occur in the appendix. Breast cancer, colon cancer, and tumors of the female genital tract may metastasize to the appendix.[10] ## Contents * 1 Diagnosis * 1.1 Carcinoid * 1.2 Mucinous neoplasm * 2 Treatment * 3 Epidemiology * 4 Notable cases * 5 References * 6 Further reading * 7 External links ## Diagnosis[edit] Appendix neoplasms by incidence and prognosis. Carcinoid tumors are the most common tumors of the appendix.[11] Other common forms are mucinous adenocarcinoma's, adenocarcinoma-not otherwise specified (NOS), and signet ring cell adenocarcinoma listed from highest to lowest incidence.[12] ### Carcinoid[edit] Histopathology of an appendiceal carcinoid. The arrow points out a cluster of neuroendocrine cells. There are also inflammatory cells consistent with acute appendicitis. A carcinoid is a neuroendocrine tumor (NET) of the intestines. Incidence rates among carcinoids occur at about .15 per 100,000 per year. This subgroup makes up a large amount of neoplasias both malignant and benign. Almost 3 out of 4 of these tumors are associated with the region at the end of the appendix, and tend to be diagnosed in the 4th to 5th decades in life. Both women and Caucasian individuals show a minor prevalence regarding Neuroendocrine tumor diagnosis without an explanation. [13] Prognosis of 5 year survival rates of carcinoids averages between 70-80% for typical cases. Advanced cases for 5 year survival range from 12-28%. ### Mucinous neoplasm[edit] Low-grade appendiceal mucinous neoplasm: Minimal cytological atypia of the epithelial cells.[14] Mucinous cystadenoma is an obsolete term for appendiceal mucinous neoplasm.[15] ## Treatment[edit] Small carcinoids (<2 cm) without features of malignancy may be treated by appendectomy if complete removal is possible. Other carcinoids and adenocarcinomas may require right hemicolectomy. Note: the term "carcinoids" is outdated: these tumors are now more accurately called "neuroendocrine tumors."[16] Pseudomyxoma peritonei treatment includes cytoreductive surgery which includes the removal of visible tumor and affected essential organs within the abdomen and pelvis. The peritoneal cavity is infused with heated chemotherapy known as HIPEC in an attempt to eradicate residual disease. The surgery may or may not be preceded or followed with intravenous chemotherapy or HIPEC.[17] ## Epidemiology[edit] A study of primary malignancies in the United States found a rate of 0.12 cases per 1,000,000 population per year. Carcinoids that were not identified as malignant were not included in this data.[18] Carcinoid is found in roughly 1 in 300-400 appendectomies for acute appendicitis.[19] In a systematic literature review where 4765 appendiceal cancer patients were identified, the incidences of appendiceal cancer were shown to have increased regardless of the type of tumor, age, sex, and stage of appendiceal cancer.[12] Roughly 75% of appendiceal cases listed in the review had some form of metastases occurring. No observed trends have been noticed as to why this increase is occurring. One theory proposed is the increased use of computed tomography imaging in emergency departments since the early 1990s allowing for detection to occur before a surgery may be performed. ## Notable cases[edit] Actress Audrey Hepburn was diagnosed with appendiceal cancer, and died of the disease in 1993.[20] In 2007, ESPN sportscast anchor Stuart Scott was diagnosed with appendiceal cancer, and died of the disease in 2015.[21][22] Serbian musician Vlada Divljan was diagnosed with the cancer in 2012, and died of subsequent complications in 2015.[23] ## References[edit] 1. ^ MedStar Georgetown Cancer Institute 2. ^ Rare Diseases article 3. ^ MedStar Georgetown Cancer Institute 4. ^ Moffitt Cancer Center 5. ^ MedStar Georgetown Cancer Institute 6. ^ MedStar Georgetown Cancer Institute 7. ^ University of Chicago Medicine 8. ^ cancer.net 9. ^ MD Anderson 10. ^ Rosai, Juan (2004) [1953]. "11. Gastrointestinal tract". Rosai and Ackerman's surgical pathology (9th ed.). Mosby. pp. 761–769. 11. ^ Sabiston Principles of Surgery (20th ed.). p. 1308. 12. ^ a b Marmor, Schelomo; Portschy, Pamela R.; Tuttle, Todd M.; Virnig, Beth A. (6 January 2015). "The Rise in Appendiceal Cancer Incidence: 2000–2009". Journal of Gastrointestinal Surgery. 19 (4): 743–750. doi:10.1007/s11605-014-2726-7. S2CID 24206562. 13. ^ Teixeira, Frederico José Ribeiro; Couto Netto, Sérgio Dias do; Akaishi, Eduardo Hiroshi; Utiyama, Edivaldo Massazo; Menegozzo, Carlos Augusto Metidieri; Rocha, Marcelo Cristiano (9 March 2017). "Acute appendicitis, inflammatory appendiceal mass and the risk of a hidden malignant tumor: a systematic review of the literature". World Journal of Emergency Surgery. 12 (1). doi:10.1186/s13017-017-0122-9. 14. ^ Hajjar, Roy; Dubé, Pierre; Mitchell, Andrew; Sidéris, Lucas (2019). "Combined Mucinous and Neuroendocrine Tumours of the Appendix Managed with Surgical Cytoreduction and Oxaliplatin-based Hyperthermic Intraperitoneal Chemotherapy". Cureus. doi:10.7759/cureus.3894. ISSN 2168-8184. 15. ^ Michael Feely, Raul S. Gonzalez. "Appendix - Other tumors - Mucinous neoplasms (LAMN and HAMN)". Topic Completed: 1 October 2017. Revised: 11 December 2019 16. ^ Griniatsos, J; Michail, O (2010). "Appendiceal neuroendocrine tumors: recent insights and clinical implications". World Journal of Gastrointestinal Oncology. 2 (4): 192–196. doi:10.4251/wjgo.v2.i4.192. PMC 2999180. PMID 21160597. 17. ^ M. Townsend, Courtney (2012) [1969]. "51. The appendix". Sabiston (18th ed.). Elsevier. p. 1289. 18. ^ McCusker, M. E.; Coté, T. R.; Clegg, L. X.; Sobin, L. H. (2002). "Primary malignant neoplasms of the appendix". Cancer. 94 (12): 3307–3312. doi:10.1002/cncr.10589. PMID 12115365. S2CID 40814989. 19. ^ Bailey and Love's Short Practice of Surgery (27th ed.). p. 1315. 20. ^ Selim, Jocelyn (Fall 2009), "The Fairest of All", CR, Philadelphia: American Association for Cancer Research, 4 (4), archived from the original on April 19, 2010, retrieved January 22, 2011 21. ^ "Stuart Scott Says, 'F U, Cancer!'". Men's Health. Retrieved 7 January 2015. 22. ^ "Stuart Scott, ESPN's Voice of Exuberance, Dies at 49". New York Times. Retrieved 7 January 2015. 23. ^ "Vlada Divljan poručio: Nisam životno ugrožen, osećam se vrlo dobro" (in Serbian). Blic. 30 January 2015. Retrieved 10 March 2015. ## Further reading[edit] * Hamilton, S.R.; Aaltonen, L.A., eds. (2000). "Ch. 5 Tumours of the Appendix". World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System (PDF). Lyon: International Agency for Research on Cancer. Archived from the original (PDF) on 2014-05-18. Retrieved 2014-05-18. * McGory, Marcia L.; Maggard, Melinda A.; Kang, Hakjung; O'Connell, Jessica B.; et al. (2005). "Malignancies of the appendix: Beyond case series reports". Diseases of the Colon & Rectum. 48 (12): 2264–71. doi:10.1007/s10350-005-0196-4. PMID 16258711. S2CID 23839281. * O'Donnell, M.E.; Carson, J.; Garstin, W.I.H. (2006). "Surgical treatment of malignant carcinoid tumours of the appendix". International Journal of Clinical Practice. 61 (3): 431–7. doi:10.1111/j.1742-1241.2006.00875.x. PMID 16911574. S2CID 24142127 – via Medscape. * Goede, A.C.; Caplin, M.E.; Winslet, M.C. (2003). "Carcinoid tumour of the appendix". British Journal of Surgery. 90 (11): 1317–22. doi:10.1002/bjs.4375. PMID 14598408. S2CID 36569061. * Stinner, B.; Rothmund, M. (2005). "Neuroendocrine tumours (carcinoids) of the appendix". Best Practice & Research: Clinical Gastroenterology. 19 (5): 729–38. doi:10.1016/j.bpg.2005.06.003. PMID 16253897. ## External links[edit] Classification D * ICD-10: C18.1, C78.5 * ICD-9-CM: 153.5 * MeSH: D001063 * Cancer.Net: Appendix Cancer * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor [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-aminobutyric 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	Appendix cancer	c0496779	27,430	wikipedia	https://en.wikipedia.org/wiki/Appendix_cancer	2021-01-18T18:44:15	{"mesh": ["D001063"], "umls": ["C0496779"], "wikidata": ["Q4781026"]}
PSP-progressive non fluent aphasia (PSP-PNFA) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease. Unlike classic PSP (Richardson syndrome) patients present with an isolated speech production problem years before developing other motor features of PSP. ## Epidemiology Prevalence is unknown, and less than ten cases have been reported in the literature. PSP-PNFA probably accounts for less than 5% of all patients with PSP-tau pathology, but may account for a third of patients with PNFA (see this term) with prominent apraxia of speech. ## Clinical description The disease manifests during the sixth decade of life with speech anomalies such as apraxia of speech, agrammatism, and phonemic errors. Cognitive impairment occurs early. The disease is characterized neuropathologically by gliosis with astrocytic plaques, accumulation of tau-immunoreactive neurofibrillary tangles and neuronal loss in specific brain areas, especially in the temporal cortex and superior frontal gyrus. ## Etiology PSP is a 4R tauopathy composed of a preponderance of four-repeat (exon 10 positive) tau isoforms and a characteristic biochemical profile (doublet tau 64 and tau 69). The MAPT H1-clade specific sub-haplotype, H1c, is a risk factor for this disease. The factors that initiate tau-neurodegeneration are unknown. ## Diagnostic methods Diagnosis is based on the clinical picture and neuropsychological evaluation. ## Differential diagnosis Differential diagnosis includes other causes of frontotemporal dementia and in particular corticobasal degeneration, Pick's disease (see these termes) and gTDP-43 positive pathologies ## Management and treatment There is no treatment curing the disease. Patients do not respond to levodopa treatment. Communication strategies can be improved with speech therapy. ## Prognosis Disease duration is typically less than 10 years, and there may be an accelerated phase of deterioration late in the course. Most patients die in their eighth decade. [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-aminobutyric 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	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome	None	27,431	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=240112	2021-01-23T16:55:39	{"icd-10": ["G23.1"], "synonyms": ["PSP-AOS", "PSP-PNFA", "Progressive supranuclear palsy-apraxia of speech syndrome"]}
Malignant pilomatricoma Other namesPilomatrical carcinoma,[1] and Pilomatrix carcinoma SpecialtyOncology, dermatology Malignant pilomatricoma is a cutaneous condition characterized by a locally aggressive tumor composed of hair matrix cells.[2]:671[3] ## See also[edit] * Pilomatricoma * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ Aherne NJ, Fitzpatrick DA, Gibbons D, Armstrong JG (2008). "Pilomatrix carcinoma presenting as an extra axial mass: clinicopathological features". Diagn Pathol. 3: 47. doi:10.1186/1746-1596-3-47. PMC 2633279. PMID 19040752. ## External links[edit] Classification D * ICD-10: C44 (ILDS C44.L45) * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed [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-aminobutyric 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	Malignant pilomatricoma	c0585475	27,432	wikipedia	https://en.wikipedia.org/wiki/Malignant_pilomatricoma	2021-01-18T18:52:44	{"umls": ["C0585475"], "icd-10": ["C44"], "wikidata": ["Q6743513"]}
## Summary ### Clinical characteristics. Generalized arterial calcification of infancy (GACI) is characterized by infantile onset of widespread arterial calcification and/or narrowing of large and medium-sized vessels resulting in cardiovascular findings (which can include heart failure, respiratory distress, edema, cyanosis, hypertension, and/or cardiomegaly). Additional findings can include typical skin and retinal manifestations of pseudoxanthoma elasticum (PXE), periarticular calcifications, development of rickets after infancy, cervical spine fusion, and hearing loss. While mortality in infancy is high, survival into the third and fourth decades has occurred. ### Diagnosis/testing. The diagnosis of GACI is established in a proband with cardiovascular symptoms during infancy associated with widespread arterial calcification on imaging (once secondary causes have been ruled out) and biallelic pathogenic variants in ENPP1 or ABCC6 identified on molecular genetic testing. ### Management. Treatment of manifestations: It remains unclear whether bisphosphonates (most commonly used is etidronate) increase survival. Standard anti-hypertensive therapy is warranted for hypertension. Aspirin therapy is warranted in those with severe coronary stenosis. Intravitreal VEDF inhibitors for choroidal neovascularization, calcitriol and oral phosphate supplement for hypophosphatemic rickets, and hearing aids (as indicated) are all used in the management of this disorder. Surveillance: No specific guidelines address the issue of surveillance. The appropriate intervals for monitoring depend on the clinical findings. Low-dose CT scan every 3-4 months is used for the first year of life to monitor arterial calcification; echocardiography and troponin are used at regular intervals to monitor cardiovascular issues. Annual (or more frequent) retinal exam for PXE retinal findings and regular lab testing to assure mineral homeostasis associated with the development of rickets. Due to risk for nephrocalcinosis with treatment for rickets, urine calcium is monitored to maintain calciuria below 4 mg/kg/d and yearly renal ultrasound is performed. Evaluate for cervical spine fusion prior to elective endotracheal intubation by a lateral cervical spine x-ray. Agents/circumstances to avoid: Although no clinical studies have been conducted, it seems prudent to avoid the use of warfarin if possible. Similarly, the use of burosumab, an anti-FGF23 monoclonal antibody, remains controversial due to theoretic concerns. Evaluation of relatives at risk: It is appropriate to evaluate the younger sibs of a proband with GACI in order to identify as early as possible those who would benefit from treatment. ### Genetic counseling. GACI is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a GACI-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither pathogenic variant. Carrier testing for at-risk relatives, prenatal diagnosis for a pregnancy at increased risk, and preimplantation genetic testing are possible if the pathogenic variants in the family are known. ## Diagnosis No consensus clinical diagnostic criteria for generalized arterial calcification of infancy (GACI) have been published. ### Suggestive Findings GACI should be suspected in individuals with a combination of the following. Clinical findings * Typical cardiovascular findings including heart failure, respiratory distress, edema, cyanosis, hypertension, and/or cardiomegaly * Characteristic imaging findings of widespread arterial calcification and/or narrowing of large and medium-sized vessels * Appearance of typical clinical and histologic skin findings of pseudoxanthoma elasticum (PXE) and/or angioid streaks on fundoscopy * Development of hypophosphatemic rickets after infancy Imaging * Computed tomography (CT) is the preferred imaging modality to assess for calcifications. Multi-detector computed tomography has been reported to detect not only arterial wall calcification but also intimal thickening causing luminal narrowing [Greenberg & Gibson 2005], which appears as a target or bull’s eye with a center of high attenuation (the lumen) surrounded by low attenuation (the thickened intima), which is again surrounded by high attenuation (the calcification of the arterial wall). * Echocardiogram can: * Detect echobrightness of the arteries near the heart, including the coronary and pulmonary arteries, ascending aorta and aortic arch, and large arteries originating from the aortic arch; * Detect the presence of left ventricular hypertrophy and/or pericardial effusion. * Ultrasound examination of the abdomen and head can be used to detect echo-bright vessels. * Plain radiographs can sometimes detect arterial calcifications, but with low sensitivity, and many times arterial calcifications are detected only on reexamination of radiographs after the diagnosis of GACI has been made post mortem [Glatz et al 2006]. * Magnetic resonance imaging and angiography are insensitive to detecting arterial wall calcification, but can detect luminal stenosis [Pao et al 1998], especially when performed with breath-hold and cardiac gating techniques [Tran & Boechat 2006]. * Coronary angiography can be normal despite the presence of extensive arterial wall calcifications, likely because widespread involvement of all coronary arteries results in diffuse narrowing without the focal areas of stenosis detectable by angiography [Hault et al 2008]. Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis. ### Establishing the Diagnosis The diagnosis of GACI is established in a proband with cardiovascular symptoms during infancy associated with widespread arterial calcification on imaging once secondary causes have been ruled out (see Differential Diagnosis), and either biallelic pathogenic variants in ENPP1 or ABCC6 on molecular genetic testing (see Table 1) or, if testing is not diagnostic, histologic findings on arterial biopsy [Morton 1978]. Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (exome sequencing, exome array, 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 findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of GACI has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 A multigene panel that includes some or all of the genes listed in Table 1 and other genes of interest (see Differential Diagnosis) is 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. #### Option 2 Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; 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 Generalized Arterial Calcification of Infancy (GACI) View in own window Gene 1, 2Proportion of GACI Attributed to Pathogenic Variants in Gene 3, 4Proportion of Pathogenic Variants 5 Detectable by Method Sequence analysis 6Gene-targeted deletion/duplication analysis 7 ABCC6~9%88% 812% 8 ENPP1~67%96% 84% 8 Unknown 9~24%NA 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. Nitschke et al [2012] 4\. While a majority of cases of GACI are caused by biallelic pathogenic variants in ENPP1, pathogenic variants in ABCC6 can cause a clinically indistinguishable phenotype. 5\. See Molecular Genetics for information on variants detected in these genes. 6\. 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. 7\. 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. 8\. Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] and personal unpublished data 9\. 22 of 92 individuals with GACI reported by Nitschke et al [2012] did not have biallelic pathogenic variants in either ENPP1 or ABCC6; however, two were heterozygous for an ENPP1 pathogenic variant, and six individuals in five unrelated families were heterozygous for an ABCC6 pathogenic variant. ## Clinical Characteristics ### Clinical Description Generalized arterial calcification of infancy (GACI) can result either from ENPP1 deficiency (ENPP1-GACI), or from ABCC6 deficiency (ABCC6-GACI) associated with biallelic pathogenic variants in ENPP1 or ABCC6 respectively. To date, around 250 individuals have been identified with GACI [Authors, personal observation]. The following description of the phenotypic features associated with this condition is based on these individuals. ### Table 2. GACI: Frequency of Select Features View in own window Feature% of Persons with FeatureComment Arterial calcification88%-95%Most common sites: aorta, pulmonary, coronary, renal Extravascular calcification50%-60%Most common site: hip; sternoclavicular joint commonly involved Pseudoxanthoma elasticum findings~20%Onset of skin findings in childhood; onset of retinal findings more commonly in adulthood Hypophosphatemic rickets / osteomalacia>90% (ENPP1-GACI only)Mediated by FGF23 Nephrocalcinosis50% (ENPP1-GACI mainly)More commonly a complication of rickets/osteomalacia treatment Cervical spine fusion~25% (ENPP1-GACI only)Affects posterior elements Hearing loss50%-75% (ENPP1-GACI only)Variable age of onset #### Presentation A review of published information on 161 individuals with GACI [Chong & Hutchins 2008] identified the following: * A bimodal age of presentation. 48% had early onset (i.e., in utero or within the first week of life) and 52% had late onset (median age three months). * In early-onset GACI, the most common initial findings were fetal distress (46%), heart failure (44%), polyhydramnios (38%), hypertension (33%), respiratory distress (30%), hydrops fetalis (28%), edema (24%), "visceral" effusions (20%), cyanosis (22%), cardiomegaly (17%), and ascites (13%). * In late-onset GACI, the most common presenting findings were respiratory distress (66%), cyanosis (43%), refusal to feed (34%), heart failure (29%), vomiting (24%), irritability (21%), failure to thrive (17%), fever (16%), hypertension (12%), and edema (7%). * No gender predilection. 43% of those with early-onset GACI and 48% of late-onset GACI were female. For individuals with fetal involvement, arterial calcifications are commonly detected at the time of prenatal ultrasound (most commonly in the third trimester, but imaging diagnosis in the second trimester is also possible). For infants with postnatal late-onset GACI, the presenting findings (respiratory distress, cyanosis, refusal to feed, heart failure) lead to imaging studies such as echocardiography and/or CT, and the detection of arterial calcification suggests the diagnosis. #### Arterial Calcification Autopsy studies (reviewed by Chong & Hutchins [2008]) noted that the most commonly calcified arteries in early-onset GACI were hepatic (81%), aorta (80%), pulmonary (67%), coronary (53%), and renal (39%). The most commonly calcified arteries in late-onset GACI were coronary (88%), renal (55%), pulmonary (49%), aorta (36%), adrenal (34%), splenic (31%), pancreatic (28%), and mesenteric (26%). In a cohort of long-term survivors of GACI, the most common sites of arterial calcification were the aorta (14/16), and renal (11/16), mesenteric (11/16), coronary (10/16), iliac (10/16), and pulmonary (10/16) arteries [Ferreira et al 2020]. Although generally spared, the cerebral arteries have been involved in several reported individuals [Glatz et al 2006, van der Sluis et al 2006]; presenting manifestations can thus include seizures [Galletti et al 2011], strokes [Van Dyck et al 1989], or recurrent transient ischemic attacks due to cerebrovascular insufficiency [Thomas et al 1990]. Cystic encephalomalacia is rarely reported [Galletti et al 2011, Nitschke et al 2012]. Peripheral arterial calcifications can present with decreased peripheral pulses; in exceptional cases, gangrene has occurred in the distal extremities [Witzleben 1970, Lussier-Lazaroff & Fletcher 1973], likely caused by a combination of vessel luminal narrowing and left ventricular systolic dysfunction. Pulmonary hypertension refractory to medical therapy is possible [Farquhar et al 2005, Shaireen et al 2013]. Spontaneous resolution of calcification has been reported in several individuals [Sholler et al 1984, Ciana et al 2006]. In those without continued evidence of calcification, arterial stenoses associated with intimal thickening have been observed [Marrott et al 1984, Thiaville et al 1994, Nitschke et al 2012]. Generalized arterial stenoses without prior evidence of arterial calcification are also possible [Nitschke et al 2012, Ferreira et al 2020]. Arterial calcifications or intimal proliferation may also explain the high frequency of recurrent pregnancy loss (≥4 miscarriages per family in 25% vs in 1%-2% in the general population) and hematochezia (15% vs 2% in the general population) [Ferreira et al 2020]. #### Extravascular Calcifications Periarticular calcifications have been noted in eight of 16 surviving individuals with GACI [Ferreira et al 2020]. The most common site of involvement is the hip; other commonly affected joints include the wrist, shoulder, elbow, knee, and sternoclavicular joint [Chong & Hutchins 2008, Ferreira et al 2020]. Other sites of extravascular calcification include the ear lobes [Vera et al 1990, Nitschke et al 2012, Brachet et al 2014], myocardium, and brain parenchyma [Ferreira et al 2020]. #### Pseudoxanthoma Elasticum (PXE) Findings Individuals with GACI can manifest PXE-like changes; these were seen in four of 20 survivors, with onset between ages two and 43 years [Ferreira et al 2020]. Skin findings typically manifest during childhood, while retinal findings (peau d’orange, angioid streaks, choroidal neovascularization with subsequent retinal hemorrhage) commonly do not appear until adulthood. However, typical retinal findings of PXE were reported in a girl age four years with ENPP1 deficiency [Freychet et al 2014], indicating that earlier onset of ocular complications is possible. It has been speculated that children with GACI and findings of PXE were not reported until recently because most died before they developed typical signs of PXE, and many features of PXE (e.g., angioid streaks and skin lesions) are frequently overlooked in the clinical examination of individuals with GACI [Nitschke & Rutsch 2012]. See Pseudoxanthoma Elasticum. #### Hypophosphatemic Rickets / Osteomalacia Individuals with GACI caused by pathogenic variants in ENPP1 who survive the first six months of life (i.e., the critical period) can develop bone deformities, hypophosphatemia, hyperphosphaturia, and elevated alkaline phosphatase, with all the clinical manifestations of autosomal recessive hypophosphatemic rickets type 2 (ARHR2; see Genetically Related Disorders). Conversely, several individuals with ARHR2 have had asymptomatic undiagnosed vascular involvement. Thus, ARHR2 and GACI represent a phenotypic spectrum. The average age for the development of hypophosphatemia was 1.6 years [Ferreira et al 2020]. In a cohort of surviving individuals with ENPP1 deficiency (mean age 11.7 years), 11 of 16 (69%) had already developed rickets, with a Kaplan-Meier estimate that almost all individuals would develop rickets/osteomalacia by age 14 years [Ferreira et al 2020]. This form of rickets/osteomalacia is mediated by FGF23, and can lead to painful calcification of the entheses (insertion sites of ligaments and tendons) in adulthood [Ferreira et al 2020, Kotwal et al 2020]. There are no reports of hypophosphatemia in individuals with GACI caused by pathogenic variants of ABCC6, although one individual in the series of Nitschke et al [2012] had GACI with hypophosphatemic rickets and was heterozygous for an ABCC6 pathogenic variant. #### Nephrocalcinosis Bilateral medullary nephrocalcinosis was seen in five of ten individuals with ENPP1 deficiency who received standard treatment for hypophosphatemic rickets/osteomalacia, while it was not detected in any of seven individuals who were naïve to treatment. Cortical nephrocalcinosis can be seen in the absence of treatment. While medullary nephrocalcinosis is likely a complication from treatment of rickets/osteomalacia (and thus seen only in ENPP1 deficiency), cortical nephrocalcinosis likely represents a consequence of ischemia (and can be seen either with ENPP1 or ABCC6 deficiency) [Ferreira et al, in press]. #### Cervical Spine Fusion Fusion of the posterior elements of the cervical spine (posterior vertebral bodies, articular processes, laminae) was seen in four of 16 individuals with ENPP1 deficiency [Ferreira et al 2020]. #### Hearing Loss In GACI, hearing loss can be conductive, sensorineural, or mixed, and can present as early as in the neonatal period [Brachet et al 2014]. It developed in ten of 16 survivors (63%) with ENPP1-GACI at a median age of 3.7 years, with a Kaplan-Meier estimate of developing hearing loss of 20% by age two years, 50% by four years, and 75% over a lifetime [Ferreira et al 2020]. Sensorineural hearing loss is presumably due to calcifications of the arteries supplying the inner ear [Lorenz-Depiereux et al 2010], while conductive hearing loss is due to stapedovestibular ankylosis [Nitschke et al 2012, Freychet et al 2014]. #### Development Although cognitive development has not been formally assessed in a cohort of individuals with GACI, the majority appear to have normal development. However, the authors are aware of a few individuals with severe global developmental delay in the setting of prior strokes or encephalomalacia. In individuals with periarticular calcifications, motor milestones can be delayed due to pain around the affected joints [Authors, personal observation]. #### Variability In one family in which the father and son were homozygous for the same ENPP1 pathogenic variant, the father presented with hypophosphatemia and rickets and later developed an aortic root dissection at age 28 years, while the son had GACI and hypophosphatemia [Lorenz-Depiereux et al 2010]. Sibs harboring the same pathogenic variants have been reported to have markedly different clinical courses [Ferreira et al 2020]. #### Prognosis In a series of 55 children, the mortality rate at age six months was 30 of 55 (55%) despite intensive therapy [Rutsch et al 2008]. Only one individual died after age six months; thus, the mortality rate was markedly decreased in those who survived the first few months of life. Causes of death were myocardial infarction, congestive heart failure, persistent arterial hypertension, or multiorgan failure. Long-term survivors, with several in their 20s, include twins age 21 years [Rutsch et al 2008], a woman age 22 years [Marrott et al 1984], individuals age 25 and 26 years at last follow up [Ferreira et al 2020], and a woman age 37 years [Authors, personal observation]. The oldest individual with ENPP1 deficiency reported to date is a woman age 62 years [Saito et al 2011]. Bisphosphonate treatment was associated with survival beyond infancy in 11 of 17 individuals, while 18 of 26 individuals not treated with bisphosphonates died in infancy [Rutsch et al 2008] (see Treatment of Manifestations). It remains unclear whether bisphosphonate use improves survival [Authors, personal observation]. ### Genotype-Phenotype Correlations Marked phenotypic heterogeneity, even among surviving sibs with identical genotypes, argues against a genotype-phenotype correlation in GACI [Ferreira et al 2020]. Otero et al [2013] (full text; see Supporting Information, Appendix) reported an affected individual with biallelic ENPP1 pathogenic variants and a heterozygous pathogenic variant in ABCC6, which theoretically could have contributed to the severity of GACI. The individual’s healthy mother and brother both were doubly heterozygous for an ENPP1 pathogenic variant and the ABCC6 pathogenic variant; thus, it appears that the presence of one heterozygous ENPP1 pathogenic variant and one ABCC6 pathogenic variant does not cause GACI. ### Nomenclature In the past, generalized arterial calcification of infancy (GACI) has been variously referred to as idiopathic obliterative arteriopathy, infantile calcifying arteriopathy, occlusive infantile arteriopathy, medial coronary sclerosis of infancy, diffuse arterial calcifying elastopathy of infancy, and arteriopathia calcificans infantum. ### Prevalence GACI shows no ethnic or racial predilection, and has been described throughout the world. The disease frequency is estimated at one in 200,000 pregnancies, and the carrier frequency at one in 223 individuals [Ferreira et al 2020]. ## Differential Diagnosis ### Disorders with Vascular Calcification Singleton-Merten syndrome (OMIM 182250 and 616298) is an autosomal dominant disorder caused by pathogenic variants in IFIH1 or DDX58. * Severe aortic calcification, dental anomalies (delayed eruption and early loss of permanent teeth, alveolar bone erosion), osteopenia, and acroosteolysis are salient features of the disease [Feigenbaum et al 2013]. * Unlike generalized arterial calcification of infancy (GACI), aortic calcification in Singleton-Merten syndrome starts later in life (age range at diagnosis: 6-39 years). Metastatic calcification due to hypervitaminosis D, hyperparathyroidism, or end-stage renal disease * Diffuse arterial calcification tends to affect the media of the vessels, and extensive extravascular calcification involves the renal tubules, bronchial walls, and basal mucosa and muscularis mucosae of the stomach. * Compared with GACI, metastatic calcification exhibits a different distribution of extravascular calcification, and the microscopic vascular changes occur in the media with little intimal proliferation. Twin-twin transfusion syndrome (TTTS) and twin reversed arterial perfusion (TRAP) sequence * Increased echogenicity due to calcification has been described in the wall of the pulmonary trunk, proximal branch pulmonary arteries [Saxena & Soni 2003, Bassil Eter et al 2009], and ascending aorta in the recipient twin of TTTS [Saxena & Soni 2003]. Pulmonary artery calcification has also been described in pump twins in TRAP sequence [Royston & Geoghegan 1983, Popek et al 1993]. Since this always occurs in the volume-overloaded fetus (recipient twin in TTTS and pump twin in TRAP sequence), it presumably results from increased cardiac output in utero [Popek et al 1993]. * Histologically, calcium is deposited primarily in the media [Popek et al 1993], whereas in GACI it is deposited along the internal elastic lamina. Additionally, in TTTS and TRAP sequence calcification does not occur elsewhere in the body [Saxena & Soni 2003]. ### Disorders with Occlusive Arteriopathy Pediatric fibromuscular dysplasia (FMD). This non-inflammatory arteriopathy can be unifocal or multifocal, is associated with hypertension, and commonly affects the renal and mesenteric arteries and the abdominal aorta [Green et al 2016, Louis et al 2018], all common sites of stenosis in GACI. In fact, a child with a clinical diagnosis of pediatric FMD was eventually found to have ENPP1 deficiency [Ferreira et al 2020]; thus, other individuals with pediatric FMD could benefit from molecular genetic testing of ENPP1. Grange syndrome (OMIM 602531) is an autosomal recessive disorder caused by pathogenic variants in YY1AP1. This extremely rare syndrome is characterized by diffuse vascular stenoses with intimal thickening [Weymann et al 2001] in a distribution pattern resembling fibromuscular dysplasia, brachysyndactyly, and osteopenia with increased bone fragility [Grange et al 1998, Volonghi et al 2012]. Chronic arsenic poisoning. Diffuse thickening of the intima of medium- and small-sized arteries (without calcification) has been described in chronic arsenic poisoning, leading to death by myocardial infarction in children as young as age two years [Rosenberg 1974]. ## Management No clinical practice guidelines for GACI have been published. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with generalized arterial calcification of infancy (GACI), 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 GACI View in own window System/ConcernEvaluationComment CardiovascularReferral to a pediatric cardiologistIncl: * ECG & echocardiogram * Assessment of blood pressure 1 & peripheral pulses CT of chest, abdomen, & pelvisTo evaluate extent & distribution of vascular calcification Serum levels of cardiac-specific troponin T or troponin IAssess for evidence of myocardial ischemia. SkeletalSkeletal radiographsAs needed to assess for periarticular calcification or cervical spine fusion Mineral metabolismMetabolic workup incl: * Serum creatinine * Serum phosphorus * Urine phosphorus * Urine creatinine * Alkaline phosphatase * Serum calcium * Serum PTH To evaluate for evidence of hypophosphatemic rickets by measuring: * Tubular reabsorption of phosphate * Ratio of renal tubular maximum reabsorption rate of phosphate to GFR Hearing lossAudiology assessmentEvaluate for conductive or sensorineural hearing loss. Genetic counselingBy genetics professionals 2To inform patients & families re nature, MOI, & implications of GACI in order to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support; * Need for home nursing referral. GFR = glomerular filtration rate; MOI = mode of inheritance; PTH = parathyroid hormone 1\. Referral to a pediatric nephrologist is indicated in the setting of refractory hypertension 2\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations ### Table 5. Treatment of Manifestations in Individuals with GACI View in own window Manifestation/ ConcernTreatmentConsiderations/Other Arterial calcificationBisphosphonate therapy 1 using one of the following: * Etidronate (20 mg/kg/d PO) * Pamidronate (0.25 mg/kg on day 1, then 0.5 mg/kg/d on days 2 & 3 for 1st cycle, then 0.5 mg/kg/d x3 days IV per cycle; cycles rptd every 2 mos) * Risedronate (1mg/kg/wk PO) * After initiation of therapy, vascular calcifications have been reported to disappear as early as 2.5 wks (as assessed by radiographs) and as late as 2 yrs [van der Sluis et al 2006, Meradji et al 1978] * Vascular calcifications do not reappear after discontinuation of treatment even after 10 yrs [van der Sluis et al 2006] * Prolonged etidronate use in persons w/GACI has been assoc w/severe skeletal toxicity, incl radiographic findings resembling hypophosphatasia 2 or osteopetrosis 3 [Otero et al 2013]. Thus, some authors recommend close monitoring for resolution of arterial calcifications during treatment so that use of bisphosphonates can be discontinued as soon as possible [Otero et al 2013]. HypertensionStandard therapySince hypertension in GACI is likely caused by renal artery stenosis, it may be beneficial to use ACE inhibitors or angiotensin II type 1 receptor blockers. Severe coronary stenosisAspirin therapy if coronary stenosis is present PXE retinal changesIntravitreal VEGF inhibitors for choroidal neovascularization Hypophosphatemic ricketsCalcitriol (15-25 ng/kg/d) & oral phosphate supplement (25-50 mg/kg/d in 3-5 daily doses)Doses adjusted based on alkaline phosphatase, PTH, & calciuria levels Orthopedics eval if bone deformities developSurgical interventions may be necessary. Hearing lossHearing aids as indicated ACE = angiotensin-converting enzyme; PTH = parathyroid hormone; VEGF = vascular endothelial growth factor 1\. It remains unclear whether bisphosphonates (etidronate in particular) are associated with improved survival. 2\. Radiographic findings resembling hypophosphatasia include pan craniosynostosis, bowing of long bones, metaphyseal cupping and fraying, and radiolucent tongues. 3\. Radiographic findings resembling osteopetrosis include osteosclerosis and femoral Erlenmeyer flask deformity. ### Surveillance No specific guidelines address the issue of surveillance. The appropriate intervals for monitoring depend on clinical findings and need to be more frequent in those with a more severe presentation. ### Table 6. Recommended Surveillance for Individuals with GACI View in own window System/ConcernEvaluationFrequency Arterial calcificationLow-dose CT scanEvery 3-4 mos in 1st yr of life Cardiovascular issues * Echocardiography * Troponin At regular intervals depending on degree of severity (as per cardiologist) PXE retinal findingsExam by retinal specialistAnnually, or more frequently as per specialist Mineral homeostasisSerum phosphate, creatinine, alkaline phosphatase, calcium, PTH; urine phosphate & creatinineAnnually before development of rickets; quarterly while on rickets treatment; after 2 wks of dosage modification Hypercalciuria assoc w/treatment of hypophosphatemic ricketsUrine calciumMaintain calciuria <4 mg/kg/d. Nephrocalcinosis assoc w/treatment of hypophosphatemic ricketsRenal ultrasoundAnnually Cervical spine fusionLateral cervical spine radiographPrior to elective endotracheal intubation / surgery PTH = parathyroid hormone ### Agents/Circumstances to Avoid Although no clinical studies have been conducted, it seems prudent to avoid the use of warfarin if possible. The matrix Gla protein (MGP), a potent anti-mineralization factor, needs to be activated by a vitamin K-dependent enzyme, and warfarin interferes with the vitamin K cycle. Warfarin has also been shown to accelerate ectopic mineralization in Abcc6 knockout mice [Li et al 2013]. One question is whether burosumab, an anti-FGF23 monoclonal antibody approved by the FDA for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia, could also treat the hypophosphatemic rickets of ENPP1 deficiency. This approach, however, remains controversial due to theoretic concerns that it could worsen ectopic calcification by lowering pyrophosphate concentrations. However, one individual with ENPP1-related rickets, who was initially thought to have X-linked hypophosphatemia, received burosumab for months without developing any vascular calcification [Boyce et al 2020]. ### Evaluation of Relatives at Risk It is appropriate to evaluate the younger sibs of a proband with GACI in order to identify as early as possible those who would benefit from institution of treatment and preventive measures. Evaluations can include: * Molecular genetic testing if the GACI-causing pathogenic variants in the family are known; * Imaging studies if the pathogenic variants in the family are not known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Enzyme replacement therapy. The administration of a recombinant form of ENPP1 prevents calcification and mortality [Albright et al 2015], improves hypertension and cardiac function [Khan et al 2018], and prevents intimal proliferation [Nitschke et al 2018] in mouse models of ENPP1 deficiency. It also prevented the osteomalacia, increased bone density, and markedly improved bone strength in mutant mice, while preventing the development of nephrocalcinosis [Ferreira et al, in press]. Magnesium. In a mouse model of ENPP1 deficiency, increased dietary magnesium during pregnancy and continued postnatally was shown to prevent ectopic mineralization, likely by competing with calcium for phosphate binding [Kingman et al 2017]. One infant who did not initially respond to etidronate administration eventually showed improvement with a combination of etidronate, magnesium, and calcium carbonate [Dursun et al 2019]; however, it is impossible to know whether this child would have shown spontaneous regression of calcification even in the absence of magnesium administration. Sodium thiosulfate. A combination of etidronate and sodium thiosulfate was administered in a child with GACI, with no improvement of calcification and demise after one month [Hollwey et al 2019]. The administration of intravenous sodium thiosulfate led to improvement of calcific stenosis of celiac and mesenteric arteries in a child with a complex genotype [Omarjee et al 2020]. Thus, the use of sodium thiosulfate has not been associated with consistent improvement, and its benefits remain unclear. Cardiac transplantation. One individual who received a heart transplant did well, with no recurrence of disease over two years of follow-up post transplant [Giovannoni et al 2014]. Another individual continues to do well several years post transplant [Authors, personal observation]. 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-aminobutyric 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	Generalized Arterial Calcification of Infancy	c1859727	27,433	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK253403/	2021-01-18T21:23:29	{"mesh": ["C537440"], "synonyms": ["GACI", "Idiopathic Infantile Arterial Calcification (IIAC)"]}
## Clinical Features Gurrieri et al. (1992) described 2 brothers with an orofaciodigital syndrome which did not seem to fit into any of the 7 previously described types (Toriello, 1988; Munke et al., 1990). The 2 brothers were mildly mentally retarded. Both showed a small notch in the upper lip. The older brother had a highly arched palate with bifid tongue and a supernumerary lower canine bilaterally. The younger brother had a lobulated, hamartomatous tongue, and multiple frenula. The specific retinal abnormalities in the brothers reported by Gurrieri et al. (1992) were retinochoroidal lacunae of colobomatous type, similar to those seen in Aicardi syndrome (304050). Nevin et al. (1994) reported a female case of OFDS with component manifestations typical of type II (252100), namely median cleft of the upper lip, multiple oral frenula, and lobulated or hamartomatous tongue, associated with retinal abnormalities as distinguishing feature. They referred to the disorder as OFDS type IX. Sigaudy et al. (1996) reported the case of a 6-month-old girl with OFD anomalies associated with areas of chorioretinal atrophy. The parents were nonconsanguineous; the maternal and paternal ages at her birth were 33 and 41 years, respectively. She showed multiple hamartomas of the oral cavity, lobulated tongue, alveolar frenula, and a small median cleft of the upper lip. The great toes were broad. Psychomotor development was delayed. CT scan showed atrophy of the frontal and parietal lobes and NMR showed a hypothalamic hamartoma. Nagai et al. (1998) described an affected female with features consistent with OFDS IX who was also noted to have Dandy-Walker malformation and retrobulbar cysts. Erickson and Bodensteiner (2007) described 2 pairs of sibs (2 females, and 1 female and 1 male) from the Navajo population with orofaciodigital syndrome. In addition to retinal colobomas and mild digital anomalies, the sibs also had severe microcephaly, mental retardation, and short stature. Erickson and Bodensteiner (2007) suggested that this condition is a variant of OFDS IX caused by a unique allele of increased frequency in the Navajo population. Inheritance Based on their report of affected males, Gurrieri et al. (1992) recognized that inheritance of OFDS IX might be either autosomal or X-linked recessive. Nevin et al. (1994) suggested that OFDS IX is inherited in an autosomal recessive manner since their reported patient was female. Erickson and Bodensteiner (2007) also supported autosomal recessive inheritance based on the finding of the disorder in sibs from the Navajo population, which has undergone several genetic 'bottlenecks.' Molecular Genetics For discussion of a possible relationship between variation in the TBC1D32 gene and orofaciodigital syndrome IX, see 615867.0001. For discussion of a possible relationship between variation in the SCLT1 gene and orofaciodigital syndrome IX, see 611399.0001. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Eyes \- Hypertelorism \- Telecanthus \- Strabismus \- Duane syndrome (rare) \- Retinal coloboma Nose \- Broad nasal tip \- Bifid nasal tip Mouth \- Median cleft lip \- Tongue lobulation \- Tongue hamartoma \- Oral frenula \- High-arched palate \- Cleft palate \- Cleft alveolar ridge Teeth \- Absent teeth RESPIRATORY Larynx \- Hypoplastic epiglottis Lung \- Recurrent aspiration pneumonia GENITOURINARY External Genitalia (Female) \- Absent clitoris (rare) SKELETAL Limbs \- Short tibiae Hands \- Polydactyly \- Syndactyly \- Brachyphalangia \- Carpal shortening \- Camptodactyly Feet \- Bifid halluces \- Forked metatarsal \- Tarsal shortening \- Syndactyly SKIN, NAILS, & HAIR Skin \- Milia NEUROLOGIC Central Nervous System \- Developmental delay \- Brain atrophy \- Migrational abnormalities MISCELLANEOUS \- Mild manifestations in carrier females (cleft lip, cleft tongue) ▲ 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-aminobutyric 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	OROFACIODIGITAL SYNDROME IX	c0796102	27,434	omim	https://www.omim.org/entry/258865	2019-09-22T16:24:06	{"doid": ["0060382"], "mesh": ["C557818"], "omim": ["258865"], "orphanet": ["141007"], "synonyms": ["Alternative titles", "OFDS IX", "ORAL-FACIAL-DIGITAL SYNDROME, TYPE IX", "ORAL-FACIAL-DIGITAL SYNDROME WITH RETINAL ABNORMALITIES", "OROFACIODIGITAL SYNDROME WITH RETINAL ABNORMALITIES"]}
A rare vulvar carcinoma characterized by a malignant epithelial neoplasm of glandular origin and/or with glandular characteristics arising in the vulva, including adenocarcinoma of mammary gland type, sweat gland type, and intestinal type, as well as adenocarcinomas of the Bartholin glands and Paget disease of the vulva. Depending on the type of tumor and disease stage, patients may present with a solitary vulvar mass, bleeding, or (in the case of Paget disease) a pruritic, erythematous, eczematous lesion. [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-aminobutyric 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	Vulvar adenocarcinoma	c1336975	27,435	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=494454	2021-01-23T18:26:22	{"synonyms": ["Adenocarcinoma of the vulva"]}
Phenformin is a biguanide that was formerly used as an oral hypoglycemic agent in maturity-onset diabetes. It is rapidly absorbed and metabolized exclusively by p-hydroxylation to a single metabolite, 4-hydroxyphenformin. The unchanged drug and its metabolite are cleared from the blood virtually exclusively by the kidneys. About two-thirds of an oral dose is excreted in the urine within 8 hours as the unchanged drug plus its metabolite. Shah et al. (1985) found that about 9% of a London population had a defect in p-hydroxylation of phenformin, inherited as an autosomal recessive. Phenformin was withdrawn from the market because it was often associated with lactic acidosis which could be fatal. Persons with the metabolic defect may have been more susceptible to this complication. Shah et al. (1985) reviewed the evidence that the same genetic defect may be responsible for both impaired debrisoquine oxidation (124030) and impaired phenformin 4-hydroxylation. Inheritance \- Autosomal recessive Lab \- Phenformin p-hydroxylation defect Metabolic \- Lactic acidosis ▲ 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-aminobutyric 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	PHENFORMIN 4-HYDROXYLATION	None	27,436	omim	https://www.omim.org/entry/261590	2019-09-22T16:23:32	{"omim": ["261590"]}
Crohn's disease is a type of inflammatory bowel disease (IBD), the general name for conditions that cause inflammation in the gastrointestinal (GI) tract. Common signs and symptoms include abdominal pain and cramping, diarrhea, and weight loss. Other general symptoms include feeling tired, nausea and loss of appetite, fever, and anemia. Complications of Crohn's disease may include intestinal blockage, fistulas, anal fissures, ulcers, malnutrition, and inflammation in other areas of the body. Crohn's disease can occur in people of all age groups but is most often diagnosed in young adults. The exact cause is unknown, but is thought to be due from a combination of certain genetic variations, changes in the immune system, and the presence of bacteria in the digestive tract. Many of the major genes related to Crohn disease, including NOD2, ATG16L1, IL23R, and IRGM, are involved in immune system function. The disease is not inherited but it appears to run in some families because in about 15% of the cases the disease is present in more than one relative. Treatment is aimed at relieving symptoms and reducing inflammation, and may include diet and medication, but some people require surgery. Surgery often involves removal of the diseased segment of bowel (resection), the two ends of healthy bowel are then joined together (anastomosis). In about 30% of people who have surgery for Crohn’s disease symptoms may come back within three years and up to 60% will have recurrence within ten years. [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-aminobutyric 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	Pediatric Crohn's disease	c2931133	27,437	gard	https://rarediseases.info.nih.gov/diseases/9856/pediatric-crohns-disease	2021-01-18T17:58:24	{"mesh": ["C536215"], "umls": ["C2931133"], "synonyms": ["Pediatric onset Crohn's disease", "Crohn's disease, pediatric"]}
## Clinical Features Ohnishi et al. (1989) described 2 unrelated Japanese patients, each with consanguineous parents, who had a motor and sensory neuropathy of the hypertrophic type with excessive myelin outfolding in myelinated fibers, as well as segmental demyelination and remyelination. One patient was a 15-year-old boy who complained of muscle weakness in both the upper and lower limbs and hypesthesia in the distal part of the lower limbs. His parents were first cousins. Insidious weakness of the legs and foot deformity began at 7 years of age. By 12 years of age he had increasing difficulty in manipulating the tiny parts of airplane models. The second patient was a 49-year-old Japanese woman who complained of weakness of the hands and disturbance of gait. Her parents were second cousins. Thenar muscle wasting had first been noted when she was in her 20s; weakness of the hands was first noted at 47 years of age. Schenone et al. (1991) studied 3 cases of recessively inherited hereditary motor and sensory neuropathy (HMSN) clearly different from other reported forms and closely resembling that in the 2 cases reported by Ohnishi et al. (1989). Focal and irregularly outfolded myelin was observed particularly in longitudinal sections of teased fibers by electron microscopy. Barbieri et al. (1994) described brother and sister, aged 35 and 37 years, respectively, in whom this disorder first became manifest at about age 10 years. Their parents were first cousins. See CMT4B1 (601382) and CMT4B2 (604563) for autosomal recessive disorders with a similar phenotype. [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-aminobutyric 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	NEUROPATHY, HEREDITARY MOTOR AND SENSORY, WITH EXCESSIVE MYELIN FOLDING COMPLEX, AUTOSOMAL RECESSIVE	c1850385	27,438	omim	https://www.omim.org/entry/256855	2019-09-22T16:24:20	{"mesh": ["C564947"], "omim": ["256855"], "synonyms": ["Alternative titles", "HMSN WITH EXCESSIVE MYELIN OUTFOLDING, AUTOSOMAL RECESSIVE", "CHARCOT-MARIE-TOOTH DISEASE WITH EXCESSIVE MYELIN FOLDING, AUTOSOMAL RECESSIVE"]}
Female genital mutilation in the United Kingdom is the ritual removal of some or all of the external female genitalia of women and girls living in the UK. According to Equality Now and City University London, an estimated 103,000 women and girls aged 15–49 were thought to be living with female genital mutilation (FGM) in England and Wales as of 2011.[n 1][2] FGM was outlawed in the UK by the Prohibition of Female Circumcision Act 1985, which made it an offence to perform FGM on children or adults.[3] The Female Genital Mutilation Act 2003 and the Prohibition of Female Genital Mutilation (Scotland) Act 2005 made it an offence to arrange FGM outside the country for British citizens or permanent residents, whether or not it is lawful in the country to which the girl is taken.[n 2][7][8] The first prosecutions for FGM took place in 2015 against a doctor for performing FGM and another man for aiding and abetting; both were found not guilty.[9] The first successful conviction was secured in February 2019. ## Contents * 1 History * 1.1 Local authority areas with highest FGM prevalence April 2015-March 2016 * 2 2000s–2010s * 2.1 Overview * 2.2 First prosecutions * 2.3 Delays in investigations * 2.4 National Curriculum changes * 2.5 Family Court * 3 See also * 4 Notes * 5 References ## History[edit] Efua Dorkenoo (1949–2014) The diaspora communities in the UK thought to be at high risk of FGM include those from Eritrea, Ethiopia, Nigeria, Somalia and Sudan. The largest is the Somalia diaspora, with nearly 42,000 women and girls in the UK believed to be affected as of 2011.[10][11] FGM has a high prevalence in several of these countries, including the most severe form, FGM Type III. Girls from communities in which FGM is commonplace are often taken to their countries of origin during the school summer holidays in order to undergo the procedure. This period of the year is known as the "cutting season".[12][13] In 1983 Efua Dorkenoo, author of Cutting the Rose (1994), founded the Foundation for Women's Health, Research and Development (FORWARD), a British NGO that supports women who have experienced FGM and tries to eliminate the practice.[14][15][16] Dorkenoo received an OBE in 1994 for her work.[17] Two years after she founded FORWARD, the Prohibition of Female Circumcision Act 1985 made it an offence in the UK to perform FGM on children or adults.[11] In 1993 a councillor at the London Borough of Brent proposed a motion that FGM should be legalised and made available on the National Health Service.[18] According to Ann John, a councillor who opposed the motion, the motion called for it to be classed as a "right specifically for African families who want to carry on their tradition whilst living in this country". John said she suffered verbal attacks, including threats that she herself would be mutilated; interviewed in 2014, she said she believed her treatment had deterred people for years from opposing FGM in case they were accused of racism. The motion was defeated.[19] In 1997 specialist midwife Comfort Momoh set up the African Well Women's Clinic in London to help women affected by FGM.[20] Momoh was awarded an MBE in 2008 for services to women's healthcare.[21] ### Local authority areas with highest FGM prevalence April 2015-March 2016[edit] Per the City University study:[22] Borough Newly recorded Borough Total attendances Birmingham 435 Brent 1250 Bristol 385 Bristol 705 Brent 325 Birmingham 520 Manchester 310 Harrow 460 Southwark 290 Ealing 355 Enfield 215 Manchester 350 Ealing 175 Southwark 320 Lambeth 175 Enfield 265 Sheffield 165 Lambeth 200 Camden 140 Sheffield 185 Greenwich 130 Camden 175 Leeds 125 Hillingdon 175 ## 2000s–2010s[edit] The number of women aged 15-49 resident in England and Wales born in FGM practising regions having migrated to the UK was 182000 in 2001 and increased to 283000 in 2011.[23] The number of women born in the Horn of Africa, where FGM is nearly universal and the most severe types of FGM, infubulation, is commonly practised, increased from 22000 in 2001 to 56000 in 2011, an increase of 34000.[23] The number of women of all ages having undergone FGM rituals was estimated to be 137000 in 2011.[23] The number of women of ages 15-49 having undergone FGM rituals was estimated to 66000 in 2001 and there was an increase to 103000 in 2011.[23] ### Overview[edit] Prevalence among the 15–49 age group in the 29 countries in which FGM is thought to be most prevalent (UNICEF, November 2014)[24] In 2007 the FGM National Clinical Group was created to train health professionals in how to deal with the practice.[25] Concern about FGM in the UK increased significantly in the mid-2010s. In November 2013 a coalition of Royal Colleges, trade unions and Equality Now produced a report, "Tackling FGM in the UK."[26] Britain's first specialist clinic for child victims of FGM opened in London in 2014.[27] Since April that year all NHS hospitals have recorded whether a patient has undergone FGM or has a family history of it, and all acute hospitals are obliged to report this data to the Department of Health on a monthly basis.[28] According to the first official figures published on the numbers of FGM cases seen by hospitals in England, over 1,700 women and girls who have undergone FGM were treated by the NHS between April and October 2014.[29] A 17-year-old student from Bristol, Fahma Mohamed, created with support from The Guardian an online petition on 6 February 2014 with Change.org, on the International Day of Zero Tolerance to Female Genital Mutilation.[30] The petition asked Michael Gove, then education secretary, to write to primary and secondary schools, encouraging them to be alert to FGM. The petition was one of the fastest growing UK petitions on Change.org, with 230,000 supporters. Gove met Mohamed and members of the youth group Integrate Bristol, who have played a key role in raising awareness of FGM. He sent a letter to all headteachers in England informing them of new guidelines on children's safety, including guidance on FGM. This marked the first time the guidelines included mention of FGM.[31][32] The city with the highest prevalence of FGM in 2015 was London, at a rate of 28.2 per 1000 women aged 15-49, by far the highest.[33] The borough with the highest rate was Southwark, at 57.5 per 1000 women, while mainly rural areas of the UK had prevalence rate below 1 per 1000.[33] In 2015 police acquired the UK’s first FGM protection order.[34] This was acquired under a new law, the Serious Crime Act 2015, which allows such protection orders.[34] It also allows the combating of FGM by judges remanding people in custody, ordering mandatory medical checks, and instructing girls believed to be at risk of FGM to live at a certain address so authorities can see whether they have been mutilated.[34] On 12 September 2016 Nottingham became the first City of Zero Tolerance towards FGM.[35] In the April 2016 - March 2017 period the NHS attended 9 179 cases.[36][37] Only 26% of the victims reported the country in which the crime took place, but of those who did 1 229 cases took place in Africa and 57 were perpetrated in the UK.[36] No prosecutions were brought. ### First prosecutions[edit] As of 2015 there have been no convictions in the UK for performing or arranging FGM. By contrast, in France over 100 parents and two practitioners had been prosecuted by 2014 in over 40 criminal cases.[38][39] The United Nations Committee on the Elimination of Discrimination against Women expressed concern in July 2013 that there had been no FGM-related convictions in the UK. The committee asked the government to "ensure the full implementation of its legislation on FGM."[40] The first charges were announced in March 2014 against Dhanuson Dharmasena, a doctor, for having performed FGM on a woman from Somalia who had just given birth at the Whittington Hospital in north London. Another man was charged with aiding and abetting in the same case.[41] During the trial in January 2015 Dharmasena said he had performed a single figure-of-eight stitch to stem bleeding following the birth. Both men were found not guilty on 4 February 2015.[9] A doctor in Birmingham, Ali Mao-Aweys, was struck off the medical register in 2014 after discussing how to arrange FGM with an undercover journalist in 2012.[42] The first successful conviction was that of a Ugandan mother, who was found guilty at the Central Criminal Court of England and Wales on 1 February 2019.[43] On 8 March 2019, she was sentenced to 11 years in prison.[44] ### Delays in investigations[edit] In September 2017, it was reported that some children had spent months on protection plans or in foster care whilst they waited to be examined to determine whether they had been victims of FGM, with those examinations demonstrating that the suspicions were false. Research by University College Hospital in 2016 found the waiting time to be almost two months, with some girls having to wait more than a year. The hospital confirmed that this remained an issue as of September 2017[update]. Anti-FGM charity Forward argued that the handling of cases was leaving some girls and their families traumatised.[45] ### National Curriculum changes[edit] In February 2019, the Observer reported that the UK government was to change the National Curriculum to include relationship education for primary age pupils and health education for pupils of all ages. Secondary aged pupils would be taught about grooming, forced marriage and domestic abuse. It requires that secondary schools to address the physical and emotional damage caused by FGM, the support available[clarification needed] and ensure that pupils know FGM is illegal.[46] [47] ### Family Court[edit] The Children Act 1989 (Amendment) (Female Genital Mutilation) Act 2019 meant that all FGM cases in England and Wales go through family courts. ## See also[edit] * Prevalence of female genital mutilation by country * Daughters of Eve ## Notes[edit] 1. ^ Alison Macfarlane and Efua Dorkenoo: "An estimated 103,000 women aged 15–49 with FGM born in countries in which it is practised were living in England and Wales in 2011, compared with the estimated 66,000 in 2001. In addition there were an estimated 24,000 women aged 50 and over with FGM born in FGM practising countries and nearly 10,000 girls aged 0-14 born in FGM practising countries who have undergone or are likely to undergo FGM. Combining the figures for the three age groups, an estimated 137,000 women and girls with FGM, born in countries where FGM is practised, were permanently resident in England and Wales in 2011.[1] 2. ^ Female Genital Mutilation Act 2003: "A person is guilty of an offence if he excises, infibulates or otherwise mutilates the whole or any part of a girl's labia majora, labia minora or clitoris," unless "necessary for her physical or mental health." Although the legislation refers to girls, it applies to women too.[4][5][6] ## References[edit] 1. ^ Alison Macfarlane and Efua Dorkenoo, "Female Genital Mutilation in England and Wales" Archived 2015-08-15 at the Wayback Machine, City University of London and Equality Now, 21 July 2014, p. 3. 2. ^ "Female genital mutilation: the case for a national plan", House of Commons Home Affairs Committee, Second Report of Session 2014–15. Also see "Female Genital Mutilation: Report of a Research Methodological Workshop on Estimating the Prevalence of FGM in England and Wales" Archived 2015-09-24 at the Wayback Machine, Equality Now, 22–23 March 2012. For an earlier report, Efua Dorkenoo, Linda Morison, Alison Macfarlane, "A Statistical Study to Estimate the Prevalence of Female Genital Mutilation in England and Wales" Archived 2013-07-26 at the Wayback Machine, FORWARD, October 2007. Richard Kerbaj, "Thousands of girls mutilated in Britain",The Times, 16 March 2009 (courtesy link Archived 2013-06-26 at the Wayback Machine). 3. ^ "Prohibition of Female Circumcision Act 1985". 4. ^ "Female Genital Mutilation Act 2003", legislation.gov.uk, and "Female Genital Mutilation Act 2003" (legal guidance), Crown Prosecution Service: "The Act refers to 'girls', though it also applies to women." 5. ^ "Female Genital Mutilation Act 2003". 6. ^ "Prohibition of Female Genital Mutilation (Scotland) Act 2005", legislation.gov.uk 7. ^ Notes on some overseas countries' laws, FGM Education and Networking Project. 8. ^ Tracy McVeigh, Tara Sutton, "British girls undergo horror of genital mutilation despite tough laws", The Guardian, 25 July 2010. 9. ^ a b Sandra Laville (4 February 2015). "Doctor found not guilty of FGM on patient at London hospital". The Guardian. 10. ^ Alison Macfarlane and Efua Dorkenoo, Mcfarlane and Dorkenoo 2014 Archived 2015-08-15 at the Wayback Machine p. 14. 11. ^ a b J. A. Black, G. D. Debelle, "Female genital mutilation in Britain", British Medical Journal, 310, 17 June 1995. PMID 7787654 12. ^ Blume, Rocco (25 July 2014). "'Cutting season' heightens threat for girls at risk of FGM". Plan UK. Retrieved 22 June 2015. 13. ^ Topping, Alexandra (6 February 2014). "Young British-Somali women fight FGM with rhyme and reason". The Guardian. Retrieved 22 June 2015. 14. ^ "Efua Dorkenoo". Equality Now. Archived from the original on 2015-03-04. Retrieved 2015-03-06. 15. ^ "FORWARD: Who we are, our vision, our mission - FORWARD". Forwarduk.org.uk. Retrieved 2015-03-06. 16. ^ Efua Dorkenoo, Cutting the Rose: Female Genital Mutilation, the Practice and its Prevention, London: Minority Rights Group, 1994. 17. ^ Douglas Martin, "Efua Dorkenoo Dies at 65; Key Foe of Genital Cutting in Africa, Middle East", The New York Times, 27 October 2014. 18. ^ Annette Scambler, "Gender, health and postmodernism," in Paul Higgs, Graham Scambler (eds.), Modernity, Medicine and Health, Routledge, 2005, p. 119, citing A. Boulton, "Calls for female circumcision on the NHS sparks storm," The Observer, 14 February 1993. 19. ^ Anna Davis (28 March 2014). "Ann John: I was branded a colonialist for fighting against 'barbaric' FGM". London Evening Standard. 20. ^ Jess Frampton, "From taboo to talking point – an eye-opening insight into Female Genital Mutilation" Archived 2014-10-27 at the Wayback Machine, UN Women, 18 June 2013. 21. ^ Suzi Dixon, "Health and beauty: New Year Honours", The Daily Telegraph, 31 December 2007. 22. ^ "House of Commons - Female genital mutilation: abuse unchecked - Home Affairs Committee". publications.parliament.uk. Retrieved 2018-11-09 – via House of Commons. 23. ^ a b c d Alison MacFarlane; et al. (July 2015). Prevalence of Female Genital Mutilation in England and Wales: National and local estimates (PDF). London: City University London. p. 5. ISBN 9781900804936. Archived from the original (PDF) on 21 January 2018. Retrieved 10 February 2018. 24. ^ The State of the World's Children 2015: Executive Summary, New York: UNICEF, November 2014, Table 9, pp. 84–89. 25. ^ "About us", FGM National Clinical Group. 26. ^ "Tackling FGM in the UK" Archived 2014-10-06 at the Wayback Machine, The Royal College of Midwives. 27. ^ "TRF-UK opens first clinic for child victims of female genital mutilation". Sf.reuters.com. 22 September 2014. 28. ^ "Female genital mutilation: Hospitals to log victims". BBC News. 6 February 2014. 29. ^ Alexandra Topping (16 October 2014). "FGM: more than 1,700 women and girls treated by NHS since April". The Guardian. 30. ^ Topping, Alexandra (28 February 2014). "Fahma Mohamed: the shy campaigner who fought for FGM education". The Guardian. Retrieved 15 June 2015. 31. ^ Alexandra Topping (11 April 2014). "Michael Gove writes to every school in England about dangers of FGM". The Guardian. 32. ^ "International Day of Zero Tolerance for Female Genital Mutilation". United Nations. 33. ^ a b Alison MacFarlane; et al. (July 2015). Prevalence of Female Genital Mutilation in England and Wales: National and local estimates (PDF). London: City University London. p. 21. ISBN 9781900804936. Archived from the original (PDF) on 21 January 2018. Retrieved 10 February 2018. 34. ^ a b c Kevin Rawlinson (1970-01-01). "Police obtain first FGM protection order \| Society". The Guardian. Retrieved 2015-07-18. 35. ^ https://blogs.nottingham.ac.uk/nipd/2016/09/12/sheriff-nottingham-take-zero-tolerance-stance-female-genital-mutilation/ 36. ^ a b Davis, Nicola (2017-07-04). "NHS attended to 9,000 FGM cases in England last year, report reveals". The Guardian. ISSN 0261-3077. Retrieved 2017-09-18. 37. ^ "Female Genital Mutilation (FGM) Annual Report 2016/17 [PAS]". digital.nhs.uk. Retrieved 2017-09-18. 38. ^ Renée Kool and Sohail Wahedi, "Criminal Enforcement in the Area of Female Genital Mutilation in France, England and the Netherlands: A Comparative Law Perspective", International Law Research, 3(1), 2014, pp. 3–5. doi:10.5539/ilr.v3n1p1 39. ^ Megan Rowling "France reduces genital cutting with prevention, prosecutions – lawyer", Thomson Reuters Foundation, 27 September 2012. 40. ^ "Concluding observations on the seventh periodic report of the United Kingdom of Great Britain and Northern Ireland" Archived 2015-09-24 at the Wayback Machine, United Nations Convention on the Elimination of All Forms of Discrimination against Women, 26 July 2013, p. 6, paras 36, 37. 41. ^ "FGM: UK's first female genital mutilation prosecutions announced", BBC News, 21 March 2014. 42. ^ "'Genital mutilation' doctor struck off after undercover press sting", BBC News, 30 May 2014. 43. ^ "FGM: Mother guilty of genital mutilation of daughter". BBC News. 1 February 2019. Retrieved 1 February 2019. 44. ^ "Mother jailed for 11 years over FGM". BBC News. 8 March 2019. Retrieved 8 March 2019. 45. ^ Kirkland, Faye (5 September 2017). "Families left devastated by false claims of FGM in girls". BBC News. Retrieved 7 September 2017. 46. ^ Iqbal, Nosheen (24 February 2019). "Children to be taught dangers of female genital mutilation". The Observer. Retrieved 24 February 2019. 47. ^ Iqbal, Nosheen (24 February 2019). "Children to be taught dangers of female genital mutilation". The Observer. Retrieved 24 February 2019. * v * t * e Female genital mutilation Health issues * Clitoridectomy * Dysmenorrhea * Dyspareunia * Gishiri cutting * Husband stitch * Infibulation * Keloid scars * Pelvic inflammatory disease * Rectovaginal fistula * Vesicovaginal fistula By country * Prevalence by country * Laws by country * FGM in India * colonial Kenya * Kurdistan * New Zealand * Nigeria * Sierra Leone * Sudan * United Kingdom * United States * Religious views on FGM Writers/groups Early writers and activists * Raqiya Haji Dualeh Abdalla * Janice Boddy * Mary Daly * Efua Dorkenoo * Asma El Dareer * Benoîte Groult * Rose Oldfield Hayes * Fran Hosken * Edna Adan Ismail * Nawal El Saadawi * Lilian Passmore Sanderson * Marion Scott Stevenson * Hulda Stumpf * Nahid Toubia * Amina Warsame Others * Fuambai Ahmadu * Ayaan Hirsi Ali * Ellen Gruenbaum * Waris Dirie * Gerry Mackie * Molly Melching * Layli Miller-Muro * Comfort Momoh * Alice Walker Groups * Babiker Bedri Scientific Association for Women's Studies * Equality Now * FORWARD * Inter-African Committee on Traditional Practices Affecting the Health of Women and Children * RAINBO * Tostan * Tahirih Justice Center * Zero Tolerance Day Media Books * Woman at Point Zero (1975) * Woman, Why Do You Weep? (1982) * Possessing the Secret of Joy (1992) * Desert Flower (1998) Films * Moolaadé (2004) * Desert Flower (2009) * My Body My Rules (2015) Legislation * Matter of Kasinga * Prohibition of Female Circumcision Act 1985 * Female Genital Mutilation Act 2003 * 2005 (Scotland) Act * Children Act 1989 (Amendment) (Female Genital Mutilation) Act 2019 Categories * Female genital mutilation * Activists against female genital mutilation [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-aminobutyric 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	Female genital mutilation in the United Kingdom	None	27,439	wikipedia	https://en.wikipedia.org/wiki/Female_genital_mutilation_in_the_United_Kingdom	2021-01-18T18:31:54	{"wikidata": ["Q18204564"]}
A number sign (#) is used with this entry because Usher syndrome type IC is caused by homozygous or compound heterozygous mutation in the gene encoding harmonin (605242) on chromosome 11p15. Description Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss. For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900). Clinical Features Kloepfer et al. (1966) identified 537 persons with hearing loss in a French-Acadian ('Cajun') group in Louisiana. Of the 468 living persons with hearing loss, at least 158 or about 30% were known to have retinitis pigmentosa and cataract. Usher syndrome in French-Acadians is predominantly type I, although some type II cases have been identified (Smith et al., 1992). Saihan et al. (2011) studied a 42-year-old woman and her 40-year-old brother from a Caucasian British family who at 4 years of age were diagnosed with severe hearing loss requiring hearing aids, and who also developed visual field loss and night blindness in the third and fourth decades of life, respectively. Language acquisition and speech development were normal, and there was no history of delay in motor milestones, consistent with normal vestibular function in infancy. Ophthalmic examination revealed that both sibs had sector retinitis pigmentosa restricted to the inferior and nasal retina, and fundus autofluorescence imaging showed a clear demarcation between normal and abnormal areas of retina, which corresponded to areas of reduced sensitivity on fine matrix mapping and loss of visual field. Mapping In the Acadian families of Louisiana, Smith et al. (1992) demonstrated that Usher syndrome was linked to D11S419 (maximum lod = 4.20 at theta = 0.0), which is situated on 11p. A homologous region on mouse chromosome 7 is the site of a recessive deaf mutant 'twister' (twt), a disorder possibly homologous to Usher syndrome. Keats et al. (1994) mapped the USH1C gene to a region of 11p15.1 by tight linkage to microsatellite markers. In addition, linkage disequilibrium was observed. Fantes et al. (1995) constructed an integrated map of this region, including the markers tightly linked to USH1C. Molecular Genetics In patients with Usher syndrome IC, Verpy et al. (2000) found a splice site mutation (605242.0001), a frameshift mutation (605242.0002), and the expansion of an intronic variable number of tandem repeats (VNTRs) (605242.0003). Verpy et al. (2000) proposed that the USH1C gene also underlies the form of nonsyndromic autosomal recessive neurosensory deafness designated DFNB18 (602092), which maps to the same region of 11p. Bitner-Glindzicz et al. (2000) identified the USH1C gene and detected 2 different homozygous mutations in exon 3, one in an Acadian family (605242.0004) and the other in a Pakistani family (605242.0002) with Usher syndrome type IC. Additionally, they identified a contiguous gene deletion syndrome (606528) that included part of the ABCC8 (600509) and USH1C genes in 2 consanguineous families. In an extensive genetic study of 9 Usher syndrome genes in 172 patients with Usher syndrome due to various genetic defects, Le Quesne Stabej et al. (2012) found that mutations in the USH1C gene were the second most common defect, accounting for 14.9% of families. Four families carried a splice site mutation (495+1G-A; 605242.0006), and haplotype analysis indicated a founder effect. Mutations in the MYO7A gene (276903) were the most common in the cohort, accounting for 53.2% of families. In 2 sibs from a Caucasian British family who were diagnosed with hearing loss at 4 years of age and who developed retinitis pigmentosa of the 'sector' type in the third and fourth decades of life, respectively, Saihan et al. (2011) identified compound heterozygosity for a missense mutation (R103H; 605242.0011) and a splice site mutation (605242.0012) in the USH1C gene. Both sibs were negative for pathogenic changes in 7 other Usher-associated genes. Their unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 866 control chromosomes. Saihan et al. (2011) noted that both the retinal and the audiovestibular phenotypes in the sibs were much milder than those previously reported in cases of USH1C-related nonsyndromic hearing loss or Usher syndrome type I. Using a combination of whole-genome SNP analysis as well as whole-exome sequencing in 2 Israeli families of Yemenite Jewish descent with retinitis pigmentosa, Khateb et al. (2012) identified a homozygous 1-bp deletion in the USH1C gene (1220delG; 605242.0013) that was confirmed by Sanger sequencing and cosegregated fully with the phenotype in both families. The mutation was part of a shared homozygous haplotype of 27 SNPs shared by the probands from the 2 families, indicating a founder mutation; screening for the 1220delG mutation in 119 ethnically matched controls revealed 1 heterozygous individual, for a carrier frequency of 0.008 in the Israeli Yemenite Jewish population. Screening 35 unrelated Yemenite Jewish patients with retinal degeneration identified 6 additional RP patients who were homozygous for the 1220delG mutation. Audiometric testing in 10 of the mutation-positive individuals revealed that 4 had mild to severe symmetric hearing impairment; the ages of the patients with deafness ranged from 38 to 72 years, whereas those of the patients with normal hearing ranged from 13 to 40 years. Khateb et al. (2012) stated that this was the first report of a mutation in a known USH1 gene causing late-onset rather than congenital sensorineural hearing loss, and noted that the mutation accounted for 23% of RP among Yemenite Jewish patients in their cohort. History In the French-Acadian ('Cajun') population of southwestern Louisiana where Usher syndrome is frequent (Kloepfer et al., 1966), Daiger et al. (1987) and Pelias et al. (1988) found a suggestion of linkage to GC (139200) on 4q (maximum lod score = 1.41 at theta = 0.17). In the same large Louisiana kindred, Smith et al. (1988, 1989) excluded the Usher syndrome locus from a large part of chromosome 4 by multipoint linkage analysis. Notably, a 17-cM region around the GC locus was excluded by reason of a lod score less than -2.0. Bonneau et al. (1990) also excluded linkage to GC. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural hearing loss, profound congenital \- Vestibular hypofunction Eyes \- Retinitis pigmentosa, progressive (prepubertal onset) \- Retinitis pigmentosa, sector type (in some patients) MISCELLANEOUS \- First described in Acadian population of Louisiana \- Allelic to deafness, neurosensory, autosomal recessive 18 ( 602092 ) \- Later onset of hearing loss in some patients MOLECULAR BASIS \- Caused by mutation in the 73-kD PDZ-domain-containing protein (USH1C, 605242.0001 ) ▲ 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-aminobutyric 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	USHER SYNDROME, TYPE IC	c0271097	27,440	omim	https://www.omim.org/entry/276904	2019-09-22T16:21:25	{"doid": ["0110830"], "mesh": ["D052245"], "omim": ["276904"], "orphanet": ["886", "231169"], "synonyms": ["Alternative titles", "USHER SYNDROME, TYPE I, ACADIAN VARIETY"], "genereviews": ["NBK1265"]}
## Description In the evaluation of male infertility, the Sertoli cell-only (SCO) syndrome is diagnosed on testicular biopsy when either no germ cells are visible in any seminiferous tubules (SCO type I) or germ cells are present in a minority of tubules (SCO type II). It is believed that the latter variant arises from a failure to complete differentiation and maturation of spermatocytes and spermatids, leading to degeneration of germ cells within most tubules (Sargent et al., 1999). There is evidence that Sertoli cell-only syndrome can be caused by interstitial deletions in the 'azoospermia factor' (AZF) region on the long arm of the Y chromosome (SPGFY1; 400042). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). Clinical Features Edwards and Bannerman (1971) observed 2 brothers, aged 14 and 12, with gynecomastia and obesity. Their disorder might have been classified simply as adolescent or pubertal gynecomastia were it not for the existence of 2 maternal uncles with a history of pubertal gynecomastia and, in the one of them available for study, clinical features and testicular biopsy consistent with the Del Castillo syndrome. By the age of 26, he showed no gynecomastia. In the 14-year-old nephew, the sperm count was probably low but sperm were present. The authors suggested that in this boy they had an opportunity to observe the Del Castillo syndrome at an earlier stage than had previously been possible. They suggested that, as in other similar conditions such as the testicular feminization syndrome (300068) and the Reifenstein syndrome (312300), the inheritance is either X-linked or male-limited autosomal dominant. Several kindreds with multiple affected males are known. Chaganti et al. (1980) suggested that the pathology may be similar to that in the mouse mutations 'white' (W) and 'steel' (SL), autosomal recessive disorders in which primordial germ cells fail to multiply and adult testes lack germ cells. Both males and females are sterile. Molecular Genetics The USP26 gene (300309), which is specifically expressed in testis tissue, has been studied as a potential infertility gene. In 8 of 111 patients (7.2%) with Sertoli cell-only syndrome, Stouffs et al. (2005) found the same 3 changes in the nucleotide sequence of the USP26 gene, all on the same allele: an insertion, 370-371insACA, and 2 transitions, 494T-C and 1423C-T. These changes were not found in 152 fertile controls or 32 patients with azoospermia with maturation arrest (270960). Stouffs et al. (2005) suggested that these changes might be involved in male infertility or increase the risk of male infertility. Stouffs et al. (2006) analyzed 146 Caucasian patients with cryptozoospermia or oligozoospermia and 202 controls and identified the USP26 haplotype only in 1 control individual who had normal spermatogenesis on testicular biopsy. Stouffs et al. (2006) concluded that the previously identified cluster of changes does not affect spermatogenesis per se. Ravel et al. (2006) demonstrated that 2 of the changes identified by Stouffs et al. (2005) in the USP26 gene, 494T-C and 370insACA, correspond to the ancestral sequence of the gene, and that the USP26 haplotype is present in significant frequencies in sub-Saharan African and South and East Asian populations, including individuals with known fertility. Ravel et al. (2006) concluded that the allele is not associated with infertility. Growth \- Obesity Lab \- Germinal cell aplasia on testicular biopsy Thorax \- Pubertal gynecomastia Inheritance \- X-linked vs. male-limited 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-aminobutyric 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	SPERMATOGENIC FAILURE, X-LINKED, 1	c1384583	27,441	omim	https://www.omim.org/entry/305700	2019-09-22T16:18:23	{"doid": ["0070189"], "mesh": ["D054331"], "omim": ["305700"], "orphanet": ["399805"], "synonyms": ["DEL CASTILLO SYNDROME", "Alternative titles", "SERTOLI CELL-ONLY SYNDROME", "GERMINAL CELL APLASIA"]}
A rare, genetic, dermis elastic tissue disorder characterized by yellowish skin papules (resembling pseudoxanthoma elasticum) located on the neck, chest and/or flexural areas associated with loose, redundant, sagging skin on trunk and upper limbs, and retinitis pigmentosa, in the absence of clotting abnormalities. Patients present reduced night and peripheral vision, as well as optic nerve pallor, retinal pigment epithelium loss, attenuated retinal vessels and/or black pigment intra-retinal clumps. [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-aminobutyric 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	Pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa	None	27,442	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=436274	2021-01-23T16:54:27	{"icd-10": ["Q82.8"], "synonyms": ["PXE-like syndrome with retinitis pigmentosa"]}
Main article: Rhinitis Nonallergic rhinitis SpecialtyOtolaryngology Nonallergic rhinitis is inflammation of the inner part of the nose that is not caused by an allergy. Nonallergic rhinitis involves symptoms including chronic sneezing or having a congested, drippy nose without an identified allergic reaction.[1] Other common terms for nonallergic rhinitis are vasomotor rhinitis[2][3] and perennial rhinitis. The prevalence of nonallergic rhinitis in otolaryngology is 40%. Allergic rhinitis is more common than nonallergic rhinitis; however, both conditions have similar presentation, manifestation and treatment. Nasal itching and paroxysmal sneezing are usually associated with nonallergic rhinitis in comparison to allergic rhinitis.[3][4] ## Contents * 1 Types * 2 Presentation * 2.1 Complications * 3 Pathophysiology * 4 Diagnosis * 4.1 Investigations * 4.2 Classification * 5 Treatment * 5.1 Medical * 5.2 Surgical * 6 References ## Types[edit] * Rhinitis medicamentosa \- topical decongestant nasal drops are notorious for causing rebound phenomenon. Their excessive use causes rhinitis if treated by withdrawal of nasal drops, short course of systemic steroid therapy and in some cases, surgical reduction of turbinates, if they have become hypertrophied. * Rhinitis of pregnancy \- pregnant women may develop persistent rhinitis due to hormonal changes. Nasal mucous become edematous and block the airway. Some may develop secondary infection and even sinusitis in such cases. Care should be taken while prescribing drugs. Generally, local measures such as limited use of nasal drops, topical steroids and limited surgery (cryosurgery) to turbinates are sufficient to relate the symptoms. Safety of developing fetus is not established for newer antihistamines and they should be avoided. * Honeymoon rhinitis \- this usually follows sexual excitement, leading to nasal stuffiness. The condition appears to be genetically determined and caused by the presence in the nose of erectile tissue which may become engorged during sexual arousal, as a side effect of the signals from the autonomic nervous system that trigger changes in the genitals of both men and women. A related condition called sexually induced sneezing also exists, where people sneeze, sometimes uncontrollably, when engaging in or even thinking about sexual activity.[5] A phenomenon presumably related to honeymoon rhinitis is the frequent side effect of nasal congestion during the use of Viagra or related phosphodiesterase type 5 antagonists.[6] * Gustatory rhinitis \- spicy and pungent food may in some people produce rhinorrhea, nasal stuffiness, lacrimation, sweating and flushing of face. It can be relieved by ipratropium bromide nasal spray (an anticholinergic), a few minutes before meal.[7] * Non-air flow rhinitis \- it is seen in patients of laryngectomy, tracheostomy and choanal atresia. Nose is not used for air flow and the turbinates become swollen due to loss of vasomotor control. In choanal atresia there is an additional factor of infection due to stagnation of discharge in the nasal cavity which should otherwise drain freely into nasopharynx. * Photic sneeze reflex is a reflexcondition that causes sneezing in response to looking at bright lights. ## Presentation[edit] Paroxysmal sneezing in morning, especially in morning while getting out of the bed. Excessive rhinorrhea - watering discharge from the nose when patient bends forward. Nasal obstruction - bilateral nasal stuffiness alternates from one site to other; this is more marked at night, when the dependent side of nose is often blocked. Postnasal drip.[8] ### Complications[edit] Nonallergic rhinitis cases may subsequently develop polyps, turbinate hypertrophy and sinusitis.[citation needed] ## Pathophysiology[edit] Nasal mucosa has a rich blood supply and has venous sinusoids or "lakes" surrounded by smooth muscle fibers. These smooth muscle fibers act as sphincters and control the filling and emptying of sinusoids. Sympathetic stimulation causes vasoconstriction and shrinkage of mucosa, which leads to decongestion of the nose. Parasympathetic stimulation causes not only excessive secretion from the nasal gland but also vasodilatation and engorgement, which lead to rhinorrhoea and congestion of the nose. The autonomic nervous system, which supplies the nasal mucosa, is under the control of the hypothalamus.[9] ## Diagnosis[edit] Nose examination: The mucosa is usually boggy and edematous with clear mucoid secretions. The turbinates are congested and hypertrophic.[citation needed] Pharynx examination: Mucosal injection and lymphoid hyperplasia involving tonsils, adenoids and base of tongue may be seen.[10] ### Investigations[edit] Absolute eosinophil count, nasal smear, skin and in vitro allergy tests to rule out allergic rhinitis, acoustic rhinometry for measuring nasal patency, smell testing, CT scan in cases of sinus disease and MRI in case of mass lesions.[10] ### Classification[edit] Type Classification Definition Specific presentation Drug Induced NSAIDS AND ASA, ACEI and Beta Blockers Intense eosinophilic inflammation with an overproduction of cysteinyl leukotrienes and other prostanoids profuse rhinorrhea, red eyes, periorbital edema, asthma attacks Hormonal Pregnancy Nasal congestion present during pregnancy without other cause, disappears after two weeks of delivery Rhinorrhea and nasal congestion Idiopathic Unknown cause Vasomotor Rhinitis and nonallergic rhinitis with eosinophilia Occupational Caused by work Inflammatory disease of the nose causing intermittent and persistent symptoms arising out of causes and conditions attributable to a particular work environment; can be elicited by single or multiple exposures. Corrosive rhinitis is the most severe form frequently associated with concurrent asthma, nonallergic form is without latency. Nasal challenge test confirms the diagnosis [11] ## Treatment[edit] ### Medical[edit] The avoidance of inciting factors such as sudden changes in temperature, humidity, or blasts of air or dust is helpful. Intranasal application of antihistamines,[11] corticosteroids, or anticholinergics may also be used for vasomotor rhinitis. Intranasal cromolyn sodium may be used in patients older than two years.[2] A Cochrane review concluded that it is unclear whether intranasal corticosteroids, when compared with a placebo, reduce patient‐reported disease severity in people with nonallergic/vasomotor rhinitis due to the low certainty of the evidence available from clinical trials.[12] However, intranasal corticosteroids probably increase risk of nosebleeds.[12] Astelin (azelastine) "is indicated for symptomatic treatment of vasomotor rhinitis including rhinorrhea, nasal congestion, and post nasal drip in adults and children 12 years of age and older."[13][14] ### Surgical[edit] Reduction of hypertrophied turbinates, correction of nasal septum deviation, removal of polyps, sectioning of the parasympathetic secretomotor fiber to nose (vidian neurectomy) for controlling refractory excessive rhinorrhea.[10] ## References[edit] 1. ^ "Nonallergic rhinitis: Definition". Mayo Clinic. Mayo Clinic. Retrieved 2015-10-15. 2. ^ a b Wheeler PW, Wheeler SF (September 2005). "Vasomotor rhinitis". American Family Physician. 72 (6): 1057–62. PMID 16190503. 3. ^ a b MedlinePlus Encyclopedia: Nonallergic rhinopathy 4. ^ Hwang SH, Cho HK, Park SH, Lee W, Lee HJ, Lee DC, et al. (2015). "Characteristics of Human Turbinate-Derived Mesenchymal Stem Cells Are Not Affected by Allergic Condition of Donor". PLOS ONE. 10 (9): e0138041. Bibcode:2015PLoSO..1038041H. doi:10.1371/journal.pone.0138041. PMC 4574043. PMID 26376485. 5. ^ "Sneezing 'can be sign of arousal'". BBC News. BBC. 2008-12-19. Retrieved 2010-01-04. 6. ^ Khan LA, Khan SA, Al-Hateeti H (September 1999). "Sildenafil (Viagra) may cause nasal stuffiness". Annals of Saudi Medicine. 19 (5): 468. doi:10.5144/0256-4947.1999.468. PMID 17277525. 7. ^ Raphael G, Raphael MH, Kaliner M (January 1989). "Gustatory rhinitis: a syndrome of food-induced rhinorrhea". The Journal of Allergy and Clinical Immunology. 83 (1): 110–5. doi:10.1016/0091-6749(89)90484-3. PMID 2643657. 8. ^ "Nonallergic rhinitis Symptoms - Mayo Clinic". mayoclinic.org. Retrieved 2015-10-11. 9. ^ Van Gerven L, Boeckxstaens G, Hellings P (September 2012). "Up-date on neuro-immune mechanisms involved in allergic and non-allergic rhinitis". Rhinology. 50 (3): 227–35. doi:10.4193/Rhino11.152. PMID 22888478. 10. ^ a b c Bansal M (2012-10-30). "Nonallergic Rhinitis". Diseases of Ear, Nose and Throat. Jaypee Brothers. pp. 330–332. ISBN 9789350259436. 11. ^ a b Brown KR, Bernstein JA (June 2015). "Clinically relevant outcome measures of novel pharmacotherapy for nonallergic rhinitis". Current Opinion in Allergy and Clinical Immunology. 15 (3): 204–12. doi:10.1097/aci.0000000000000166. PMID 25899692. S2CID 22343815. 12. ^ a b Segboer C, Gevorgyan A, Avdeeva K, Chusakul S, Kanjanaumporn J, Aeumjaturapat S, et al. (Cochrane ENT Group) (November 2019). "Intranasal corticosteroids for non-allergic rhinitis". The Cochrane Database of Systematic Reviews. 2019 (11). doi:10.1002/14651858.CD010592.pub2. PMC 6824914. PMID 31677153. 13. ^ Product Information: Astelin, azelastine. Wallace Laboratories, Cranbury, NJ. (PI Revised 08/2000) PI Reviewed 01/2001 14. ^ Gehanno P, Deschamps E, Garay E, Baehre M, Garay RP (2001). "Vasomotor rhinitis: clinical efficacy of azelastine nasal spray in comparison with placebo". ORL; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 63 (2): 76–81. doi:10.1159/000055714. PMID 11244365. S2CID 23292869. * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * 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-aminobutyric 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	Nonallergic rhinitis	c0035460	27,443	wikipedia	https://en.wikipedia.org/wiki/Nonallergic_rhinitis	2021-01-18T18:56:55	{"mesh": ["D012223"], "umls": ["C0035460"], "icd-9": ["472.0"], "wikidata": ["Q2403156"]}
A rare syndrome characterised by severe reduction or absence of the fibula and complex brachydactyly. Less than 30 cases have been described in the literature so far. The syndrome is inherited in an autosomal recessive manner and is caused by mutations in the cartilage-derived morphogenetic protein-1 gene (GDF5). [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-aminobutyric 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	Fibular aplasia-complex brachydactyly syndrome	c1856738	27,444	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2639	2021-01-23T18:20:51	{"gard": ["2329", "9879"], "mesh": ["C537931"], "omim": ["228900"], "umls": ["C1856738"], "icd-10": ["Q73.8"], "synonyms": ["Du Pan syndrome"]}
A rare hyperkinetic movement disorder characterized by delayed motor development and infantile onset of axial hypotonia and a generalized hyperkinetic movement disorder, principally with dyskinesia of the limbs and trunk, and facial involvement including orolingual dyskinesia, drooling, and dysarthria. Variable hyperkinetic movements may include a jerky quality, intermittent chorea and ballismus. Brain imaging is normal and cognitive performance is typically preserved. [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-aminobutyric 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	Infantile-onset generalized dyskinesia with orofacial involvement	c4310792	27,445	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=494526	2021-01-23T17:50:06	{"omim": ["616921"], "synonyms": ["Infantile-onset orofacial-trunk-limbs dyskinesia"]}
## Clinical Features By the electroimmunoassay of Laurell, Bergqvist and Nilsson (1979) found deficient alpha-2-macroglobulin (103950) in a 37-year-old man, his mother, and one daughter. The deficient persons were apparently heterozygotes. No clinical disadvantage resulted from the deficiency. Poller et al. (1989) detected an alteration in the A2M gene in a patient with serum A2M deficiency and chronic lung disease since childhood. The alteration involved restriction sites detected with 10 different enzymes and was thought to have been caused by major deletion or rearrangement in the gene. Nine of the restriction enzymes used detected no polymorphism in 40 healthy control subjects and 39 patients with chronic obstructive pulmonary disease. The patient was heterozygous for the A2M alteration; Poller et al. (1989) suggested that this was responsible for the pulmonary disease. INHERITANCE \- Autosomal dominant LABORATORY ABNORMALITIES \- Decreased serum alpha-2 macroglobulin levels ▲ 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-aminobutyric 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	ALPHA-2-MACROGLOBULIN DEFICIENCY	c3279661	27,446	omim	https://www.omim.org/entry/614036	2019-09-22T15:56:43	{"mesh": ["C566304"], "omim": ["614036"]}
Opitz G/BBB syndrome is an inherited condition that affects several structures along the midline of the body. The most common features are wide-spaced eyes and defects of the larynx, trachea, and/or esophagus causing breathing problems and difficulty swallowing. Affected males usually have a urethra opening on the underside of the penis (hypospadias). Other features can include mild intellectual disability, cleft lip and/or a cleft palate, heart defects, an obstruction of the anal opening (imperforate anus), agenesis of the corpus callosum, and facial abnormalities. These features may vary, even among members of the same family. There are two forms of Opitz G/BBB syndrome, which are distinguished by their genetic causes and patterns of inheritance. The X-linked form is caused by mutations in the MID1 gene. Autosomal dominant Opitz G/BBB syndrome is caused by a deletion of 22q11.2, and is often referred to as 22q11.2 deletion syndrome. Treatment depends on the individual’s specific needs. [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-aminobutyric 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	Opitz G/BBB syndrome	c2936904	27,447	gard	https://rarediseases.info.nih.gov/diseases/193/opitz-gbbb-syndrome	2021-01-18T17:58:36	{"mesh": ["C567932"], "omim": ["300000", "145410"], "orphanet": ["2745"], "synonyms": ["Hypospadias-dysphagia, syndrome", "Opitz-Frias syndrome", "G syndrome", "Opitz-G syndrome, type 2", "Hypertelorism hypospadias syndrome", "Hypertelorism with esophageal abnormality and hypospadias", "BBB syndrome", "Telecanthus with associated abnormalities", "Opitz BBBG syndrome", "GBBB syndrome"]}
A number sign (#) is used with this entry because myxoid liposarcoma can be caused by chromosomal translocations, most commonly t(12;16)(q13;p11) (Panagopoulos et al., 1996). Description Myxoid liposarcoma is a soft tissue tumor that tends to occur in the limbs (especially the thigh) of patients ranging in age from 35 to 55 years. It is defined by the presence of a hypocellular spindle cell proliferation set in a myxoid background, often with mucin pooling. Lipoblasts tend to be small and often monovacuolated and to cluster around vessels or at the periphery of the lesion (review by Dei Tos, 2000). Cytogenetics Limon et al. (1986) and Turc-Carel et al. (1986) described a specific chromosome change, t(12;16)(q13;p11), in the tumors of all 4 cases of myxoid liposarcoma studied. One patient had a history of multiple lipomatosis. A relationship to the INT1 oncogene on chromosome 12 or to a fragile site on that chromosome was suggested. Turc-Carel et al. (1987) found, however, by Southern blot analysis of DNA from 2 myxoid liposarcomas carrying the translocation t(12;16)(q13;p11), that the translocation did not disrupt the INT1 gene (164820). In 9 different solitary subcutaneous lipomas, all with clonal abnormalities affecting 12q13-q15, Arheden et al. (1989) found no rearrangement or amplification of the INT1 gene. Karakousis et al. (1987) found the specific translocation between chromosomes 12 and 16 in 5 cases of myxoid liposarcoma. Walter et al. (1988) and Bridge et al. (1988) reported a 12;16 translocation in myxoid liposarcoma. See also Smith et al. (1987) and Mertens et al. (1987). Mandahl et al. (1987) studied 10 consecutive lipomas; supernumerary ring chromosomes were found in 3; balanced rearrangements in 6; and a normal karyotype in 1. Chromosome 12 was involved in 5 of the balanced rearrangements and probably in all the ring chromosomes, with breakpoints localized to 12q13 or 12q14. They suggested that the development of myxoid liposarcoma requires the recombination of 2 specific chromosome bands, 12q13 and 16p11, whereas for some types of benign lipogenic tumors structural changes in 12q13-q14 may be sufficient for neoplastic growth. In a follow-up study of 25 additional solitary lipomas, Mandahl et al. (1988) found supernumerary ring chromosomes in 2 cases; balanced rearrangements involving 12q13-q14 in 8; hypodiploid or diploid chromosomes involving aberrations other than rings or rearrangements of 12q13-q14 in 7; and normal karyotypes in 8. Heim et al. (1988) concluded, on the basis of cytogenetic analysis of tumor cells from 50 lipomas, that 4 main cytogenetic subtypes can be recognized: (1) tumors with normal karyotype (18 cases); (2) tumors with rearrangements of 12q13-q14 (18 cases); (3) tumors with ring chromosomes (6 cases); and (4) tumors with other clonal changes (8 cases). All 6 tumors with ring marker chromosomes were histopathologically classified as atypical lipomas. All 7 multiple lipomas were karyotypically normal. Eneroth et al. (1990) narrowed the localization of the chromosome breaks in t(12;16) of myxoid liposarcomas to 12q13.3 and 16p11.2. Mrozek et al. (1993) demonstrated that the chromosome 12 breakpoint in benign lipoma (151900) is at 12q15, whereas the breakpoint in myxoid liposarcoma is at 12q13.3. ### CHOP (DDIT3)/FUS (TLS) Fusion Gene Aman et al. (1992) used the Southern blot technique to demonstrate that CHOP (126337), a gene of the CCAAT/enhancer binding protein (C/EBP) family which maps to 12q13 and is assumed to be involved in adipocyte differentiation, is rearranged in myxoid liposarcomas. Rabbitts et al. (1993) demonstrated that the translocation t(12;16)(q13;p11) in malignant liposarcoma can result in a fusion of the CHOP dominant-negative transcription factor gene with a novel gene called FUS (137070). ### CHOP/EWS Fusion Gene In an analysis of peripheral blood samples from 19 patients with myxoid liposarcoma due to t(12;16) and in 1 patient with myxoid liposarcoma due to t(12;22;20), resulting in the fusion of the CHOP and EWS (133450) genes, Panagopoulos et al. (1996) found FUS/CHOP hybrid fragments in 3 patients with t(12;16) and an EWS/CHOP hybrid in the patient with the latter translocation. [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-aminobutyric 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	MYXOID LIPOSARCOMA	c0206634	27,448	omim	https://www.omim.org/entry/613488	2019-09-22T15:58:32	{"doid": ["5363"], "mesh": ["D018208"], "omim": ["613488"], "orphanet": ["99967", "69078"]}
A number sign (#) is used with this entry because of evidence that posterior polymorphous corneal dystrophy-3 (PPCD3) is caused by heterozygous mutation in the TCF8 gene (ZEB1; 189909) on chromosome 10p11. For a general phenotypic description and a discussion of genetic heterogeneity of posterior polymorphous corneal dystrophy, see PPCD1 (122000). Clinical Features Moroi et al. (2003) reported a woman with PPCD who had a prominent retrocorneal membrane. The authors stated that this feature had not previously been reported with PPCD. Many of the woman's relatives were affected by PPCD with apparent autosomal dominant inheritance. In the family reported by Moroi et al. (2003), Shimizu et al. (2004) noted that guttae, a common corneal finding sometimes observed along with PPCD, were found among both affected and unaffected members of the proband's sibship, but were absent in the younger generations of the family. Because the expressivity of the PPCD phenotype varied widely in this family, Shimizu et al. (2004) suggested that differences in disease severity could be due to genetic background or other factors independent of the PPCD3 locus. Krafchak et al. (2005) noted that patients with PPCD3 have been reported with inguinal hernia, hydrocele, and possible bone anomalies. They suggested that these patients should be examined for nonocular anomalies. Mapping In a family segregating PPCD, Moroi et al. (2003) excluded the candidate genes VSX1 (605020) and COL8A2 (120252) by linkage and haplotype analysis. They also excluded linkage to the PPCD1 (122000) and CHED (217700) loci. Shimizu et al. (2004) performed a genome scan in 26 members of the family reported by Moroi et al. (2003) and found significant linkage of PPCD to markers on chromosome 10, with a maximum multipoint lod score of 4.35 at marker D10S1780. Affected family members shared a haplotype in an 8.55-cM critical interval that was bounded by markers D10S213 and D10S578. Pathogenesis Krafchak et al. (2005) detected transcripts of all 3 identified PPCD-associated genes in the cornea: VSX1, COL8A2, and TCF8. They demonstrated a complex (core plus secondary) binding site for TCF8 in the promoter of the COL4A3 gene (120070), which is mutant in Alport syndrome (203780), and presented immunohistochemical evidence of ectopic expression of COL4A3 in corneal endothelium of the proband of the original PPCD3 family. Identification of TCF8 as the PPCD3 gene provided a valuable tool for the study of critical gene regulation events in PPCD pathology and suggested a possible role for TCF8 mutations in altered structure and function of cells lining body cavities other than the anterior chamber of the eye. This study identified TCF8 as the gene responsible for approximately half of the cases of PPCD, implicated TCF8 mutations in developmental abnormalities outside the eye, and revealed COL4A3, the TCF8 regulatory target, as a key, shared molecular component of 2 different diseases, PPCD and Alport syndrome. Molecular Genetics Krafchak et al. (2005) identified a heterozygous frameshift mutation in the TCF8 (ZEB1) gene (189909.0001) in affected members of the family with PPCD reported by Moroi et al. (2003) and 4 different heterozygous nonsense and frameshift mutations in TCF8 in 4 other PPCD probands. Liskova et al. (2007) analyzed the ZEB1 gene in 6 Czech and 4 British families with PPCD, and identified 4 pathogenic mutations in 4 of the families. The authors noted that although a systematic clinical examination was not performed, their findings did not support an association between ZEB1 changes and self-reported nonocular anomalies. [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-aminobutyric 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	CORNEAL DYSTROPHY, POSTERIOR POLYMORPHOUS, 3	c0339284	27,449	omim	https://www.omim.org/entry/609141	2019-09-22T16:06:35	{"doid": ["0110857"], "omim": ["609141"], "orphanet": ["98973"]}
A rare variant of cutaneous lichen planus characterized by the development of pale papules or plaques with an atrophic center. ## Epidemiology The prevalence is unknown. ## Clinical description Lesions develop on the trunk or lower extremities on skin areas previously affected by classic lichen planus. ## Etiology Etiology is unknown. [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-aminobutyric 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	Atrophic lichen planus	c0023647	27,450	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254449	2021-01-23T17:11:56	{"gard": ["12675"], "umls": ["C0023647"], "icd-10": ["L43.8"], "synonyms": ["Atrophic LP"]}
Transient hypogammaglobulinemia of infancy SpecialtyImmunology Transient hypogammaglobulinemia of infancy is a form of hypogammaglobulinemia appearing after birth, leading to a reduction in the level of IgG, and also sometimes IgA[1][2] and IgM.[3] (The ratios of immunoglobulins vary rapidly in all infants, and the term dysgammaglobulinemia, although theoretically applicable, is not usually used in this context.) It can result in increased infections, but it can also present without symptoms.[4] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 818. ISBN 978-1-4160-2999-1. 2. ^ "Transient Hypogammaglobulinemia of Infancy: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01. 3. ^ Kiliç SS, Tezcan I, Sanal O, Metin A, Ersoy F (2000). "Transient hypogammaglobulinemia of infancy: clinical and immunologic features of 40 new cases". Pediatr Int. 42 (6): 647–50. doi:10.1046/j.1442-200x.2000.01301.x. PMID 11192522. 4. ^ Hsueh KC, Chiu HH, Lin HC, Hsu CH, Tsai FJ (2005). "Transient hypogammaglobulinemia of infancy presenting as Staphylococcus aureus sepsis with deep neck infection". J Microbiol Immunol Infect. 38 (2): 141–4. PMID 15843860. ## External links[edit] Classification D * ICD-10: D80.7 * ICD-9-CM: 279.09 External resources * eMedicine: ped/2280 * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency 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-aminobutyric 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	Transient hypogammaglobulinemia of infancy	c0272238	27,451	wikipedia	https://en.wikipedia.org/wiki/Transient_hypogammaglobulinemia_of_infancy	2021-01-18T19:07:23	{"umls": ["C0272238"], "icd-9": ["279.09"], "orphanet": ["169139"], "wikidata": ["Q3801600"]}
A number sign (#) is used with this entry because juvenile hemochromatosis type 2A (HFE2A) is caused by homozygous or compound heterozygous mutation in the gene encoding hemojuvelin (HJV; 608374) on chromosome 1q21. For a general phenotypic description and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200. Description Juvenile, or type 2, hemochromatosis is an autosomal recessive inborn error of iron metabolism that leads to severe iron loading and organ failure before 30 years of age. The common complications of iron overload, including liver cirrhosis, cardiac disease, endocrine failure, diabetes, arthropathy, and skin pigmentation, are similar to those of adult-onset hereditary hemochromatosis, but hypogonadism and cardiomyopathy are the most common symptoms at presentation. Heart failure and/or major arrhythmias are usually the cause of death in the absence of treatment. Early detection of the disorder is important because iron depletion by phlebotomy can prevent organ damage and all disease manifestations (summary by Roetto et al., 1999). ### Genetic Heterogeneity of Hemochromatosis Type 2 Hemochromatosis type 2B (HFE2B; 613313) is caused by mutation in the hepcidin gene (HAMP; 606464) on chromosome 19q13. Clinical Features Cazzola et al. (1983) emphasized the special characteristics of juvenile hemochromatosis: onset with abdominal pain in the first decade, hypogonadotropic hypogonadism in the second decade, and cardiac arrhythmias and intractable heart failure in the third decade. Males and females are affected about equally. Cazzola et al. (1983) described the disorder in an Italian brother and sister and in German identical twins. They pointed to the cases of Perkins et al. (1965), Felts et al. (1967), Charlton et al. (1967), and Lamon et al. (1979) as examples of the same disorder. Although the organ damage in JH is more severe, parenchymal iron distribution is similar to that in HFE, as inferred by liver biopsies or autopsy findings (Molitch and Kirkham, 1983; Haddy et al., 1988). Reports of functional studies on iron metabolism in JH are limited. Camaschella et al. (1997) cited 1 published case in which iron absorption was 100%, despite the severe iron load, a value never reached in HFE. Camaschella et al. (1997) described 7 Italian patients belonging to 5 unrelated families with features typical of JH. In 4 of the 5 families, the parents were consanguineous. Analysis of HFE gene (613609) mutations in all cases and nucleotide sequence of the gene in one case excluded the HFE gene as responsible for JH. Furthermore, segregation analysis of 6p markers closely associated with HFE showed that JH is unlinked to 6p and thus genetically distinct from HFE. Cazzola et al. (1998) reported molecular studies in 2 Italian families with juvenile hemochromatosis, 1 of which was reported by Cazzola et al. (1983). Both families had an affected brother and sister. Of the 4 affected individuals, 3 presented with hypogonadotropic hypogonadism at 14 to 21 years of age. The affected male of 1 family presented with cardiac failure at 20 years of age and died at 21 years of age with congestive cardiomyopathy. All the family members examined were negative for the C282Y (613609.0001) and H63D (613609.0002) mutations of the HFE gene. Three of the patients underwent regular phlebotomies. Based on the amount of iron mobilized by bleedings, Cazzola et al. (1998) estimated that these patients had body iron stores ranging from 220 to 329 mg/kg of body weight at the time of diagnosis at 17 to 21 years of age. Based on phlebotomy requirements for maintenance of normal iron balance, the rate of estimated iron accumulation ranged from 3.2 to 3.9 mg/d. This was clearly higher than the rate of 0.8 to 1.6 mg/d found in 5 adult males homozygous for the C282Y mutation. This remarkable difference in iron overprocurement suggested completely different pathogenetic mechanisms. Kelly et al. (1998) reported 4 patients (2 of each sex) from 3 pedigrees affected by juvenile hemochromatosis with a mean onset at 22 years. All had endocrine deficiency with postpubertal gonadal failure secondary to pituitary disease; 2 suffered near-fatal cardiomyopathy with heart failure. A 24-year-old man listed for heart transplantation because of cardiomyopathy responded to intravenous iron chelation with desferrioxamine combined with phlebotomy and did not require transplantation. A 27-year-old woman required orthotopic cardiac transplantation before the diagnosis was established. These 2 patients with cardiomyopathy from unrelated families were heterozygous for the C282Y mutation of the HFE gene and did not have the H63D mutation. De Gobbi et al. (2002) analyzed the phenotype of 29 patients with JH, from 20 families of different ethnic origin, with linkage to chromosome 1q. They also compared the clinical expression in 26 of these patients with that of 93 males homozygous for the C282Y mutation (613609.0001) and with that of 11 patients with hemochromatosis type 3 (604250), which is caused by mutation in the transferrin receptor-2 gene (TFR2; 604720). Patients with JH were statistically younger at presentation and had a more severe iron burden than C282Y homozygotes and hemochromatosis type 3 patients. They were more frequently affected by cardiopathy, hypogonadism, and reduced glucose tolerance. In contrast, cirrhosis was not statistically different among the 3 groups. The data suggested that the rapid iron accumulation in JH causes preferential tissue damage. The results clarified the natural history of the disease and were compatible with the hypothesis that the implicated gene at the HFE2 locus on 1q has greater influence on iron absorption than other hemochromatosis-associated genes. Murugan et al. (2008) reported a 23-year-old African American man of West Indies descent who was first diagnosed with iron overload at age 4 years. At that time, he had iron deposition in the liver and began treatment with phlebotomy. He developed normally as a teen but developed splenomegaly with cirrhosis and portal hypertension by age 23. However, he did not have cardiomyopathy or hypogonadotrophic hypogonadism. His paternal grandparents came from Tobago and Grenada, and his maternal grandparents were from Trinidad and Grenada. There was no family history of consanguinity, iron overload, or Caucasian or white admixture. His parents and sister had normal iron phenotypes. Mapping Roetto et al. (1999) performed a genomewide search to map the HFE2 locus in 9 families, 6 consanguineous and 3 with multiple affected persons. They located the gene on 1q, with a maximum lod score of 5.75 at a recombination fraction of 0.0 with marker D1S498, and a lod score of 5.16 at a recombination fraction of 0.0 with marker D1S2344. Homozygosity mapping in consanguineous families defined the limits of the candidate region in an interval of approximately 4 cM between D1S442 and D1S2347 on 1q21. The HFE2 locus did not correspond to the chromosomal localization of any known gene involved in iron metabolism. Rivard et al. (2003) performed linkage analysis of 17 French Canadian patients with JH from the Saguenay-Lac-Saint-Jean region and confirmed linkage to the HFE2A locus on chromosome 1q. They obtained a maximum lod of 4.07 at theta = 0.0 with markers D1S2344 and D1S1156. Rivard et al. (2003) identified a common ancestral haplotype, suggesting the presence of a founder mutation. Molecular Genetics Papanikolaou et al. (2004) reported the positional cloning of the 1q locus associated with juvenile hemochromatosis and the identification of a gene (HJV) crucial to iron metabolism, the product of which they called hemojuvelin. Analysis of Greek, Canadian, and French families indicated that 1 mutation in the HJV gene, gly320 to val (G320V; 608374.0001), was present in all 3 populations and accounted for two-thirds of the mutations found. Lanzara et al. (2004) studied 34 patients with hepcidin-unrelated JH from 29 families and identified 17 different mutations in the HJV gene. Seventeen patients from 12 families of the isolated region of Saguenay-Lac-Saint-Jean in Quebec, who were previously studied by Rivard et al. (2003), were all homozygous for the G320V mutation (608374.0001). In contrast, there was a large variety of HJV mutations among JH patients in 13 Italian families in the study; the only Italian G320V homozygote was likely of Greek ancestry, because he lived in an isolated southern Italian region where a dialect resembling Greek was still spoken. Gehrke et al. (2005) analyzed the HAMP (606464) and HJV genes in 7 patients with JH from 6 unrelated central European families from Germany, Slovakia, and Croatia. No mutations were found in the HAMP gene. Six of the 7 (86%) patients carried at least 1 copy of the G320V mutation, and 4 were homozygous for the mutation. Gehrke et al. (2005) concluded that the genetic background of JH might be more homogeneous than initially believed. In a Croatian patient who had the most severe phenotype, with liver cirrhosis, severe dilated cardiomyopathy, and hypogonadism, Gehrke et al. (2005) also found a heterozygous C282Y mutation in the HFE gene (613609.0001) and suggested that HFE mutations might influence the phenotypic expression in HJV-related JH. In a 23-year-old African American man of West Indies descent with hemochromatosis, Murugan et al. (2008) identified a homozygous mutation in the HJV gene (R54X; 608374.0009). Murugan et al. (2008) commented that this disorder is uncommon among African Americans. In a 21-year-old male patient who initially presented with ventricular fibrillation and developed cardiogenic shock due to global cardiac insufficiency, who was found to have excessive iron storage and hypertrophy on myocardial biopsy, Brakensiek et al. (2009) confirmed the diagnosis of hemochromatosis with serum iron parameters and identified homozygosity for the G320V mutation in the HJV gene. The patient, who died of low cardiac output and multiorgan failure, was also compound heterozygous for the H63D (613609.0002) and S65C (613609.0003) mutations in the HFE gene, but did not have any mutations in the HAMP gene. Brakensiek et al. (2009) suggested that severity of the clinical course in this patient might be related to the complex genotype. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Heart failure \- Arrhythmia \- Cardiomyopathy, dilated ABDOMEN Liver \- Cirrhosis \- Fibrosis \- Hepatomegaly Spleen \- Splenomegaly GENITOURINARY External Genitalia (Male) \- Hypogonadism External Genitalia (Female) \- Hypogonadism Internal Genitalia (Male) \- Azoospermia \- Infertility Internal Genitalia (Female) \- Amenorrhea SKELETAL \- Arthritis SKIN, NAILS, & HAIR Skin \- Hyperpigmentation MUSCLE, SOFT TISSUES \- Weakness NEUROLOGIC Behavioral Psychiatric Manifestations \- Lethargy LABORATORY ABNORMALITIES \- Increased serum iron \- Increased serum ferritin \- Increased transferrin saturation \- Increased transaminase values MISCELLANEOUS \- Onset is usually before age 30 MOLECULAR BASIS \- Caused by mutation in the hemojuvelin gene (HJV, 608374.0001 ) ▲ 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-aminobutyric 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	HEMOCHROMATOSIS, TYPE 2A	c0268060	27,452	omim	https://www.omim.org/entry/602390	2019-09-22T16:13:53	{"doid": ["0111027"], "mesh": ["C537247"], "omim": ["602390"], "orphanet": ["79230"], "genereviews": ["NBK1170"]}
A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome kyphoscoliotic type 2 (EDSKSCL2) is caused by homozygous or compound heterozygous mutation in the FKBP14 gene (614505) on chromosome 7p15. Description Ehlers-Danlos syndrome kyphoscoliotic type 2 is characterized by severe muscle hypotonia at birth, progressive scoliosis, joint hypermobility, hyperelastic skin, myopathy, sensorineural hearing impairment, and normal pyridinoline excretion in urine (Baumann et al., 2012). For a discussion of genetic heterogeneity of the kyphoscoliotic type of EDS, see 225400. Clinical Features Baumann et al. (2012) reported a 16-year-old Austrian boy who was born with severe muscle hypotonia, paucity of antigravity movements, poor sucking, hypermobile joints, and slightly bluish sclerae. At 2 months of age, the first signs of spinal deformity developed. Muscle weakness and hypotonia improved over subsequent months, with unsupported sitting at 13 months and unassisted walking at 2.5 years. He underwent surgical repair of an inguinal hernia at 2 years of age, placement of subdural-peritoneal shunt for chronic subdural hygroma at 3 years of age, and repair of a large bladder diverticulum at 9 years of age. Bilateral high frequency sensorineural hearing impairment requiring a hearing aid was diagnosed at 6 years of age. Progression of scoliosis resulted in a restrictive ventilation disorder, with a forced vital capacity of 34%. Echocardiography and thoracoabdominal CT scan at 13 years of age showed no signs of cardiomyopathy or dilation of the aorta or other large vessels. At age 16, he had severe kyphoscoliosis and marked hypermobility of the large and small joints (Beighton score, 6/9), but no contractures. He had a characteristic handshake 'like a bag of little bones' due to seeming collapse of the musculoskeletal structure of the hand on pressure. His skin was thin, soft, and hyperelastic, with follicular hyperkeratosis but no signs of increased fragility or atrophic scars; he had 2 keloids in the left deltoid area, where a skin biopsy had been taken. There was no skin wrinkling of the palms. He was myopic with normal corneal diameter. The proband's father had a female cousin who had severe muscle hypotonia and weakness at birth, scoliosis from age 2 years, and moderate bilateral high frequency sensorineural hearing impairment requiring hearing aids at 6 years of age. In her fifth decade, she developed progressive weakness of the lower limbs, and at 48 years of age, had difficulty climbing stairs and could not do toe or heel walking. Clinical examination showed a moderate degree of muscular atrophy in the legs and intrinsic hand muscles, without sensory deficit. She had marked instability of the knees and her Beighton score was 6/9. Her skin was soft and hyperelastic with easy bruisability, without abnormal scarring. She was myopic with normal corneal diameter. She had an older sister who was born with hypotonia, developed mild but progressive kyphoscoliosis and follicular hyperkeratosis, and died unexpectedly at 12 years of age from aortic rupture. Baumann et al. (2012) identified 4 additional patients from 4 unrelated families of Italian, French, Turkish, and German origin with similar presentations. Radiography showed mild to moderate osteopenia in all patients, but no increased bone fragility. Electromyopathy showed a myopathic pattern in adolescence and adulthood, but results obtained in infancy were mostly reported as normal. Histopathologic features of muscle biopsies ranged from nonspecific mild myopathic changes with increased variation in muscle fiber diameter to more pronounced changes with profound fiber atrophy and proliferation of fatty tissue. Electron microscopy of patient fibroblasts showed dilated cisterns filled with flocculent material, and immunofluorescence experiments demonstrated disturbed distribution and assembly of several extracellular matrix (ECM) components, including collagens type I and type III and fibronectin as well as their receptors. Baumann et al. (2012) noted that the disorder shared many features with the kyphoscoliotic form of EDS (225400) and Ullrich congenital muscular dystrophy (254090). Aldeeri et al. (2014) studied a 3-year-old boy in whom slow feeding and floppiness were evident shortly after birth. At 19 months of age, he had just taken his first steps and was observed to be borderline microcephalic with subtle dysmorphic features, including sloping forehead, square nasal root, mild hypotelorism, epicanthal folds, and hypotonia. He also had excessively redundant umbilical skin. At 2.5 years of age, he was making 2-word sentences and exhibited an immature waddling gait. He had appreciable skin laxity, with a Beighton score of 8/9. No specific mention was made of kyphoscoliosis or hearing loss, but at age 3 the child had an 'abnormal gait' and 'only 50% of his speech was understandable by strangers.' No hearing test was reported. Echocardiography revealed patent ductus arteriosus. Electromyography showed myopathic changes; muscle biopsy showed a predominance of type I fibers. Dordoni et al. (2016) described an 8-year-old Italian boy with Ehlers-Danlos syndrome and compound heterozygous mutations in the FKBP14 gene (see MOLECULAR GENETICS) who had mixed hearing loss, mild nonprogressive kyphoscoliosis, and muscle hypotonia. In addition to these cardinal features of EDSKSCL2, at age 6 years he had left hypogastric artery pseudoaneurysm rupture. Thoracic and abdominal magnetic resonance angiography did not reveal any other arterial malformations. Also at age 6, flexion/extension x-rays of the cervical spine showed asymptomatic atlantoaxial instability, with enlarged atlantoaxial distance in flexion. The authors suggested that cerebrovascular monitoring is warranted in patients with FKBP14-associated EDS. Giunta et al. (2018) reported a cohort of 17 individuals with kyphoscoliotic Ehlers-Danlos syndrome and the follow-up of 3 previously reported patients, and provided an extensive overview of the disorder and its natural history. In a summary (Table 2) of features present in the 17 patients reported by Giunta et al. (2018) and 6 reported by Baumann et al. (2012), all reported patients had soft-textured skin, small-joint hypermobility, foot deformities, muscle hypotonia at birth, poor head control in infancy, improving weakness over time, and delayed motor development. More than two-thirds of these 23 patients presented with hyperextensible skin, hypermobile large joints, progressive kyphoscoliosis, and hearing impairment. Muscle atrophy was present in 63%, cardiac valve anomalies in 40%, vascular anomalies in 30%, visual refraction anomalies in 60%, and hernias in 47%. A variety of other features were associated with a minority of patients. Diagnosis Based on the frequency of clinical features of 23 patients with EDSKSCL2 reported to that time, Giunta et al. (2018) stated that the major diagnostic criteria are (i) severe generalized hypotonia at birth with marked muscle weakness that improves in infancy, and delayed gross motor milestones; (ii) early-onset progressive kyphoscoliosis; (iii) joint hypermobility without pronounced contractures; (iv) foot deformities; and (v) normal or decreased ratio of lysyl pyridinoline to hydroxylysyl pyridinoline in urine. Minor criteria include (i) hyperelastic skin with follicular hyperkeratosis, easy bruising, and occasional abnormal scarring; (ii) myopathy as seen clinically by reduced strength and endurance and confirmed in some patients by histology and muscle imaging; and (iii) hearing impairment that is predominantly sensorineural and may not be present in all individuals. Mapping Using genomic DNA from 23 members of an Austrian family segregating autosomal recessive Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss, Baumann et al. (2012) performed a genomewide scan followed by haplotype analysis and autozygosity mapping and identified only 2 linkage regions for which the 2 affected individuals were homozygous identical by descent, on chromosomes 7p15.1 and 16q12.2. The 670,554-bp homozygous linkage interval on chromosome 7 was flanked by SNPs rs767430 and rs2709800, whereas the 724,063-bp region on chromosome 16 was flanked by SNPs rs211085 and rs1486733. Molecular Genetics In 2 affected individuals from an Austrian family with Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss, Baumann et al. (2012) sequenced the candidate gene FKBP14 (614505) and identified homozygosity for a 1-bp insertion (614505.0001). Analysis of FKBP14 in 4 additional unrelated probands with EDSKMH from Italian, Turkish, French, and German families revealed homozygosity for the 1-bp insertion in 3 and compound heterozygosity for the insertion and a 19-bp deletion (614505.0002) in 1. In a 3-year-old boy with Ehlers-Danlos syndrome and myopathy, Aldeeri et al. (2014) performed exome sequencing and identified homozygosity for a 4-bp splice site deletion in the FKBP14 gene (614505.0003). In an 8-year-old Italian boy with EDSKSCL, Dordoni et al. (2016) sequenced the FKBP14 gene and identified compound heterozygosity for the recurrent 1-bp duplication (614505.0001) and a 3-bp deletion (614505.0004). His unaffected parents were each heterozygous for 1 of the mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Retrogenia in infancy (in some patients) Ears \- Hearing loss, sensorineural, high-frequency \- Hearing loss, conductive (in some patients) \- Hearing loss, mixed (in some patients) Eyes \- Myopia (in most patients) \- Bluish sclerae in infancy (rare) Mouth \- Cleft soft palate (in some patients) CARDIOVASCULAR Heart \- Insufficiency of tricuspid valve (in some patients) \- Insufficiency of mitral valve (rare) Vascular \- Patent ductus arteriosus (in some patients) \- Aortic rupture (rare) \- Hypogastric artery rupture (rare) RESPIRATORY Lung \- Restrictive ventilation disorder due to severe scoliosis (in some patients) ABDOMEN External Features \- Umbilical hernia (in some patients) \- Redundant umbilical skin (in some patients) \- Inguinal hernia (in some patients) GENITOURINARY External Genitalia (Male) \- Inguinal hernia (in some patients) Bladder \- Bladder diverticulum (in some patients) SKELETAL \- Hypermobility of large and small joints (Beighton score ranging from 6/9 to 9/9) \- Dislocations, recurrent (rare) \- Osteopenia, mild to moderate \- Fractures (rare) \- Atlantoaxial instability (rare) Spine \- Kyphoscoliosis, progressive Limbs \- Hypermobility of large joints Hands \- Hypermobility of small joints Feet \- Hypermobility of small joints \- Pes planus \- Club foot (in some patients) SKIN, NAILS, & HAIR Skin \- Hyperelastic skin \- Soft skin \- Plantar softness \- Follicular hyperkeratosis \- Easy bruising (in some patients) \- Hypertrophic scarring (rare) Electron Microscopy \- Endoplasmic reticulum cisterns dilated and filled with flocculent material in skin fibroblasts \- Collagen fibrils normal in shape and diameter MUSCLE, SOFT TISSUES \- Severe muscle hypotonia at birth \- Poor head control in infancy \- Muscular weakness, improving in infancy (Medical Research Council muscle score of 3 to 4) \- Muscular atrophy \- Myopathy, mild to severe \- Increased variation in muscle fiber diameter \- Proliferation of fatty tissue in muscle (in some patients) \- Muscle fiber atrophy, profound (rare) NEUROLOGIC Central Nervous System \- Delayed motor development \- Walking independently at 2.5 years to 4 years of age PRENATAL MANIFESTATIONS Movement \- Decreased movements in utero (in some patients) LABORATORY ABNORMALITIES \- Normal pyridinoline excretion in urine MISCELLANEOUS \- Electromyography may be normal in infancy, but shows myopathic pattern in adolescence and adulthood \- Variable phenotype MOLECULAR BASIS \- Caused by mutation in the FK506-binding protein-14 gene (FKBP14, 614505.0001 ) ▲ 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-aminobutyric 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	EHLERS-DANLOS SYNDROME, KYPHOSCOLIOTIC TYPE, 2	c3281160	27,453	omim	https://www.omim.org/entry/614557	2019-09-22T15:54:53	{"omim": ["614557"], "orphanet": ["300179"], "synonyms": ["FKBP14-related EDS", "kEDS-FKBP14", "EHLERS-DANLOS SYNDROME WITH PROGRESSIVE KYPHOSCOLIOSIS, MYOPATHY, AND HEARING LOSS", "Alternative titles", "FKBP22-deficient EDS", "Kyphoscoliotic EDS due to FKBP22 deficiency", "Ehlers-Danlos syndrome with kyphoscoliosis, myopathy, and hearing loss"], "genereviews": ["NBK541503"]}
Steppage gait (High stepping, Neuropathic gait) is a form of gait abnormality characterised by foot drop or ankle equinus due to loss of dorsiflexion.[1] The foot hangs with the toes pointing down, causing the toes to scrape the ground while walking, requiring someone to lift the leg higher than normal when walking.[2][3][4] Foot drop can be caused by damage to the deep peroneal nerve.[5] ## Conditions associated with a steppage gait[edit] * Foot drop * Charcot–Marie–Tooth disease * Polio * Multiple sclerosis * Syphilis * Guillain–Barré syndrome * Spinal disc herniation * Anterior Compartment Muscle Atrophy * Deep fibular nerve injury * Spondylolisthesis * Slipped Femoral Epiphysis * ALS/PLS ## References[edit] 1. ^ "Definition: steppage gait from Online Medical Dictionary". 2. ^ "Walking abnormalities". MedlinePlus. Retrieved 23 March 2013. 3. ^ Med Terms 4. ^ GP Notebook 5. ^ Saint, Sanjay; Wiese, Jeff; Bent, Stephen (2006). Clinical clerkships: the answer book. Hagerstown, MD: Lippincott Williams & Wilkins. p. 219. ISBN 0-7817-3754-0. ## External links[edit] * A video of a neuropathic gait * v * t * e Symptoms and signs relating to movement and gait Gait * Gait abnormality * CNS * Scissor gait * Cerebellar ataxia * Festinating gait * Marche à petit pas * Propulsive gait * Stomping gait * Spastic gait * Magnetic gait * Truncal ataxia * Muscular * Myopathic gait * Trendelenburg gait * Pigeon gait * Steppage gait * Antalgic gait Coordination * Ataxia * Cerebellar ataxia * Dysmetria * Dysdiadochokinesia * Pronator drift * Dyssynergia * Sensory ataxia * Asterixis Abnormal movement * Athetosis * Tremor * Fasciculation * Fibrillation Posturing * Abnormal posturing * Opisthotonus * Spasm * Trismus * Cramp * Tetany * Myokymia * Joint locking Paralysis * Flaccid paralysis * Spastic paraplegia * Spastic diplegia * Spastic paraplegia * Syndromes * Monoplegia * Diplegia / Paraplegia * Hemiplegia * Triplegia * Tetraplegia / Quadruplegia * General causes * Upper motor neuron lesion * Lower motor neuron lesion Weakness * Hemiparesis Other * Rachitic rosary * Hyperreflexia * Clasp-knife response 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-aminobutyric 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	Steppage gait	c0427149	27,454	wikipedia	https://en.wikipedia.org/wiki/Steppage_gait	2021-01-18T19:05:32	{"mesh": ["D020233"], "wikidata": ["Q3498706"]}
For other uses, see Purpura (disambiguation). Human disease Purpura Petechiae and purpura on the lower limb due to medication-induced vasculitis SpecialtyDermatology, hematology Purpura (/ˈpɜːrpjʊərə/[1]) is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, or other causes.[2] They measure 3–10 mm,[3] whereas petechiae measure less than 3 mm, and ecchymoses greater than 1 cm.[4] Purpura is common with typhus and can be present with meningitis caused by meningococci or septicaemia. In particular, meningococcus (Neisseria meningitidis), a Gram-negative diplococcus organism, releases endotoxin when it lyses. Endotoxin activates the Hageman factor (clotting factor XII), which causes disseminated intravascular coagulation (DIC). The DIC is what appears as a rash on the affected individual. ## Contents * 1 Classification * 2 Etymology and pronunciation * 3 See also * 4 References * 5 External links ## Classification[edit] Purpura are a common and nonspecific medical sign; however, the underlying mechanism commonly involves one of: * Platelet disorders (thrombocytopenic purpura) * Primary thrombocytopenic purpura * Secondary thrombocytopenic purpura * Post-transfusion purpura * Vascular disorders (nonthrombocytopenic purpura) * Microvascular injury, as seen in senile (old age) purpura, when blood vessels are more easily damaged * Hypertensive states * Deficient vascular support * Vasculitis, as in the case of Henoch–Schönlein purpura * Coagulation disorders * Disseminated intravascular coagulation (DIC) * Scurvy (vitamin C deficiency) – defect in collagen synthesis due to lack of hydroxylation of procollagen results in weakened capillary walls and cells * Meningococcemia * Clumping fibrillary protein deposits caused by Amyloidosis * Cocaine use with concomitant use of the one-time chemotherapy drug and now veterinary deworming agent levamisole can cause purpura of the ears, face, trunk, or extremities, sometimes needing reconstructive surgery.[5] Levamisole is purportedly a common cutting agent. * Decomposition of blood vessels including purpura is a symptom of acute radiation poisoning in excess of 2 Grays of radiation exposure. This is an uncommon cause in general, but is commonly seen in victims of nuclear disaster. Cases of psychogenic purpura are also described in the medical literature,[6] some claimed to be due to "autoerythrocyte sensitization". Other studies[7] suggest the local (cutaneous) activity of tissue plasminogen activator can be increased in psychogenic purpura, leading to substantial amounts of localized plasmin activity, rapid degradation of fibrin clots, and resultant bleeding. Petechial rash is also characteristic of a rickettsial infection. ## Etymology and pronunciation[edit] The word purpura (/ˈpɜːrpɜːrə/) comes from Latin purpura, "purple", which came from ancient Greek πορφύρα. Purpura is a mass noun naming the condition or state, not the name of an individual spot (thus there is no pupurum, purpura or purpura, purpurae count declension). ## See also[edit] * Bruise, which is a hematoma caused by trauma * Petechia, which is a small type of hematoma (<3 mm) * Ecchymosis, which is a large type of hematoma (>1 cm) * Purpura secondary to clotting disorders * Purpura hemorrhagica in horses * Pigmented purpuric dermatosis * Schamberg disease (progressive pigmentary purpura) ## References[edit] 1. ^ https://www.lexico.com/en/definition/purpura 2. ^ "UCSF Purpura Module" (PDF). Archived from the original (PDF) on 2013-10-02. 3. ^ McKenzie, Shirlyn B. (2014). Clinical Laboratory Hematology. Williams, Joanne Lynne; Landis-Piwowar, Kristin (3rd ed.). Boston. p. 665. ISBN 978-0133076011. OCLC 878098857. 4. ^ Robbins basic pathology. Kumar, Vinay; Abbas, Abul K.; Aster, Jon C.; Perkins, James A. (10th ed.). Philadelphia, Pennsylvania. 2017-03-28. p. 101. ISBN 978-0323353175. OCLC 960844656.CS1 maint: others (link) 5. ^ Muirhead, Trevor T.; Eide, Melody J. (2011). "Toxic Effects of Levamisole in a Cocaine User". New England Journal of Medicine. The New England Journal of Medicine. 364 (24): e52. doi:10.1056/NEJMicm1008722. PMID 21675882. 6. ^ Anderson JE, DeGoff W, McNamara M (1999). "Autoerythrocyte sensitization (psychogenic purpura): a case report and review of the literature". Pediatric Emergency Care. 15 (1): 47–48. doi:10.1097/00006565-199902000-00014. PMID 10069314. 7. ^ Lotti T, Benci M, Sarti MG, Teofoli P, Senesi C, Bonan P, et al. (1993). "Psychogenic purpura with abnormally increased tPA dependent cutaneous fibrinolytic activity". International Journal of Dermatology. 32 (7): 521–23. doi:10.1111/j.1365-4362.1993.tb02840.x. PMID 8340191. S2CID 38433734. ## External links[edit] Classification D * ICD-10: D69 * ICD-9-CM: 287 * MeSH: D011693 * DiseasesDB: 25619 External resources * MedlinePlus: 003232 * Evaluating the Child with Purpura from American Academy of Family Physicians * v * t * e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause * Clotting factors * Antithrombin III deficiency * Protein C deficiency * Activated protein C resistance * Protein S deficiency * Factor V Leiden * Prothrombin G20210A * Platelets * Sticky platelet syndrome * Thrombocytosis * Essential thrombocythemia * DIC * Purpura fulminans * Antiphospholipid syndrome Clots * Thrombophilia * Thrombus * Thrombosis * Virchow's triad * Trousseau sign of malignancy By site * Deep vein thrombosis * Bancroft's sign * Homans sign * Lisker's sign * Louvel's sign * Lowenberg's sign * Peabody's sign * Pratt's sign * Rose's sign * Pulmonary embolism * Renal vein thrombosis Bleeding By cause Thrombocytopenia * Thrombocytopenic purpura: ITP * Evans syndrome * TM * TTP * Upshaw–Schulman syndrome * Heparin-induced thrombocytopenia * May–Hegglin anomaly Platelet function * adhesion * Bernard–Soulier syndrome * aggregation * Glanzmann's thrombasthenia * platelet storage pool deficiency * Hermansky–Pudlak syndrome * Gray platelet syndrome Clotting factor * Hemophilia * A/VIII * B/IX * C/XI * von Willebrand disease * Hypoprothrombinemia/II * Factor VII deficiency * Factor X deficiency * Factor XII deficiency * Factor XIII deficiency * Dysfibrinogenemia * Congenital afibrinogenemia Signs and symptoms * Bleeding * Bruise * Hematoma * Petechia * Purpura * Nonthrombocytopenic purpura By site * head * Epistaxis * Hemoptysis * Intracranial hemorrhage * Hyphema * Subconjunctival hemorrhage * torso * Hemothorax * Hemopericardium * Pulmonary hematoma * abdomen * Gastrointestinal bleeding * Hemobilia * Hemoperitoneum * Hematocele * Hematosalpinx * joint * Hemarthrosis [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-aminobutyric 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	Purpura	c0034150	27,455	wikipedia	https://en.wikipedia.org/wiki/Purpura	2021-01-18T18:45:23	{"mesh": ["D011693"], "umls": ["C0034150"], "icd-9": ["287"], "wikidata": ["Q935293"]}
## Description Vasovagal syncope (VVS) is an exaggerated tendency toward the common faint caused by a sudden and profound hypotension with or without bradycardia. Several lines of evidence indicate central and peripheral abnormalities of sympathetic function. Newton et al. (2005) stated that a definitive diagnosis of VVS is made only when a patient has reproduction of symptoms in association with hypotension or bradycardia. The head up tilt (HUT) test is the investigation carried out to induce these hemodynamic changes (Parry and Kenny, 1999). This disorder may be the same as Streeten-type orthostatic hypotensive disorder (143850). Clinical Features Newton et al. (2005) described a large 3-generation family with vasovagal syncope in which they characterized clinically affected members by use of standardized cardiovascular testing including autonomic function tests. There were no discernible cardiac or autonomic abnormalities, and hypotension on tilt table testing was reproducible in affected family members. Klein et al. (2013) reported a large 3-generation family of Irish descent in which 30 individuals had VVS. The median age at onset was 8 to 9 years, and most patients (69%) had at least 1 typical presyncopal symptom, such as dizziness, lightheadedness, visual symptoms, feeling hot or sweaty, and nausea. Almost half of patients reported convulsive twitches or tonic activity. The relevant triggers varied considerably within the family and included warm environment, sight of blood, injury, illness, prolonged standing, frightening thoughts, pain, and dehydration/no food. Only 2 patients had cooccurrence of epilepsy and VVS; 2 patients had breathholding attacks. Five patients for whom information was available did not have a cardiac cause for the syncope, and 2 patients showed no evidence of postural orthostatic hypotension. Tilt testing without pharmacologic provocation was negative in 2 patients. Klein et al. (2013) also identified 5 additional unrelated smaller families with VVS. The patients had onset in the first 2 decades, and almost all had a typical prodrome and triggers, although there was considerable variation in the triggers. Two individuals from 1 family had cardiac arrhythmias, but both were diagnosed with VVS before the arrhythmias. Breathholding attacks were present in 2 families. Several individuals showed a positive tilt table test, but only with pharmacologic provocation. Inheritance VVS appears to be clustered in families (Camfield and Camfield, 1990; Mathias et al., 1998). The transmission pattern of VVS in the family reported by Newton et al. (2005) was consistent with autosomal dominant inheritance. Klein et al. (2012) found evidence for genetic factors in VVS by analyzing 51 same-sex twin pairs, including 33 monozygotic (MZ) and 18 dizygotic (DZ) pairs, in which at least 1 twin had syncope. The data were ascertained via a questionnaire. There was a trend toward higher concordance in MZ compared to DZ twin pairs (0.75 compared to 0.50) for any syncope. There was a stronger effect for fainting at least twice unrelated to external factors (MZ: 0.71 vs DZ: 0.27) and for syncope associated with typical vasovagal triggers (MZ: 0.62 vs DZ: 0.00). Twelve of 19 concordant MZ twin pairs reported few or no other affected family members, whereas in the other 7 pairs multiple close relatives were affected. The findings suggested complex inheritance, with rarer families possibly segregating an autosomal dominant gene. Klein et al. (2013) reported 6 unrelated families with VVS in which the transmission pattern was consistent with autosomal dominant inheritance. Mapping By linkage analysis of a large 3-generation family of Irish origin with autosomal dominant transmission of VVS, Klein et al. (2013) found linkage to 2 regions on chromosome 15q26: a 1.7-Mb region on 15q26.1 and a 0.05-Mb region on 15q26.2 (both with a parametric lod score of 3.28). Sanger sequencing of protein-coding exons of the SLCO3A1 (612435), ST8SIA2 (602546), and NR2F2 (107773) genes did not identify any mutations. Of 4 additional smaller families with VVS, linkage to chromosome 15q26 was excluded in 2 and not excluded in 2. Klein et al. (2013) postulated that the mutated gene is likely to be part of a pathophysiologic pathway shared by different vasovagal triggers. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Syncope, vasovagal \- Fainting \- Dizziness \- Lightheadedness MISCELLANEOUS \- Onset in first or second decade \- Triggers are variable, even within a family ▲ 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-aminobutyric 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	SYNCOPE, FAMILIAL VASOVAGAL	c1836438	27,456	omim	https://www.omim.org/entry/609289	2019-09-22T16:06:18	{"mesh": ["C536849"], "omim": ["609289"], "synonyms": ["Alternative titles", "SYNCOPE, FAMILIAL NEUROCARDIOGENIC"]}
Pyoderma gangrenosum Pyoderma gangrenosum on the leg of a person with ulcerative colitis. SpecialtyDermatology Usual onset40s or 50s[1] TreatmentCorticosteroids, ciclosporin, infliximab, canakinumab[2] Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow.[3] Pyoderma gangrenosum is not infectious.[3] Treatments may include corticosteroids, ciclosporin, infliximab, or canakinumab.[2] The disease was identified in 1930. It affects approximately 1 person in 100,000 in the population. Though it can affect people of any age, it mostly affects people in their 40s and 50s.[1] ## Contents * 1 Types * 2 Presentation * 2.1 Associations * 3 Causes * 4 Diagnosis * 4.1 Diagnostic criteria * 5 Treatment * 6 See also * 7 References * 8 External links ## Types[edit] Pyoderma gangrenosum There are two main types of pyoderma gangrenosum:[1] * the 'typical' ulcerative form, which occurs in the legs * an 'atypical' form that is more superficial and occurs in the hands and other parts of the body Other variations are:[4] * Peristomal pyoderma gangrenosum comprises 15% of all cases of pyoderma * Bullous pyoderma gangrenosum * Pustular pyoderma gangrenosum[5] * Vegetative pyoderma gangrenosum[6] ## Presentation[edit] ### Associations[edit] The following are conditions commonly associated with pyoderma gangrenosum:[7] * Inflammatory bowel disease: * Ulcerative colitis * Crohn's disease * Arthritides: * Rheumatoid arthritis * Seronegative arthritis * Hematological disease: * Myelocytic leukemia[8] * Hairy cell leukemia * Myelofibrosis * Myeloid metaplasia * Monoclonal gammopathy * Autoinflammatory disease: * Pyogenic sterile arthritis, and acne syndrome (PAPA syndrome) ## Causes[edit] Though the cause is not well understood, the disease is thought to be due to immune system dysfunction, and particularly improper functioning of neutrophils. In support of an immune cause, a variety of immune mediators such as interleukin (IL)-8, IL-1β, IL-6, interferon (IFN)-γ, granulocyte colony-stimulating factor, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-9, MMP10, and elafin have all been reported to be elevated in patients with pyoderma gangrenosum.[9] Also in support of an immune cause is the finding that at least half of all pyoderma gangrenosum patients suffer from immune-mediated diseases.[1] For instance, ulcerative colitis, rheumatoid arthritis, and multiple myeloma (MM) have all been associated with pyoderma gangrenosum. It can also be part of a syndromes such as PAPA syndrome.[citation needed] One hallmark of pyoderma gangrenosum is pathergy, which is the appearance of new lesions at sites of trauma, including surgical wounds.[10] ## Diagnosis[edit] Diagnosis of PG is challenging owing to its variable presentation, clinical overlap with other conditions, association with several systemic diseases, and absence of defining histopathologic or laboratory findings. Misdiagnosis and delayed diagnosis are common. It has been shown that up to 39% of patients who initially received a diagnosis of PG have an alternative diagnosis.[11] In light of this, validated diagnostic criteria have recently been developed for ulcerative pyoderma gangrenosum.[12] ### Diagnostic criteria[edit] In addition to a biopsy demonstrating a neutrophilic infiltrate, patients must have at least 4 minor criteria to meet diagnostic criteria.[12] These criteria are based on histology, history, clinical examination and treatment.[citation needed] * Histology: Exclusion of infection (including histologically indicated stains and tissue cultures) * Pathergy (ulcer occurring at sites of trauma, with ulcer extending past area of trauma) * Personal history of inflammatory bowel disease or inflammatory arthritis * History of papule, pustule, or vesicle that rapidly ulcerated * Clinical examination (or photographic evidence) of peripheral erythema, undermining border, and tenderness at site of ulceration * Multiple ulcerations (at least 1 occurring on an anterior lower leg) * Cribriform or “wrinkled paper” scar(s) at sites of healed ulcers * Decrease in ulcer size within 1 mo of initiating immunosuppressive medication(s) ## Treatment[edit] First-line therapy for disseminated or localized instances of pyoderma gangrenosum is systemic treatment by corticosteroids and ciclosporin. Topical application of clobetasol, mupirocin, and gentamicin alternated with tacrolimus can be effective.Pyoderma gangrenosum ulcers demonstrate pathergy, that is, a worsening in response to minor trauma or surgical debridement. Significant care should be taken with dressing changes to prevent potentially rapid wound growth. Many patients respond differently to different types of treatment, for example some benefit from a moist environment, so treatment should be carefully evaluated at each stage.[citation needed] Papules that begin as small "spouts" can be treated with Dakin's solution to prevent infection and wound clusters also benefit from this disinfectant. Wet to dry applications of Dakins can defeat spread of interior infection. Heavy drainage can be offset with Coban dressings. Grafting is not recommended due to tissue necrosis. If ineffective, alternative therapeutic procedures include systemic treatment with corticosteroids and mycophenolate mofetil; mycophenolate mofetil and ciclosporin; tacrolimus; thalidomide; infliximab; or plasmapheresis.[13] ## See also[edit] * Superficial granulomatous pyoderma * Brown recluse spider bite ## References[edit] 1. ^ a b c d Jackson JM, Callen JP (April 23, 2012). Elston DM (ed.). "Pyoderma Gangrenosum". EMedicine. 2. ^ a b Partridge AC, Bai JW, Rosen CF, Walsh SR, Gulliver WP, Fleming P (August 2018). "Effectiveness of systemic treatments for pyoderma gangrenosum: a systematic review of observational studies and clinical trials". The British Journal of Dermatology. 179 (2): 290–295. doi:10.1111/bjd.16485. PMID 29478243. S2CID 3504429. 3. ^ a b Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G (September 2009). "Pyoderma gangrenosum: an updated review". Journal of the European Academy of Dermatology and Venereology. 23 (9): 1008–17. doi:10.1111/j.1468-3083.2009.03199.x. PMID 19470075. S2CID 29773727. 4. ^ Brooklyn T, Dunnill G, Probert C (July 2006). "Diagnosis and treatment of pyoderma gangrenosum". BMJ. 333 (7560): 181–4. doi:10.1136/bmj.333.7560.181. PMC 1513476. PMID 16858047. 5. ^ Shankar S, Sterling JC, Rytina E (November 2003). "Pustular pyoderma gangrenosum". Clinical and Experimental Dermatology. 28 (6): 600–3. doi:10.1046/j.1365-2230.2003.01418.x. PMID 14616824. S2CID 11350602. 6. ^ Langan SM, Powell FC (August 2005). "Vegetative pyoderma gangrenosum: a report of two new cases and a review of the literature". International Journal of Dermatology. 44 (8): 623–9. doi:10.1111/j.1365-4632.2005.02591.x. PMID 16101860. S2CID 34574262. 7. ^ Brooklyn T, Dunnill G, Probert C (July 2006). "Diagnosis and treatment of pyoderma gangrenosum". BMJ. 333 (7560): 181–4. doi:10.1136/bmj.333.7560.181. PMC 1513476. PMID 16858047. 8. ^ Tendas A, Niscola P, Barbati R, Abruzzese E, Cuppelli L, Giovannini M, et al. (May 2011). "Tattoo related pyoderma/ectyma gangrenous as presenting feature of relapsed acute myeloid leukaemia: an exceptionally rare observation". Injury. 42 (5): 546–7. doi:10.1016/j.injury.2010.08.014. PMID 20883993. 9. ^ Patel F, Fitzmaurice S, Duong C, He Y, Fergus J, Raychaudhuri SP, et al. (May 2015). "Effective strategies for the management of pyoderma gangrenosum: a comprehensive review". Acta Dermato-Venereologica. 95 (5): 525–31. doi:10.2340/00015555-2008. PMID 25387526. 10. ^ Rashid RM (November 2008). "Seat belt pyoderma gangrenosum: minor pressure as a causative factor". Journal of the European Academy of Dermatology and Venereology. 22 (10): 1273–4. doi:10.1111/j.1468-3083.2008.02626.x. PMID 18837131. S2CID 27476857. 11. ^ Weenig RH, Davis MD, Dahl PR, Su WP (October 2002). "Skin ulcers misdiagnosed as pyoderma gangrenosum". The New England Journal of Medicine. 347 (18): 1412–8. doi:10.1056/NEJMoa013383. PMID 12409543. 12. ^ a b Maverakis E, Ma C, Shinkai K, Fiorentino D, Callen JP, Wollina U, et al. (April 2018). "Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of International Experts". JAMA Dermatology. 154 (4): 461–466. doi:10.1001/jamadermatol.2017.5980. PMID 29450466. S2CID 4774649. 13. ^ Reichrath J, Bens G, Bonowitz A, Tilgen W (August 2005). "Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients". Journal of the American Academy of Dermatology. 53 (2): 273–83. doi:10.1016/j.jaad.2004.10.006. PMID 16021123. ## External links[edit] Classification D * ICD-10: L88 * ICD-9-CM: 686.01 * MeSH: D017511 * DiseasesDB: 11064 * SNOMED CT: 74578003 External resources * eMedicine: article/1123821 * Orphanet: 48104 Wikimedia Commons has media related to Pyoderma gangrenosum. * v * t * e Neutrophilic and eosinophilic dermatoses Eosinophilic dermatosis With vasculitis * Eosinophilic vasculitis * Eosinophilic granulomatosis with polyangiitis Without vasculitis * Arthropod assault * Eosinophilic cellulitis * Hypereosinophilic syndrome * Papuloerythroderma of Ofuji * Granuloma faciale * Eosinophilic folliculitis Ungrouped * Angiolymphoid hyperplasia with eosinophilia/Kimura's disease * Annular erythema of infancy * Eosinophilic fasciitis * Eosinophilic granuloma * Eosinophilic ulcer of the oral mucosa * Erythema toxicum neonatorum * Incontinentia pigmenti * Itchy red bump disease * Juvenile xanthogranuloma * Pachydermatous eosinophilic dermatitis * Papular eruption of blacks * Pruritic papular eruption of HIV disease Reactive neutrophilic dermatoses Epidermis * Keratoderma blennorrhagicum * Subcorneal pustular dermatosis Dermis without vasculitis: * Sweet's syndrome * Pyoderma gangrenosum * Bowel-associated dermatosis–arthritis syndrome with vasculitis: * Neutrophilic dermatosis of the dorsal hands Ungrouped * Acute erythema nodosum * Marshall syndrome * Neutrophilic eccrine hidradenitis * Pyogenic arthritis–pyoderma gangrenosum–acne syndrome * Rheumatoid neutrophilic dermatitis * Superficial granulomatous pyoderma * Sweet's syndrome-like dermatosis * Vesicopustular dermatosis * v * t * e Cutaneous keratosis, ulcer, atrophy, and necrobiosis Epidermal thickening * keratoderma: Keratoderma climactericum * Paraneoplastic keratoderma * Acrokeratosis paraneoplastica of Bazex * Aquagenic keratoderma * Drug-induced keratoderma * psoriasis * Keratoderma blennorrhagicum * keratosis: Seborrheic keratosis * Clonal seborrheic keratosis * Common seborrheic keratosis * Irritated seborrheic keratosis * Seborrheic keratosis with squamous atypia * Reticulated seborrheic keratosis * Dermatosis papulosa nigra * Keratosis punctata of the palmar creases * other hyperkeratosis: Acanthosis nigricans * Confluent and reticulated papillomatosis * Callus * Ichthyosis acquisita * Arsenical keratosis * Chronic scar keratosis * Hyperkeratosis lenticularis perstans * Hydrocarbon keratosis * Hyperkeratosis of the nipple and areola * Inverted follicular keratosis * Lichenoid keratosis * Multiple minute digitate hyperkeratosis * PUVA keratosis * Reactional keratosis * Stucco keratosis * Thermal keratosis * Viral keratosis * Warty dyskeratoma * Waxy keratosis of childhood * other hypertrophy: Keloid * Hypertrophic scar * Cutis verticis gyrata Necrobiosis/granuloma Necrobiotic/palisading * Granuloma annulare * Perforating * Generalized * Subcutaneous * Granuloma annulare in HIV disease * Localized granuloma annulare * Patch-type granuloma annulare * Necrobiosis lipoidica * Annular elastolytic giant-cell granuloma * Granuloma multiforme * Necrobiotic xanthogranuloma * Palisaded neutrophilic and granulomatous dermatitis * Rheumatoid nodulosis * Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction Foreign body granuloma * Beryllium granuloma * Mercury granuloma * Silica granuloma * Silicone granuloma * Zirconium granuloma * Soot tattoo * Tattoo * Carbon stain Other/ungrouped * eosinophilic dermatosis * Granuloma faciale Dermis/ localized CTD Cutaneous lupus erythematosus * chronic: Discoid * Panniculitis * subacute: Neonatal * ungrouped: Chilblain * Lupus erythematosus–lichen planus overlap syndrome * Tumid * Verrucous * Rowell's syndrome Scleroderma/ Morphea * Localized scleroderma * Localized morphea * Morphea–lichen sclerosus et atrophicus overlap * Generalized morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma Atrophic/ atrophoderma * Lichen sclerosus * Anetoderma * Schweninger–Buzzi anetoderma * Jadassohn–Pellizzari anetoderma * Atrophoderma of Pasini and Pierini * Acrodermatitis chronica atrophicans * Semicircular lipoatrophy * Follicular atrophoderma * Linear atrophoderma of Moulin Perforating * Kyrle disease * Reactive perforating collagenosis * Elastosis perforans serpiginosa * Perforating folliculitis * Acquired perforating dermatosis Skin ulcer * Pyoderma gangrenosum Other * Calcinosis cutis * Sclerodactyly * Poikiloderma vasculare atrophicans * Ainhum/Pseudo-ainhum * v * t * e Paraneoplastic syndromes Endocrine * Hypercalcaemia * SIADH * Zollinger–Ellison syndrome * Cushing's syndrome Hematological * Multicentric reticulohistiocytosis * Nonbacterial thrombotic endocarditis Neurological * Paraneoplastic cerebellar degeneration * Encephalomyelitis * Limbic encephalitis * Opsoclonus * Polymyositis * Transverse myelitis * Lambert–Eaton myasthenic syndrome * Anti-NMDA receptor encephalitis Musculoskeletal * Dermatomyositis * Hypertrophic osteopathy Mucocutaneous reactive erythema * Erythema gyratum repens * Necrolytic migratory erythema papulosquamous * Acanthosis nigricans * Ichthyosis acquisita * Acrokeratosis paraneoplastica of Bazex * Extramammary Paget's disease * Florid cutaneous papillomatosis * Leser-Trélat sign * Pityriasis rotunda * Tripe palms Other * Febrile neutrophilic dermatosis * Pyoderma gangrenosum * Paraneoplastic pemphigus [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-aminobutyric 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	Pyoderma gangrenosum	c0085652	27,457	wikipedia	https://en.wikipedia.org/wiki/Pyoderma_gangrenosum	2021-01-18T18:29:42	{"gard": ["7510"], "mesh": ["D017511"], "umls": ["C0085652"], "icd-10": ["L88"], "orphanet": ["48104"], "wikidata": ["Q1526459"]}
For background information on susceptibility and resistance to Mycobacterium tuberculosis, see 607948. Description The tuberculin skin test (TST), or Mantoux test, measures induration of the skin after intradermal inoculation of M. tuberculosis purified protein derivative and thereby detects M. tuberculosis-infected and -noninfected persons. The TST triggers a classical T cell-mediated delayed-type hypersensitivity reaction against mycobacterial antigens. About 20% of individuals living in areas hyperendemic for tuberculosis show persistent absence of TST reactivity, suggesting T cell-independent resistance to M. tuberculosis infection. Genetic epidemiologic studies in endemic areas have suggested that host genetic factors contribute to resistance to M. tuberculosis infection and to the immune reactions underlying TST reactivity (summary by Cobat et al., 2009). Mapping Cobat et al. (2009) performed genomewide linkage analysis for TST reactivity in 128 families, including 186 parents and 350 children, from a suburb of Cape Town, South Africa, hyperendemic for tuberculosis. They identified a locus for the absence of TST reactivity, which they called TST1, on chromosome 11p14 with a lod score of 3.81 at position 26.37 Mb (P = 1.4 x 10(-5)). Suggestive linkage for absence of TST reactivity was also observed at chromosome 5p15 (lod score = 2.39; P = 0.0005) at the same position as TST2 (613637), a quantitative trait locus for TST reactivity in millimeters. Cobat et al. (2009) proposed that TST1 represents a major locus for T cell-independent resistance to M. tuberculosis, since a substantial portion of individuals who exhibit absence of TST reactivity are most likely resistant to M. tuberculosis infection. [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-aminobutyric 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	TUBERCULIN SKIN TEST REACTIVITY, ABSENCE OF	c3150892	27,458	omim	https://www.omim.org/entry/613636	2019-09-22T15:58:04	{"omim": ["613636"], "synonyms": ["Alternative titles", "TST REACTIVITY, ABSENCE OF", "TST1"]}
Childhood cataract is cataract that occurs at birth or in childhood.[1] It may be congenital or acquired. ## See also[edit] * Blindness ## References[edit] 1. ^ Medsinge, Anagha; Nischal, Ken K. (2015-01-01). "Pediatric cataract: challenges and future directions". Clinical Ophthalmology. Auckland, N.Z. 9: 77–90. doi:10.2147/OPTH.S59009. ISSN 1177-5467. PMC 4293928. PMID 25609909. ## Further reading[edit] * Childhood cataracts at NHS Choices * Cataracts in Children, Congenital and Acquired at EyeWiki * 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 * t * e Optical illusions (list) Illusions * Afterimage * Ambiguous image * Ames room * Barberpole * Bezold * Café wall * Checker shadow * Chubb * Cornsweet * Delboeuf * Ebbinghaus * Ehrenstein * Flash lag * Fraser spiral * Gravity hill * Grid * Hering * Impossible trident * Jastrow * Lilac chaser * Mach bands * McCollough * Müller-Lyer * Necker cube * Orbison * Penrose stairs * Penrose triangle * Peripheral drift * Poggendorff * Ponzo * Rubin vase * Sander * Schroeder stairs * Shepard tables * Spinning Dancer * Ternus * Vertical–horizontal * White's * Wundt * Zöllner Popular culture * Op art * Trompe-l'œil * Spectropia (1864 book) * Ascending and Descending (1960 drawing) * Waterfall (1961 drawing) * The dress (2015 photograph) Related * Accidental viewpoint * Auditory illusions * Tactile illusions * Temporal illusion 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-aminobutyric 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	Childhood cataract	c0302254	27,459	wikipedia	https://en.wikipedia.org/wiki/Childhood_cataract	2021-01-18T18:53:32	{"umls": ["C0302254"], "orphanet": ["91492"], "wikidata": ["Q18387306"]}
Rare autosomal recessive human diseases D-glycerate dehydrogenase deficiency Other names3-phosphoglycerate dehydrogenase Condition is acquired via an autosomal recessive pattern SpecialtyMetabolism SymptomsCongenital microcephaly, psychomotor retardation and seizures in infants, moderate developmental delay and behavioral disorders juveniles.[1] Usual onsetAdolescent, Infancy, Childhood CausesGenetic PreventionN/A TreatmentDiet MedicationSerine PrognosisShortened life expectancy Frequency<1 / 1 000 000 D-glycerate dehydrogenase deficiency or PHGDH is a rare autosomal metabolic disease where the young patient is unable to produce an enzyme necessary to convert 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the only way for humans to synthesize serine.This disorder is called Neu-Laxova syndrome in neonates. ## Contents * 1 Symptoms and signs * 2 Cause * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 References * 7 External links ## Symptoms and signs[edit] In addition significantly shortening lifespan, PHGDH deficiencies are known to cause congenital microcephaly, psychomotor retardation, and seizures in both humans and rats, presumably due to the essential signaling within the nervous system that serine, glycine, and other downstream molecules are intimately involved with.[citation needed] ## Cause[edit] Homozygous or compound heterozygous mutations in 3-phosphoglycerate dehydrogenase (PHGDH) cause Neu-Laxova syndrome[2][3] and phosphoglycerate dehydrogenase deficiency.[4] ## Mechanism[edit] 3-Phosphoglycerate dehydrogenase catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the committed step in the phosphorylated pathway of L-serine biosynthesis. It is also essential in cysteine and glycine synthesis, which lie further downstream.[5] This pathway represents the only way to synthesize serine in most organisms except plants, which uniquely possess multiple synthetic pathways. Nonetheless, the phosphorylated pathway that PHGDH participates in is still suspected to have an essential role in serine synthesis used in the developmental signaling of plants.[6][7] ## Diagnosis[edit] This section is empty. You can help by adding to it. (June 2020) ## Treatment[edit] Treatment typically involves oral supplementation of serine and glycine.[8][9] ## References[edit] 1. ^ "Orphanet: Search by disease name". Retrieved 1 December 2019. 2. ^ Shaheen R, Rahbeeni Z, Alhashem A, Faqeih E, Zhao Q, Xiong Y, Almoisheer A, Al-Qattan SM, Almadani HA, Al-Onazi N, Al-Baqawi BS, Saleh MA, Alkuraya FS (Jun 2014). "Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH". American Journal of Human Genetics. 94 (6): 898–904. doi:10.1016/j.ajhg.2014.04.015. PMC 4121479. PMID 24836451. 3. ^ Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, Grigelioniene G, Nilsson D, Nordenskjöld M, Wedell A, Freyer C, Wredenberg A, Wieczorek D, Gillessen-Kaesbach G, Kayserili H, Elcioglu N, Ghaderi-Sohi S, Goodarzi P, Setayesh H, van de Vorst M, Steehouwer M, Pfundt R, Krabichler B, Curry C, MacKenzie MG, Boycott KM, Gilissen C, Janecke AR, Hoischen A, Zenker M (Sep 2014). "Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway". American Journal of Human Genetics. 95 (3): 285–93. doi:10.1016/j.ajhg.2014.07.012. PMC 4157144. PMID 25152457. 4. ^ Jaeken J, Detheux M, Van Maldergem L, Foulon M, Carchon H, Van Schaftingen E (Jun 1996). "3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis". Archives of Disease in Childhood. 74 (6): 542–5. doi:10.1136/adc.74.6.542. PMC 1511571. PMID 8758134. 5. ^ "MetaCyc L-serine biosynthesis". biocyc.org. Retrieved 2016-03-01. 6. ^ Ros R, Muñoz-Bertomeu J, Krueger S (Sep 2014). "Serine in plants: biosynthesis, metabolism, and functions". Trends in Plant Science. 19 (9): 564–9. doi:10.1016/j.tplants.2014.06.003. PMID 24999240. 7. ^ Ho CL, Noji M, Saito M, Saito K (Jan 1999). "Regulation of serine biosynthesis in Arabidopsis. Crucial role of plastidic 3-phosphoglycerate dehydrogenase in non-photosynthetic tissues". The Journal of Biological Chemistry. 274 (1): 397–402. doi:10.1074/jbc.274.1.397. PMID 9867856. 8. ^ de Koning TJ, Duran M, Dorland L, Gooskens R, Van Schaftingen E, Jaeken J, Blau N, Berger R, Poll-The BT (Aug 1998). "Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency". Annals of Neurology. 44 (2): 261–5. doi:10.1002/ana.410440219. PMID 9708551. 9. ^ de Koning TJ, Klomp LW, van Oppen AC, Beemer FA, Dorland L, van den Berg I, Berger R (2004-12-18). "Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency". Lancet. 364 (9452): 2221–2. doi:10.1016/S0140-6736(04)17596-X. PMID 15610810. S2CID 40121728. ## External links[edit] Classification D * ICD-10: Q74.8 * OMIM: 260000 * MeSH: C536415 [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-aminobutyric 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	D-glycerate dehydrogenase deficiency	c0268165	27,460	wikipedia	https://en.wikipedia.org/wiki/D-glycerate_dehydrogenase_deficiency	2021-01-18T19:09:19	{"gard": ["2836"], "mesh": ["C536415"], "umls": ["C0268165"], "wikidata": ["Q85845764"]}
Paraparetic variant of Guillain-Barré syndrome is a rare variant of Guillain-Barré syndrome characterized by isolated leg weakness, areflexia and radicular leg pain that may simulate a cauda equina or spinal cord syndrome. The arms, ocular, facial, and oropharyngeal muscles are spared, and sphincteric function 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-aminobutyric 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	Paraparetic variant of Guillain-Barré syndrome	c4707803	27,461	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231445	2021-01-23T17:55:16	{"icd-10": ["G61.0"], "synonyms": ["Paraparetic variant of GBS"]}
A number sign (#) is used with this entry because of evidence that Seckel syndrome-10 (SCKL10) is caused by compound heterozygous mutation in the NSMCE2 gene (617246) on chromosome 8q24. For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600). Clinical Features Payne et al. (2014) studied 2 unrelated 46,XX women with severe short stature and microcephaly; facial dysmorphism with small jaw and prominent midface; extremely insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. One of the women was congenitally blind, reportedly due to retinal detachment, and died suddenly at age 33 years, presumably due to rupture of a previously documented abdominal aortic aneurysm. Molecular Genetics In a Welsh woman with severe short stature, microcephaly, insulin resistance, and primary gonadal failure, Payne et al. (2014) performed exome sequencing and identified compound heterozygosity for a 1-bp deletion (617246.0001) and a 4-bp insertion (617246.0002) in the NSMCE2 gene. In a similarly affected French woman, Sanger sequencing of NSMCE2 revealed compound heterozygosity for the same 2 mutations. The parents in both families were heterozygous for the mutations; haplotype analysis confirmed that both patients inherited the same rare 2 haplotypes within a region greater than 510 kb, suggesting shared common ancestral haplotypes. Neither of the mutations or haplotypes were found in a sample of 54 controls from Great Britain, in 4,190 internal control exomes and genomes, or in the 1000 Genomes Project database (July 2012); however, the 1-bp deletion was found in heterozygous state in 2 of 6,250 individuals in the NHLBI Exome Sequencing Project database (April 2013; allele frequency, 0.00016). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, extreme Weight \- Low weight, extreme HEAD & NECK Head \- Microcephaly Face \- Prominent midface \- Microretrognathia Eyes \- Retinal detachment, bilateral congenital (patient A) Teeth \- Small secondary teeth (patient B) CARDIOVASCULAR Heart \- Ventricular hypertrophy (patient A) \- Heart failure (patient A) Vascular \- Hypertension (patient A) \- Abdominal aortic aneurysm (patient A) ABDOMEN External Features \- Subcutaneous fat accumulation (patient A) Liver \- Fatty liver Pancreas \- Acute pancreatitis (patient A) \- Pancreatic exocrine insufficiency (patient A) GENITOURINARY Internal Genitalia (Female) \- Prepubertal uterus \- Prepubertal or undetectable ovaries SKELETAL Skull \- Microcephaly Limbs \- Gracile long bones (patient A) \- Widened metaphyses (patient A) \- Cone-shaped epiphyses (patient A) SKIN, NAILS, & HAIR Skin \- Acanthosis nigricans \- Skin tags MUSCLE, SOFT TISSUES \- Accumulation of subcutaneous adipose tissue in limbs and abdomen (patient A) NEUROLOGIC Central Nervous System \- Global learning difficulties, mild METABOLIC FEATURES \- Extreme insulin resistance ENDOCRINE FEATURES \- Impaired glucose tolerance \- Diabetes mellitus, poorly controlled \- Primary gonadal failure \- Elevated luteinizing hormone (LH) \- Elevated follicle-stimulating hormone (FSH) \- Undetectable estrogen LABORATORY ABNORMALITIES \- Glycosuria \- Elevated fasting blood glucose \- Elevated HbA1c \- Markedly elevated fasting plasma insulin \- Elevated fasting serum triglycerides \- Lipemic serum \- Low serum high density lipoprotein (HDL) cholesterol \- Elevated serum aspartate aminotransferase (AST) \- Elevated serum alanine aminotransferase (ALT) MISCELLANEOUS \- Based on report of 2 unrelated patients (last curated December 2016) MOLECULAR BASIS \- Caused by mutation in the homolog of S. cerevisiae non-SMC element-2 gene (NSMCE2, 617246.0001 ) ▲ 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-aminobutyric 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	SECKEL SYNDROME 10	c4310647	27,462	omim	https://www.omim.org/entry/617253	2019-09-22T15:46:20	{"doid": ["0070008"], "omim": ["617253"], "orphanet": ["436182"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (NEDBAF) is caused by heterozygous mutation in the RAC3 gene (602050) on chromosome 17q25. Clinical Features White et al. (2018) reported a girl (BAB8740) with global developmental delay, poor language, seizures, and thin corpus callosum on brain imaging. She had dysmorphic features, including midface hypoplasia, micrognathia, hypertelorism, long eyelashes, prominent eyes, anteverted nares, wide nasal bridge, short nose, long philtrum, and dental anomalies. She also had clinodactyly, fetal finger and toe pads, and genital hypoplasia. There was no family history of a similar disorder, and the authors suggested that her features were reminiscent of Robinow syndrome (see 180700). Costain et al. (2019) reported 5 patients, including 2 maternal half sibs, with a similar neurodevelopmental disorder. They had global developmental delay with severely to profoundly impaired intellectual development, and abnormal muscle tone. Two patients had seizures and 3 had scoliosis. Brain imaging showed variable structural abnormalities in all patients, including absence of or thin corpus callosum, enlarged ventricles, and cerebral dysgenesis with polymicrogyria and heterotopia. The 2 half sibs had Chiari type I malformation. Dysmorphic features were nonspecific and variable: frontal bossing, brachycephaly with sloping forehead, prominent glabella, hypertelorism, narrow palpebral fissures, high-arched eyebrows, depressed nasal bridge with broad nasal tip, short philtrum, high-arched palate, dental crowding, simple ears, full lips, tapered fingers, and clinodactyly. Molecular Genetics In a girl with NEDBAF, White et al. (2018) identified a de novo heterozygous missense mutation in the RAC3 gene (A59G; 602050.0001). The mutation was found by exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant and studies of patient cells were not performed. In 5 patients, including 2 half sibs, with NEDBAF, Costain et al. (2019) identified heterozygous missense mutations in the RAC3 gene (602050.0002-602050.0004). The mutations occurred de novo in 3 patients and were suspected to result from maternal gonadal mosaicism in the affected half sibs. The mutations, which were found by exome sequencing, were not present in the gnomAD database. Functional studies of the variants and studies of patient cells were not performed, but the authors postulated a toxic gain-of-function effect due to constitutive activation and abnormal GTPase signaling. [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-aminobutyric 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	NEURODEVELOPMENTAL DISORDER WITH STRUCTURAL BRAIN ANOMALIES AND DYSMORPHIC FACIES	None	27,463	omim	https://www.omim.org/entry/618577	2019-09-22T15:41:52	{"omim": ["618577"]}
For a general phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease, see 104300. Mapping Liu et al. (2007) conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that was conducted in an isolated population from the southwestern area of the Netherlands. Genealogic information resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees to reduce the computational burden of linkage analysis. The strongest evidence for linkage, hlod = 5.20 at marker D1S498, was obtained at chromosome 1q21 (AD13). Approximately 30 cM upstream of this locus, at 1q25 (AD14; 611154), another peak was found (hlod = 4.0 at marker D1S218). Liu et al. (2007) noted that these 2 loci were in a linkage region spanning 1q21-q31 identified by Zubenko et al. (1998), Hiltunen et al. (2001), Myers et al. (2002), and Blacker et al. (2003). Haplotype analysis showed that the 2 linkage peaks on chromosome 1q21 and 1q25 are explained by different haplotypes, of 15 cM and 21 cM, respectively, segregating in different families. The 1q21 region was not replicated when testing for association with cognitive function as an endophenotype of AD in 197 distantly related subjects. Liu et al. (2007) concluded that although they could not exclude the possibility of a false positive finding, given the strength of the linkage signal and previous evidence it was more likely that there is a rare mutation in a major gene in this region that could not be identified by association analysis in a small sample. [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-aminobutyric 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	ALZHEIMER DISEASE 13	c0276496	27,464	omim	https://www.omim.org/entry/611152	2019-09-22T16:03:34	{"doid": ["0110046"], "mesh": ["D000544"], "omim": ["611152"], "orphanet": ["1020"]}
Human genetic disease that impairs the body's ability to make blood clots, a process needed to stop bleeding "Hemophiliac" redirects here. For the band, see Hemophiliac (band). Haemophilia Other namesHemophilia A drawing of clotting factor VIII Pronunciation * /hiːməˈfɪliə/ SpecialtyHaematology SymptomsEasy and prolonged bleeding[1] Usual onsetAt birth[2] CausesUsually genetic[3] Diagnostic methodBlood test[4] PreventionPreimplantation screening[4] TreatmentReplace missing blood clotting factors[3] Frequency1 in 7,500 males (haemophilia A), 1 in 40,000 males (haemophilia B)[2][5] Haemophilia is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding.[2][3] This results in people bleeding for a longer time after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain.[1] Those with a mild case of the disease may have symptoms only after an accident or during surgery.[1] Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a decreased level of consciousness.[1] There are two main types of haemophilia: haemophilia A, which occurs due to low amounts of clotting factor VIII, and haemophilia B, which occurs due to low levels of clotting factor IX.[2] They are typically inherited from one's parents through an X chromosome carrying a nonfunctional gene.[6] Rarely a new mutation may occur during early development or haemophilia may develop later in life due to antibodies forming against a clotting factor.[2][6] Other types include haemophilia C, which occurs due to low levels of factor XI, and parahaemophilia, which occurs due to low levels of factor V.[7][8] Acquired haemophilia is associated with cancers, autoimmune disorders, and pregnancy.[9][10] Diagnosis is by testing the blood for its ability to clot and its levels of clotting factors.[4] Prevention may occur by removing an egg, fertilizing it, and testing the embryo before transferring it to the uterus.[4] Treatment is by replacing the missing blood clotting factors.[3] This may be done on a regular basis or during bleeding episodes.[3] Replacement may take place at home or in hospital.[11] The clotting factors are made either from human blood or by recombinant methods.[11] Up to 20% of people develop antibodies to the clotting factors which makes treatment more difficult.[3] The medication desmopressin may be used in those with mild haemophilia A.[11] Studies of gene therapy are in early human trials.[12] Haemophilia A affects about 1 in 5,000–10,000, while haemophilia B affects about 1 in 40,000, males at birth.[2][5] As haemophilia A and B are both X-linked recessive disorders, females are rarely severely affected.[6] Some females with a nonfunctional gene on one of the X chromosomes may be mildly symptomatic.[6] Haemophilia C occurs equally in both sexes and is mostly found in Ashkenazi Jews.[5] In the 1800s haemophilia B was common within the royal families of Europe.[5] The difference between haemophilia A and B was determined in 1952.[5] The word is from the Greek haima αἷμα meaning blood and philia φιλία meaning love.[13] ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Genetics * 2.1 Severity * 3 Diagnosis * 3.1 Before pregnancy * 3.2 During pregnancy * 3.3 After birth * 3.4 Classification * 4 Management * 4.1 Clotting factors * 4.2 Other * 4.3 Contraindications * 5 Prognosis * 6 Epidemiology * 7 History * 7.1 Scientific discovery * 7.2 European royalty * 7.3 Treatment * 7.4 Blood contamination * 8 Research * 8.1 Gene therapy * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] A woman with hemophilia Characteristic symptoms vary with severity. In general symptoms are internal or external bleeding episodes, which are called "bleeds".[14][15] People with more severe haemophilia suffer more severe and more frequent bleeds, while people with mild haemophilia usually suffer more minor symptoms except after surgery or serious trauma. In cases of moderate haemophilia symptoms are variable which manifest along a spectrum between severe and mild forms.[16][citation needed] In both haemophilia A and B, there is spontaneous bleeding but a normal bleeding time, normal prothrombin time, normal thrombin time, but prolonged partial thromboplastin time. Internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces.[17] This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement.[17] Bleeding into soft tissues such as muscles and subcutaneous tissues is less severe but can lead to damage and requires treatment. Children with mild to moderate haemophilia may not have any signs or symptoms at birth, especially if they do not undergo circumcision. Their first symptoms are often frequent and large bruises and haematomas from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints, soft tissue, and muscles may also occur. Children with mild haemophilia may not have noticeable symptoms for many years. Often, the first sign in very mild haemophiliacs is heavy bleeding from a dental procedure, an accident, or surgery. Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs. ### Complications[edit] Severe complications are much more common in cases of severe and moderate haemophilia. Complications may arise from the disease itself or from its treatment:[18] * Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb. * Joint damage from haemarthrosis (haemophilic arthropathy), potentially with severe pain, disfigurement, and even destruction of the joint and development of debilitating arthritis. * Transfusion transmitted infection from blood transfusions that are given as treatment. * Adverse reactions to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective. * Intracranial haemorrhage is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation, nausea, loss of consciousness, brain damage, and death. Haemophilic arthropathy is characterized by chronic proliferative synovitis and cartilage destruction.[19] If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans. The hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more likely to easily rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis. In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in cartilage and bone destruction.[20] ## Genetics[edit] X-linked recessive inheritance Typically, females possess two X-chromosomes, and males have one X and one Y-chromosome. Since the mutations causing the disease are X-linked recessive, a female carrying the defect on one of her X-chromosomes may not be affected by it, as the equivalent dominant allele on her other chromosome should express itself to produce the necessary clotting factors, due to X inactivation. Therefore, heterozygous females are just carriers of this genetic disposition. However, the Y-chromosome in the male has no gene for factors VIII or IX. If the genes responsible for production of factor VIII or factor IX present on a male's X-chromosome are deficient there is no equivalent on the Y-chromosome to cancel it out, so the deficient gene is not masked and the disorder will develop. Since a male receives his single X-chromosome from his mother, the son of a healthy female silently carrying the deficient gene will have a 50% chance of inheriting that gene from her and with it the disease; and if his mother is affected with haemophilia, he will have a 100% chance of being a haemophiliac. In contrast, for a female to inherit the disease, she must receive two deficient X-chromosomes, one from her mother and the other from her father (who must therefore be a haemophiliac himself). Hence, haemophilia is expressed far more commonly among males than females, while double-X females are far more likely to be silent carriers, survive childhood and to submit each of her genetic children to an at least 50% risk of receiving the deficient gene. However, it is possible for female carriers to become mild haemophiliacs due to lyonisation (inactivation) of the X-chromosomes. Haemophiliac daughters are more common than they once were, as improved treatments for the disease have allowed more haemophiliac males to survive to adulthood and become parents. Adult females may experience menorrhagia (heavy periods) due to the bleeding tendency. The pattern of inheritance is criss-cross type. This type of pattern is also seen in colour blindness. A mother who is a carrier has a 50% chance of passing the faulty X-chromosome to her daughter, while an affected father will always pass on the affected gene to his daughters. A son cannot inherit the defective gene from his father. This is a recessive trait and can be passed on if cases are more severe with carrier. Genetic testing and genetic counselling is recommended for families with haemophilia. Prenatal testing, such as amniocentesis, is available to pregnant women who may be carriers of the condition. As with all genetic disorders, it is also possible for a human to acquire it spontaneously through mutation, rather than inheriting it, because of a new mutation in one of their parents' gametes. Spontaneous mutations account for about 33% of all cases of haemophilia A.[21] About 30% of cases of haemophilia B are the result of a spontaneous gene mutation. If a female gives birth to a haemophiliac son, either the female is a carrier for the blood disorder or the haemophilia was the result of a spontaneous mutation. Until modern direct DNA testing, however, it was impossible to determine if a female with only healthy children was a carrier or not. Generally, the more healthy sons she bore, the higher the probability that she was not a carrier. If a male is afflicted with the disease and has children with a female who is not a carrier, his daughters will be carriers of haemophilia. His sons, however, will not be affected with the disease. The disease is X-linked and the father cannot pass haemophilia through the Y-chromosome. Males with the disorder are then no more likely to pass on the gene to their children than carrier females, though all daughters they sire will be carriers and all sons they father will not have haemophilia (unless the mother is a carrier). ### Severity[edit] There are numerous different mutations which cause each type of haemophilia. Due to differences in changes to the genes involved, people with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those with 1–5% active factor have moderate haemophilia, and those with mild haemophilia have between 5% and 40% of normal levels of active clotting factor.[17] ## Diagnosis[edit] Haemophilia can be diagnosed before, during or after birth if there is a family history of the condition. Several options are available to parents. If there is no family history of haemophilia, it is usually only diagnosed when a child begins to walk or crawl. They may experience joint bleeds or easy bruising.[22] Mild haemophilia may only be discovered later, usually after an injury or a dental or surgical procedure. ### Before pregnancy[edit] Genetic testing and counselling are available to help determine the risk of passing the condition onto a child.[22] This may involve testing a sample of tissue or blood to look for signs of the genetic mutation that causes haemophilia.[22] ### During pregnancy[edit] A pregnant woman with a history of haemophilia in her family can test for the haemophilia gene. Such tests include: * chorionic villus sampling (CVS): a small sample of the placenta is removed from the womb and tested for the haemophilia gene, usually during weeks 11–14 of pregnancy[23] * amniocentesis: a sample of amniotic fluid is taken for testing, usually during weeks 15–20 of pregnancy[24] There is a small risk of these procedures causing problems such as miscarriage or premature labour, so the woman may discuss this with the doctor in charge of her care.[22] ### After birth[edit] If haemophilia is suspected after a child has been born, a blood test can usually confirm the diagnosis. Blood from the umbilical cord can be tested at birth if there's a family history of haemophilia. A blood test will also be able to identify whether a child has haemophilia A or B, and how severe it is.[22] ### Classification[edit] There are several types of haemophilia: haemophilia A, haemophilia B, haemophilia C, parahaemophilia, acquired haemophilia A, and acquired haemophilia B.[25][26][27][28] Haemophilia A, is a recessive X-linked genetic disorder resulting in a deficiency of functional clotting Factor VIII.[26] Haemophilia B, is also a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX.[29] Haemophilia C, is an autosomal genetic disorder involving a lack of functional clotting Factor XI. Haemophilia C is not completely recessive, as heterozygous individuals also show increased bleeding.[27] The type of haemophilia known as parahaemophilia is a mild and rare form and is due to a deficiency in factor V. This type can be inherited or acquired.[8] A non-genetic form of haemophilia is caused by autoantibodies against factor VIII and so is known as acquired haemophilia A.[10] It is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors.[30] Acquired haemophilia can be associated with cancers, autoimmune disorders and following childbirth.[31] ## Management[edit] There is no long-term cure. Treatment and prevention of bleeding episodes is done primarily by replacing the missing blood clotting factors.[3] ### Clotting factors[edit] Commercially produced factor concentrates such as "Advate", a recombinant Factor VIII, come as a white powder in a vial which must be mixed with sterile water prior to intravenous injection. Clotting factors are usually not needed in mild haemophilia.[11] In moderate haemophilia clotting factors are typically only needed when bleeding occurs or to prevent bleeding with certain events.[11] In severe haemophilia preventive use is often recommended two or three times a week and may continue for life.[11] Rapid treatment of bleeding episodes decreases damage to the body.[11] Factor VIII is used in haemophilia A and factor IX in haemophilia B. Factor replacement can be either isolated from human blood serum, recombinant, or a combination of the two. Some people develop antibodies (inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as porcine factor VIII.[citation needed] If a person becomes refractory to replacement coagulation factor as a result of high levels of circulating inhibitors, this may be partially overcome with recombinant human factor VIII. In early 2008, the US Food and Drug Administration (FDA) approved anti-haemophilic factor genetically engineered from the genes of Since 1993 recombinant factor products (which are typically cultured in Chinese hamster ovary (CHO) tissue culture cells and involve little, if any human plasma products) have been available and have been widely used in wealthier western countries. While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world. In many cases, factor products of any sort are difficult to obtain in developing countries.[citation needed] Clotting factors are either given preventively or on-demand. Preventive use involves the infusion of clotting factor on a regular schedule in order to keep clotting levels sufficiently high to prevent spontaneous bleeding episodes. On-demand (or episodic) treatment involves treating bleeding episodes once they arise. In 2007, a trial comparing on-demand treatment of boys (< 30 months) with haemophilia A with prophylactic treatment (infusions of 25 IU/kg body weight of Factor VIII every other day) in respect to its effect on the prevention of joint-diseases. When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on MRI.[32] Preventative treatment, however, resulted in average costs of $300,000 per year. The author of an editorial published in the same issue of the NEJM supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related haemorrhage may be more cost effective than waiting until the fixed age to begin.[33] Most haemophiliacs in third world countries have limited or no access to commercial blood clotting factor products.[34] ### Other[edit] Desmopressin (DDAVP) may be used in those with mild haemophilia A.[11] Tranexamic acid or epsilon aminocaproic acid may be given along with clotting factors to prevent breakdown of clots.[11] Pain medicines, steroids, and physical therapy may be used to reduce pain and swelling in an affected joint.[11] In those with severe hemophilia A already receiving FVIII, emicizumab may provide some benefit.[35] Different treatments are used to help those with an acquired form of hemophilia in addition to the normal clotting factors. Often the most effective treatment is corticosteroids which remove the auto-antibodies in half of people. As a secondary route of treatment, cyclophosphamide and cyclosporine are used and are proven effective for those who did not respond to the steroid treatments. In rare cases a third route or treatment is used, high doses of intravenous immunoglobulin or immunosorbent that works to help control bleeding instead of battling the auto-antibodies. [36] ### Contraindications[edit] Anticoagulants such as heparin and warfarin are contraindicated for people with haemophilia as these can aggravate clotting difficulties. Also contraindicated are those drugs which have "blood thinning" side effects. For instance, medicines which contain aspirin, ibuprofen, or naproxen sodium should not be taken because they are well known to have the side effect of prolonged bleeding.[37] Also contraindicated are activities with a high likelihood of trauma, such as motorcycling and skateboarding. Popular sports with very high rates of physical contact and injuries such as American football, hockey, boxing, wrestling, and rugby should be avoided by people with haemophilia.[37][38] Other active sports like soccer, baseball, and basketball also have a high rate of injuries, but have overall less contact and should be undertaken cautiously and only in consultation with a doctor.[37] ## Prognosis[edit] Like most aspects of the disorder, life expectancy varies with severity and adequate treatment. People with severe haemophilia who don't receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years.[17] By the 1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years.[17] Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.[39] Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from haemorrhage to HIV/AIDS acquired through treatment with contaminated blood products.[17] The second leading cause of death related to severe haemophilia complications is intracranial haemorrhage which today accounts for one third of all deaths of people with haemophilia. Two other major causes of death include hepatitis infections causing cirrhosis and obstruction of air or blood flow due to soft tissue haemorrhage.[17] ## Epidemiology[edit] Haemophilia is rare, with only about 1 instance in every 10,000 births (or 1 in 5,000 male births) for haemophilia A and 1 in 50,000 births for haemophilia B.[40] About 18,000 people in the United States have haemophilia. Each year in the US, about 400 babies are born with the disorder. Haemophilia usually occurs in males and less often in females.[41] It is estimated that about 2,500 Canadians have haemophilia A, and about 500 Canadians have haemophilia B.[42] ## History[edit] "About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is unfortunately subject, and had been the source not only of great solicitude, but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted. (…) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation." John C. Otto, 1803[43] ### Scientific discovery[edit] The excessive bleeding was known to ancient people. The Talmud instructs that a boy must not be circumcised if he had two brothers who died due to complications arising from their circumcisions, and Maimonides says that this excluded paternal half-brothers. This may have been due to a concern about hemophilia.[44] The first medical professional to describe the disease was Arab surgeon Al-Zahrawi, also known as Abulcasis. In the tenth century he described families whose males died of bleeding after only minor traumas.[45] While many other such descriptive and practical references to the disease appear throughout historical writings, scientific analysis did not begin until the start of the nineteenth century. In 1803, John Conrad Otto, a Philadelphian physician, wrote an account about "a hemorrhagic disposition existing in certain families" in which he called the affected males "bleeders".[46] He recognised that the disorder was hereditary and that it affected mostly males and was passed down by healthy females. His paper was the second paper to describe important characteristics of an X-linked genetic disorder (the first paper being a description of colour blindness by John Dalton who studied his own family). Otto was able to trace the disease back to a woman who settled near Plymouth, NH in 1720. The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John F. Hay, published an account in The New England Journal of Medicine.[47][48] In 1924, a Finnish doctor discovered a hereditary bleeding disorder similar to haemophilia localised in the Åland Islands, southwest of Finland.[49] This bleeding disorder is called "Von Willebrand Disease". The term "haemophilia" is derived from the term "haemorrhaphilia" which was used in a description of the condition written by Friedrich Hopff in 1828, while he was a student at the University of Zurich.[46][50] In 1937, Patek and Taylor, two doctors from Harvard, discovered anti-haemophilic globulin.[51] In 1947, Pavlosky, a doctor from Buenos Aires, found haemophilia A and haemophilia B to be separate diseases by doing a lab test. This test was done by transferring the blood of one haemophiliac to another haemophiliac. The fact that this corrected the clotting problem showed that there was more than one form of haemophilia. ### European royalty[edit] Main article: Haemophilia in European royalty Haemophilia in European royalty Haemophilia has featured prominently in European royalty and thus is sometimes known as 'the royal disease'. Queen Victoria passed the mutation for haemophilia B[52][53] to her son Leopold and, through two of her daughters, Alice and Beatrice, to various royals across the continent, including the royal families of Spain, Germany, and Russia. In Russia, Tsarevich Alexei, the son and heir of Tsar Nicholas II, famously suffered from haemophilia, which he had inherited from his mother, Empress Alexandra, one of Queen Victoria's granddaughters. The haemophilia of Alexei would result in the rise to prominence of the Russian mystic Grigori Rasputin, at the imperial court. It was claimed that Rasputin was successful at treating Tsarevich Alexei's haemophilia. At the time, a common treatment administered by professional doctors was to use aspirin, which worsened rather than lessened the problem. It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Tsarevich Alexei.[citation needed] In Spain, Queen Victoria's youngest daughter, Princess Beatrice, had a daughter Victoria Eugenie of Battenberg, who later became Queen of Spain. Two of her sons were haemophiliacs and both died from minor car accidents. Her eldest son, Prince Alfonso of Spain, Prince of Asturias, died at the age of 31 from internal bleeding after his car hit a telephone booth.[54] Her youngest son, Infante Gonzalo, died at age 19 from abdominal bleeding following a minor car accident in which he and his sister hit a wall while avoiding a cyclist. Neither appeared injured or sought immediate medical care and Gonzalo died two days later from internal bleeding.[55] ### Treatment[edit] The method for the production of an antihaemophilic factor was discovered by Judith Graham Pool from Stanford University in 1964,[56] and approved for commercial use in 1971 in the United States under the name Cryoprecipitated AHF.[57] Together with the development of a system for transportation and storage of human plasma in 1965, this was the first time an efficient treatment for haemophilia became available.[58] ### Blood contamination[edit] Main article: Contaminated haemophilia blood products Ryan White was an American haemophiliac who became infected with HIV/AIDS through contaminated blood products. Up until late-1985 many people with haemophilia received clotting factor products that posed a risk of HIV and hepatitis C infection. The plasma used to create the products was not screened or tested, neither had most of the products been subject to any form of viral inactivation. Tens of thousands worldwide were infected as a result of contaminated factor products including more than 10,000 people in the United States,[59] 3,500 British, 1,400 Japanese,[60] 700 Canadians,[61] 250 Irish,[62] and 115 Iraqis.[63] Infection via the tainted factor products had mostly stopped by 1986 by which time viral inactivation methods had largely been put into place,[64] although some products were shown to still be dangerous in 1987.[65] ## Research[edit] ### Gene therapy[edit] In those with severe haemophilia, gene therapy may reduce symptoms to those that a mild or moderate person with haemophilia might have.[12] The best results have been found in haemophilia B.[12] In 2016 early stage human research was ongoing with a few sites recruiting participants.[12] In 2017 a gene therapy trial on nine people with haemophilia A reported that high doses did better than low doses.[66][67] It is not currently an accepted treatment for haemophilia.[11] ## See also[edit] * Coagulopathy * Purpura secondary to clotting disorders * World Federation of Hemophilia ## References[edit] 1. ^ a b c d "What Are the Signs and Symptoms of Hemophilia?". NHLBI. July 13, 2013. Archived from the original on 17 September 2016. Retrieved 8 September 2016. 2. ^ a b c d e f "What Is Hemophilia?". NHLBI. July 13, 2013. Archived from the original on 4 October 2016. Retrieved 8 September 2016. 3. ^ a b c d e f g "Hemophilia Facts". CDC. August 26, 2014. Archived from the original on 27 August 2016. Retrieved 8 September 2016. 4. ^ a b c d "How Is Hemophilia Diagnosed?". NHLBI. July 13, 2013. Archived from the original on 15 September 2016. Retrieved 10 September 2016. 5. ^ a b c d e Wynbrandt, James; Ludman, Mark D. (1 January 2009). The Encyclopedia of Genetic Disorders and Birth Defects. Infobase Publishing. p. 194. ISBN 978-1-4381-2095-9. Archived from the original on 8 January 2014. Retrieved 25 August 2013. 6. ^ a b c d "What Causes Hemophilia?". NHLBI. July 13, 2013. Archived from the original on 8 September 2016. Retrieved 10 September 2016. 7. ^ Franchini, M; Mannucci, PM (October 2011). "Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice". British Journal of Clinical Pharmacology. 72 (4): 553–62. doi:10.1111/j.1365-2125.2010.03899.x. PMC 3195733. PMID 21204915. 8. ^ a b Thalji, N; Camire, RM (September 2013). "Parahemophilia: new insights into factor v deficiency". Seminars in Thrombosis and Hemostasis. 39 (6): 607–12. doi:10.1055/s-0033-1349224. PMID 23893775. 9. ^ Franchini, M; Mannucci, PM (December 2013). "Acquired haemophilia A: a 2013 update". Thrombosis and Haemostasis. 110 (6): 1114–20. CiteSeerX 10.1.1.684.7962. doi:10.1160/TH13-05-0363. PMID 24008306. 10. ^ a b Mulliez, SM; Vantilborgh, A; Devreese, KM (June 2014). "Acquired hemophilia: a case report and review of the literature". International Journal of Laboratory Hematology. 36 (3): 398–407. doi:10.1111/ijlh.12210. PMID 24750687. S2CID 205194015. 11. ^ a b c d e f g h i j k "How Is Hemophilia Treated?". NHLBI. July 13, 2013. 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PMID 29224412. ## External links[edit] Wikimedia Commons has media related to Hemophilia. * Haemophilia at Curlie Classification D * ICD-10: D66-D68 * ICD-9-CM: 286 * ICD-O: 0117 * OMIM: 306700 306900 264900 * MeSH: D025861 * DiseasesDB: 5555 External resources * MedlinePlus: 000537 * eMedicine: med/3528 * Scholia: Q134003 * v * t * e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause * Clotting factors * Antithrombin III deficiency * Protein C deficiency * Activated protein C resistance * Protein S deficiency * Factor V Leiden * Prothrombin G20210A * Platelets * Sticky platelet syndrome * Thrombocytosis * Essential thrombocythaemia * DIC * Purpura fulminans * Antiphospholipid syndrome Clots * Thrombophilia * Thrombus * Thrombosis * Virchow's triad * Trousseau sign of malignancy By site * Deep vein thrombosis * Bancroft's sign * Homans sign * Lisker's sign * Louvel's sign * Lowenberg's sign * Peabody's sign * Pratt's sign * Rose's sign 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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-aminobutyric 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	Haemophilia	c0684275	27,465	wikipedia	https://en.wikipedia.org/wiki/Haemophilia	2021-01-18T18:29:33	{"gard": ["10418"], "umls": ["C0684275"], "icd-9": ["286"], "icd-10": ["D68", "D66"], "orphanet": ["448", "98429"], "wikidata": ["Q134003"]}
The various forms of epidermolysis bullosa can be classified into 3 major histologic groups: epidermolytic, junctional, and dermolytic. Distribution of lesions, extracutaneous manifestations, age of onset, and inheritance further divide these types into many subtypes. Nakar et al. (1992) described a brother and sister, born of healthy Bulgarian Jewish parents with no known consanguinity, who had late-onset epidermolysis bullosa localized to the anterior aspect of the legs associated with a defect of the dental enamel, dystrophic toenails, and mental retardation. Subluxation of the lenses was found in the only patient in whom complete ophthalmologic examination was performed. Both had a similar facial appearance including short midface and philtrum, prognathism, and thin vermilion border of the upper lip. The girl was born with a cleft palate. There was no homocystinuria. The skin lesions began at ages 7 and 9 years. The blistering lesions recurred especially in warm humid weather. A few blisters also appeared on the dorsal aspects of the hands and forearms. Reports suggesting the existence of an autosomal recessive form of epidermolysis bullosa were provided by Heagerty et al. (1985), Gamborg Nielsen and Sjolund (1985), and Niemi et al. (1988). The school-age onset of skin blistering apparently of junctional type, associated with enamel defect and nail dystrophy, were features identical to those in the female offspring of first-cousin parents reported by Anton-Lamprecht and Schnyder (1979). The histopathologic findings suggested degeneration of the basal layer with a subepidermal split and subepidermal bulla formation. The family reported by Niemi et al. (1988) appears to be different because of the associated muscular dystrophy and possibly more severe skin disease (see 226670). Eyes \- Lens subluxation Neuro \- Mental retardation Facies \- Short midface \- Short philtrum \- Prognathism \- Thin vermilion border of upper lip Inheritance \- Autosomal recessive Skin \- Epidermolysis bullosa localized to anterior legs Mouth \- Cleft palate Nails \- Dystrophic toenails Teeth \- Enamel defect Misc \- Late-onset ▲ 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-aminobutyric 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	EPIDERMOLYSIS BULLOSA, LATE-ONSET LOCALIZED JUNCTIONAL, WITH MENTAL RETARDATION	c1856969	27,466	omim	https://www.omim.org/entry/226440	2019-09-22T16:28:12	{"mesh": ["C535492"], "omim": ["226440"], "orphanet": ["231556"]}
## Clinical Features Humans, like other mammals, depend on rhythmic breathing to regulate one of the foremost aspects of homeostasis: the appropriate exchange of oxygen and carbon dioxide. The neuromechanisms responsible for respiratory rhythmogenesis were elucidated by in vitro studies of brainstem preparations from neonatal rodents. In the rostral ventrolateral medulla, a set of neurons known as the 'preBotzinger complex' act as an inspiratory pacemaker that plays a vital role in respiratory rhythmogenesis; see review of Feldman et al. (2003). Bilateral outflow of the preBotzinger complex and its associated 'distributed' network in the lower brainstem is transmitted to the spinal motor neurons (hypoglossal nerve and phrenic nerve) to produce rhythmic contraction. The function of respiratory rhythmogenesis is critically important in sleep disorders, such as sleep apnea (207720). Mapping De Geus et al. (2005) performed a sib pair-base linkage analysis on ambulatory respiratory rate, using the data from 270 sib pairs who were genotyped at 374 markers on autosomes. Linkage analyses were performed for respiratory rate during 3 daytime periods (morning, afternoon, and evening) and during nighttime sleep. The strongest evidence of linkage was found for respiratory rate during sleep, with lod scores of 2.36 at 3q27, 3.86 at 10q26, and 1.59 at 22q12. In a simultaneous analysis of these 3 loci, more than 50% of the variance in sleep respiratory rate could be attributed to a quantitative trait locus near marker D10S1248 at 10q. Genes in this area that could be considered promising positional candidates for genetic association studies of respiratory control during sleep included the following: GFRA1 (601496) on 10q26, ADORA2L (102777) on 10q25.3-q26.3, FGFR2 (176943) on 10q26, EMX2 (600035) on 10q26.1, and HMX2 (600647) on 10q25.2-q26.3. [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-aminobutyric 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	RESPIRATORY RHYTHMICITY IN SLEEP	c1836764	27,467	omim	https://www.omim.org/entry/609116	2019-09-22T16:06:37	{"omim": ["609116"], "synonyms": ["Alternative titles", "RRIS"]}
Hemoglobin Lepore syndrome Other namesHb Lepore syndrome A crossover between the delta and beta globin gene loci results in the mutation which causes the Hb Lepore trait. Hemoglobin Lepore syndrome is typically an asymptomatic hemoglobinopathy, which is caused by an autosomal recessive genetic mutation. The Hb Lepore variant, consisting of two normal alpha globin chains (HBA) and two delta-beta globin fusion chains which occurs due to a "crossover" between the delta (HBD) and beta globin (HBB) gene loci during meiosis and was first identified in the Lepore family, an Italian-American family, in 1958.[1] There are three varieties of Hb Lepore, Washington (Hb Lepore Washington, AKA Hb Lepore Boston or Hb Lepore Washington-Boston), Baltimore (Hb Lepore Baltimore) and Hollandia (Hb Hollandia). All three varieties show similar electrophoretic and chromatographic properties and hematological findings bear close resemblance to those of the beta-thalassemia trait; a blood disorder that reduces the production of the iron-containing protein hemoglobin which carries oxygen to cells and which may cause anemia. The homozygous state for Hb Lepore is rare. Patients of Balkan descent tend to have the most severe presentation of symptoms including severe anemia during the first five years of life. They also presented with significant splenomegaly, hepatomegaly, and skeletal abnormalities identical to those of homozygous beta-thalassemia. The amount of Hb Lepore in the patients blood ranged from 8 to 30%, the remainder being fetal hemoglobin (Hb F) which is present in minute quantities (typically<1 percent) in the red blood cells of adults. Known as F- cells they are present in a small proportion of overall RBCs.[2] Homozygous Hb Lepore is similar to beta-thalassemia major; however, the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11–13 g/dl) but presents with a significant hypochromia (deficiency of hemoglobin in the red blood cells) and microcytosis.[3][4] ## Contents * 1 Presentation * 1.1 Complications * 2 Cause * 3 Diagnosis * 4 Treatment * 4.1 Homozygous Hb Lepore * 4.2 Heterozygous Hb Lepore * 5 Epidemiology * 6 References ## Presentation[edit] ### Complications[edit] A potential complication that may occur in children that suffer acute anemia with a hemoglobin count below 5.5 g/dl is silent stroke[5] A silent stroke is a type of stroke that does not have any outward symptoms (asymptomatic), and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms a silent stroke still causes damage to the brain, and places the patient at increased risk for both transient ischemic attack and major stroke in the future.[6] ## Cause[edit] Sickle cell-Hb Lepore Boston syndrome is a type of sickle cell disease (HbS) that differs from homozygous sickle cell disease where both parents carry sickle hemoglobin. In this variant one parent has the sickle cell hemoglobin the second parent has Hb Lepore Boston, the only one of the three variants described in association with HbS.[7] ## Diagnosis[edit] The diagnosis of Hb Lepore syndrome may be performed antenatally or postnatally via the use of a variety of tests * Complete blood count (CBC) * Cation Exchange High-performance liquid chromatography (CE-HPLC): a chromatographic technique used to separate and quantify various normal and abnormal hemoglobin components in blood.[8] * Hemoglobin electrophoresis * DNA analysis[9] ## Treatment[edit] ### Homozygous Hb Lepore[edit] Those homozygous (Hb LeporeLepore; a very rare situation) or compound heterozygous (Hb Lepore-Β-thalassaemia) might suffer from a severe anaemia. They should be managed in a comprehensive multi-disciplinary program of care.[10] Management includes a regular course of blood transfusions, although the clinical severity in compound (double) heterozygotes can range from minor to major, depending on the combination of genes that have caused the condition.[11] ### Heterozygous Hb Lepore[edit] Individuals heterozygous for the Hb Lepore require no particular treatment. There is no anemia or, if there is, it is very mild.[12] ## Epidemiology[edit] The Hb Lepore trait has a worldwide distribution and may affect individuals of various ethnicities however the three main varieties which been defined tend to be more prevalent among specific ethnic groups, typically Caucasians of the Southern regions Central and Eastern Europe. The three main varieties are named for the geographical areas they were first identified in with various subtypes, the three main varieties are:[citation needed] * Washington (Hb Lepore Washington, also known as Hb Lepore Boston or Hb Lepore Washington-Boston); most common in Italians from Southern Italy * Baltimore (Hb Lepore Baltimore); first described in a family with African ancestry; most common in people from the Balkan countries, Albanians Croats, Serbs, Slovenes and Romanians. It has also been described in Turks and in regions of Spain and Portugal. A rare case of the Baltimore variety was discovered in an African American woman in the Bronx, New York and dubbed Hn Lepore-Bronx[13] and another variety was discovered in the city of Saskatoon, Saskatchewan, Canada and dubbed Hb E-Lepore Saskatoon[14] * Hollandia (Hb Lepore Hollandia); identified in Papua New Guinea and Bangladesh. ## References[edit] 1. ^ Gerald PS, Diamond LK (September 1958). "A new hereditary hemoglobinopathy (the Lepore trait) and its interaction with thalassemia trait". Blood. 13 (9): 835–44. doi:10.1182/blood.v13.9.835.835. PMID 13572441. 2. ^ Rochette J, Craig JE, Thein SL (December 1994). "Fetal hemoglobin levels in adults". Blood Rev. 8 (4): 213–24. doi:10.1016/0268-960x(94)90109-0. PMID 7534152. 3. ^ Ricci G, Scutellari PN, Franceschini F, Gualandi G (February 1982). "[A new case of hemoglobin Lepore-beta-thalassemia disease]". Minerva Med. (in Italian). 73 (5): 191–7. PMID 7063135. 4. ^ Efremov GD, Rudivić R, Niazi GA, et al. (February 1976). "An individual with Hb-Lepore-Baltimore- delta beta-thalassaemia in a Yugoslavian family". Scand J Haematol. 16 (2): 81–9. doi:10.1111/j.1600-0609.1976.tb01122.x. PMID 1257702. 5. ^ Dowling MM, Quinn CT, Plumb P, Rogers ZR, Rollins N, Koral K, Barber R, Buchanan GR (11 February 2011). "Acute anemia linked to silent strokes in children American Stroke Association Meeting Report: Abstract 185". American Heart Association. Archived from the original on 26 July 2011.[unreliable medical source?] 6. ^ Miwa K, Rudivić R, Niazi GA, et al. (2010). "Silent cerebral infarction is associated with incident stroke and TIA independent of carotid intima-media thickness". Intern Med. 49 (9): 817–22. doi:10.2169/internalmedicine.49.3211. PMID 20453400. 7. ^ Stevens MC, Lehmann H, Mason KP (January 1982). "Sickle cell-Hb Lepore Boston syndrome. Uncommon differential diagnosis to homozygous sickle cell disease". Am J Dis Child. 136 (1): 19–22. doi:10.1001/archpedi.1982.03970370021004. PMID 7055103. 8. ^ Gupta LCPK; Kumar CH; Kumar CCS; Jaiprakash BM (2009). "Cation exchange high performance liquid chromatography for diagnosis of haemoglobinopathies" (PDF). Med J Armed Forces India. 65 (1): 33–37. doi:10.1016/s0377-1237(09)80051-8. PMC 4921438. PMID 27408187. Archived from the original (PDF) on 11 August 2016. 9. ^ Almon McKusick; Stylianos E. Antonarakis (1998). Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders (12th ed.). Johns Hopkins University Press. p. 849. ISBN 0-8018-5742-2. 10. ^ "Haemoglobin Lepore – Anaemias – Enerca". 11. ^ http://nefeli.lib.teicrete.gr/browse/seyp/nos/2009/AmyrialakiMaria,LerakiDimitra,SifalakiIouliaNektaria/attached-document-1285754310-610362-24189/Amyrialaki2009.pdf 12. ^ "Haemoglobin Lepore – Anaemias – Enerca". 13. ^ McKeown SM, Carmichael H, Markowitz RB, Kutlar A, Holley L, Kutlar F (June 2009). "Rare occurrence of Hb Lepore-Baltimore in African Americans: molecular characteristics and variations of Hb Lepores". Ann Hematol. 88 (6): 545–8. doi:10.1007/s00277-008-0631-4. PMID 18989669. S2CID 8931267. 14. ^ Ropero P, Murga MJ, González FA, Polo M, Benavente C, Salvador M, Villegas A (2005). "The first case of Hb E-Saskatoon associated with Hb Lepore-Baltimore found in Spain". Hemoglobin. 29 (3): 215–9. doi:10.1081/hem-200066321. PMID 16114185. [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-aminobutyric 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	Hemoglobin Lepore syndrome	c4683758	27,468	wikipedia	https://en.wikipedia.org/wiki/Hemoglobin_Lepore_syndrome	2021-01-18T18:51:34	{"wikidata": ["Q5712491"]}
Levin (1986) told me of a family with this anomaly in an autosomal dominant pedigree pattern. Mouth \- Hamartoma of lower lip 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-aminobutyric 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	LIP, HAMARTOMATOUS	c1835395	27,469	omim	https://www.omim.org/entry/151640	2019-09-22T16:38:50	{"mesh": ["C563621"], "omim": ["151640"], "synonyms": ["Alternative titles", "ENLARGEMENT OF LOWER LIP"]}
Canadian craniopagus conjoined twins Krista and Tatiana Hogan Born Krista and Tatiana Hogan (2006-10-25) October 25, 2006 (age 14) Vernon, British Columbia, Canada NationalityCanadian Parent(s)Brendan Hogan and Felicia Simms Krista and Tatiana Hogan (born October 25, 2006) are Canadians who are conjoined craniopagus twins. They are joined at the head (the top, back, and sides). They were born in Vancouver, British Columbia, and are the only unseparated conjoined twins of that type currently alive in Canada.[1] They live with their mother, Felicia Simms, in Vernon, British Columbia, have two sisters and a brother and often travel to Vancouver for care at BC Children's Hospital and Sunny Hill Health Centre for Children.[2] ## Contents * 1 Birth * 2 Early infant life * 3 Progression to childhood * 4 See also * 5 References * 6 Further reading * 7 External links ## Birth[edit] The twins were given a 20 percent chance of survival at birth.[citation needed] At birth at B.C. Women's Hospital & Health Centre, they were described as "wriggly, vigorous and very vocal".[3] They weighed 12 and a half pounds[4] when they were born by caesarean section. ## Early infant life[edit] Tatiana is smaller and less robust than Krista. Tests on them in April 2007 showed that Tatiana's heart was working harder than Krista's and that she had high blood pressure because of it—Tatiana's heart was supplying part of her blood to Krista's brain. A surgery was planned to give Krista's heart a "jump start" so Tatiana's would not have to work so hard.[5] The twins' nervous systems are highly interconnected. Their doctors reported that when one of them is tickled, the other jumps, and that putting a pacifier in the mouth of one could cause the other to stop crying.[5] The twins' birth, potential separation, depth of community support and their family's financial situation have been subject to significant media coverage in Canada. They and their mother were also guests on The Tyra Banks Show in the U.S. In August 2007, it was declared the twins cannot be separated, due to the likelihood of the surgery killing or paralyzing one or both girls.[1] The family reduced the twins' public profile due to a contract giving exclusive access to a documentary crew for National Geographic and the Discovery Channel UK. The show was broadcast first in Britain in spring 2010, and then aired in June in Canada and the U.S.[6] The documentary followed a year in the twins' life and included a "particularly poignant" meeting between the family and Lori and George Schappell, 51, the world’s oldest twins to survive being joined at the head.[7] There is evidence[8] that the twins can see through each other's eyes due to brain conjoining. Their thalami are joined. ## Progression to childhood[edit] In January 2009, a documentary was filmed which reported on the twins, and followed their progress up to their third birthday. This documentary was released and aired in October, 2010. In this documentary, it was confirmed that they share a thalamus which connects their brainstems. Through this shared brain tissue structure and the interconnected neurons, one brain receives signals from the other brain and vice versa. This documentary also reported on experiments that were carried out that confirmed that visual cortex signals based on what one girl saw, were received by both girls' brains. So in effect, one twin could see what the other twin was seeing, making them unique even among craniopagus twins. At this time, Tatiana suffered from a sleep apnea condition that occasionally caused her to stop breathing for up to 20 seconds. A sleep apnea specialist, Dr. Fred Kozak, surgically treated her sleep apnea. Not long after the surgery, her heart shrank to a more normal size and its rate dropped such that it no longer carried all of the burden of circulating blood for both brains.[9] The documentary reports that the twins are progressing well, and have achieved all the normal childhood milestones, such as walking, talking, and counting. A 2014 CBC Radio documentary described how they can feel and taste what the other is experiencing.[10] Later it was also confirmed that they can see through each other's eyes.[11] ## See also[edit] * Polycephaly ## References[edit] 1. ^ a b "Doctors won't separate conjoined twins". Canada.com. 2007-08-04. Retrieved 2011-05-12. 2. ^ https://www.cbc.ca/cbcdocspov/m_features/the-hogan-twins-share-a-brain-and-see-out-of-each-others-eyes 3. ^ Statement from BC Women's regarding Felicia Simms delivery Archived 2007-06-19 at the Wayback Machine., News release, BC Women's Hospital & Health Centre, October 25, 2006 4. ^ The Twins Who Share a Brain 5. ^ a b "CTV British Columbia - Family learns B.C. twins can't be separated - CTV News, Shows and Sports - Canadian Television". Ctvbc.ctv.ca. 2007-08-03. Retrieved 2011-05-12. 6. ^ Tatiana and Krista on the move, By Ken MacQueen, Macleans. February 8, 2010. 7. ^ Today's TV, The Mirror, May 25, 2010 8. ^ Dominus, Susan (May 25, 2011). "Could Conjoined Twins Share a Mind?". New York Times. Retrieved 19 December 2012. 9. ^ Twins Who Share A Brain, Doc Zone Video documentary, October 14, 2010 CBC.ca 10. ^ The Hogan sisters; how conjoined twins share body and mind The Current, March 13, 2014 11. ^ "Inseparable: Ten Years Joined At The Head". June 27, 2019. Archived from the original on 2020-05-07. ## Further reading[edit] * Dominus, Susan (25 May 2011). "Could Conjoined Twins Share a Mind?". Magazine. The New York Times. Retrieved 17 September 2012. * Squair, Jordan (2012). Sarwal, Amara (ed.). "Craniopagus: Overview and the implications of sharing a brain". University of British Columbia's Undergraduate Journal of Psychology. 1. Archived from the original on 1 January 2013. Retrieved 17 September 2012. * Armstrong, Jane (14 December 2006). "Tissue 'bridge' joins twins' brains". The Globe and Mail. Retrieved 17 September 2012. ## External links[edit] * The Twins, Article about the twins at About.com, www.about.com, retrieved on January 27, 2008 * Photos: At home with conjoined twins Tatiana and Krista Hogan, Windsor Star, 2014 * http://dailygleaner.canadaeast.com/canadaworld/article/458621(subscription required) [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-aminobutyric 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	Krista and Tatiana Hogan	None	27,470	wikipedia	https://en.wikipedia.org/wiki/Krista_and_Tatiana_Hogan	2021-01-18T18:38:22	{"wikidata": ["Q6437699"]}
Anastomosis of the median and ulnar nerves was described as a frequent 'normal' variant by Martin (1763) in Sweden and by Gruber (1870) in Leipzig. Axons descend in the median nerve, joining the ulnar nerve in the forearm before innervating intrinsic muscles of the hand. Crutchfield and Gutmann (1980) found median-ulnar communications in 28% of the general population and in 62% of family members. They proposed autosomal dominant inheritance. No male-to-male transmission was noted in a small series of families. Most often the anomalous axons innervated the first dorsal interosseous muscles and less often the hypothenar and thenar muscles. Gruber (1870) reported a frequency of 15.1% on dissection of 125 cadaver arms. Srinivasan and Rhodes (1981) found bilateral median-ulnar anastomoses in all 8 trisomy 21 fetuses studied, but no bilateral anastomoses were found in 7 trisomy 18, 1 trisomy 13, or 10 anencephaly fetuses. Awareness of the variation is important in the evaluation of median and ulnar neuropathies. A comparable anomaly has been observed in innervations of the extensor digitorum brevis muscle by the accessory deep peroneal nerve (170980). Neuro \- Anastomosis of median and ulnar nerves 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-aminobutyric 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	MEDIAN-ULNAR NERVE COMMUNICATIONS	c1835086	27,471	omim	https://www.omim.org/entry/155150	2019-09-22T16:38:30	{"mesh": ["C563598"], "omim": ["155150"], "synonyms": ["Alternative titles", "MARTIN-GRUBER MEDIAN-ULNAR ANASTOMOSIS"]}
Fear of the number 13 "Fear of 13" redirects here. For the film, see The Fear of 13. Stall numbers at Santa Anita Park progress from 12 to 12A to 14, as does Eaton Square, London Triskaidekaphobia (/ˌtrɪskaɪˌdɛkəˈfoʊbiə/ TRIS-kye-DEK-ə-FOH-bee-ə, /ˌtrɪskə-/ TRIS-kə-; from Ancient Greek τρεισκαίδεκα (treiskaídeka) 'thirteen', and Ancient Greek φόβος (phóbos) 'fear')[1] is fear or avoidance of the number 13. It is also a reason for the fear of Friday the 13th, called paraskevidekatriaphobia (from Greek Παρασκευή (Paraskevi) 'Friday', Greek δεκατρείς (dekatreís) 'thirteen', and Ancient Greek φόβος (phóbos) 'fear') or friggatriskaidekaphobia (from Old Norse Frigg 'Frigg', Ancient Greek τρεισκαίδεκα (treiskaídeka) 'thirteen', and Ancient Greek φόβος (phóbos) 'fear'). The term was used as early as in 1910 by Isador Coriat in Abnormal Psychology.[2] ## Contents * 1 Origins * 1.1 Norse mythology * 1.2 Judas theory * 2 Events related to "unlucky" 13 * 2.1 Effect on US Shuttle program mission naming * 2.2 Omission of 13th rooms, floors and decks * 3 Famous people with triskaidekaphobia * 4 Similar phobias * 5 Lucky 13 * 6 See also * 7 Notes * 8 References * 9 External links ## Origins[edit] ### Norse mythology[edit] According to folklore historian Donald Dossey, the unlucky nature of the number "13" originated with a Norse myth about 12 gods having a dinner party in Valhalla. The trickster god Loki, who was not invited, arrived as the 13th guest, and arranged for Höðr to shoot Balder with a mistletoe-tipped arrow. Dossey: "Balder died, and the whole Earth got dark. The whole Earth mourned. It was a bad, unlucky day." This major event in Norse mythology caused the number 13 to be considered unlucky.[3][4] ### Judas theory[edit] From the 1890s, a number of English language sources have related the "unlucky" number thirteen to an idea that at the Last Supper, Judas, the disciple who betrayed Jesus, was the 13th to sit at the table.[5] The Bible says nothing about the order in which the Apostles sat, but there were thirteen people at the table. ## Events related to "unlucky" 13[edit] The exposed lift shaft of an apartment block under construction. The lift shaft has numbers marking the levels, but the 13th level is instead marked with a heart. * Apollo 13 was launched on April 11, 1970 at 13:13:00 CST and suffered an oxygen tank explosion on April 13 at 21:07:53 CST. It returned safely to Earth on April 17.[6][7] * On Friday, October 13, 1307, the arrest of the Knights Templar was ordered by Philip IV of France. While the number 13 was considered unlucky, Friday the 13th was not considered unlucky at the time. The incorrect idea that their arrest was related to the phobias surrounding Friday the 13th was invented early in the 21st century and popularized by the novel The Da Vinci Code.[8] * In 1881 an influential group of New Yorkers, led by US Civil War veteran Captain William Fowler, came together to put an end to this and other superstitions. They formed a dinner cabaret club, which they called the Thirteen Club. At the first meeting, on January 13, 1881, at 8:13 p.m., thirteen people sat down to dine in Room 13 of the venue. The guests walked under a ladder to enter the room and were seated among piles of spilled salt. Many "Thirteen Clubs" sprang up all over North America over the next 45 years. Their activities were regularly reported in leading newspapers, and their numbers included five future US presidents, from Chester A. Arthur to Theodore Roosevelt. Thirteen Clubs had various imitators, but they all gradually faded due to a lack of interest.[9] * Friday the 13th mini-crash * Vehicle registration plates in Ireland are such that the first two digits represent the year of registration of the vehicle (i.e., 11 is a 2011 registered car, 12 is 2012, and so on). In 2012, there were concerns among members of the Society of the Irish Motor Industry (SIMI) that the prospect of having "13" registered vehicles might discourage motorists from buying new cars because of superstition surrounding the number thirteen, and that car sales and the motor industry (which was already failing) would suffer as a result. The government, in consultation with SIMI, introduced a system whereby 2013 registered vehicles would have their registration plates' age identifier string modified to read "131" for vehicles registered in the first six months of 2013 and "132" for those registered in the latter six months of the year.[10][11]1 * In July 2020, the 13th flight of Rocket Lab's Electron rocket failed to reach orbit during the second engine burn, resulting in a loss of vehicle. This was the first failure of an Electron rocket to cause the loss of a customer's payload and the second overall failure of the rocket.[12][13] ### Effect on US Shuttle program mission naming[edit] The disaster that occurred on Apollo 13 may have been a factor that led to a renaming that prevented a mission called STS-13[14][15] Alternate mission patch of STS-41C, with a 13 and a black cat, as it landed on April 13th, which was a Friday the 13th and this was the mission originally scheduled as STS-13.[16] > At first glance, it may seem surprising that an agency whose focus lies in science and technology should devote such an emphasis to an ancient superstition, but for one thing: the unlucky voyage of Apollo 13. > > — Ben Evans (2012)[17] STS-41-G was the name of the thirteenth Space Shuttle flight.[18] However, originally STS-41-C was the mission originally numbered STS-13[19][20] STS-41-C was the eleventh orbital flight of the space shuttle program.[21] The numbering system of the Space Shuttle was changed to a new one after STS-9.[22] The new naming scheme started with STS-41B, the previous mission was STS-9, and the thirteenth mission (what would have been STS-13) would be STS-41C.[22] The new scheme had first number stand for the U.S. fiscal year, the next number was a launch site (1 or 2), and the next was the number of the mission numbered with a letter for that period.[22] In the case of the actual 13th flight, the crew was apparently not superstitious and made a humorous mission patch that had a black cat on it.[22] Also, that mission re-entered and landed on Friday the 13th which one crew described as being "pretty cool".[22] Because of the way the designations and launch manifest work, the mission numbered STS-13 might not have actually been the 13th to launch as was common throughout the shuttle program; indeed it turned out to be the eleventh.[23][21] One of the reasons for this was when a launch had to be scrubbed, which delayed its mission.[24] NASA said in a 2016 news article it was due to a much higher frequency of planned launches (pre-Challenger disaster).[22] As it was, the Shuttle program did have a disaster on its one-hundred and thirteenth mission going by date of launch, which was STS-107.[25] The actual mission STS-113 was successful, and had actually launched earlier due to the nature of the launch manifest.[26] ### Omission of 13th rooms, floors and decks[edit] Many ships, including cruise liners have omitted having a 13th deck due to triskaidekaphobia. Instead, the decks are numbered up to 12 and skip straight to number 14. Hotels, buildings and elevator manufacturers have also avoided using the number 13 for rooms and floors based on triskaidekaphobia.[27] ## Famous people with triskaidekaphobia[edit] This section contains information of unclear or questionable importance or relevance to the article's subject matter. Please help improve this section by clarifying or removing indiscriminate details. If importance cannot be established, the section is likely to be moved to another article, pseudo-redirected, or removed. Find sources: "Triskaidekaphobia" – news · newspapers · books · scholar · JSTOR (Learn how and when to remove this template message) * Arnold Schoenberg[28] * Franklin Roosevelt[29] * Sholom Aleichem[30] * Stephen King[31] * Nick Yarris[32] ## Similar phobias[edit] An elevator in a residential apartment building in Shanghai: the 4th, 13th and 14th floors in height are deliberately not so named, such numbers are skipped. * Number 4 (Tetraphobia). In China, Taiwan, Singapore, Japan, Korea and Vietnam, as well as in some other East Asian and South East Asian countries, it is not uncommon for buildings (including offices, apartments, hotels) to omit floors with numbers that include the digit 4, and Finnish mobile phone manufacturer Nokia's 1xxx-9xxx series of mobile phones does not include any model numbers beginning with a 4 (except Series 40, Nokia 3410 and Nokia 4.2). This originates from Classical Chinese, in which the pronunciation of the word for "four" (四, sì in Mandarin) is very similar to that of the word for "death" (死, sǐ in Mandarin), and remains so in the other countries' Sino-Xenic vocabulary (Korean sa for both; Japanese shi for both; Vietnamese tứ "four" vs. tử "death"). * Friday the 13th (Paraskevidekatriaphobia or Friggatriskaidekaphobia) is considered to be a day of bad luck in a number of western cultures. In Greece and some areas of Spain and Latin America, Tuesday the 13th is similarly considered unlucky.2 * Number 17 (Heptadekaphobia). In Italy, perhaps because in Roman numerals 17 is written XVII, which can be rearranged to VIXI, which in Latin means "I have lived" but can be a euphemism for "I am dead." In Italy, some planes have no row 17 and some hotels have no room 17.[33] * Number 39 (Triakontenneaphobia). There is a belief in some parts of Afghanistan that the number 39 (thrice thirteen) is cursed or a badge of shame.[34] * Number 616 (Hexakosioihekkaidekaphobia) or 666 (Hexakosioihexekontahexaphobia). ## Lucky 13[edit] In some regions, 13 is or has been considered a lucky number. For example, prior to the First World War, 13 was considered to be a lucky number in France, even being featured on postcards and charms.[35] In more modern times, 13 is lucky in Italy except in some contexts, such as sitting at the dinner table.[36] In Cantonese-speaking areas, including Hong Kong and Macau, the number 13 is considered lucky because it sounds similar to the Cantonese words meaning "sure to live" (as opposed to the unlucky number 14 which in Cantonese sounds like the words meaning "sure to die"). Colgate University was started by 13 men with $13 and 13 prayers, so 13 is considered a lucky number. Friday the 13th is the luckiest day at Colgate.[37] A number of sportspeople are known for wearing the number 13 jersey and performing successfully. On November 23, 2003, the Miami Dolphins retired the number 13 for Dan Marino, who played for the Dolphins from 1983-1999. In 1966, the Portugal national football team achieved their best-ever result at the World Cup final tournaments by finishing third, thanks to a Mozambican-born striker, Eusebio, who has scored nine goals at World Cup — four of them in a 5-3 quarterfinal win over North Korea — and won the Golden Boot award as the tournament's top scorer while wearing the number 13. In the 1954 and 1974 World Cup finals, Germany's Max Morlock and Gerd Müller, respectively, played and scored in the final, wearing the number 13.[38] More recent footballers playing successfully despite wearing #13, include Michael Ballack, Alessandro Nesta, and Rafinha.[39] Among other sportspeople who have chosen 13 as squad number, are the Venezuelans Dave Concepción, Omar Vizquel, Oswaldo Guillén and Pastor Maldonado. ## See also[edit] * List of phobias * National Accident Day (Finland) ## Notes[edit] ^1 The main reason for this was stated to be to increase the number of car sales in the second half of the year. Even though 70% of new cars are bought during the first four months of the year, some consumers believe that the calendar year of registration does not accurately reflect the real age of a new car, since cars bought in January will most likely have been manufactured the previous year, while those bought later in the year will be actually made in the same year. ^2 Tuesday is generally unlucky in Greece for the fall of Byzantium Tues 29th May 1453.[40] In Spanish-speaking countries, there is a proverb: En martes no te cases, ni te embarques 'On Tuesday, do not get married or set sail'.[41] ## References[edit] 1. ^ "triskaidekaphobia - Origin and meaning of triskaidekaphobia by Online Etymology Dictionary". Etymonline.com. Retrieved 5 November 2017. 2. ^ "Abnormal Psychology" p. 319, published in 1910, Moffat, Yard and company (New York). Library of Congress Control No. 10011167. 3. ^ Friday the 13th Superstitions Rooted in Bible and More, National Geographic 4. ^ Why is Friday the 13th Considered Unlucky?, Mental Floss 5. ^ Cecil Adams (1992-11-06). "Why is the number 13 considered unlucky?". The Straight Dope. Retrieved 2011-05-13. 6. ^ "13 Things That Saved Apollo 13, Part 9: Position of the Tanks - Universe Today". Universetoday.com. 21 April 2010. Retrieved 5 November 2017. 7. ^ "WHAT REALLY HAPPENED TO APOLLO 13 HOME PAGE". Spaceacts.com. Retrieved 5 November 2017. 8. ^ Robinson, John J. (1990). Born in Blood: The Lost Secrets of Freemasonry. ISBN 978-0-87131-602-8. 9. ^ Nick Leys, If you bought this, you've already had bad luck, review of Nathaniel Lachenmayer's Thirteen: The World's Most Popular Superstition, Weekend Australian, 8–9 January 2005 10. ^ 2013 number plates to be changed to avoid ‘unlucky 13’ , Irish Independent, 24 August 2012 11. ^ "2013 Number Plates To Be Changed To Avoid 'Unlucky 13'". Irish Independent. 12. ^ https://www.rocketlabusa.com/news/updates/rocket-lab-mission-fails-to-reach-orbit/ 13. ^ https://arstechnica.com/science/2020/07/on-its-13th-launch-rocket-lab-loses-a-mission/?utm_brand=arstechnica&utm_source=twitter&utm_social-type=owned&utm_medium=social 14. ^ Almeida, Andres (5 December 2016). "Behind the Space Shuttle mission numbering system". nasa.gov. Retrieved 5 November 2017. 15. ^ Evans, Ben (1 June 2012). Tragedy and Triumph in Orbit: The Eighties and Early Nineties. Springer Science & Business Media. p. 211. ISBN 9781461434306. 16. ^ Evans, Ben (2007). Space Shuttle Challenger: Ten Journeys into the Unknown. ISBN 9780387496795. Retrieved 30 May 2012 – via Google Books. 17. ^ Evans, Ben (1 June 2012). Tragedy and Triumph in Orbit: The Eighties and Early Nineties. Springer Science & Business Media. p. 211. ISBN 9781461434306. 18. ^ "Challenger mission No. 6 (13th shuttle program mission overall)". Orlando Sentinel. 41-G. Retrieved 5 November 2017. 19. ^ "James D. A. van Hoften" (PDF). Oral History Project. NASA Johnson Space Center. 5 December 2007. Retrieved 20 July 2013. 20. ^ "Terry J. Hart" (PDF). Oral History Project. NASA Johnson Space Center. 10 April 2003. Retrieved 20 July 2013. 21. ^ a b "STS-41-C Information". Astonautix. Retrieved 28 December 2017. 22. ^ a b c d e f Almeida, Andres (5 December 2016). "Behind the Space Shuttle Mission Numbering System". NASA. Retrieved 17 January 2017. 23. ^ Evans, Ben (1 June 2012). Tragedy and Triumph in Orbit: The Eighties and Early Nineties. Springer Science & Business Media. ISBN 9781461434306. 24. ^ Evans, Ben (1 June 2012). Tragedy and Triumph in Orbit: The Eighties and Early Nineties. Springer Science & Business Media. p. 211. ISBN 9781461434306 – via Google Books. 25. ^ "The Columbia Disaster". Space Safety Magazine. Retrieved 28 December 2017. 26. ^ Warnock, Lynda. "NASA STS-113". KSC. nasa.gov. Retrieved 17 January 2017. 27. ^ "Cruise secrets: Why can passengers never find this mysterious location on a cruise ship?". www.express.co.uk. Retrieved 2020-09-30. 28. ^ "Fear of 13 and Other Superstitions Embedded in Compositions". WQXR-FM. May 13, 2016. Retrieved 2019-01-24. 29. ^ Perry, Warren. "Fears of the Fearless FDR: A President's Superstitions for Friday the 13th". Smithsonian Institution. Retrieved 2019-01-24. 30. ^ Haberman, Clyde (May 17, 2010). "A Reading to Recall the Father of Tevye". The New York Times. Retrieved 2019-01-24. 31. ^ Chan, Melissa. "Why Friday the 13th Is a Real Nightmare for Some People". Retrieved 8 December 2018. 32. ^ Tobias, Scott (March 29, 2016). "Film Review: 'The Fear of 13'". Variety. Retrieved 2019-01-24. 33. ^ Harris, Nick (15 November 2007). "Bad Omen for Italy as Their Unlucky Number Comes Up". The Independent. London. 34. ^ Jon Boone. "The curse of number 39 and the steps Afghans take to avoid it". The Guardian. Retrieved 28 December 2017. 35. ^ Davies, Owen (2018). A Supernatural War: Magic, Divination, and Faith During the First World War. Oxford: Oxford University Press. p. 136. ISBN 9780198794554. 36. ^ "Aggiungi un posto a tavola, siamo in 13!" [Add a seat at the table, we are 13!]. Di cibo e altre storie [Of food and other stories] (in Italian). 13 January 2012. 37. ^ "Lucky 13". Colgate University. Retrieved 20 February 2015. 38. ^ Dpa (1 July 2010). "Unlucky 13, unless your name is Mueller". Thehindu.com. Retrieved 5 November 2017. 39. ^ "Football Facts: Who Wears Number 13?". Thefootballnation.co.uk. Retrieved 5 November 2017. 40. ^ Margarita Papantoniou. "Why Are Tuesday and 13 Bad Luck?". GreekReporter. Retrieved 28 December 2017. 41. ^ "Tuesday the 13th… the Friday the 13th of the Spanish-speaking world (and vice-versa)". WordPress. Retrieved 28 December 2017. ## External links[edit] Look up triskaidekaphobia in Wiktionary, the free dictionary. Wikimedia Commons has media related to Triskaidekaphobia. * 'Unlucky' airline logo grounded BBC, 21 February 2007 * Would you buy a number 13 house? BBC Magazine, Friday, 12 December 2008 * Triskaidekaphobia on MathWorld * Who's Afraid Of Friday The 13th? on NPR * v * t * e Superstition Main topics * Amulet * Evil eye * Luck * Omen * Talismans * Myth and ritual Lists * List of superstitions * List of lucky symbols * List of bad luck signs * Sailors' superstitions * Theatrical superstitions Africa * Buda * Gris-gris * Sampy * Sleeping child Americas * Ascalapha odorata * Carranca * Cooties * Curupira * Djucu * Fortune cookie * Groundhog Day * I'noGo tied * Oscar love curse * Susto * White lighter myth * Witch window Asia * Superstition in India * Superstition in Pakistan * Japanese superstitions * Bhoot (ghost) * Chhaupadi * Churel * Ghosts in Bengali culture * Jackal's horn * Kuai Kuai culture * Muhurta * Navaratna * Nazar battu * Pichal Peri * Puppy pregnancy syndrome * Akabeko * Kanai Anzen * Maneki-neko * Okiagari-koboshi * Omamori * Fan death * Agimat * Arbularyo * Barang * Kulam * Lihi * Pagtatawas * Pasma * Usog * Kuman Thong 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Cramp-ring * Curse * Davy Jones' Locker * Dead man's hand * End-of-the-day betting effect * Fear of frogs * Fear of ghosts * First-foot * Flying Dutchman * Four Eleven Forty Four * Gambler's conceit * Good luck charm * Human sacrifice * Jinx * Knocking on wood * Law of contagion * Literomancy * Lock of hair * Maternal impression * Miasma theory * Nelson * Numismatic charm * Penny * Rabbit's foot * Rainmaking * Ship sponsor * Shoes on a table * Sign of the horns * Something old * Spilling salt * Statue rubbing * Three on a match * Threshold * Toi toi toi * 27 Club * Wishing well * Witch ball * Witching hour Related * Apotropaic magic * Astrology and science * Coincidence * Debunker * Divination * Folk religion * Fortune-telling * Magic and religion * Magical thinking * Numerology * Perceptions of religious imagery in natural phenomena * Post hoc ergo propter hoc * Traditional medicine * Urban legend * Jew * Muslim [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-aminobutyric 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	Triskaidekaphobia	None	27,472	wikipedia	https://en.wikipedia.org/wiki/Triskaidekaphobia	2021-01-18T18:59:46	{"wikidata": ["Q13"]}
A number sign (#) is used with this entry because of evidence that X-linked mental retardation-106 (MRX106) is caused by hemizygous mutation in the OGT gene (300255) on chromosome Xq13. Clinical Features Willems et al. (2017) reported 2 unrelated boys with X-linked mental retardation. One patient had more notable dysmorphic features including hypertelorism, low-set ears, broad nose, full lips, supernumerary nipple, hypoplastic toe, mild retrognathia, long and thin fingers, clinodactyly, microcephaly, amblyopia, and possible astigmatism. Additional neurologic symptoms were also present, including pyramidal syndrome, mild spastic diplegia, and behavioral conduct disorder. He had a bicuspid aortic valve and periventricular leukomalacia on brain imaging. The second patient had mouth hypotonia with drooling, nystagmus, astigmatism, and hypermetropia. Other features included a small phallus, bitemporal narrowing, and ventricular septal defect. Vaidyanathan et al. (2017) reported 3 male patients from a family with intellectual disability. The patients were 56.5, 14.7, and 6.7 years of age, and their IQs ranged from 49 to 61. Variable additional minor abnormalities included small head circumference, fifth finger clinodactyly, hair whorls, open mouth, thin upper lip, hypospadias, and small testes. Inheritance The transmission pattern of MRX106 in the family reported by Vaidyanathan et al. (2017) was consistent with X-linked recessive inheritance. Molecular Genetics In 3 affected males from a family (K9427) with MRX106, Vaidyanathan et al. (2017) identified a hemizygous missense mutation in the OGT gene (L254F; 300255.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed decreased levels of OGT protein, suggesting instability of the mutant protein, but cellular transfection studies showed that mutant enzyme retained OGT catalytic activity. Patient cells had normal steady-state global O-GlcNAc levels due to a compensatory mechanism, namely a decrease in OGA (MGEA5; 604039) protein and mRNA levels. Decreased OGA promoter activity was associated with enrichment of an OGT-containing transcriptional repressor complex containing mSin3A (607776) and HDAC1 (601241) that localized to the proximal promoter region of OGA. Transcriptome analysis of mutant cells showed differential expression of several genes. Female mutation carriers showed highly skewed X inactivation. In 2 unrelated boys with MRX106, Willems et al. (2017) identified hemizygous mutations in the OGT gene (300255.0002 and 300255.0003). The mutations were found by exome sequencing and confirmed by Sanger sequencing; one of the mutations occurred de novo, whereas the other was inherited from the unaffected mother. Patient cells showed slightly reduced levels of OGT protein and reduced levels of OGA protein, but global O-GlcNAc levels were similar to controls. Recombinant studies of 1 of the mutations (R284P; 300255.0002) showed that mutant OGT was prone to unfolding and had reduced glycosylation activity against complex array of glycosylation substrates. Proteolytic processing of HCFC1 (300019) was also decreased. The findings suggested that defects in O-GlcNAc homeostasis and HCFC1 proteolysis may play a role in intellectual disability in patients with OGT mutations. INHERITANCE \- X-linked recessive HEAD & NECK Head \- Microcephaly Eyes \- Hypertelorism \- Amblyopia \- Nystagmus \- High hypermetropia Mouth \- Open mouth \- Mouth hypotonia GENITOURINARY External Genitalia (Male) \- Hypospadias \- Small testis \- Small phallus Internal Genitalia (Male) \- Cryptorchidism NEUROLOGIC Central Nervous System \- Delayed psychomotor development (in all patients) \- Intellectual disability (in all patients) MISCELLANEOUS \- Variable features reported MOLECULAR BASIS \- Caused by mutation in the O-linked N-acetylglucosamine transferase gene (OGT, 300255.0001 ) ▲ 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-aminobutyric 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	MENTAL RETARDATION, X-LINKED 106	c4478379	27,473	omim	https://www.omim.org/entry/300997	2019-09-22T16:19:00	{"omim": ["300997"]}
A number sign (#) is used with this entry because of evidence that recessive intermediate Charcot-Marie-Tooth disease B (CMTRIB) is caused by compound heterozygous mutation in the KARS gene (KARS1; 601421) on chromosome 16q23. One such patient has been reported. For a discussion of genetic heterogeneity of recessive intermediate Charcot-marie-Tooth disease, see CMTRIA (608340). Clinical Features McLaughlin et al. (2010) reported a patient with intermediate Charcot-Marie-Tooth disease, developmental delay, self-abusive behavior, dysmorphic features, and vestibular Schwannoma. The patient was identified from a larger cohort of 355 patients with peripheral neuropathy. Electrophysiologic studies of this patient showed motor nerve conduction velocities (NCV) of 39.5 and 30.6 m/s in the median and ulnar nerves, respectively, consistent with an intermediate phenotype between that of demyelinating and axonal CMT. There were also severely decreased amplitudes of evoked motor responses (CMAP) in these nerves. In a review of intermediate CMT, Berciano et al. (2017) suggested that CMTRIB should be reclassified as CMT2 (see, e.g., 118210), because the severe CMAP attenuation in the patient reported by McLaughlin et al. (2010) likely results from axonal loss. Molecular Genetics In a patient with recessive intermediate CMT with additional features, including developmental delay, McLaughlin et al. (2010) identified compound heterozygous mutations in the KARS gene (601421.0001 and 601421.0002). The patient was adopted, and parental studies were not possible. McLaughlin et al. (2010) noted that mutations in 3 genes encoding aminoacyl-tRNA synthetases (ARS), GARS (600287), YARS (603623), and AARS (601065), had been implicated in Charcot-Marie-Tooth disease primarily associated with an axonal pathology (CMT2D, 601472; CMTDIC, 608323; and CMT2N, 613287, respectively). Thus, KARS was the fourth ARS gene associated with CMT disease, indicating that this family of enzymes is specifically critical for axon function. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Dysmorphic features SKELETAL Feet \- Pes cavus NEUROLOGIC \- Delayed development Peripheral Nervous System \- Lower limb muscle weakness due to peripheral neuropathy \- Lower limb muscle atrophy due to peripheral neuropathy \- Clumsy gait \- 'Steppage' gait \- Foot drop \- Hyporeflexia \- Areflexia \- Distal sensory impairment \- EMG shows neuropathic changes \- Nerve conduction velocities (NCV) vary from normal to decreased Behavioral Psychiatric Manifestations \- Self-abusive behavior NEOPLASIA \- Vestibular Schwannoma MISCELLANEOUS \- One patient has been reported (last curated November 2010) MOLECULAR BASIS \- Caused by mutation in the lysyl-tRNA synthetase 1 gene (KARS1, 601421.0001 ) ▲ 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-aminobutyric 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	CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	c3150897	27,474	omim	https://www.omim.org/entry/613641	2019-09-22T15:58:04	{"doid": ["0110204"], "omim": ["613641"], "orphanet": ["254334"], "synonyms": ["RI-CMT type B", "Alternative titles", "CHARCOT-MARIE-TOOTH NEUROPATHY, RECESSIVE INTERMEDIATE B"]}
## Summary ### Clinical characteristics. Biotin-thiamine-responsive basal ganglia disease (BTBGD) may present in childhood, early infancy, or adulthood. * The classic presentation of BTBGD occurs in childhood (age 3-10 years) and is characterized by recurrent subacute encephalopathy manifest as confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and/or dysphagia which, if left untreated, can eventually lead to coma and even death. Dystonia and cogwheel rigidity are nearly always present; hyperreflexia, ankle clonus, and Babinski responses are common. Hemiparesis or quadriparesis may be seen. Episodes are often triggered by febrile illness or mild trauma or stress. Simple partial or generalized seizures are easily controlled with antiepileptic drugs. * An early-infantile Leigh-like syndrome / atypical infantile spasms presentation occurs in the first three months of life with poor feeding, vomiting, acute encephalopathy, and severe lactic acidosis. * An adult-onset Wernicke-like encephalopathy presentation is characterized by acute onset of status epilepticus, ataxia, nystagmus, diplopia, and ophthalmoplegia in the second decade of life. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement within days in the childhood and adult presentations, but most with the infantile presentation have had poor outcome even after supplementation with biotin and thiamine. ### Diagnosis/testing. The diagnosis of BTBGD is established in a proband with biallelic pathogenic variants in SLC19A3 by molecular genetic testing. ### Management. Treatment of manifestations: Biotin (5-10 mg/kg/day) and thiamine (up to 40 mg/kg/day with a maximum of 1500 mg daily) are given orally as early in the disease course as possible and are continued lifelong. Symptoms typically resolve within days. Acute encephalopathic episodes may require care in an ICU to manage seizures and increased intracranial pressure; during acute decompensations thiamine may be increased to double the regular dose and be given intravenously. Antiepileptic drugs are used to control seizures. Treatment of dystonia is symptomatic and includes administration of trihexyphenidyl or L-dopa. Rehabilitation, physiotherapy, occupational therapy, and speech therapy as needed and adaptation of educational programs to meet individual needs. Education of the family regarding the importance of lifelong compliance with medical therapy. Prevention of primary manifestations: Prompt administration of biotin and thiamine early in the disease course. Surveillance: Clinical review of neurologic status every six months; annual assessment of developmental progress and educational needs; social support and care coordination each visit. Agents/circumstances to avoid: Infections, stress, profuse exercise, and trauma. Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives (e.g., sibs ) of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment with biotin and thiamine and preventive measures (avoidance of stress and trauma). Pregnancy management: Affected women should continue thiamine and biotin during pregnancy. ### Genetic counseling. BTBGD is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing and preimplantation genetic testing for pregnancies at increased risk are possible if the SLC19A3 pathogenic variants in the family have been identified. ## Diagnosis ### Suggestive Findings Biotin-thiamine-responsive basal ganglia disease (BTBGD) should be suspected in individuals with the following: * Acute/subacute encephalopathy with seizures, extrapyramidal manifestations (dystonia, cogwheel rigidity, dysarthria, dysphagia), and pyramidal tract signs (quadriparesis, hyperreflexia) typically in a child age three to ten years and usually preceded by febrile illness or some other stress. Cerebellar signs, supranuclear facial nerve palsy, external ophthalmoplegia, and ataxia are variably present. * Brain MRI showing the following: * Swelling and bilateral and symmetric increased T2-weighted signal intensity in the caudate nucleus, putamen, thalamus, infra- and supratentorial brain cortex, and brain stem [Ozand et al 1998] * Vasogenic edema during acute crises as demonstrated by diffusion-weighted imaging / apparent diffusion coefficient MRI * Chronic changes including atrophy and necrosis of caudate and putamen with diffuse cerebral cortical and (to a lesser extent) cerebellar atrophy [Yamada et al 2010] * Spinal cord involvement (seen in 1 affected individual) [Alfadhel et al 2013] * Normal laboratory investigations, including tandem mass spectrometry of blood; urine gas chromatography-mass spectrometry (GC-MS); serum concentrations of lactic acid,* ammonia, biotin, and thiamine; serum biotinidase enzyme activity; urine amino acids; plasma amino acids; liver enzymes; coagulation profile; lipid profile; and cerebrospinal fluid (CSF) cell count, protein, glucose, and cultures. * In the early-onset form, high lactate levels in the blood and CSF; high alanine, leucine, and isoleucine in the plasma; and elevated excretion of α-ketoglutarate in the urinary organic acid assays can be observed. * Family history consistent with autosomal recessive inheritance. Note: (1) Presumably affected (but undiagnosed) sibs may have had unexplained coma or encephalopathy. (2) Consanguinity has been reported in a large number of families [Alfadhel et al 2013, Tabarki et al 2013]. ### Establishing the Diagnosis The diagnosis of BTBGD is established in a proband with biallelic pathogenic variants in SLC19A3 identified by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing or multigene panel) and comprehensive genomic testing (exome sequencing, exome array, 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 biotin-thiamine-responsive basal ganglia disease 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 biotin-thiamine-responsive basal ganglia disease 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 BTBGD, molecular genetic testing approaches can include single-gene testing or use of a multigene panel. * Single-gene testing. Sequence analysis of SLC19A3 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one pathogenic variant or no pathogenic variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. * A multigene panel that includes SLC19A3 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 this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). 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 BTBGD 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, 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. ### Table 1. Molecular Genetic Testing Used in BTBGD View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method SLC19A3Sequence analysis 3~95% 4 Gene-targeted deletion/duplication analysis 5~5% 4, 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. 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\. Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] 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\. A 45-kb deletion including the promoter region but no coding exons of SLC19A3 has been reported [Flønes et al 2016]. ## Clinical Characteristics ### Clinical Description To date, 135 individuals have been identified with a pathogenic variant in SLC19A3 [Alfadhel et al 2019]. The following description of the phenotypic features associated with biotin-thiamine-responsive basal ganglia disease (BTBGD) is based on this report. While the classic presentation of BTBGD occurs in childhood, early infantile-onset and adult-onset presentations are reported as well. ### Table 2. Features of BTBGD View in own window Feature% of Persons with Feature Encephalopathy50 Dystonia45 Spasticity40 Seizures37 Dysphagia35 Ataxia30 Dysarthria15 Ophthalmoplegia15 Opisthotonus10 Classic BTBGD usually presents in children of preschool or early school age (i.e., ages 3-10 years). In one report onset was at age one month [Pérez-Dueñas et al 2013] and in another at age 20 years [Debs et al 2010]. Classic BTBGD is most commonly characterized by recurrent acute/subacute onset of encephalopathy manifest as confusion, generalized seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and dysphagia, eventually leading to coma and even death. This encephalopathy may be associated with a variable degree of raised intracranial pressure. Dystonia and cogwheel rigidity are nearly always present. Hyperreflexia, ankle clonus, and Babinski responses are common. Hemiparesis or quadriparesis may be seen. Episodes are often triggered by febrile illness, mild trauma, or stress. Seizures are mainly simple partial or generalized seizures and are easily controlled with antiepileptic drugs. Infantile spasms also occur [Yamada et al 2010]. Administration of biotin and thiamine early in the disease course results in complete clinical improvement within days (see Management). Lifelong treatment is required. Treatment initiated later in the disease course or lack of treatment may result in death or chronic neurologic sequelae including dystonia, quadriparesis, epilepsy, or mild intellectual disability. The early-infantile Leigh-like syndrome / atypical infantile spasms presentation is characterized by the occurrence in the first three months of life of poor feeding, vomiting, acute encephalopathy, and severe lactic acidosis. Four individuals with atypical infantile spasms have been described [Yamada et al 2010]. Most individuals in this group have had poor outcome or even death (even after supplementation with biotin and thiamine). Adult Wernicke-like encephalopathy is characterized by acute onset of status epilepticus, ataxia, nystagmus, diplopia, and ophthalmoplegia in the second decade of life [Kono et al 2009]. Affected individuals show dramatic response to high dose of thiamine. ### Prevalence The disorder is pan ethnic; however, it is most prevalent in Saudi Arabia. The carrier frequency of a pathogenic variant in SLC19A3 is 1:500 in Saudi newborns [Alfadhel et al 2019]. ### Genotype-Phenotype Correlations SLC19A3 genotype-phenotype correlations are poorly defined; however: * Biallelic predicted loss-of-function variants are more likely to present early and develop into the severe Leigh-like phenotype. * Compound heterozygosity for one missense variant and one predicted loss-of-function variant has been associated with the classic childhood form of BTBGD. * The founder Saudi variant, c.1264A>G (p.Thr422Ala), is associated with the classic childhood form. ## Differential Diagnosis Acute biotin-thiamine-responsive basal ganglia disease (BTBGD). See Table 3. ### Table 3. Genes of Interest in the Differential Diagnosis of Acute Biotin-Thiamine-Responsive Basal Ganglia Disease (BTBGD) View in own window Gene(s)DisorderMOI BCKDHA BCKDHB DBT IVD MCEE MMAA MMAB MMADHC MMUT PCCA PCCB 1Organic acid disorders (e.g, IVA [OMIM 243500], MMA, MSUD, PA) 2AR See footnote 3.Mitochondrial disorders (incl Leigh syndrome) 4AR AD Mat HTTJuvenile Huntington diseaseAD ATP7BWilson diseaseAR THTyrosine hydroxylase deficient dopa-responsive dystonia (See Tyrosine Hydroxylase Deficiency.)AR GCH1GTP cyclohydrolase 1-deficient dopa-responsive dystoniaAD SLC5A6Infantile-onset biotin-responsive neurodegeneration 5AR SPRSepiapterin reductase deficiencyAR AD = autosomal dominant; AR = autosomal recessive; BTBGD = biotin-thiamine-responsive basal ganglia disease; IVA = isovaleric acidemia; Mat = maternal; MMA = methylmalonic acidemia; MOI = mode of inheritance; MSUD = maple syrup urine disease; PA = propionic acidemia 1\. More than 65 organic acids are known [Ramsay et al 2018]; listed genes represent those associated with the selected organic acidemias in the Disorder column. 2\. Major clinical features are developmental delay, seizures, lethargy, coma, hypotonia, vomiting, failure to thrive, hepatomegaly, respiratory distress, cardiac dysfunction, hypoglycemia, and acidosis. 3\. Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA (mtDNA). More than 1,000 genes associated with mitochondrial function have been identified [Calvo et al 2006]. 4\. See also Nuclear Gene-Encoded Leigh Syndrome Overview. 5\. Byrne et al [2019] Note: Dopa-responsive dystonia and Wilson disease are important to consider because they are treatable. Acquired disorders in the differential diagnosis * Wernicke encephalopathy * Toxic encephalopathy * Infectious encephalopathy * Inflammatory disease (including CNS vasculitis) * Acute disseminated encephalomyelitis (ADEM) Chronic BTBGD. In its chronic stage BTBGD shares clinical features with several conditions including Wilson disease, juvenile Huntington disease, and DYT1 early-onset isolated dystonia; however, BTBGD can be differentiated by its acute to subacute presentation. See Thiamine-responsive dysfunction syndrome: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with BTBGD, the evaluations summarized in Table 3 (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 BTBGD View in own window System/ConcernEvaluationComment NeurologicPediatric neurologistBaseline exam & evaluation for seizures Dystonia & developmental delayRehabilitation medicineEvaluate status & need for therapies. Physiotherapist Occupational therapist Speech therapist PsychologistAssess IQ. OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations ### Table 5. Treatment of Manifestations in Individuals with BTBGD View in own window Manifestation/ ConcernTreatmentConsiderations/Other Acute encephalopathyICU care incl treatment of seizures & ↑ intracranial pressureEmpiric treatment w/antimicrobial/antiviral agents recommended until infectious causes of acute/subacute encephalopathy are ruled out Neurologic disorderBoth biotin & thiamine oral therapy: * Biotin: 5-10 mg/kg/day * Thiamine: ≤40 mg/kg/day; max of 1500 mg/day * Note: Some individuals respond only to thiamine. * Lifelong treatment required w/biotin & thiamine * During acute decompensation thiamine may be ↑ to 2x regular dose & given intravenously. Fever controlFever exacerbates the disease. SeizuresAntiepileptic drugs to control seizuresAvoid sodium valproate. DystoniaSymptomatic treatment incl trihexyphenidyl or L-dopa Developmental delaysRehab, PT, OT, speech therapy, & educational programs adapted to individual needs SocialEducation of family re importance of lifelong compliance w/medical therapy OT = occupational therapy; PT = physical therapy ### Prevention of Primary Manifestations Appropriate measures include the following: * Prompt administration of biotin and thiamine early in the disease course (See Treatment of Manifestations.) * Avoidance of triggers/stressors including trauma and optional surgery ### Surveillance ### Table 6. Recommended Surveillance for Individuals with BTBGD View in own window System/ConcernEvaluationFrequency Nervous systemClinical review of neurologic status2x/yr Development/ EducationMonitor developmental progress & educational needsAnnually Miscellaneous/ OtherAssess family need for social work support (e.g., home nursing, other local resources) & care coordination.At each visit ### Agents/Circumstances to Avoid Infections, stress, profuse exercise, and trauma should be avoided as they can precipitate acute attacks. Use of sodium valproate for epilepsy should be avoided. ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives (e.g., sibs) of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment with biotin and thiamine and preventive measures (avoidance of stress and trauma). See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Affected women should continue biotin and thiamine therapy during pregnancy. No information regarding risk to the fetus of an affected mother is available. ### 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. ### Other Routine administration of immunizations is recommended (without any specific precautions). [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-aminobutyric 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	Biotin-Thiamine-Responsive Basal Ganglia Disease	c1843807	27,475	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK169615/	2021-01-18T21:39:57	{"mesh": ["C537658"], "synonyms": ["Biotin-Responsive Basal Ganglia Disease (BBGD)", "BTBGD", "Thiamine Metabolism Dysfunction Syndrome-2", "Thiamine Transporter-2 Deficiency"]}
This article is about boron deficiency in animals. For the same deficiency in plants, see boron deficiency (plant disorder). Boron deficiency is a pathology which may occur in animals due to a lack of boron. A report given by E. Wayne Johnson et al. at the 2005 Alan D. Leman Swine Conference[1] suggests that boron deficiency produces osteochondrosis in swine that is correctable by addition of 50 ppm of boron to the diet. The tolerable daily intake (TDI) set by the World Health Organization (WHO) is 0.16 mg/kg of body weight for humans.[2][3] ## See also[edit] * Ultratrace element ## References[edit] 1. ^ Allen D. Leman Swine Conference - Veterinary Continuing Education - the University of Minnesota 2. ^ https://www.who.int/water_sanitation_health/dwq/chemicals/boronsum.pdf 3. ^ "Archived copy". Archived from the original on 2019-11-09. Retrieved 2019-11-09.CS1 maint: archived copy as title (link) This article about a disease, disorder, or medical condition 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-aminobutyric 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	Boron deficiency (medicine)	None	27,476	wikipedia	https://en.wikipedia.org/wiki/Boron_deficiency_(medicine)	2021-01-18T18:58:38	{"wikidata": ["Q4946250"]}
## Summary ### Clinical characteristics. The X-linked otopalatodigital (X-OPD) spectrum disorders, characterized primarily by skeletal dysplasia, include the following: * Otopalatodigital syndrome type 1 (OPD1) * Otopalatodigital syndrome type 2 (OPD2) * Frontometaphyseal dysplasia type 1 (FMD1) * Melnick-Needles syndrome (MNS) * Terminal osseous dysplasia with pigmentary skin defects (TODPD) In OPD1, most manifestations are present at birth; females can present with severity similar to affected males, although some have only mild manifestations. In OPD2, females are less severely affected than related affected males. Most males with OPD2 die during the first year of life, usually from thoracic hypoplasia resulting in pulmonary insufficiency. Males who live beyond the first year of life are usually developmentally delayed and require respiratory support and assistance with feeding. In FMD1, females are less severely affected than related affected males. Males do not experience a progressive skeletal dysplasia but may have joint contractures and hand and foot malformations. Progressive scoliosis is observed in both affected males and females. In MNS, wide phenotypic variability is observed; some individuals are diagnosed in adulthood, while others require respiratory support and have reduced longevity. MNS in males results in perinatal lethality in all recorded cases. TODPD, seen only in females, is characterized by a skeletal dysplasia that is most prominent in the digits, pigmentary defects of the skin, and recurrent digital fibromata. ### Diagnosis/testing. The diagnosis of an X-OPD spectrum disorder is established in a male proband with characteristic clinical and radiographic features and a family history consistent with X-linked inheritance. Identification of a hemizygous pathogenic variant in FLNA by molecular genetic testing can confirm the diagnosis if clinical features, radiographic features, and/or family history are inconclusive. The diagnosis of an X-OPD spectrum disorder is usually established in a female proband with characteristic clinical and radiographic features and a family history consistent with X-linked inheritance. Identification of a heterozygous pathogenic variant in FLNA by molecular genetic testing can confirm the diagnosis if clinical features, radiographic features, and/or family history are inconclusive. ### Management. Treatment of manifestations: Surgical treatment may be required for hand and foot malformations. Monitoring and surgical intervention as needed for scoliosis; physiotherapy for contractures; cosmetic surgery may correct the fronto-orbital deformity; continuous positive airway pressure (CPAP) and mandibular distraction can improve airway complications related to micrognathia; hearing aids for deafness; evaluation with anesthesiology if intubation and ventilation are required due to laryngeal stenosis. Surveillance: Annual clinical evaluation for orthopedic complications including contractures and scoliosis; monitor head size and shape with each clinical evaluation in infancy for craniosynostosis; annual clinical evaluation for apnea with somnography studies as indicated; annual audiology evaluation. Evaluation of relatives at risk: Consider molecular genetic testing for the family-specific pathogenic variant in at-risk relatives. ### Genetic counseling. The X-OPD spectrum disorders are by definition inherited in an X-linked manner. If a parent of a proband with OPD1, OPD2, or FMD1 has the FLNA pathogenic variant, the chance of transmitting the variant in each pregnancy is 50%. * When the mother has an FLNA pathogenic variant, males who inherit the variant will be affected; females who inherit the variant have a range of phenotypic expression. If the mother of a proband with TODPD or MNS has the FLNA pathogenic variant, the chance of transmitting the variant in each pregnancy is 50%. Males who inherit the variant will be affected and usually exhibit embryonic lethality or die perinatally (MNS); females who inherit the variant have a range of phenotypic expression. * Males with OPD2 do not reproduce; males with OPD1 or FMD1 transmit the pathogenic variant to all of their daughters and none of their sons. Prenatal testing and preimplantation genetic testing are possible if the pathogenic variant in the family is known. ## Diagnosis The X-linked otopalatodigital (X-OPD) spectrum disorders, a heterogeneous group of disorders characterized primarily by a skeletal dysplasia of variable severity, include the following: * Otopalatodigital syndrome type 1 (OPD1) * Otopalatodigital syndrome type 2 (OPD2) * Frontometaphyseal dysplasia type 1 (FMD1) * Melnick-Needles syndrome (MNS) * Terminal osseous dysplasia with pigmentary skin defects (TODPD) ### Suggestive Findings X-OPD spectrum disorders should be suspected in an individual with the following clinical (Table 1) and radiographic (Table 2) features. ### Table 1. X-Linked Otopalatodigital Spectrum Disorders: Clinical Features View in own window PhenotypeCraniofacial FeaturesSkeletal FeaturesOther OPD1 (male phenotype)Cleft palate & characteristic facies: prominent supraorbital ridges, downslanted palpebral fissures, hypertelorism, broad nasal bridge & nasal tip, hypodontia, oligodontiaDigits: short proximally placed thumbs, hypoplastic distal phalanges, great toe hypoplasia, long 2nd toe, prominent sandal gap; limited joint mobility; limbs w/mild bowingConductive & sensorineural hearing loss; normal intelligence Heterozygous females 1: variable features; some females as affected as male relatives. OPD2 (male phenotype)Pierre Robin sequence; characteristic facies (more severe than OPD1)Digits: hypoplastic thumbs & great toes, absent halluces, camptodactyly; thoracic hypoplasia; delayed closure of fontanelles; bowed limbs; short statureConductive & SNHL; cardiac: septal defects, obstructive lesions to the right ventricular outflow tract; omphalocele; GU: ureteric obstruction w/hydronephrosis, hypospadias; CNS: hydrocephalus, cerebellar hypoplasia; DD; death in neonatal period Heterozygous females 1: often subclinical phenotype; characteristic facies (prominent supraorbital ridges, wide nasal bridge & broad nasal tip) are most common findings. Occasionally conductive HL, cleft palate, skeletal & digital anomalies. FMD1 (male phenotype)Characteristic facies (more severe than OPD2)Digits: distal phalangeal hypoplasia, progressive contractures of the hands; limited joint mobility (wrists, elbows, knees, ankles); scoliosis; bowed limbsConductive & SNHL; underdevelopment of musculature (shoulder girdle, intrinsic muscles of the hands); subglottic stenosis w/congenital stridor; GU: ureteric & urethral stenosis, hydronephrosis; normal intelligence Heterozygous females: characteristic facies similar to affected males MNS (female phenotype)Prominent lateral margins of the supraorbital ridges, proptosis, full cheeks, micrognathia, oligohypodontia, facial asymmetryDigits: long w/mild distal phalangeal hypoplasia; thoracic hypoplasia; bowed limbs; joint subluxation; short statureConductive & SNHL; ureteric obstruction w/hydronephrosis; coloboma; normal intelligence Hemizygous males: phenotype ranges from lethal phenotype similar to severe OPD2 to mildly affected. TODPD (female phenotype)Widely spaced eyes, oral frenulae, hyperpigmented lesions over the temporal region, alopeciaDigits: fibromata in infancy, camptodactyly; bowed limbs; short statureCardiac: septal defects; normal intelligence Hemizygous males: phenotype has not been described in males. DD = developmental delay; FMD1 = frontometaphyseal dysplasia type 1; GU = genitourinary; MNS = Melnick-Needles syndrome; OPD1 = otopalatodigital syndrome type 1; OPD2 = otopalatodigital syndrome type 2; SNHL = sensorineural hearing loss; TODPD = terminal osseous dysplasia with pigmentary skin defects 1\. OPD1 and OPD2 cannot be clinically differentiated in a single affected female in a family with no affected males. ### Table 2. X-Linked Otopalatodigital Spectrum Disorders: Radiographic Features View in own window PhenotypeSkullSpineThoraxLong BonesHands / FeetPelvis OPD1 (male phenotype)Sclerosis of skull base; thickened calvarium; underdeveloped frontal sinuses; mastoids under-pneumatizedFailure of fusion of posterior vertebral arches (especially cervical)Mild bowing; dislocation of radial headsThumb w/short, broad metacarpal; distal phalangeal hypoplasia; accessory proximal ossification center of 2nd metacarpal; accessory carpal bones; fusion of carpal & tarsal bonesContracted; no iliac flaring OPD2 (male phenotype)Same as OPD1; large fontanellesSame as OPD1; segmentation anomaliesHypoplastic; thin ribsBowed; splayed metaphyses; absent fibulaeBroad, poorly modeled phalanges, metacarpals & metatarsals; ± duplicated terminal phalangesSame as OPD1 FMD1 (male phenotype)Same as OPD1; occasionally, craniosynostosisFusion of C2-3-4; deficiency of posterior vertebral arches± coat-hanger shape ribsMild bowing; undertubulationCarpal & tarsal fusions; later erosion of carpal bones; elongation, poor modeling of phalanges, metacarpals & metatarsals; distal phalangeal hypoplasia (thumbs & great toes) MNS (female phenotype)Same as OPD1↑ vertebral body height, especially lumbar; scoliosisHypoplasia; ribs irregular; wavy clavicle w/expansion of proximal endBowed, sometimes ribbon-like; cortical irregularityElongation & undermodeling of phalanges, metacarpals & metatarsalsSupra-acetabular constriction; iliac flaring TODPD (female phenotype)NormalScoliosisNo abnormalities consistently describedIrregular ossification; cystic lesions near epiphyses; bowed; radial head dislocationHypoplasia, shortening, irregular ossification &/or fusions of carpals & metacarpals; irregular corticesNarrow ilia; coxa vara FMD1 = frontometaphyseal dysplasia type 1; MNS = Melnick-Needles syndrome; OPD1 = otopalatodigital syndrome type 1; OPD2 = otopalatodigital syndrome type 2; TODPD = terminal osseous dysplasia with pigmentary skin defects ### Establishing the Diagnosis Male proband. The diagnosis of an X-OPD spectrum disorder is established in a male proband with characteristic clinical (Table 1) and radiographic (Table 2) features and a family history consistent with X-linked inheritance. Identification of a hemizygous pathogenic variant in FLNA by molecular genetic testing can confirm the diagnosis if clinical features, radiographic features, and/or family history are inconclusive (see Table 3). Female proband. The diagnosis of an X-OPD spectrum disorder is usually established in a female proband with characteristic clinical (Table 1) and radiographic (Table 2) features and a family history consistent with X-linked inheritance. Identification of a heterozygous pathogenic variant in FLNA by molecular genetic testing can confirm the diagnosis if clinical features, radiographic features, and/or family history are inconclusive (see Table 3). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, 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. Because the phenotype of X-OPD spectrum disorders 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 an X-OPD spectrum disorder 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 an X-OPD spectrum disorder, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Perform sequence analysis of FLNA to detect small intragenic deletions/insertions and missense variants. Note: Whole-gene deletions cause periventricular nodular heterotopia in females and are likely to be embryonic lethal in males. Partial-gene deletions or duplications have not been associated with X-OPD spectrum disorders. Whole-gene duplications (in association with neighboring genes) have been associated with intellectual disability and seizures (see Genetically Related Disorders). Targeted analysis for variant c.5217G>A can be performed first in individuals with a phenotype suggestive of TODPD; however, this test is not exclusionary for TODPD. * A multigene panel that includes FLNA 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. #### Option 2 When the diagnosis of an X-OPD spectrum disorder 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 3. Molecular Genetic Testing Used in X-Linked Otopalatodigital Spectrum Disorders View in own window Gene 1MethodPhenotypeProportion of Probands with a Pathogenic Variant 2 Detectable by Method FLNASequence analysis 3OPD194% (n=15) 4 OPD2100% (n=19) 4 FMD171% (n=47) 5 MNS100% (n=27) 4 Targeted analysis for c.5217G>ATODPD100% (n=6) 6 Gene-targeted deletion/duplication analysis 7None 8 FMD1 = frontometaphyseal dysplasia type 1; MNS = Melnick-Needles syndrome; OPD1 = otopalatodigital syndrome type 1; OPD2 = otopalatodigital syndrome type 2; TODPD = terminal osseous dysplasia with pigmentary skin defects 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\. Robertson et al [2006b] 5\. Robertson et al [2006a], Wade et al [2016] 6\. All reported individuals with TODPD have been heterozygous for the synonymous change c.5217G>A, which induces a splicing abnormality that results in a loss of 48 bases from the mature transcript and predicts the deletion of 16 amino acids from the resultant FLNA protein (p.Val1724_Thr1739del) [Sun et al 2010]. This pathogenic variant appears to define this disorder. 7\. 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. 8\. Large deletions and duplications have been associated with allelic conditions such as myxomatous cardiac valvular dystrophy (see Genetically Related Disorders), periventricular nodular heterotopia, and intellectual disability. Partial- and whole-gene deletions do not cause an X-OPD spectrum disorder phenotype. ## Clinical Characteristics ### Clinical Description To date, more than 150 individuals with an X-OPD syndrome spectrum disorder have been identified with a pathogenic variant in FLNA [Robertson et al 2003, Robertson et al 2006a, Robertson et al 2006b]. The following description of the phenotypic features associated with this condition is based on these reports. ### Table 4. Features of X-Linked Otopalatodigital Spectrum Disorders View in own window DisorderFeatures% of Persons with Feature OPD1 in malesDigital anomalies100% Deafness100% Mild limb bowingUnknown Cleft Palate75% OPD2 in malesThoracic hypoplasia100% Cleft palate80% FMD1 in malesSupraorbital hyperostosis100% Urinary Tract obstructionUnknown MNS in femalesMicrognathia100% Limb bowing100% Short stature100% Thoracic hypoplasia100% TODPD in femalesDigital fibromata100% Erosive changes on radiographs100% Limb bowingUnknown FMD1 = frontometaphyseal dysplasia type 1; MNS = Melnick-Needles syndrome; OPD1 = otopalatodigital syndrome type 1; OPD2 = otopalatodigital syndrome type 2; TODPD = terminal osseous dysplasia with pigmentary skin defects Little is known about the natural history of the X-linked otopalatodigital (X-OPD) spectrum disorders. All manifestations can begin in childhood in both sexes. In males, the spectrum of severity ranges from mild manifestations in otopalatodigital syndrome type 1 (OPD1) to a more severe presentation in frontometaphyseal dysplasia type 1 (FMD1) and otopalatodigital syndrome type 2 (OPD2). Prenatal lethality is the only clinical phenotype described in males with Melnick-Needles syndrome (MNS) [Spencer et al 2018]. Females exhibit variable expressivity. In OPD1, females can present with similar severity to affected males. In contrast, some females have only the mildest of manifestations [Gorlin et al 1973]. In OPD2 and FMD1, females are less severely affected than related affected males [Robertson et al 1997, Moutton et al 2016]. #### OPD1 Most manifestations are evident at birth. Nothing reported in the literature suggests any late-onset orthopedic complications, reduction in longevity, or reduction in fertility. Males with OPD1 present with the following: * A skeletal dysplasia manifest clinically by: * Digital anomalies including short, often proximally placed thumbs with hypoplasia of the distal phalanges. The distal phalanges of the other digits can also be hypoplastic with a squared (or "spatulate") disposition to the finger tips. The toes present a characteristic pattern of hypoplasia of the great toe, a long second toe, and a prominent sandal gap. * Limitation of joint movement (elbow extension, wrist abduction) in almost all affected individuals * Limbs that may exhibit mild bowing * Mildly reduced final height in some, although individuals have been characterized with pathogenic variants in FLNA and stature greater than the 90th percentile. Pubertal development and intelligence is normal in affected individuals. * Characteristic facial features (prominent supraorbital ridges, downslanted palpebral fissures, widely spaced eyes, wide nasal bridge and broad nasal tip) * Deafness (secondary either to ossicular malformation, neurosensory deficit, or a combination of both). The conductive hearing loss can be caused by fused and misshapen ossicles; attempts to separate the ossicles are usually unsuccessful and can lead to formation of a perilymphatic gusher. * Cleft palate * Oligohypodontia * Normal intelligence Females with OPD1 exhibit variable expressivity. Some females can manifest a phenotype similar to that of affected, related males. Females may develop conductive or neurosensory hearing loss. Note: One cannot confidently differentiate OPD1 from OPD2 in a single affected female in a family with no affected males [Moutton et al 2016]. #### OPD2 Males with OPD2 present with the following [André et al 1981, Fitch et al 1983]: * A skeletal dysplasia manifest clinically as: * Thoracic hypoplasia * Bowed long bones * Short stature * Digital anomalies (most commonly: hypoplasia of the first digit of the hands and feet or absent halluces, camptodactyly) * Delayed closure of the fontanelles * Scoliosis (occasional) * Characteristic craniofacial features similar to but more pronounced than those in OPD1. Pierre Robin sequence is commonly observed. * Sensorineural and conductive deafness (common) * Cardiac septal defects and obstructive lesions to the right ventricular outflow tract in some affected individuals * Associated omphalocele, hydronephrosis secondary to ureteric obstruction, and hypospadias [Young et al 1993, Robertson et al 1997] * Central nervous system anomalies including hydrocephalus, cerebellar hypoplasia, and (rarely) encephalocele and meningomyelocele [Brewster et al 1985, Stratton & Bluestone 1991] * Developmental delay (common) * Death commonly in the neonatal period as a result of respiratory insufficiency. Survival into the third year of life has been described with intensive medical treatment [Verloes et al 2000]. Females with OPD2 usually present with a subclinical phenotype. Characteristic craniofacial features (prominent supraorbital ridges, wide nasal bridge and a broad nasal tip) are the most common findings. Occasionally, conductive hearing loss has been described. Occasionally, females can manifest a phenotype similar in severity to that of males (craniofacial dysmorphism, cleft palate, conductive hearing loss, skeletal and digital anomalies). Note: One cannot confidently differentiate OPD1 from OPD2 in a single affected female in a family with no affected males. #### Frontometaphyseal Dysplasia Type 1 Frontometaphyseal dysplasia type 1 (FMD1) shares many characteristics with OPD1, with some authors considering them the same condition [Superti-Furga & Gimelli 1987]. Males with FMD1 present with the following: * A skeletal dysplasia manifest clinically as: * Distal phalangeal hypoplasia * Progressive contractures of the hand over the first two decades resulting in marked limitation of movement at the interphalangeal and metacarpophalangeal joints * Joint limitation at the wrists, elbows, knees, and ankles * Scoliosis that may be progressive [Morava et al 2003] * Limb bowing * Characteristic craniofacial features with very pronounced supraorbital hyperostosis, widely spaced eyes, and downslanted palpebral fissures [Gorlin & Cohen 1969]. Craniosynostosis, an occasional finding, can evolve postnatally. * Oligohypodontia (frequent) * Conductive and sensorineural hearing loss in almost all affected individuals * Underdevelopment of the musculature, most notably around the shoulder girdle and in the intrinsic muscles of the hands (common) * Extraskeletal anomalies including subglottic stenosis (which can present as congenital stridor [Leggett 1988, Mehta & Schou 1988]), urethral stenosis, and hydronephrosis * Cleft palate (rare) * Normal intelligence Females with FMD1 present with characteristic craniofacial features similar to those of affected males [Gorlin & Winter 1980]. The digital, subglottic, and urologic anomalies observed in males with FMD1 either do not occur in females or are observed in markedly attenuated form. #### Melnick-Needles Syndrome Substantial variability is observed in females. Some individuals are diagnosed in adulthood after ascertainment of an affected family member [Kristiansen et al 2002]. Others require substantial respiratory support; several individuals have required ambulatory oxygen supplementation, typically starting in the second decade. Longevity is reduced in these individuals. The phenotype of four males with a pathogenic variant known to lead to conventional MNS in females has been reported. These individuals have previously described skeletal (flexed upper limbs, hypoplastic thumbs, post-axial polydactyly, bowed lower limbs, clubfeet, kyphoscoliosis and hypoplastic halluces), craniofacial (large fontanelles, malar flattening, bilateral cleft palate, bifid tongue, severe micrognathia), and visceral (fibrosis of pancreas and spleen, bilateral cystic renal dysplasia secondary to obstructive uropathy and omphalocele) findings and unusual ophthalmologic signs (exophthalmia, widely spaced eyes, sclerocornea, cataracts, retinal angiomatosis, and a cleavage defect of the anterior chambers of both eyes) [Santos et al 2010, Naudion et al 2016, Spencer et al 2018]. Males with MNS usually present with a phenotype that is indistinguishable from, or more severe than, that associated with OPD2. Several women with classic MNS have had affected male pregnancies diagnosed in utero with a lethal phenotype reminiscent of a severe form of OPD2 [Santos et al 2010, Naudion et al 2016, Spencer et al 2018]. Females with MNS present with the following: * A skeletal dysplasia characterized by: * Short stature * Thoracic hypoplasia * Limb bowing * Joint subluxation * Scoliosis * Digits of both the hands and the feet that are typically long with mild distal phalangeal hypoplasia * Characteristic craniofacial features (prominent lateral margins of the supraorbital ridges, proptosis, full cheeks, micrognathia, facial asymmetry) [Foley et al 2010] * Oligohypodontia (frequent) * Sensorineural and conductive deafness (common) * Hydronephrosis secondary to ureteric obstruction (common) * Bleeding diathesis [Moutton et al 2016] * Normal intelligence * Normal pubertal development #### Terminal Osseous Dysplasia with Pigmentary Defects The natural history for females with terminal osseous dysplasia with pigmentary skin defects (TODPD) has been documented in one large family [Brunetti-Pierri et al 2010]. A male presentation of TODPD has never been described. Females exhibit pronounced abnormalities of the face, hands, and skin: * The major skeletal findings are in the hands. There is variable shortening, fusion, and disorganized ossification of the carpals and metacarpals. Camptodactyly can be marked and forms no clear pattern. Additional features include cystic lesions and bowing of the long bones, radial head dislocation, short stature, and scoliosis. * Digital fibromata appear in infancy, can grow to a large size, and may re-grow after excision – but eventually involute before age ten years. * Cardiac septal defects * Ureteric obstruction (occasional) * Alopecia is a variable clinical finding. * The most characteristic craniofacial findings are widely spaced eyes, oral frenulae, and punched out hyperpigmented lesions characteristically over the temporal region. Unlike the fibromata they do not involute with age. * Normal intelligence * A male presentation of TODPD has never been described and an excess of early miscarriage in affected females has been recorded but not statistically verified. ### Genotype-Phenotype Correlations Pathogenic variants associated with the X-OPD spectrum disorders are predicted to maintain the translational reading frame and to produce full-length protein. These variants are clustered in discrete regions of the gene. Genotype-phenotype correlation is strong. Two large studies have been published to date [Robertson et al 2006a]: * OPD1. All males with this diagnosis had pathogenic variants in exons 3, 4, or 5. * OPD2. All males with this diagnosis had pathogenic variants in exons 3, 4, or 5. Females with a phenotype similar to males with typical OPD2 had pathogenic variants in exons 28 and 29. * Frontometaphyseal dysplasia * Out of 13 males with FMD1, all had pathogenic variants in FLNA (exons 3-5, 22, 28-29) [Robertson et al 2006a]. Pathogenic variants in females with FMD1 (found in 68% of affected females) are more widely distributed over the gene (exons 3-5, 11, 22, 28-29, 41, 44-47) than pathogenic variants identified in males. * One female with a combined FMD1-periventricular nodular heterotopia phenotype had a missense variant that also created an ectopic splice site [Zenker et al 2004]. * Some pathogenic variants are associated with a male-lethal phenotype caused by cardiac and urologic malformations [Stefanova et al 2005, Robertson et al 2006a]. * Melnick-Needles syndrome. The vast majority (>90%) of individuals with MNS have pathogenic variants in exon 22 of FLNA, with the two preponderant variants being p.Ala1188Thr and p.Ser1199Leu. Rare individuals have had pathogenic variants identified in exons 6 and 23. ### Penetrance Penetrance in males with an FLNA pathogenic variant leading to an X-OPD spectrum disorder is complete. Some obligate heterozygote females with FLNA pathogenic variants leading to OPD1 have a normal clinical appearance. The proportion of heterozygous females with radiographic features of OPD1 is unknown ### Nomenclature Melnick-Needles syndrome was originally referred to as osteodysplasty. OPD1 was also called Taybi syndrome after its first description in 1963. Verloes et al [2000] suggested the term "fronto-otopalatodigital osteodysplasia" for the X-OPD spectrum disorders, indicative of his prediction that they would prove allelic to one another, which subsequently proved correct. This term has not gained acceptance because some of these disorders are clinically discrete, and therefore diagnosis, management, and prognostication are not served by aggregating them under one term. ### Prevalence No population-based studies have been performed to adequately assess prevalence. ## Differential Diagnosis ### Table 6. Other Genes of Interest in the Differential Diagnosis of Otopalatodigital Spectrum Disorders View in own window GeneDisorderMOIClinical Features of the Differential Diagnosis Disorder Overlapping w/X-OPD-SDDifferentiating from X-OPD-SD AMER1Osteopathia striata congenita (OMIM 300373)XLIn males: similar skeletal dysplasia to that in OPD2; occasionally, extraskeletal anomalies similar to those in OPD2In females: striations of the long bones, macrocephaly, & deafness; in males: similar skeletal phenotype to OPD2 in males FLNBLarsen syndrome (LS) & atelosteogenesis type III (AOIII) (see FLNB-Related Disorders)ADSimilar facial features to those in OPD1 & FMD1, cleft palate, hearing loss, spatulate fingers & toesLarge joint dislocations (in both LS & AOIII) & varying degrees of disordered ossification (in AOIII) MAP3K7Frontometaphyseal dysplasia type 2ADVery similar to FMD1Very similar to FMD1, although individuals w/MAP3K7-FMD are more likely to have cleft palate, scoliosis, cervical fusions, hearing loss, & keloid NOTCH2Serpentine fibula-polycystic kidney disease (Hajdu-Cheney syndrome) (OMIM 102500)ADBowing of long bones, especially fibulaAcro-osteolysis, osteopenia, basilar indentation of the skull base. MNS does not incl cystic kidney disease. SH3PXD2BFrank-ter Haar syndrome (OMIM 249420)ARSkeletal dysplasia similar to but considerably milder than in MNSMacrocornea w/or w/o glaucoma in Frank-ter Haar syndrome SKIShprintzen-Goldberg syndrome (SGS)ADSkeletal dysplasia similar to MNS & FMD1 (e.g., tall, square-shaped vertebrae; bowed tibiae; occasionally, fusion of upper cervical vertebrae)ID & craniosynostosis in SGS TAB2Frontometaphyseal dysplasia type 3ADVery similar to FMD1Very similar to FMD1, although individuals w/TAB2-FMD are more likely to have cleft palate, scoliosis, cervical fusions, hearing loss, & keloid AD = autosomal dominant; AR = autosomal recessive; FMD = frontometaphyseal dysplasia; FMD1 = frontometaphyseal dysplasia type 1; ID = intellectual disability; MNS = Melnick-Needles syndrome; MOI = mode of inheritance; X-OPD-SD = X-linked otopalatodigital spectrum disorders; XL = X-linked Possible autosomal recessive form of otopalatodigital syndrome type I. A single report of a possible autosomal recessive phenocopy of otopalatodigital syndrome type I has been described but has not been subject to molecular analysis [Zaytoun et al 2002]. The appearance of the facies and hands make this condition clinically quite distinct from the filaminopathies described here. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with an X-linked otopalatodigital (X-OPD) spectrum disorder, the evaluations summarized in Table 6 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 7. Recommended Evaluations Following Initial Diagnosis in Individuals with X-Linked Otopalatodigital Spectrum Disorders View in own window System/ConcernEvaluationComment Musculoskeletal * Clinical examination of extremities, joints, & spine * Complete skeletal survey w/scoliosis series if indicated To evaluate for contractures, joint subluxations, scoliosis CraniofacialClinical examination for facial or skull growth asymmetryTo evaluate for craniosynostosis Audiology evaluationTo evaluate for conduction & sensorineural hearing loss Clinical examination of palate & referral to ENT as necessaryTo evaluate for cleft palate & subglottic stenosis RespiratoryReferral to pulmonologist if indicatedTo evaluate for respiratory complications assoc w/thoracic hypoplasia CardiacEchocardiogramTo evaluate for septal defects & right ventricular outflow tract obstructive lesions DentalDental evaluationTo evaluate for hypodontia, oligodontia GenitourinaryRenal tract ultrasound examinationTo evaluate for ureteric & urethral obstruction & hydronephrosis OphthalmologyClinical assessment for proptosisMonitoring for proptosis OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations ### Table 8. Treatment of Manifestations in Individuals with X-Linked Otopalatodigital Spectrum Disorders View in own window Manifestation/ConcernTreatmentConsiderations/Other Hand & foot malformationsSurgical treatment may be required. ScoliosisMonitoring & surgical intervention as requiredSurgery for scoliosis has had satisfactory results in several individuals. ContracturesPhysiotherapy Limb bowingSurgical correction of limb bowing has not been reported. Fronto-orbital deformityCosmetic surgerySurgery attempted in some individuals; regrowth following surgery does not appear to occur [Kung & Sloan 1998]. Thoracic hypoplasiaChest expansion surgeryHas been attempted in several individuals w/MNS w/marginal clinical benefit Apnea * CPAP [Lan et al 2006] * Mandibular distraction Micrognathia & tracheobronchomalacia in severely affected individuals can → airway collapse & sleep apnea that have been successfully corrected in the most severe instances of MNS. DeafnessHearing aidsAttempts to separate fused & misshapen ossicles are usually unsuccessful & can → formation of a perilymphatic gusher. Laryngeal stenosisEvaluation w/anesthesiology if intubation & ventilation are required due to laryngeal stenosisLaryngeal stenosis rarely requires surgical intervention & is non-progressive w/growth. CPAP = continuous positive airway pressure; MNS = Melnick-Needles syndrome ### Surveillance ### Table 9. Recommended Surveillance for Individuals with X-Linked Otopalatodigital Spectrum Disorders View in own window System/ConcernEvaluationFrequency Orthopedic manifestationsClinical evaluation for development of: * Hand contractures in FMD1 * Scoliosis in FMD1 & MNS Annually CraniosynostosisHead size & shape should be monitored.W/each clinical evaluation during infancy ApneaHistory &somnography studies as indicatedYearly DeafnessAudiology evaluations; sensorineural component can be progressive.Yearly FMD1 = Frontometaphyseal dysplasia type 1; MNS = Melnick-Needles syndrome ### 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 early evaluations for hearing loss and orthopedic complications, including scoliosis. 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-aminobutyric 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	X-Linked Otopalatodigital Spectrum Disorders	None	27,477	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1393/	2021-01-18T20:48:15	{"synonyms": ["Otopalatodigital Spectrum Disorders (OPDSD)"]}
Frank (1973) and Lichstein et al. (1974) suggested that a diagonal crease of the earlobe is an indication of increased risk of coronary heart disease. Whether the trait is mendelian is not clear. The frequency of the trait seems to increase with the age of the cohort. Elliot (1983) confirmed an association between earlobe crease and coronary artery disease independent of patient age. On the other hand, Gral and Thornburg (1983) could find no statistically significant correlation. See 130650 and 186350 for syndromes in which an earlobe crease is observed. Inheritance \- Autosomal dominant Misc \- ? indication of increased risk of coronary heart disease Ears \- Diagonal earlobe crease ▲ 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-aminobutyric 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	EARLOBE CREASE	c1851897	27,478	omim	https://www.omim.org/entry/128950	2019-09-22T16:41:58	{"omim": ["128950"]}
Not to be confused with tuberculosis. Tuberous sclerosis Other namesTuberous sclerosis complex (TSC), Bourneville disease A case of tuberous sclerosis showing facial angiofibromas in characteristic butterfly pattern SpecialtyNeurology, medical genetics Frequency7 to 12 per 100,000[1] Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease. TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin, respectively, with TSC2 mutations accounting for the majority and tending to cause more severe symptoms.[2] These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation.[3] Prognosis is highly variable and depends on the symptoms, but life expectancy is normal for many.[3] The prevalence of the disease is estimated to be 7 to 12 in 100,000.[1] The disease is often abbreviated to tuberous sclerosis, which refers to the hard swellings in the brains of patients, first described by French neurologist Désiré-Magloire Bourneville in 1880.[4] ## Contents * 1 Signs and symptoms * 1.1 Neurological * 1.2 Neuropsychiatric * 1.3 Kidneys * 1.4 Lungs * 1.5 Heart * 1.6 Skin * 1.7 Eyes * 1.8 Pancreas * 1.9 Variability * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 5 Management * 6 Prognosis * 7 Epidemiology * 8 History * 9 References * 10 External links ## Signs and symptoms[edit] The physical manifestations of TSC are due to the formation of hamartia (malformed tissue such as the cortical tubers), hamartomas (benign growths such as facial angiofibroma and subependymal nodules), and very rarely, cancerous hamartoblastomas. The effect of these on the brain leads to neurological symptoms such as seizures, intellectual disability, developmental delay, and behavioral problems.[citation needed] ### Neurological[edit] TSC in MRI Three types of brain tumours are associated with TSC: * Giant cell astrocytoma: (grows and blocks the cerebrospinal fluid flow, leading to dilatation of ventricles causing headache and vomiting) * Cortical tubers: after which the disease is named * Subependymal nodules: form in the walls of ventricles Classic intracranial manifestations of TSC include subependymal nodules and cortical/subcortical tubers.[5] The tubers are typically triangular in configuration, with the apex pointed towards the ventricles, and are thought to represent foci of abnormal neuronal migration. The T2 signal abnormalities may subside in adulthood, but will still be visible on histopathological analysis. On magnetic resonance imaging (MRI), TSC patients can exhibit other signs consistent with abnormal neuron migration such as radial white matter tracts hyperintense on T2WI and heterotopic gray matter.[citation needed] Subependymal nodules are composed of abnormal, swollen glial cells and bizarre multinucleated cells which are indeterminate for glial or neuronal origin. Interposed neural tissue is not present. These nodules have a tendency to calcify as the patient ages. A nodule that markedly enhances and enlarges over time should be considered suspicious for transformation into a subependymal giant cell astrocytoma, which typically develops in the region of the foramen of Monro, in which case it is at risk of developing an obstructive hydrocephalus.[citation needed] A variable degree of ventricular enlargement is seen, either obstructive (e.g. by a subependymal nodule in the region of the foramen of Monro) or idiopathic in nature.[citation needed] ### Neuropsychiatric[edit] About 90% of people with TSC develop a range of neurodevelopmental, behavioural, psychiatric, and psychosocial difficulties. The "TSC‐associated neuropsychiatric disorders" are abbreviated TAND. These difficulties are less frequently identified and thus undertreated when compared with the neurological symptoms.[6] Most problems are associated with more severe intellectual delay or associated with childhood and adolescence, and some (for example depressed mood) may be unreported if the person is unable to communicate. TAND can be investigated and considered at six levels: behavioural, psychiatric, intellectual, academic, neuropsychological, and psychosocial.[6] Behavioural problems most commonly seen include overactivity, impulsivity and sleeping difficulties. Also common are anxiety, mood swings, and severe aggression. Less common are depressed mood, self-injury, and obsessional behaviours.[6] People with TSC are frequently also diagnosed psychiatric disorders: autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), anxiety disorder and depressive disorder. TSC is one of the most common genetic causes of autism spectrum disorder, which affects nearly half of people with TSC. ASD is more common in TSC2 than TSC1 and more common with earlier and more severe epilepsy, and with lower intellectual ability. ADHD is nearly as frequently seen in TSC as ASD (up to half of all people with TSC). Anxiety and depressive disorders, when they occur, are typically diagnosed in early adulthood and among those intellectually able to express their moods.[6] Schizophrenia (and symptoms like hallucinations or psychosis) is no more common in TSC than the general population.[citation needed] The intellectual ability of people with TSC varies enormously. About 40–50% have a normal IQ. A normal IQ is much more commonly seen in TSC1 than TSC2, and profound intellectual disability seen in 34% of TSC2 compared with 10% of TSC1 in one study. Many studies have examined whether early onset, type and severity of epilepsy associates with intellectual ability. Academic issues occur even in people with TSC who have normal intellectual ability. These are often specific learning disorders such as dyscalculia (understanding mathematics), but also include other aspects affecting school life such as anxiety, lack of social skills or low self-esteem.[6] About half of people with TSC, when assessed for neuropsychological skills, are in the bottom 5th percentile in some areas, which indicates a severe impairment. These include problems with attention (for example, being able to concentrate on two separate things like looking and listening), memory (particularly recall, verbal and spatial working memory) and executive function (for example, planning, self-monitoring, cognitive flexibility).[6] The psychosocial impacts of TSC include low self-esteem and self-efficacy in the individual, and a burden on the family coping with a complex and unpredictable disorder.[6] ### Kidneys[edit] Computed tomography showing multiple angiomyolipomas of the kidney in a patient with lung lymphangioleiomyomatosis on CT: suspected TSC Between 60 and 80% of TSC patients have benign tumors (once thought hamartomatous, but now considered true neoplasms) of the kidneys called angiomyolipomas frequently causing hematuria. These tumors are composed of vascular (angio–), smooth muscle (–myo–), and fat (–lip-) tissue. Although benign, an angiomyolipoma larger than 4 cm is at risk for a potentially catastrophic hemorrhage either spontaneously or with minimal trauma. Angiomyolipomas are found in about one in 300 people without TSC. However, those are usually solitary, whereas in TSC they are commonly multiple and bilateral.[citation needed] About 20-30% of people with TSC have renal cysts, causing few problems. However, 2% may also have autosomal dominant polycystic kidney disease.[citation needed] Very rare (< 1%) problems include renal cell carcinoma and oncocytomas (benign adenomatous hamartoma).[citation needed] ### Lungs[edit] Patients with TSC can develop progressive replacement of the lung parenchyma with multiple cysts, known as lymphangioleiomyomatosis (LAM). Recent genetic analysis has shown that the proliferative bronchiolar smooth muscle in TSC-related lymphangioleiomyomatosis is monoclonal metastasis from a coexisting renal angiomyolipoma. Cases of TSC-related lymphangioleiomyomatosis recurring following lung transplant have been reported.[7] ### Heart[edit] Small tumours of the heart muscle, called cardiac rhabdomyomas, are rare in the general population (perhaps 0.2% of children) but very common in people with TSC. Around 80% of children under two-years-old with TSC have at least one rhabdomyoma, and about 90% of those will have several. The vast majority of children with at least one rhabdomyoma, and nearly all children with multiple rhabdomyomas will be found to have TSC. Prenatal ultrasound, performed by an obstetric sonographer specializing in cardiology, can detect a rhabdomyoma after 20 weeks. Rhabdomyoma vary in size from a few millimetres to several centimetres, and are usually found in the lower chambers (ventricles) and less often in the upper chambers (atria). They grow in size during the second half of pregnancy, but regress after birth, and are seen in only around 20% of children over two years old.[8] Most rhabdomyomas cause no problems but some may cause heart failure in the foetus or first year of life. Rhabdomyomas are believed to be responsible for the development of heart arrhythmia later in life, which is relatively common in TSC. Arrhythmia can be hard to spot in people with TSC, other than by performing routine ECG. For example, arrhythmia may cause fainting that is confused with drop seizures, and symptoms of arrhythmia such as palpitations may not be reported in an individual with developmental delay.[8] ### Skin[edit] Some form of dermatological sign is present in 96% of individuals with TSC. Most cause no problems, but are helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin abnormalities include: * Hypomelanic macules ("ash leaf spots") are present in about 90% of people with TSC.[9] These small white or lighter patches of skin may appear anywhere on the body, and are caused by a lack of melanin. They are usually the only visible sign of TSC at birth. In fair-skinned individuals, a Wood's lamp (ultraviolet light) may be required to see them. On the scalp, the effect may be a white patch of hair (poliosis). Patches smaller than 3mm are known as "confetti" skin lesions.[9] * Facial angiofibromas are present in about 75% of people with TSC.[9] These are a rash of reddish spots or bumps on the nose and cheeks in a butterfly distribution, which consist of blood vessels and fibrous tissue. This potentially socially embarrassing rash starts to appear during childhood. * Ungual fibromas: Also known as Koenen's tumors, these are small fleshy tumors that grow around and under the toenails or fingernails. These are rare in childhood, but common by middle age.[10] They are generally more common on toes than on fingers, develop at 15–29 years, and are more common in women than in men. * Fibrous cephalic plaques are present in about 25% of people with TSC.[9] These are raised, discoloured areas usually found on the forehead, but sometimes on the face or elsewhere on the scalp. * Shagreen patches are present in about half of people with TSC, appearing in childhood.[9] They are areas of thick leathery skin that are dimpled like an orange peel, and pigmented, they are usually found on the lower back or nape of the neck, or scattered across the trunk or thighs. The frequency of these lesions rises with age. * Dental enamel pits are found in almost all adults with TSC.[9] * Intraoral fibromas are small surface-tumours found in the gums, inside the cheeks or tongue. Gum (gingival) fibromas are found in about 20-50% of people with TSC, more commonly in adults.[9] ### Eyes[edit] Retinal lesions, called astrocytic hamartomas (or "phakomas"), which appear as a greyish or yellowish-white lesion in the back of the globe on the ophthalmic examination. Astrocytic hamartomas can calcify, and they are in the differential diagnosis of a calcified globe mass on a CT scan.[11] Nonretinal lesions associated with TSC include: * Coloboma[11] * Angiofibromas of the eyelids[11] * Papilledema (related to hydrocephalus) ### Pancreas[edit] Pancreatic neuroendocrine tumours have been described in rare cases of TSC.[12] ### Variability[edit] Individuals with TSC may experience none or all of the clinical signs discussed above. The following table shows the prevalence of some of the clinical signs in individuals diagnosed with TSC. The frequency of signs in children with TSC, grouped by age[13] ## Genetics[edit] TSC is inherited in an autosomal dominant fashion. TSC is a genetic disorder with an autosomal dominant pattern of inheritance, variable expressivity, and incomplete penetrance.[10][14] Two-thirds of TSC cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in roughly 20% of individuals diagnosed with the disease. So far, it has been mapped to two genetic loci, TSC1 and TSC2.[citation needed] TSC1 encodes for the protein hamartin, is located on chromosome 9 q34, and was discovered in 1997.[15] TSC2 encodes for the protein tuberin, is located on chromosome 16 p13.3, and was discovered in 1993.[16] TSC2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with TSC who also develop polycystic kidney disease in childhood.[17] TSC2 has been associated with a more severe form of TSC.[18] However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of TSC caused by TSC2 range from 55% to 90%.[2] TSC1 and TSC2 are both tumor suppressor genes that function according to Knudson's "two hit" hypothesis. That is, a second random mutation must occur before a tumor can develop. This explains why, despite its high penetrance, TSC has wide expressivity.[citation needed] Hamartin Identifiers SymbolTSC1 NCBI gene7248 HGNC12362 OMIM605284 RefSeqNM_000368 UniProtQ92574 Other data LocusChr. 9 q34 Search for StructuresSwiss-model DomainsInterPro Tuberin Identifiers SymbolTSC2 NCBI gene7249 HGNC12363 OMIM191092 RefSeqNM_000548 UniProtP49815 Other data LocusChr. 16 p13.3 Search for StructuresSwiss-model DomainsInterPro ## Pathophysiology[edit] Hamartin and tuberin function as a complex which is involved in the control of cell growth and cell division. The complex appears to interact with RHEB GTPase, thus sequestering it from activating mTOR signalling, part of the growth factor (insulin) signalling pathway. Thus, mutations at the TSC1 and TSC2 loci result in a loss of control of cell growth and cell division, and therefore a predisposition to forming tumors. TSC affects tissues from different germ layers. Cutaneous and visceral lesions may occur, including angiofibroma, cardiac rhabdomyomas, and renal angiomyolipomas. The central nervous system lesions seen in this disorder include hamartomas of the cortex, hamartomas of the ventricular walls, and subependymal giant cell tumors, which typically develop in the vicinity of the foramina of Monro.[citation needed] Molecular genetic studies have defined at least two loci for TSC. In TSC1, the abnormality is localized on chromosome 9q34, but the nature of the gene protein, called hamartin, remains unclear. No missense mutations occur in TSC1. In TSC2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a guanosine triphosphatase–activating protein. The specific function of this protein is unknown. In TSC2, all types of mutations have been reported; new mutations occur frequently. Few differences have yet been observed in the clinical phenotypes of patients with mutation of one gene or the other.[citation needed] Cells from individuals with pathogenic mutations in the TSC2 gene display abnormal accumulation of glycogen that is associated with depletion of lysosomes and autophagic impairment. The defective degradation of glycogen by the autophagy-lysosome pathway is, at least in part, independent of impaired regulation of mTORC1 and is restored, in cultured cells, by the combined use of PKB/Akt and mTORC1 pharmacological inhibitors.[19] ## Diagnosis[edit] Tuberous sclerosis complex is diagnosed with clinical and genetic tests. There are many different mutations in the TSC1 and TSC2 genes that have been identified in individuals with TSC. A pathogenic mutation in the gene prevents the proteins from being made or inactivates the proteins. If such a pathogenic mutation is found then this alone is sufficient to diagnose TSC. However, some mutations are less clear in their effect, and so not sufficient alone for diagnosis. Between 1 in 10 and 1 in 4 of individuals with TSC have no mutation that can be identified. Once a particular mutation is identified in someone with TSC, this mutation can be used to make confident diagnoses in other family members.[9] For clinical diagnosis, there isn't one sign that is unique (pathognomonic) to TSC, nor are all signs seen in all individuals. Therefore, several signs are considered together, classed as either major or minor features. An individual with two major features, or one major feature and at least two minor features can be given a definite diagnosis of TSC. If only one major feature or at least two minor features are present, the diagnosis is only regarded as possibly TSC.[9] Diagnostic Criteria for Tuberous Sclerosis Complex[9] Major Features Location Sign Onset[20] Note 1 Skin Hypomelanotic macules Infant – child At least three, at least 5 mm in diameter. 2 Head Facial angiofibromas or fibrous cephalic plaque Infant – adult At least three angiofibromas 3 Fingers and toes Ungual fibroma Adolescent – adult At least two 4 Skin Shagreen patch (connective tissue nevus) Child 5 Eyes Multiple retinal nodular hamartomas Infant 6 Brain Cortical dysplasias (includes tubers and cerebral white matter radial migration lines) Fetus 7 Brain Subependymal nodule Child – adolescent 8 Brain Subependymal giant cell astrocytoma Child – adolescent 9 Heart Cardiac rhabdomyoma Fetus 10 Lungs Lymphangioleiomyomatosis Adolescent – adult 11 Kidneys Renal angiomyolipoma Child – adult At least two. Together, 10 and 11 count as one major feature. Minor Features Location Sign Note 1 Skin "Confetti" skin lesions 2 Teeth Dental enamel pits At least three 3 Gums Intraoral fibromas At least two 4 Eyes Retinal achromic patch 5 Kidneys Multiple renal cysts 6 Liver, spleen and other organs Nonrenal hamartoma TSC can be first diagnosed at any stage of life. Prenatal diagnosis is possible by chance if heart tumours are discovered during routine ultrasound. In infancy, epilepsy, particularly infantile spasms, or developmental delay may lead to neurological tests. The white patches on the skin may also first become noticed. In childhood, behavioural problems and autism spectrum disorder may provoke a diagnosis. During adolescence, the skin problems appear. In adulthood, kidney and lung problems may develop. An individual may also be diagnosed at any time as a result of genetic testing of family members of another affected person.[21] ## Management[edit] Tuberous sclerosis complex affects multiple organ systems so a multidisciplinary team of medical professionals is required.[citation needed] In suspected or newly diagnosed TSC, the following tests and procedures are recommended by 2012 International Tuberous Sclerosis Complex Consensus Conference.[22] * Take a personal and family history covering three generations. Genetic counselling and tests determine if other individuals are at risk. * A magnetic resonance imaging (MRI) of the brain to identify tubers, subependymal nodules (SEN) and sub-ependymal giant cell astrocytomas (SEGA). * Children undergo a baseline electroencephalograph (EEG) and family educated to identify seizures if/when they occur. * Assess children for behavioural issues, autism spectrum disorder, psychiatric disorders, developmental delay, and neuropsychological problems. * Scan the abdomen for tumours in various organs, but most importantly angiomyolipomata in the kidneys. MRI is superior to CT or ultrasound. Take blood pressure and test renal function. * In adult women, test pulmonary function and perform a high-resolution computed tomography (HRCT) of the chest. * Examine the skin under a Wood's lamp (hypomelanotic macules), the fingers and toes (ungual fibroma), the face (angiofibromas), and the mouth (dental pits and gingival fibromas). * In infants under three, perform an echocardiogram to spot rhabdomyomas, and electrocardiogram (ECG) for any arrhythmia. * Use a fundoscope to spot retinal hamartomas or achromic patches. The various symptoms and complications from TSC may appear throughout life, requiring continued surveillance and adjustment to treatments. The following ongoing tests and procedures are recommended by 2012 International Tuberous Sclerosis Complex Consensus Conference.[22] * In children and adults younger than 25 years, a magnetic resonance imaging (MRI) of the brain is performed every one to three years to monitor for subependymal giant cell astrocytoma (SEGA). If a SEGA is large, growing or interfering with ventricles, the MRI is performed more frequently. After 25 years, if there are no SEGAs then periodic scans may no longer be required. A SEGA causing acute symptoms are removed with surgery, otherwise either surgery or drug treatment with an mTOR inhibitor may be indicated. * Repeat screening for TSC-associated neuropsychiatric disorders (TAND) at least annually. Sudden behavioural changes may indicate a new physical problem (for example with the kidneys, epilepsy or a SEGA). * Routine EEG determined by clinical need. * Infantile spasms are best treated with vigabatrin and adrenocorticotropic hormone used as a second-line therapy. Other seizure types have no TSC-specific recommendation, though epilepsy in TSC is typically difficult to treat (medically refractory). * Repeat MRI of abdomen every one to three years throughout life. Check renal (kidney) function annually. Should angiomyolipoma bleed, this is best treated with embolisation and then corticosteroids. Removal of the kidney (nephrectomy) is strongly to be avoided. An asymptomatic angiomyolipoma that is growing larger than 3 cm is best treated with an mTOR inhibitor drug. Other renal complications spotted by imaging include polycystic kidney disease and renal cell carcinoma. * Repeat chest HRCT in adult women every five to 10 years. Evidence of lymphangioleiomyomatosis (LAM) indicates more frequent testing. An mTOR inhibitor drug can help, though a lung transplant may be required. * A 12-lead ECG should be performed every three to five years. The mTOR inhibitor everolimus was approved in the US for treatment of TSC-related tumors in the brain (subependymal giant cell astrocytoma) in 2010 and in the kidneys (renal angiomyolipoma) in 2012.[23][24] Oral everolimus (rapalog) reduces tumour size, is effective in terms of response to skin lesions and does not increase the risk of adverse events.[25] Everolimus also showed evidence of effectiveness at treating epilepsy in some people with TSC.[26][27] In 2017, the European Commission approved everolimus for treatment of refractory partial-onset seizures associated with TSC.[28] Neurosurgical intervention may reduce the severity and frequency of seizures in TSC patients.[29][30] Embolization and other surgical interventions can be used to treat renal angiomyolipoma with acute hemorrhage. Surgical treatments for symptoms of lymphangioleiomyomatosis (LAM) in adult TSC patients include pleurodesis to prevent pneumothorax and lung transplantation in the case of irreversible lung failure.[22] Other treatments that have been used to treat TSC manifestations and symptoms include a ketogenic diet for intractable epilepsy and pulmonary rehabilitation for LAM.[31] Facial angiofibromas can be reduced with laser treatment and the effectiveness of mTOR inhibitor topical treatment is being investigated. Laser therapy is painful, requires anaesthesia, and has risks of scarring and dyspigmentation.[32] ## Prognosis[edit] The prognosis for individuals with TSC depends on the severity of symptoms, which range from mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe intellectual disability, uncontrollable seizures, and kidney failure. Those individuals with mild symptoms generally do well and live long, productive lives, while individuals with the more severe form may have serious disabilities. However, with appropriate medical care, most individuals with the disorder can look forward to normal life expectancy.[3] A study of 30 TSC patients in Egypt found, "...earlier age of seizures commencement (<6 months) is associated with poor seizure outcome and poor intellectual capabilities. Infantile spasms and severely epileptogenic EEG patterns are related to the poor seizure outcome, poor intellectual capabilities and autistic behavior. Higher tubers numbers is associated with poor seizure outcome and autistic behavior. Left-sided tuber burden is associated with poor intellect, while frontal location is more encountered in ASD [autism spectrum disorders]. So, close follow up for the mental development and early control of seizures are recommended in a trial to reduce the risk factors of poor outcome. Also early diagnosis of autism will allow for earlier treatment and the potential for better outcome for children with TSC."[33] Leading causes of death include renal disease, brain tumour, lymphangioleiomyomatosis of the lung, and status epilepticus or bronchopneumonia in those with severe mental handicap.[34] Cardiac failure due to rhabdomyomas is a risk in the fetus or neonate but is rarely a problem subsequently. Kidney complications such as angiomyolipoma and cysts are common and more frequent in females than males and in TSC2 than TSC1. Renal cell carcinoma is uncommon. Lymphangioleiomyomatosis is only a risk for females with angiomyolipomas.[35] In the brain, the subependymal nodules occasionally degenerate to subependymal giant cell astrocytomas. These may block the circulation of cerebrospinal fluid around the brain, leading to hydrocephalus.[citation needed] Detection of the disease should be followed by genetic counselling. It is also important to realise that though the disease does not have a cure, symptoms can be treated symptomatically. Hence, awareness regarding different organ manifestations of TSC is important.[citation needed] ## Epidemiology[edit] TSC occurs in all races and ethnic groups, and in both genders. The live-birth prevalence is estimated to be between 10 and 16 cases per 100,000. A 1998 study[1] estimated total population prevalence between about 7 and 12 cases per 100,000, with more than half of these cases undetected. Prior to the invention of CT scanning to identify the nodules and tubers in the brain, the prevalence was thought to be much lower, and the disease associated with those people diagnosed clinically with learning disability, seizures and facial angiofibroma. Whilst still regarded as a rare disease, TSC is common when compared to many other genetic diseases, with at least 1 million individuals affected worldwide.[13] ## History[edit] Main article: Timeline of tuberous sclerosis Désiré-Magloire Bourneville TSC first came to medical attention when dermatologists described the distinctive facial rash (1835 and 1850). A more complete case was presented by von Recklinghausen (1862), who identified heart and brain tumours in a newborn who had only briefly lived. However, Bourneville (1880) is credited with having first characterized the disease, coining the name "tuberous sclerosis", thus earning the eponym Bourneville's disease. The neurologist Vogt (1908) established a diagnostic triad of epilepsy, idiocy, and adenoma sebaceum (an obsolete term for facial angiofibroma).[36] Symptoms were periodically added to the clinical picture. The disease as presently understood was first fully described by Gomez (1979). The invention of medical ultrasound, CT and MRI has allowed physicians to examine the internal organs of live patients and greatly improved diagnostic ability.[citation needed] In 2002, treatment with rapamycin was found to be effective at shrinking tumours in animals. This has led to human trials of rapamycin as a drug to treat several of the tumors associated with TSC.[37] ## References[edit] 1. ^ a b c O'Callaghan FJ, Shiell AW, Osborne JP, Martyn CN (May 1998). "Prevalence of tuberous sclerosis estimated by capture-recapture analysis". Lancet. 351 (9114): 1490. doi:10.1016/S0140-6736(05)78872-3. PMID 9605811. S2CID 9262685. 2. ^ a b Rendtorff ND, Bjerregaard B, Frödin M, Kjaergaard S, Hove H, Skovby F, Brøndum-Nielsen K, Schwartz M (October 2005). "Analysis of 65 tuberous sclerosis complex (TSC) patients by TSC2 DGGE, TSC1/TSC2 MLPA, and TSC1 long-range PCR sequencing, and report of 28 novel mutations". Human Mutation. 26 (4): 374–83. doi:10.1002/humu.20227. PMID 16114042. 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PMID 25776100. S2CID 72874. 33. ^ Samir H, Ghaffar HA, Nasr M (March 2011). "Seizures and intellectual outcome: clinico-radiological study of 30 Egyptian cases of tuberous sclerosis complex". European Journal of Paediatric Neurology. 15 (2): 131–37. doi:10.1016/j.ejpn.2010.07.010. PMID 20817577. 34. ^ Shepherd CW, Gomez MR, Lie JT, Crowson CS (August 1991). "Causes of death in patients with tuberous sclerosis". Mayo Clinic Proceedings. 66 (8): 792–96. doi:10.1016/s0025-6196(12)61196-3. PMID 1861550. 35. ^ Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA (November 2006). "Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors". Kidney International. 70 (10): 1777–82. doi:10.1038/sj.ki.5001853. PMID 17003820. 36. ^ Curatolo P, ed. (2003). "Historical Background". Tuberous Sclerosis Complex: From Basic Science to Clinical Phenotypes. International review of child neurology. London: Mac Keith Press. ISBN 978-1-898683-39-1. OCLC 53124670. 37. ^ Rott HD, Mayer K, Walther B, Wienecke R (March 2005). "Zur Geschichte der Tuberösen Sklerose (The History of Tuberous Sclerosis)" (PDF) (in German). Tuberöse Sklerose Deutschland e.V. Archived from the original (PDF) on 15 March 2007. Retrieved 8 January 2007. * ## External links[edit] Wikimedia Commons has media related to Tuberous sclerosis. Classification D * ICD-10: Q85.1 * ICD-9-CM: 759.5 * OMIM: 191100 613254 * MeSH: D014402 * DiseasesDB: 13433 External resources * MedlinePlus: 000787 * eMedicine: neuro/386 derm/438 ped/2796 radio/723 * Patient UK: Tuberous sclerosis * GeneReviews: Tuberous Sclerosis Complex * Orphanet: 805 * tuberous-sclerosis at NIH/UW GeneTests * GeneReview/NCBI/NIH/UW entry on Tuberous Sclerosis Complex * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Phakomatosis Angiomatosis * Sturge–Weber syndrome * Von Hippel–Lindau disease Hamartoma * Tuberous sclerosis * Hypothalamic hamartoma (Pallister–Hall syndrome) * Multiple hamartoma syndrome * Proteus syndrome * Cowden syndrome * Bannayan–Riley–Ruvalcaba syndrome * Lhermitte–Duclos disease Neurofibromatosis * Type I * Type II Other * Abdallat–Davis–Farrage syndrome * Ataxia telangiectasia * Incontinentia pigmenti * Peutz–Jeghers syndrome * Encephalocraniocutaneous lipomatosis * v * t * e Deficiencies of intracellular signaling peptides and proteins GTP-binding protein regulators GTPase-activating protein * Neurofibromatosis type I * Watson syndrome * Tuberous sclerosis Guanine nucleotide exchange factor * Marinesco–Sjögren syndrome * Aarskog–Scott syndrome * Juvenile primary lateral sclerosis * X-Linked mental retardation 1 G protein Heterotrimeic * cAMP/GNAS1: Pseudopseudohypoparathyroidism * Progressive osseous heteroplasia * Pseudohypoparathyroidism * Albright's hereditary osteodystrophy * McCune–Albright syndrome * CGL 2 Monomeric * RAS: HRAS * Costello syndrome * KRAS * Noonan syndrome 3 * KRAS Cardiofaciocutaneous syndrome * RAB: RAB7 * Charcot–Marie–Tooth disease * RAB23 * Carpenter syndrome * RAB27 * Griscelli syndrome type 2 * RHO: RAC2 * Neutrophil immunodeficiency syndrome * ARF: SAR1B * Chylomicron retention disease * ARL13B * Joubert syndrome 8 * ARL6 * Bardet–Biedl syndrome 3 MAP kinase * Cardiofaciocutaneous syndrome Other kinase/phosphatase Tyrosine kinase * BTK * X-linked agammaglobulinemia * ZAP70 * ZAP70 deficiency Serine/threonine kinase * RPS6KA3 * Coffin-Lowry syndrome * CHEK2 * Li-Fraumeni syndrome 2 * IKBKG * Incontinentia pigmenti * STK11 * Peutz–Jeghers syndrome * DMPK * Myotonic dystrophy 1 * ATR * Seckel syndrome 1 * GRK1 * Oguchi disease 2 * WNK4/WNK1 * Pseudohypoaldosteronism 2 Tyrosine phosphatase * PTEN * Bannayan–Riley–Ruvalcaba syndrome * Lhermitte–Duclos disease * Cowden syndrome * Proteus-like syndrome * MTM1 * X-linked myotubular myopathy * PTPN11 * Noonan syndrome 1 * LEOPARD syndrome * Metachondromatosis Signal transducing adaptor proteins * EDARADD * EDARADD Hypohidrotic ectodermal dysplasia * SH3BP2 * Cherubism * LDB3 * Zaspopathy Other * NF2 * Neurofibromatosis type II * NOTCH3 * CADASIL * PRKAR1A * Carney complex * PRKAG2 * Wolff–Parkinson–White syndrome * PRKCSH * PRKCSH Polycystic liver disease * XIAP * XIAP2 See also intracellular signaling peptides and proteins Authority control * GND: 4186390-2 [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-aminobutyric 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	Tuberous sclerosis	c0041341	27,479	wikipedia	https://en.wikipedia.org/wiki/Tuberous_sclerosis	2021-01-18T19:06:08	{"gard": ["946", "7830"], "mesh": ["D014402"], "umls": ["C0041341", "C1368816", "C0265319"], "orphanet": ["805"], "wikidata": ["Q1362721"]}
Distal hereditary motor neuropathy type V Other namesdHMN V Distal hereditary motor neuropathy type V is a particular type of neuropathic disorder. In general, distal hereditary motor neuropathies affect the axons of distal motor neurons and are characterized by progressive weakness and atrophy of muscles of the extremities.[1] It is common for them to be called "spinal forms of Charcot-Marie-Tooth disease (CMT)", because the diseases are closely related in symptoms and genetic cause. The diagnostic difference in these diseases is the presence of sensory loss in the extremities.[2] There are seven classifications of dHMNs, each defined by patterns of inheritance, age of onset, severity, and muscle groups involved. Type V (sometimes notated as Type 5) is a disorder characterized by autosomal dominance, weakness of the upper limbs that is progressive and symmetrical, and atrophy of the small muscles of the hands.[3] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] Onset usually occurs within the first two decades of life, commonly in the teenage years or the twenties. Life expectancy is normal. High arch of the foot (pes cavus) seen in dHMN V and other related motor neuropathy disorders High arch of the foot (pes cavus) is common. Patients also have trouble controlling their hands, due to muscle loss on the thumb side of the index finger and palm below the thumb.[4] It is rare for a person with this disorder to lose the ability to walk, though changes in gait may occur later in life.[5] Frequency of this disorder is unknown.[6] ## Genetics[edit] dHMN V has a pattern of autosomal dominance, meaning that only one copy of the gene is needed for the development of the disease. However, there is incomplete penetrance of this disorder, meaning that some individuals with the disease-causing mutations will not display any symptoms.[3] Mutations on chromosome 7 have been linked to this disease. It is allelic (i.e., caused by mutations on the same gene) with Charcot–Marie–Tooth disease and with Silver’s Syndrome, a disorder also characterized by small muscle atrophy in the hands.[1][7] Another rare form of dHMN V is associated with a splicing mutation in REEP-1, a gene often associated with hereditary spastic neuroplegia.[8] ## Diagnosis[edit] In an individual with dHMN V, electromyography will show pure motor neuropathy, patterns of weakness without upper motor neuron damage, in the hands. Tendon reflexes will also appear normal.[9] Clinical, electrophysiological, and pathological testing will show a lack of damage to sensory neurons, differentiating this disease from CMT.[10] ## Treatment[edit] Physical therapy is the predominant treatment of symptoms. Orthopedic shoes and foot surgery can be used to manage foot problems.[5] ## References[edit] 1. ^ a b Seo, Ah Jung; Park, Byung Sun; Jeong, Na Young; Kim, Doyen; Kim, Sunghoon; Park, Chan; Jung, Junyang; Huh, Youngbuhm (2014). "Adenoviral-mediated mouse model of motor impairment in distal spinal muscular atrophy type V". Animal Cells and Systems. 18 (5): 311–317. doi:10.1080/19768354.2014.950330. ISSN 1976-8354. 2. ^ Middleton, L. T.; Christodoulou, K.; Mubaidin, A.; Zamba, E.; Tsingis, M.; Kyriacou, K.; Abu-Sheikh, S.; Kyriakides, T.; Neocleous, V.; Georgiou, D. M.; El-Khateeb, M.; Al-Qudah, A.; Horany, K. (1999). "Distal Hereditary Motor Neuronopathy of the Jerash Type". Annals of the New York Academy of Sciences. 883 (1 CHARCOT–MARIE): 439–442. Bibcode:1999NYASA.883..439M. doi:10.1111/j.1749-6632.1999.tb08604.x. ISSN 0077-8923. PMID 29086938. 3. ^ a b Rakočević-Stojanović, V.; Milić-Rašić, V.; Perić, S.; Baets, J.; Timmerman, V.; Dierick, I.; Pavlović, S.; De Jonghe, P. (2010). "N88S mutation in the BSCL2 gene in a Serbian family with distal hereditary motor neuropathy type V or Silver syndrome". Journal of the Neurological Sciences. 296 (1–2): 107–109. doi:10.1016/j.jns.2010.06.015. ISSN 0022-510X. PMID 20598714. 4. ^ "Distal hereditary motor neuropathy, type V". Think Genetic. 10 June 2016. Retrieved 5 November 2016. 5. ^ a b Ito, Daisuke; Suzuki, Norihiro (2007). "Molecular pathogenesis of seipin/BSCL2-related motor neuron diseases". Annals of Neurology. 61 (3): 237–250. doi:10.1002/ana.21070. ISSN 0364-5134. PMID 17387721. 6. ^ Reference, Genetics Home. "distal hereditary motor neuropathy, type V". Genetics Home Reference. 7. ^ Dubourg, O.; Azzedine, H.; Yaou, R. B.; Pouget, J.; Barois, A.; Meininger, V.; Bouteiller, D.; Ruberg, M.; Brice, A.; LeGuern, E. (12 June 2006). "The G526R glycyl-tRNA synthetase gene mutation in distal hereditary motor neuropathy type V". Neurology. 66 (11): 1721–1726. doi:10.1212/01.wnl.0000218304.02715.04. PMID 16769947. 8. ^ Beetz, Christian; Pieber, Thomas R.; Hertel, Nicole; Schabhüttl, Maria; Fischer, Carina; Trajanoski, Slave; Graf, Elisabeth; Keiner, Silke; Kurth, Ingo; Wieland, Thomas; Varga, Rita-Eva; Timmerman, Vincent; Reilly, Mary M.; Strom, Tim M.; Auer-Grumbach, Michaela (2012). "Exome Sequencing Identifies a REEP1 Mutation Involved in Distal Hereditary Motor Neuropathy Type V". The American Journal of Human Genetics. 91 (1): 139–145. doi:10.1016/j.ajhg.2012.05.007. ISSN 0002-9297. PMC 3397265. PMID 22703882. 9. ^ Antonellis, Anthony; Ellsworth, Rachel E.; Sambuughin, Nyamkhishig; Puls, Imke; Abel, Annette; Lee-Lin, Shih-Queen; Jordanova, Albena; Kremensky, Ivo; Christodoulou, Kyproula; Middleton, Lefkos T.; Sivakumar, Kumaraswamy; Ionasescu, Victor; Funalot, Benoit; Vance, Jeffery M.; Goldfarb, Lev G.; Fischbeck, Kenneth H.; Green, Eric D. (2003). "Glycyl tRNA Synthetase Mutations in Charcot-Marie-Tooth Disease Type 2D and Distal Spinal Muscular Atrophy Type V". The American Journal of Human Genetics. 72 (5): 1293–1299. doi:10.1086/375039. ISSN 0002-9297. PMC 1180282. PMID 12690580. 10. ^ Pareyson, Davide; Marchesi, Chiara (2009). "Diagnosis, natural history, and management of Charcot–Marie–Tooth disease". The Lancet Neurology. 8 (7): 654–667. doi:10.1016/S1474-4422(09)70110-3. ISSN 1474-4422. PMID 19539237. ## External links[edit] Classification D * OMIM: 600794 [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-aminobutyric 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	Distal hereditary motor neuropathy type V	c1833308	27,480	wikipedia	https://en.wikipedia.org/wiki/Distal_hereditary_motor_neuropathy_type_V	2021-01-18T19:00:25	{"mesh": ["C563443"], "umls": ["C1833308"], "orphanet": ["139536"], "wikidata": ["Q28134983"]}
Cutaneous polyarteritis nodosa (CPAN) is a rare limited form of polyarteritis nodosa (PAN, see this term), characterized by cutaneous vasculitis and mild and transient extracutaneous manifestations such as mild arthralgia, arthritis,myalgia, and rarely peripheral neuropathy. [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-aminobutyric 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	Cutaneous polyarteritis nodosa	c0343190	27,481	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=439729	2021-01-23T16:55:08	{"gard": ["7415"], "icd-10": ["M30.0"], "synonyms": ["Cutaneous PAN", "Cutaneous periarteritis nodosa"]}
Early myoclonic encephalopathy[1] SpecialtyNeurology Early myoclonic encephalopathy (EME) is an epilepsy syndrome where myoclonic seizures develop in the neonatal period. After several months, the seizure pattern may develop to infantile spasms (West syndrome). Various genetic and metabolic disorders are responsible. The seizures are resistant to treatment. The neurology is very abnormal and patients often do not live beyond one year.[2][3] ## References[edit] 1. ^ Berg, AT; Berkovic, SF; Brodie, MJ; Buchhalter, J; Cross, JH; et al. (Apr 2010). "Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009". Epilepsia. 51 (4): 676–85. doi:10.1111/j.1528-1167.2010.02522.x. PMID 20196795. 2. ^ Richardson S, Alarcon G, Nashef L, Cross H, Nightingale J. Epilepsy (Oxford Specialist Handbooks in Neurology). Oxford University Press;2009. p.82. ISBN 0-19-857073-2 3. ^ Djukic A, Vigevano F, Plouin P, Moshé S. Early Myoclonic Encephalopathy. In: Dichter MA, Engel J, Pedley TA, Aicardi J, editors. Epilepsy: a comprehensive textbook. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008. ch. 224. ISBN 0-7817-5777-0 ## External links[edit] Classification D * MeSH: D004831 External resources * Orphanet: 1935 [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-aminobutyric 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	Early myoclonic encephalopathy	c0270855	27,482	wikipedia	https://en.wikipedia.org/wiki/Early_myoclonic_encephalopathy	2021-01-18T18:39:43	{"mesh": ["C562695"], "umls": ["C0270855"], "wikidata": ["Q5326887"]}
Uterine incarceration during pregnancy SpecialtyObstetrics Uterine incarceration is an obstetrical complication whereby a growing retroverted uterus becomes wedged into the pelvis after the first trimester of pregnancy.[1] ## Contents * 1 Causes * 2 Development * 3 Diagnosis * 4 Sequelae * 5 Management * 6 References * 7 External links ## Causes[edit] A number of situations may interfere with the natural process that would antevert a retroverted uterus during pregnancy. Such situations include pelvic adhesions, endometriosis, uterine malformations, leiomyomata, and pelvic tumors.[2] ## Development[edit] When the uterus is tilted backwards, it is considered to be retroverted; this situation is common and regarded a normal variation. It has been estimated that about 15% of pregnancies begin in a retroverted uterus.[3] Normally, during the first trimester, the growing uterus changes spontaneously to an anteverted position, thus allowing expansion of the enlarging uterus into the abdomen. The cervix is then inferior to the body of the uterus. Thus, the presence of an early pregnancy in a retroverted uterus is not considered a problem.[1] On rare occasions the uterus fails to become anteverted, and the pregnancy continues to expand the retroverted uterus within the confines of the pelvis. By about 14 weeks the size of the uterus fills out most of the pelvis, pushing up the cervix. At this point the uterus may get trapped below the sacral promontory and symphysis. With further growth the pregnant woman may experience lower abdominal and pelvic pain, back pain, and difficulty, even inability to void, as the bladder is pushed upward and its outflow becomes obstructed. Constipation may be encountered. The frequency of this complication has been estimated to be about 1 in 3,000 pregnancies.[2] ## Diagnosis[edit] A transvaginal ultrasonography showing a retroverted uterus during pregnancy. The cervix lies posteriorly to the urinary bladder, and the uterus normally extends superiorly from it, but the direction of the body of the fetus reveals that the uterus extends backwards. In a pregnant woman who is entering her second trimester, the combination of urinary difficulties and pelvic pain may alert the physician to consider uterine incarceration as a possibility. On physical examination, the cervix is pushed up and anterior, and the pelvis entirely filled by the soft mass of the body of the pregnant uterus. Sonography may indicate the retroverted position of the uterus, check on the viability of the fetus, and demonstrate the location of the bladder being pushed cranially and unable to be emptied.[4] Also magnetic resonance imaging has been found to be helpful in the diagnosis of the condition.[4][5] ## Sequelae[edit] Spontaneous resolution of the condition can occur during the second trimester.[6] An unresolved incarcerated uterus can lead to further pain, vaginal bleeding, loss of pregnancy or premature delivery. Also, the uterus may develop a uterine sacculation, that is a part of its back wall softens like an aneurysm and allows expansion of the fetus into the abdomen with a risk of uterine rupture.[3] Further, urinary complications may develop such as cystitis, and bladder distention could eventually lead to rupture of the bladder.[7] ## Management[edit] A pregnant woman with an incarcerated uterus may present in the emergency room because of pain, bleeding, inability to void and constipation. Upon diagnosis steps can be taken to manually position the uterus into an anteverted position. The bladder is decompressed by a Foley catheter and the obstetrician may attempt to manipulate the uterus if necessary using general or spinal anesthesia.[3] Rarely will a woman with an incarcerated uterus reach term, - if so, a cesarean delivery is called for.[8] ## References[edit] 1. ^ a b Lettieri L, Rodis JF, McLean DA, Campbell WA, Vintzileos AM (September 1994). "Incarceration of the gravid uterus". Obstet. Gynecol. Surv. 49 (9): 642–6. PMID 7991232. 2. ^ a b van der Tuuk K, Krenning RA, Krenning G, Monincx WM (2009). "Recurrent incarceration of the retroverted gravid uterus at term - two times transvaginal caesarean section: a case report". Journal of Medical Case Reports. 3 (1): 103. doi:10.1186/1752-1947-3-103. PMC 2783044. PMID 19946581. 3. ^ a b c Amy N. Sweigart; Michael J. Matteucci (2008). "Fever, Sacral Pain, and Pregnancy: An Incarcerated Uterus". West J Emerg Med. 9 (4): 232–4. PMC 2672273. PMID 19561753. 4. ^ a b Fernandes DD, Sadow CA, Economy KE, Benson CB (April 2012). "Sonographic and magnetic resonance imaging findings in uterine incarceration". J Ultrasound Med. 31 (4): 645–50. PMID 22441922. 5. ^ Hachisuga N, Hidaka N, Fujita Y, Fukushima K, Wake N (2012). "Significance of pelvic magnetic resonance imaging in preoperative diagnosis of incarcerated retroverted gravid uterus with a large anterior leiomyoma: a case report". J Reprod Med. 57 (1–2): 77–80. PMID 22324275. 6. ^ Rose CH, Brost BC, Watson WJ, Davies NP, Knudsen JM (January 2008). "Expectant management of uterine incarceration from an anterior uterine myoma: a case report". J Reprod Med. 53 (1): 65–6. PMID 18251368. 7. ^ J. Whitridge Williams. Obstetrics. D. Appleton and Co, 1906. p. 474. 8. ^ Al Wadi K, Helewa M, Sabeski L (July 2011). "Asymptomatic uterine incarceration at term: a rare complication of pregnancy". J Obstet Gynaecol Can. 33 (7): 729–32. PMID 21749750. ## External links[edit] Classification D Classification D * ICD-10: O34.5 * ICD-9-CM: 654.3 [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-aminobutyric 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	Uterine incarceration	c0341831	27,483	wikipedia	https://en.wikipedia.org/wiki/Uterine_incarceration	2021-01-18T18:42:56	{"umls": ["C0341831"], "icd-9": ["654.30", "654.3"], "icd-10": ["O34.5"], "wikidata": ["Q7902650"]}
Tola et al. (1994) examined HLA antigens in 47 Italian patients with sporadic myasthenia gravis. The frequency of B8 and DR3 in patients was 19.1 and 27.3%, respectively, compared to 9.7 and 14.1% in controls. There was also an association between the B8 allele and early onset of generalized myasthenia gravis sustained by thymic hyperplasia. The DR1 antigen was found in 55% of patients with ocular myasthenia and in only 2.8% of patients with generalized myasthenia. DR3 was present in 50% of patients with concurrent autoimmune conditions and in only 4.54% of patients without a more generalized disorder of autoimmunity. According to Celesia (1965), the disease has been limited to one generation in 18 of the 22 reported families with multiple cases. In the other 4 families, 2 generations were affected. The familial form usually affects young children or adolescents and onset in adulthood is rare. The familial form is, furthermore, static or only slowly progressive. Affected brother-sister pairs have been reported by Teng and Osserman (1956) and Celesia (1965), among others. Affected parent and offspring were reported by Foldes and McNall (1960), among others. Kurland and Alter (1961) reviewed the reports of familial aggregation and twin cases and concluded that 'there is as yet insufficient evidence to suggest that genetic factors are of significance in the etiology of myasthenia gravis.' Bundey (1972) concluded that there are 2 forms of childhood myasthenia. A form with onset before 2 years of age and milder though persistent course may be autosomal recessive. Cases with onset between ages 2 and 20 years resemble adult myasthenia, which is associated with autoimmunity and increased incidence of thyroid dysfunction. Noyes (1930) noted myasthenia gravis in a father and 2 daughters. Herrmann (1966) reported affected father and son. The familial aggregation, although definite, does not conform to a simple mendelian pattern. In a sample of 70 patients with myasthenia gravis, Jacob et al. (1968) found no instance of familial occurrence. They provided a comprehensive survey of the reported familial cases and pointed out differences from their own series, particularly earlier onset in the familial cases. Namba et al. (1971) pointed out, on the basis of 85 families with multiple cases (excluding transient neonatal myasthenia in offspring of myasthenic mothers), that the familial cases most often involved sibs. In Finland, Pirskanen (1977) found 264 patients with MG of whom 19 (17 females and 2 males) were familial cases from 8 families: 11 sibs, 2 mother-offspring and 6 cousins. Clinically, familial and nonfamilial cases were closely similar. No concordance was found among 45 sets of twins. No definite clustering of grandparental birthplaces, such as occurs in Finland for many mendelian disorders, was observed. Parental consanguinity was found in 7 of 192 families. An increase in 'connective tissue disease' and thyroid disease was observed in the families of both familial and nonfamilial MG. The author concluded that the familial predisposition may be due to autoimmunity in general (see 109100). Nakao et al. (1980) found association between myasthenia gravis and a particular Gm type. Cases with thymoma showed an especially strong association. Provenzano et al. (1988) described father and son with myasthenia gravis. The father had typical antibodies against the acetylcholine receptor, whereas the son seemed to have antibodies directed against some other antigen. Both patients showed the HLA-DR2 antigen, which is found in increased frequency in patients with myasthenia gravis. Bergoffen et al. (1992, 1994) described a family in which the parents were first cousins and 5 of 10 sibs had autoimmune myasthenia gravis with onset ranging from age 50 to 72 years. Three sibs had elevated antiacetylcholine receptor antibody titers. One affected sister had a history of thyroid disease. Two affected brothers and 1 unaffected brother had diabetes. By molecular analysis, Bergoffen et al. (1994) excluded the major histocompatibility complex, the beta subunit of the acetylcholine receptor (CHRNB1; 100710), and the alpha (see 186880) and beta (see 186930) subunits of the T-cell receptor as candidate genes for the disorder in this family; different alleles at these loci were demonstrated by the patients. The results were uninformative concerning CHRNA1 (100690), CHRNG (100730), and CHRND. Usually a sporadic disorder, autoimmune myasthenia gravis has a frequency of about 1 in 30,000. The proportion of cases that are familial is estimated to be between 1.2 and 4.3%. Several mothers with clinically diagnosed myasthenia gravis have given birth to infants with the Pena-Shokeir syndrome (208150), which is characterized by pulmonary hypoplasia, multiple ankyloses, and facial abnormalities. Brueton et al. (1994) reported 2 mothers with no neurologic symptoms of myasthenia gravis but with increased titers of antiacetylcholine receptor antibody who gave birth to 8 infants with the Pena-Shokeir phenotype. Myasthenia gravis was diagnosed in these mothers. In the case of maternal myasthenia gravis, the recurrence risk for Pena-Shokeir syndrome is high, and there has been no instance of a normal child being born following the affected pregnancy. Mullaney et al. (2000) reviewed the natural history and ophthalmic involvement in childhood myasthenia gravis in 34 patients. Among the 7 children with congenital myasthenic syndromes, severity varied. The diagnosis in severe cases was often obscured by apnea attacks, aspiration, and failure to thrive. Ophthalmic signs and symptoms (strabismus, ophthalmoplegia, and ptosis) were more prominent in mild cases and did not resolve during remissions. Croxen et al. (2002) reported 2 sisters diagnosed in childhood with congenital myasthenic syndrome, each of whom was found to carry 2 mutations in the AChR epsilon-subunit gene, near the N terminus. Serum anti-AChR antibody levels were negative in both patients. At the age of 34 years, the younger sister's condition deteriorated, with respiratory failure necessitating tracheostomy and assisted ventilation. Serum anti-AChR titers were elevated, indicating autoimmune myasthenia gravis, and the patient was successfully treated with plasmapheresis, immunosuppression, and thymectomy. Croxen et al. (2002) suggested that the epsilon-AChR gene mutations may predispose to later development of anti-AChR antibodies. The authors also noted that the younger sister had recently had 3 children and, unlike her sister, was homozygous for the HLA-DR3-B8-A1 phenotype, which is known to associate with autoimmune myasthenia gravis. Using microarray analysis, Feferman et al. (2005) found increased expression of Cxl10 (147310) and its receptor, Cxcr3 (300574), in lymph node cells of rats with experimental autoimmune MG. Real-time RT-PCR, FACS, and immunohistochemistry analyses confirmed these findings and revealed upregulated expression of another Cxcr3 chemoattractant, Cxcl9 (601704), and of Tnf (191160) and Il1b (147720), which act synergistically with Ifng (147570) to induce Cxcl10, in both lymph node cells and muscle of myasthenic rats. Upregulation of these genes was reduced after mucosal tolerance induction with an AChR fragment. Using RT-PCR, flow cytometric, and fluorescence microscopy analyses, Feferman et al. (2005) found increased expression of CXL10 and CXCR3 in thymus and muscle of MG patients compared with age-matched controls, validating their findings in the rat model of MG. They concluded that CXCL10/CXCR3 signaling is associated with MG pathogenesis and proposed that CXCL10 and CXCR3 may serve as novel drug targets to treat MG. The CHRNA1 gene (100690) encodes the alpha subunit of the muscle acetylcholine receptor, which is the main target of pathogenic autoantibodies in autoimmune myasthenia gravis. Giraud et al. (2007) identified a functional biallelic variant in the CHRNA1 promoter (16862847) that was associated with early onset of autoimmune myasthenia gravis in 2 independent human populations (France and U.K.). They showed that this variant prevented binding of interferon regulatory factor-8 (IRF8; 601565) and abrogated CHRNA1 promoter activity in thymic epithelial cells in vitro. Notably, both the CHRNA1 promoter variant and AIRE (607358) modulated CHRNA1 mRNA levels in human medullary thymic epithelial cells ex vivo and also in a transactivation assay. Giraud et al. (2007) concluded that their findings revealed a critical function of AIRE and the interferon signaling pathway in regulating quantitative expression of this autoantigen in the thymus, suggesting that together they set the threshold for self-tolerance versus autoimmunity. Animal Model In an attempt to develop an antigen-specific therapy for myasthenia gravis as an autoimmune disorder, Im et al. (1999) administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha subunit, protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the oral tolerance induced by the agent seemed to be active suppression, mediated by a shift from a T-helper-1 (Th1) to a Th2/Th3 response. The results in experimental myasthenia suggested that oral administration of AChR-specific recombinant fragments should be considered for antigen-specific immunotherapy of myasthenia gravis. Lin et al. (2002) demonstrated enhanced susceptibility to experimental autoimmune myasthenia gravis in mice lacking decay-accelerating factor (DAF; 125240), an intrinsic complement regulator. Following anti-AChR Ab injection, Daf1 -/- mice (devoid of neuromuscular DAF protein) showed dramatically greater muscle weakness than their Daf1 +/+ littermates. Reversal of the weakness by edrophonium was consistent with a myasthenic disorder. Immunohistochemistry revealed greatly augmented C3b deposition localized at postsynaptic junctions, and radioimmunoassays showed more profound reductions in AChR levels. Electron microscopy demonstrated markedly greater junctional damage in the Daf1 -/- mice compared with the Daf1 +/+ littermates. Voice \- Nasal speech Immunology \- Autoimmunity \- Thymoma \- Antibodies to acetylcholine receptor (AChR) \- Association with Gm type Inheritance \- Usually sporadic \- 1 to 4 % of cases are familial without a simple mendelian pattern \- Familial predisposition may be due to autoimmunity in general. Endocrine \- Thyrotoxicosis HEENT \- Ptosis \- Diplopia \- Difficulty chewing \- Dysarthria \- Facial muscle weakness Pulmonary \- Ventilatory insufficiency Muscle \- Proximal limb muscle weakness. Misc \- Childhood or adolescent onset \- Static or only slowly progressive GI \- Dysphagia ▲ 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-aminobutyric 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	MYASTHENIA GRAVIS	c0026896	27,484	omim	https://www.omim.org/entry/254200	2019-09-22T16:24:42	{"doid": ["437"], "mesh": ["D009157"], "omim": ["254200"], "icd-9": ["358.0"], "icd-10": ["G70.0", "G70.00"], "orphanet": ["589"]}
Variegate porphyria Other namesMixed hepatic porphyria,[1] Mixed porphyria,[1] South African genetic porphyria,[1]:525 and South African porphyria.[2] Protoporphyrinogen IX SpecialtyEndocrinology Symptomsskin problems, Enzyme difficiency. Causesgenetic mutations. Treatmentliver transplants. Variegate porphyria, also known by several other names, is an autosomal dominant porphyria[3] that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the enzyme responsible for the seventh step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References * 7 External links ## Signs and symptoms[edit] When symptoms occur, they can include acute attacks (similar to acute intermittent porphyria) or skin damage. Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhoea and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. These signs and symptoms are triggered by nongenetic factors such as certain drugs, dieting or fasting, certain hormones and stress. Some people with variegate porphyria have skin that is overly sensitive to sunlight (photosensitive). Areas of skin exposed to the sun develop severe blistering, scarring, changes in pigmentation, and increased hair growth. Exposed skin becomes fragile and is easily damaged. Rarely, the signs and symptoms of variegate porphyria can begin in infancy or early childhood. In such cases, the signs and symptoms are usually more severe than those starting later in life. In addition to the health problems described above, children with this disorder may have mental retardation and grow more slowly than other children. ## Genetics[edit] Variegate porphyria has an autosomal dominant pattern of inheritance. Mutations in the PPOX gene cause variegate porphyria.[4] The PPOX gene makes a membrane bound mitochondrial enzyme called protoporphyrinogen oxidase, which is critical to the chemical process that leads to heme production. The activity of this enzyme is reduced by 50 percent in most people with variegate porphyria. In severe cases that begin early in life, the enzyme is almost completely inactive. Nongenetic factors such as certain drugs, stress, and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity of protoporphyrinogen oxidase disrupts heme production and allows byproducts of the process to accumulate in the liver, triggering an acute attack. Variegate porphyria is inherited in an autosomal dominant pattern, which means the defective gene is located on an autosome, and inheriting one copy of the defective gene from an affected parent is sufficient to cause the disorder. More severe cases result from inheriting two copies of the defective gene. The entire PPOX gene has about 8kb with 13 exon sequences. It was successfully cloned from a cDNA library in 1995 revealing that, after processing, it is 477 nucleotides long. It has previously been thought that the PPOX gene was located on human chromosome 14,[5] however mapping experiments (FISH) have shown that it is near 1q23.[6] An additional aggravating mutation affecting variegate porphyria can be found at 6p21.3 on the HFE gene.[7] A 2006 clinical, biochemical and mutational study of eight Swiss variegate porphyria patients and their families found four novel PPOX gene mutations believed to be unique to the Swiss population.[8] ## Diagnosis[edit] Diagnosis is by finding raised urine porphyrins, raised faecal porphyrins, markedly raised plasma porphyrins (pathognomic) and finding photosensitive cutaneous lesions on clinical examination. ## Treatment[edit] Liver transplant has been used in the treatment of this condition.[9] ## Epidemiology[edit] In South Africa, the prevalence of variegate porphyria is approximately 1 in 300.[10] In Finland, the prevalence is approximately 1 in 75,000.[11] It is also found in Argentina,[12] Sweden,[13] and Australia.[14] ## References[edit] 1. ^ a b c James, William D, Berger, Timothy G, et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 3. ^ "porphyria variegata" at Dorland's Medical Dictionary 4. ^ Frank J, Christiano AM (1998). "Variegate porphyria: past, present and future". Skin Pharmacol. Appl. Skin Physiol. 11 (6): 310–20. doi:10.1159/000029854. PMID 10343202. 5. ^ Bissbort S, Hitzeroth HW, du Wentzel DP, et al. (July 1988). "Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14". Hum. Genet. 79 (3): 289–90. doi:10.1007/BF00366255. PMID 3261272. 6. ^ Roberts AG, Whatley SD, Daniels J, et al. (December 1995). "Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23". Hum. Mol. Genet. 4 (12): 2387–90. doi:10.1093/hmg/4.12.2387. PMID 8634714. 7. ^ de Villiers JN, Hillermann R, Loubser L, Kotze MJ (August 1999). "Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria". Hum. Mol. Genet. 8 (8): 1517–22. doi:10.1093/hmg/8.8.1517. PMID 10401000. 8. ^ Schneider-Yin X, Minder EI (August 2006). "Swiss patients with variegate porphyria have unique mutations". Swiss Med Wkly. 136 (31–32): 515–9. PMID 16947091. Archived from the original on 2013-01-15. 9. ^ Stojeba N, Meyer C, Jeanpierre C, et al. (July 2004). "Recovery from a variegate porphyria by a liver transplantation". Liver Transpl. 10 (7): 935–8. doi:10.1002/lt.20136. PMID 15237381. 10. ^ Arceci, Robert.; Hann, Ian M.; Smith, Owen P. (2006). Pediatric hematolog. Malden, Mass.: Blackwell Pub. ISBN 978-1-4051-3400-2. 11. ^ Mustajoki, P. (1980). "Variegate porphyria. Twelve years' experience in Finland". The Quarterly Journal of Medicine. 49 (194): 191–203. PMID 7433635. 12. ^ Rossetti MV, Granata BX, Giudice J, Parera VE, Batlle A (2008). "Genetic and biochemical studies in Argentinean patients with variegate porphyria". BMC Med. Genet. 9: 54. doi:10.1186/1471-2350-9-54. PMC 2467414. PMID 18570668. 13. ^ Wiman A, Harper P, Floderus Y (August 2003). "Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria". Clin. Genet. 64 (2): 122–30. doi:10.1034/j.1399-0004.2003.00116.x. PMID 12859407. 14. ^ Rossi E, Chin CY, Beilby JP, Waso HF, Warnich L (September 2002). "Variegate porphyria in Western Australian Aboriginal patients". Internal Medicine Journal. 32 (9–10): 445–450. doi:10.1046/j.1445-5994.2002.00274.x. PMID 12380696.CS1 maint: multiple names: authors list (link) This article incorporates public domain text from The U.S. National Library of Medicine ## External links[edit] Classification D * ICD-10: E80.2 (ILDS E80.230) * ICD-9-CM: 277.1 * OMIM: 176200 * MeSH: D046350 * DiseasesDB: 13738 External resources * eMedicine: derm/450 * Variegate porphyria at NIH's Office of Rare Diseases * v * t * e Heme metabolism disorders Porphyria, hepatic and erythropoietic (porphyrin) early mitochondrial: * ALAD porphyria * Acute intermittent porphyria cytoplasmic: * Gunther disease/congenital erythropoietic porphyria * Porphyria cutanea tarda/Hepatoerythropoietic porphyria late mitochondrial: * Hereditary coproporphyria * Harderoporphyria * Variegate porphyria * Erythropoietic protoporphyria Hereditary hyperbilirubinemia (bilirubin) unconjugated: * Gilbert's syndrome * Crigler–Najjar syndrome * Lucey–Driscoll syndrome conjugated: * Dubin–Johnson syndrome nd sheet * Rotor syndrome [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-aminobutyric 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	Variegate porphyria	c2936913	27,485	wikipedia	https://en.wikipedia.org/wiki/Variegate_porphyria	2021-01-18T19:09:01	{"gard": ["7848"], "mesh": ["C538659", "D046350"], "umls": ["C2936913", "C3149848"], "icd-9": ["277.1"], "icd-10": ["E80.2"], "orphanet": ["79473"], "wikidata": ["Q275385"]}
## Summary ### Clinical characteristics. Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome. ### Diagnosis/testing. The diagnosis of genetic prion disease is established in a proband with suggestive findings and a heterozygous PRNP pathogenic variant identified by molecular genetic testing. ### Management. Treatment of manifestations: No treatment of the underlying cause of genetic prion disease is available. Supportive care by a multidisciplinary team of specialists including neurologists, psychiatrists, physical therapists, occupational therapists, speech and language therapists, and social workers is recommended. Surveillance: Because of very rapid disease progression, close periodic monitoring by the multidisciplinary team is needed, typically every 14 days to evaluate needs for symptomatic treatment. ### Genetic counseling. Genetic prion disease is inherited in an autosomal dominant manner. Some individuals diagnosed with genetic prion disease may have a parent who is heterozygous for a PRNP pathogenic variant (some of whom may be asymptomatic because of reduced penetrance). Other individuals with genetic prion disease may have the disorder as the result of a de novo PRNP pathogenic variant. Each child of an individual with a PRNP pathogenic variant has a 50% chance of inheriting the variant. Although predictive testing (i.e., testing of asymptomatic at-risk adults) is possible, the capabilities and limitations of predictive testing as well as possible socioeconomic and medical care issues should be discussed in the context of formal genetic counseling prior to testing. Predictive testing in minors (i.e., testing of asymptomatic at-risk individuals younger than age 18 years) is considered inappropriate. ## Diagnosis ### Suggestive Findings Genetic prion disease should be suspected in individuals with the following clinical, laboratory, and imaging findings and family history. #### Clinical Geneic prion disease is a progressive neurodegenerative syndrome with rapid evolution of clinical signs (which reflect involvement of various neuroanatomic structures) – typically, dementia in combination with the following developing within a few months or (rarely) a few years: * Extrapyramidal/pyramidal involvement * Ataxia * Myoclonus In fatal familial insomnia (FFI) early autonomic disturbances and weight loss are frequent. #### Laboratory Cerebrospinal fluid analysis may be abnormal with high levels of 14-3-3 protein and protein tau. Abnormally conformed prion protein using aggregation assays (RT QuIC) is typically positive in genetic Creutzfeldt-Jakob disease (gCJD), but not always in FFI or Gerstmann-Sträussler-Scheinker syndrome (GSS). #### Imaging MRI * In some individuals with genetic CJD, MRI may display high signal abnormalities in the basal ganglia (caudate nucleus) and cortical areas, mostly in diffusion-weighted imaging (DWI), but also T2-weighted-fluid-attenuated inversion recovery (FLAIR) images. * In individuals with FFI and GSS, MRI is typically not suggestive. FDG PET (typically displaying hypometabolism in the thalamic areas) may be helpful in individuals FFI. #### Family History Family history is consistent with autosomal dominant inheritance (i.e., multiple affected family members in successive generations or a single affected family member). Absence of a known family history does not preclude the diagnosis. ### Establishing the Diagnosis The diagnosis of genetic prion disease is established in a proband with suggestive findings and a heterozygous PRNP pathogenic variant identified by molecular genetic testing [Ladogana & Kovacs 2018] (see Table 1). Note: Identification of a heterozygous PRNP variant of uncertain significance does not establish or rule out the diagnosis of this disorder. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (exome sequencing or 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 genetic prion disease has not been considered may be more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 Single-gene testing. Sequence analysis of PRNP is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Typically, if no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications; however, to date such variants have not been identified as a cause of this disorder. Note: Targeted analysis for pathogenic variants can be performed first in individuals of European ancestry; the following five common variants account for approximately 85% of the PRNP pathogenic variants in this population (see Table 4 for details): * P102L (c.305C>T; p.Pro102Leu) * D178N (c.532G>A; p.Asp178Asn) * V180I (c.538G>A; p.Val180Ile) * E200K (c.598G>A; p.Glu200Lys) * V210I (c.628G>A; p.Val210Ile) A multigene panel that includes PRNP 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. #### Option 2 Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; 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 Genetic Prion Disease View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method PRNPSequence 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 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\. Schmitz et al [2017] and Takada et al [2017] include the five pathogenic variants of targeted sequence analysis and the octapeptide insertion/duplication/deletion variants that are detectable by sequence analysis (see Table 4). 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 Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from ages 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome. Table 2 provides information on the frequency of neurologic features in the most frequent genetic prion disease phenotypes that emerge during the disease course. While some PRNP pathogenic variants are associated with specific neuropathologic phenotypes, individuals in the same family who are heterozygous for the same PRNP variant may develop distinct clinicopathologic phenotypes [Cracco et al 2018]. ### Table 2. Select Features of Genetic Prion Disease by Phenotype and PRNP Pathogenic Variant View in own window Feature% of Persons with Feature by Phenotype & PRNP Variant gCJDFFIGSS E200KV210ID178NP102L Dementia95%92%96%62% Ataxia100%100%82%100% Myoclonus85%92%89%25% Extrapyramidal65%92%82%50% Pyramidal70%71%79%75% Visual/Cortical blindness70%85%79% Other characteristic featuresDysarthriaYesYesYesYes Sleep disturbancesYesYesYes Sensory symptomsYesYes Weight lossYesYes HyperhidrosisYes Adapted from Krasnianski et al [2016] (based on 108 affected individuals ascertained by the CJD Surveillance Unit in Göttingen, Germany, from 1993 to 2005) #### Genetic Creutzfeldt-Jakob Disease (gCJD) Genetic prion disease caused by pathogenic variants E200K and V210I frequently resembles the phenotype of sporadic CJD (see Differential Diagnosis). Typical disease onset is in the sixth decade; after a nonspecific prodromal phase with dizziness, fatigue, blurred vision, depressive mood, and weight loss, the disease starts frequently with cognitive decline that progresses over several weeks. Within a few months of progressive neurologic decline, affected individuals become bedridden and akinetic/mute. The advanced disease stage is characterized by rapid involuntary muscle jerks (myoclonus), muscle stiffness (either rigidity or spasticity), and ataxia. The median survival following disease onset is six months. #### Fatal Familial Insomnia (FFI) A prodromal phase with marked autonomic disturbances, hyperhidrosis, weight loss, and sleep disturbances is common. Polysomnography shows complete disruption of the physiologic EEG sleep pattern. After a nonspecific stage as described for gCJD, affected individuals develop progressive dementia, ataxia, muscle rigidity and involuntary movements. At the end stage of the disease, the clinical manifestations are similar to those of other genetic prion disease phenotypes. The median age at onset is between 50 and 60 years. The median survival is 16 months. See Genotype-Phenotype Correlations for information on a variant associated with a shorter disease course. #### Gerstmann-Sträussler-Scheinker (GSS) Syndrome The typical clinical manifestations are a rapidly progressive cerebellar syndrome with ataxia at onset followed by cognitive decline and other neurologic signs within a few weeks, or at most a few months. The typical age at onset, earlier than in the other genetic prion diseases, is early in the sixth decade (51 years) with disease duration typically up to four years. Tesar et al [2019], who used cluster analysis to address the clinical heterogeneity of GSS syndrome, reported the following four clinical phenotypes: * Typical GSS syndrome with early ataxia, late dementia, and long disease duration (up to 4 years) * GSS syndrome beginning with areflexia and paresthesias, and later ataxia and dementia * Pure dementia GSS syndrome with early onset (age 35 years) with predominant dementia and late ataxia * Creutzfeldt-Jakob disease-like GSS syndrome with dementia and ataxia at onset and rapid disease progression ### Genotype-Phenotype Correlations Although some PRNP pathogenic variants are associated with specific neuropathologic phenotypes (see Table 2), evidence also suggests that heterozygotes for the same variant in the same family may develop distinct clinicopathologic phenotypes [Cracco et al 2018]. Note that the phenotype may be modified by the presence of the polymorphic codon 129 (p.Asp178Asn) in cis configuration with the PRNP variant. The phenotype in individuals with the p.Asp178Asn pathogenic variant typically depends on which variant – Met129 or Val129 – is in cis configuration with the PRNP variant. In general, the onset of genetic prion disease is earlier and its course shorter (11 months) in individuals homozygous for Met129 compared to either heterozygotes or homozygotes for Val129, in whom the phenotype is usually typical genetic CJD. See Table 4. ### Penetrance The penetrance for genetic prion disease in general is assumed to be 100%; however, only a limited number of studies have been performed to address this issue. The penetrance for the E200K variant (which has been studied more extensively than for other variants) was 60%-70% in Italian and Slovak families [D'Alessandro et al 1998, Mitrová & Belay 2002] and 100% in Libyan Jewish families [Spudich et al 1995]. ### Prevalence Epidemiologic studies utilizing reports of prion disease from centers around the world are frequently consistent with respect to the prevalence of genetic prion disease, as 15% of all individuals with newly diagnosed prion disease have genetic prion disease (i.e., are heterozygous for a PRNP pathogenic variant). The E200K variant has been identified in populations worldwide, including in Slovakia, in Jewish families from Libya, Chile, and Tunisia, and in individuals of non-Jewish origin in other countries. Studies of ancestral origins by microsatellite markers flanking PRNP on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at PRNP codon 129 demonstrated that the E200K variant may have originated from a single event, potentially in Spain, and spread to Libya, Tunisia, Chile, and Italy. Families from Slovakia and Poland show similar linked genetic markers as well as those from Germany, Austria, and Sicily; however, in affected individuals from Japan, different linked genetic markers have been identified, suggesting the independent origin of the variants [Lee at al 1999, Ladogana & Kovacs 2018]. ## Differential Diagnosis Because of the progressive neurologic decline, the range of neurologic signs, and the heterogeneous presentation of genetic prion disease, the differential diagnosis is broad and needs to include other hereditary neurodegenerative disorders as well as a variety of acquired disorders. Because potential treatment options depend on identification of the underlying cause, autoimmune and paraneoplastic disorders need to be considered (see Table 3). ### Table 3. Disorders Potentially Associated with Rapid Progression of Interest in the Differential Diagnosis of Genetic Prior Disease View in own window EtiologyDisorder/CommentGene(s) Hereditary neurodegenerative disordersCSF1R-related adult-onset leukoencephalopathy w/axonal spheroids & pigmented gliaCSF1R Dementia w/Lewy bodies (OMIM 127750)GBA SNCA SNCB Familial Alzheimer disease (See Alzheimer Disease Overview. 1)APP PSEN1 PSEN2 Frontotemporal dementia (e.g., ALS/FTD, CHMP2B-FTD, GRN-FTD, IBMPFD)C9orf72 2 CHMP2B FUS GRN HNRNPA1 HNRNPA2B1 TARDBP 3 VCP Hereditary ataxia (e.g., SCA1, SCA2, SCA3, SCA6, SCA7, SCA8) 4ATXN1 ATXN2 ATXN3 ATXN7 ATXN8 CACNA1A Huntington diseaseHTT Pick disease (OMIM 172700)MAPT PSEN1 Progressive supranuclear palsy (OMIM 601104)MAPT Autoimmunee.g., Hashimoto thyroiditis w/related encephalopathy, multiple sclerosis, antibody-mediated dementia/encephalopathy, CNS lupus, acute disseminated encephalomyelitis Iatrogenice.g., medication toxicity (e.g., lithium, methotrexate, chemotherapy), illicit drug use Infectiouse.g., viral encephalitis (incl herpes simplex virus), HIV dementia, progressive multifocal leukoencephalopathy Metastases/ Neoplasm relatede.g., paraneoplastic diseases-limbic encephalopathy, metastases to CNS, primary CNS lymphoma Systemic/Seizures/ Structurale.g., sarcoidosis, epilepsy, nonconvulsive status epilepticus Toxic-metabolice.g., heavy metals (incl bismuth), electrolyte disturbances (sodium, calcium, magnesium, phosphorus), endocrine abnormalities (thyroid, parathyroid, adrenal), extrapontine myelinolysis Vascular/Ischemiae.g., multi-infarct, thalamic or callosum infarcts, cerebral amyloid angiopathy Adapted from Geschwind [2016], Table 7-4: Partial Differential Diagnosis for Rapidly Progressive Dementias by Etiologic Category ALS = amyotrophic lateral sclerosis; CNS = central nervous system; FTD = frontotemporal dementia; HIV = human immunodeficiency virus; IBMPFD = inclusion body myopathy associated with Paget disease of bone and/or frontotemporal dementia 1\. Listed genes are associated with early-onset familial Alzheimer disease (EOFAD): Alzheimer disease that occurs in multiple members of a family with a mean onset usually before age 65 years. EOFAD represents fewer than 2% of Alzheimer disease cases. Late-onset familial Alzheimer disease (age >60-65 years), representing 15%-25% of Alzheimer disease cases, is thought to be a complex disorder possibly involving multiple susceptibility genes (see Alzheimer Disease Overview). 2\. See C9orf72-ALS/FTD. 3\. See TARDBP-ALS. 4\. The hereditary ataxias are a large group of autosomal dominant, autosomal recessive, and X-linked disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements; see Hereditary Ataxia Overview for molecular genetic and clinical information. For a detailed review of disorders to consider in an individual with rapidly progressive dementia, see Geschwind [2016]. ### Other Prion Diseases Sporadic CJD (i.e., CJD of unknown cause diagnosed in an individual with a negative family history and no pathogenic PRNP variant) is the most common human prion disease. Sporadic CJD is generally regarded as a spontaneous neurodegenerative illness. While genetic CJD caused by the PRNP variants E200K and V210 can be clinically almost indistinguishable from sporadic CJD, some evidence suggests earlier age of onset in genetic CJD (60 years) than in sporadic CJD (65 years). Iatrogenic CJD has been recognized after exposure of nervous-tissue-contaminated surgical instruments and in dura mater or human growth hormone extracted from cadaveric pituitary glands. Variant CJD. Following the bovine spongiform encephalopathy (BSE) epidemic in the UK and elsewhere in the 1990s, variant CJD was identified as the only human prion disease with a confirmed zoonotic origin. The clinical syndrome is characterized by early disease onset (frequently before age 30 years) with psychiatric manifestations and prominent paresthesias that are followed by cognitive decline, ataxia, muscle stiffness, myoclonus, and akinetic mutism. In contrast to sporadic CJD, in variant CJD abnormal prion protein deposits are present in the tonsils and appendix. Brain imaging reveals typical high signal intensities in the posterior thalamus ("hockey stick sign") [Zeidler et al 1997]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with genetic prion disease, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended. Because of very rapid disease progression and short survival time after the diagnosis, evaluations for supportive patient care must be performed early. They include the following: * Need for gastric tube feeding for nutrition and to reduce risk of aspiration * Evaluation for bladder and bowel incontinence * Need for physical therapy and occupational therapy for mobility and activities of daily living * Psychiatric manifestations * Consultation with a social worker (or other medical professional) to determine need for: * Caregiver support including use of community resources & support/advocacy organizations * Specific 24-hour/day care assistance * Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of genetic prion disease in order to facilitate medical and personal decision making ### Treatment of Manifestations No treatment of the underlying cause of genetic prion disease is available. Only a few controlled trials have been performed. Some data point toward slowing of disease progression with doxycycline (100-200 mg/day) when administered early in the disease course [Varges et al 2017]. Supportive care by a multidisciplinary team of specialists including neurologists, psychiatrists, physical therapists, occupational therapists, speech and language therapists, and social workers is recommended. Symptomatic treatment may include the following: * For psychiatric manifestations such as depression or psychosis, antidepressant or neuroleptic treatment * Myoclonic jerks respond well to clonazepam. * Muscle rigidity may require dopamine or dopaminergic drugs. * Spasticity may respond to regular antispastic medication. * Physical therapy for exercises and/or stretching to prevent contractures; durable medical devices for positioning and/or mobility * Occupational therapy for home adaptation to improve safety and activities of daily living * Feeding issues addressed by nutritionists, speech pathologists * Communication (including alternative means of communication) by speech pathologists ### Surveillance Because of very rapid disease progression, close periodic monitoring by the multidisciplinary team is needed, typically every 14 days to evaluate need for treatment of symptoms. ### 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-aminobutyric 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	Genetic Prion Disease	None	27,486	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1229/	2021-01-18T21:23:24	{"synonyms": []}
A variant of lichen planopilaris characterized by the clinical triad of progressive cicatricial (scarring) alopecia of the scalp, follicular keratotic papules on glabrous skin, and variable alopecia of the axillae and groin. ## Epidemiology It is a very rare disease but the exact prevalence is not known. It mainly affects women during adulthood (30-60 years of age). ## Clinical description Scarring alopecia presents as small confluent patches that are atrophic and cicatricial in the center but erythematous and squamous around the edges. Follicular keratosis presents as pruritic, red-brown, follicular spiny papules on the trunk and extremities. Generally, the three clinical features appear simultaneously but in some cases, scalp alopecia precedes the follicular keratosis. ## Etiology Etiology is unknown. [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-aminobutyric 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	Graham Little-Piccardi-Lassueur syndrome	c4273658	27,487	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=505	2021-01-23T18:04:21	{"gard": ["3195"], "icd-10": ["L66.1"], "synonyms": ["Graham Little syndrome", "Piccardi-Lassueur-Little syndrome"]}
## Summary ### Clinical characteristics. X-linked congenital stationary night blindness (CSNB) is characterized by non-progressive retinal findings of reduced visual acuity ranging from 20/30 to 20/200; defective dark adaptation; refractive error, most typically myopia ranging from low (-0.25 diopters [D] to -4.75 D) to high (≥-10.00 D) but occasionally hyperopia; nystagmus; strabismus; normal color vision; and normal fundus examination. Characteristic ERG findings can help distinguish between complete X-linked CSNB and incomplete X-linked CSNB. ### Diagnosis/testing. The diagnosis of X-linked CSNB is established in a male proband with characteristic clinical and electroretinogram (ERG) findings and a family history consistent with X-linked inheritance. Identification of a hemizygous pathogenic variant in CACNA1F or NYX by molecular genetic testing can confirm the diagnosis if clinical features are inconclusive. The diagnosis of X-linked CSNB may be established in a female proband with ERG findings suggestive of X-linked CSNB and identification of a heterozygous or biallelic pathogenic variant in CACNA1F or NYX by molecular genetic testing. ### Management. Treatment of manifestations: Glasses or contact lenses to treat refractive error (myopia or hyperopia); conventional strabismus surgery may be required to improve binocularity or head posture. Surveillance: At a young age yearly eye examinations with refraction to identify and treat myopia as early as possible. Agents/circumstances to avoid: Reduced visual acuity and difficulties seeing at night may preclude driving a car or restrict the class of driving license. ### Genetic counseling. By definition, X-linked CSNB is inherited in an X-linked manner. The father of an affected male will not have X-linked CSNB nor will he be hemizygous for the pathogenic variant. If the mother of the proband is a carrier, the chance of transmitting the pathogenic variant in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will usually not be affected. Males with X-linked CSNB will pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible for families in which the pathogenic variant has been identified. ## Diagnosis ### Suggestive Findings Males. X-linked congenital stationary night blindness (CSNB) should be suspected in a male proband with the following characteristic clinical and electroretinogram (ERG) findings characteristicec of complete X-linked CSNB or incomplete X-linked CSNB (see Table 1): Characteristic clinical findings: * Reduced visual acuity * Night blindness * Myopia * Nystagmus (not universal) and strabismus (50%-70%) * Normal color vision * Normal fundus examination * Family history consistent with X-linked inheritance Characteristic findings on ERG examination: * ERG is used to assess the changes in electrical activity of the retina in response to light. The b-wave is caused by the depolarization of ON bipolar cells in response to light stimuli and is strictly dependent on synaptic transmission from photoreceptors to ON bipolar cells. * Individuals with X-linked CSNB have reduced scotopic b-wave amplitudes in response to bright flashes after dark adaptation (Figure 1). The resulting ERG waveform is essentially a negative wave (amplitude of the a-wave is larger than the b-wave, not reaching the baseline) [Miyake et al 1986], referred to as the Schubert-Bornschein form [Schubert & Bornschein 1952]. * The ERG can define specific retinal dysfunctions and, in general, differentiate the forms of X-linked CSNB (Table 1), thereby identifying the gene most likely to be involved (see Establishing the Diagnosis). #### Figure 1. Representative full-field ERGs recorded from three males: A. Age 35 years, unaffected ### Table 1. Electroretinogram Findings in Complete and Incomplete X-Linked Congenital Stationary Night Blindness View in own window ERG FindingComplete (NYX X-linked CSNB)Incomplete (CACNA1F X-linked CSNB) Scotopic rod b-waveSeverely reduced or absentReduced Mixed scotopic a-waveNormalSlightly reduced Mixed scotopic b-waveReducedReduced Scotopic OPAbsentSlightly reduced Photopic a-waveNormal, slightly reduced, sawtooth (square) shapedReduced Photopic b-waveSlightly reducedReduced Photopic OPLost, except for OP4All OPs are lost. 30-Hz flickerNormal / slightly reducedReduced w/double peak OP = oscillatory potential Note: Pupillary responses have been described in the literature and in textbooks as "paradoxic" (i.e., miosis of pupils when lights are turned off, as opposed to dilation). This description predates genotyping. In 17 individuals with incomplete X-linked CSNB ages five to 51 years examined by one of the authors, none clearly demonstrated a paradoxic pupillary response. Further clarification of the presence or absence of this phenomenon in individuals with X-linked CSNB may require measurement with pupillometry. Heterozygous females. X-linked CSNB should be suspected in a female proband with the following ERG findings (observed in some heterozygous females): * Reduced oscillatory potentials (OPs) associated with rod activity [Rigaudière et al 2003] * Reduced b-wave amplitudes (with unaffected OPs) in one heterozygous female [Rigaudière et al 2003] ### Establishing the Diagnosis Male proband. The diagnosis of X-linked CSNB is established in a male proband with the characteristic clinical and ERG findings described in Suggestive Findings and a family history consistent with X-linked inheritance. Identification of a hemizygous pathogenic variant in CACNA1F or NYX by molecular genetic testing can confirm the diagnosis if clinical features are inconclusive (see Table 2). Female proband. The diagnosis of X-linked CSNB may be established in a female proband with ERG findings suggestive of X-linked CSNB and a heterozygous or biallelic pathogenic variant in CACNA1F or NYX identified by molecular genetic testing (see Table 2). #### Molecular Genetic Testing Approaches can include serial single-gene testing (recommended in individuals with a clear family history consistent with X-linked inheritance) or a multigene panel (recommended in individuals without a clear family history consistent with X-linked inheritance). Serial single-gene testing. For individuals with a clear family history consistent with X-linked inheritance, ERG findings can be used to direct molecular genetic testing to the appropriate gene (see Table 1). * Sequence analysis of NYX should be performed first in individuals with ERG findings consistent with complete X-linked CSNB to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Note: Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis. * Sequence analysis of CACNA1F should be performed first in individuals with ERG findings consistent with incomplete X-linked CSNB to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Note: Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis. Note: Targeted analysis for the CACNA1F founder variant c.3167_3168dupC can be performed first in individuals of Dutch-German Mennonite ancestry [Bech-Hansen et al 1998, Boycott et al 2000]. Multigene panel. For individuals without a clear family history consistent with X-linked inheritance, a CSNB multigene panel that includes CACNA1F, NYX, 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 this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 2). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 2. Molecular Genetic Testing Used in X-Linked Congenital Stationary Night Blindness View in own window Gene 1, 2Proportion of X-Linked CSNB Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4, 5Gene-targeted deletion/duplication analysis 6 CACNA1F55% 7, 8>98% 7, 85 reported 9 NYX45% 7, 10>99% 7, 10, 114 reported 11 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. 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\. Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis. 6\. 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. 7\. Zeitz [2007] 8\. Bijveld et al [2013], Zeitz et al [2015] 9\. Bijveld et al [2013], Hauke et al [2013], Zeitz et al [2015], Carss et al [2017] 10\. Bech-Hansen et al [2000], Pusch et al [2000] 11\. Pusch et al [2000], Bijveld et al [2013] ## Clinical Characteristics ### Clinical Description X-linked congenital stationary night blindness (CSNB) is a congenital non-progressive retinal disorder characterized by defective night vision, reduced visual acuity, myopia, nystagmus, and strabismus that primarily affects males. #### Males Reduced visual acuity. Vision is reduced in all affected males in the range of 20/30 (6/9; log MAR 0.1) to 20/200 (6/60; log MAR 1.0). Defective dark adaptation. Night blindness is a subjective finding. Individuals with NYX X-linked CSNB generally report severe night blindness. Individuals with CACNA1F X-linked CSNB do not uniformly report severe night blindness. Myopia may range from low (-0.25 diopters [D] to -4.75 D) to high (≥ -10.00 D) [Boycott et al 2000, Allen et al 2003]. A few affected individuals have hyperopia. Nystagmus and strabismus are reported in 50%-70% of affected individuals [Boycott et al 2000, Allen et al 2003]. Transient head posture with nystagmus was noted in the first two years of life in eight individuals with CACNA1F X-linked CSNB and one with NYX X-linked CSNB [Simonsz et al 2009]. In a large Mennonite cohort with incomplete (i.e., CACNA1F) X-linked CSNB, at least one of the following was not present in 72% of individuals: myopia, nystagmus, or night blindness [Boycott et al 2000]. Normal color vision is present in most individuals. Individuals with a severe X-linked CSNB may show mild color vision deficits. Normal fundus examination is present in most individuals, although those with high myopia may show myopic degeneration. Females * In general, heterozygous females do not exhibit clinical signs of X-linked CSNB. * Females who are homozygous for pathogenic variants in CACNA1F with features similar to those in males have been reported [Bech-Hansen et al 1998]. ### Phenotype Correlations by Gene NYX pathogenic variants are associated with the complete form of X-linked CSNB (see Table 1) [Bech-Hansen et al 2000, Pusch et al 2000]. Individuals with NYX X-linked CSNB generally report severe night blindness. CACNA1F pathogenic variants are associated with the incomplete form of X-linked CSNB [Bech-Hansen et al 1998, Strom et al 1998] (see Table 1). Individuals with CACNA1F X-linked CSNB do not uniformly report severe night blindness. ### Genotype-Phenotype Correlations No genotype-phenotype correlations are known. ### Penetrance Penetrance of X-linked CSNB is probably 100%, but expressivity is variable [Boycott et al 2000]; individuals with mild presentations may be missed if electroretinography is not performed. ### Nomenclature X-linked CSNB has in the past been referred to as Schubert-Bornschein CSNB, which is a reference to the characteristic "negative" waveform (a-wave larger than the b-wave in response to a bright flash in the scotopic state) of the ERG seen in both X-linked forms of CSNB [Schubert & Bornschein 1952]. The terms "CSNB1" and "CSNB2" are sometimes used as abbreviations for complete and incomplete CSNB irrespective of the mode of inheritance; originally the terms referred to the two X-linked entities of CSNB. ### Prevalence The prevalence of X-linked CSNB is not known. A CACNA1F founder variant, c.3166dupC (alias: c.3167_3168dupC), has been reported in individuals of Dutch-German Mennonite descent [Bech-Hansen et al 1998, Boycott et al 1998, Boycott et al 2000]. A common pathogenic variant in NYX, c.856delG, has been identified in Flemish individuals from Belgium [Leroy et al 2009]. A common founder variant in NYX, c.85_108del, has been identified in the United States [Bech-Hansen et al 2000]. ## Differential Diagnosis Only a few conditions may initially be confused with the X-linked form of congenital stationary night blindness (CSNB). ### Table 4. Disorders to Consider in the Differential Diagnosis of X-Linked Congenital Stationary Night Blindness View in own window Fundus 1DisorderGene(s)MOIClinical Features of Differential Diagnosis Disorder Overlapping w/X-linked CSNBDistinguishing from X-linked CSNB Normal fundusCSNB (non-X-linked)See footnote 2AR ADMost autosomal CSNB is clinically identical, w/exception of AD CSNB, Nougaret type. * Family history consistent w/X-linked inheritance may differentiate X-linked forms of CSNB from AD & AR forms. * In AD CSNB, Nougaret type (OMIM 610444) there is no significant refractive error & ERG waveform is Riggs type (not Schubert-Bornshein) 3 w/minimal a-wave in response to scotopic bright flash. Blue cone monochromacy (OMIM 303700)OPN1LW OPN1MWXL * Poor vision * Nystagmus * Abnormal color vision * Almost completely abolished photopic ERG contrasting w/normal or minimally affected scotopic ERG * Fundus examination in young males is normal; some males develop macular atrophy in late adulthood. FRMD7-related infantile nystagmusFRMD7XL * Poor vision * Nystagmus * Normal ERG * Normal VEP * Normal foveal contour Abnormal fundusX-linked ocular albinismOA1XL * Poor vision * Nystagmus * Iris transillumination * Foveal hypoplasia * Heterozygous females have fundus signs (hypopigmentation of retinal pigment epithelium). 4 * Absence of selective reduction in amplitude of b-wave on ERG * VEP responses show propensity for more crossing fibers than expected at level of chiasm. X-linked juvenile retinoschisisRS1XL * Visual acuity reduced to same range seen in X-linked CSNB * Selective reduction in amplitude of b-wave on ERG Fundus examination shows foveal schisis or foveal findings in virtually all affected males & ~50% have areas of peripheral retinoschisis. Oguchi disease 5 (OMIM 258100, 613411)SAG GRK1ARNon-progressiveFundus has abnormal color that becomes normal w/prolonged dark adaptation (Mizuo phenomenon). 6 Fundus albipunctatus 7 (OMIM 136880)RDH5 RLBP1AR ADNon-progressive * Fundus shows discretely scattered white retinal dots. * ERG, when recorded under standard conditions, shows selective reduction in b-wave that normalizes w/prolonged dark adaptation. 6 AD = autosomal dominant; AR = autosomal recessive; ERG = electroretinogram; MOI = mode of inheritance; VEP = visual evoked potential; XL = X-linked 1\. X-linked CSNB is characterized by a normal fundus. 2\. See Night blindness, congenital stationary: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. 3\. Riggs [1954] 4\. Charles et al [1993] 5\. Oguchi disease is a form of CSNB reported in the Japanese. 6\. Dryja [2000] 7\. Fundus albipunctatus is a form of CSNB. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with X-linked congenital stationary night blindness (CSNB), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Ophthalmologic examination * Electroretinography * Dark adaptation (optional) * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Coincident high myopia or hyperopia can be managed with glasses or contact lenses. Occasionally, a boy with X-linked CSNB may adopt a cosmetically unacceptable or functionally awkward head posture to dampen the degree of nystagmus in a particular position of gaze (the so-called "null point"). In some instances the position of gaze for the null point may be shifted to a better functional range by carefully planned strabismus surgery. ### Surveillance Regular (yearly) eye examinations are recommended with refraction at a young age to monitor for the development of myopia. ### Agents/Circumstances to Avoid Reduced visual acuity and difficulties seeing at night may preclude driving a car or restrict the class of driving license. ### Evaluation of Relatives at Risk For infants identified with high myopia, unusual head posture, or nystagmus and a family history of CSNB, ophthalmic examination and molecular genetic testing may confirm the diagnosis of CSNB, obviating the need for neuroimaging or clinical electrophysiologic testing under sedation or general anesthesia. 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 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-aminobutyric 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	X-Linked Congenital Stationary Night Blindness	c1848172	27,488	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1245/	2021-01-18T20:49:15	{"mesh": ["C536122"], "synonyms": ["X-Linked CSNB"]}
## Clinical Features Duodenal atresia (223400) predominantly represents an isolated entity, but also can be part of a complexly structured intestinal malformation such as apple peel small bowel syndrome (243600) or familial intestinal polyatresia syndrome (FIPA; 243150). Pumberger et al. (2002) described 4 children, including 2 from 1 family, with duodenojejunal atresia associated with malrotation, volvulus, and absent parietal attachment of the mesentery. Gross absence of the mesentery and absence of distal parts of the superior mesenteric artery were the most remarkable findings. The small intestine was supplied retrogradely from the right colic artery. Consideration of embryologic theories of this malformation took into account the important role of the duodenojejunal flexure during the process of entry of the small bowel loops into the abdomen. Familial occurrence suggested autosomal recessive inheritance. Because of the constant association with malrotation and the normal length of the small bowel, Pumberger et al. (2002) proposed differentiating the pathoanatomic findings in these patients from those of classic apple peel small bowel syndrome. [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-aminobutyric 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	DUODENOJEJUNAL ATRESIA WITH VOLVULUS, ABSENT DORSAL MESENTERY, AND ABSENT SUPERIOR MESENTERIC ARTERY	c1847196	27,489	omim	https://www.omim.org/entry/606894	2019-09-22T16:09:50	{"mesh": ["C535722"], "omim": ["606894"]}
A number sign (#) is used with this entry because of evidence that diarrhea-10 (DIAR10) is caused by homozygous mutation in the PLVAP gene (607647) on chromosome 19p13. Description Diarrhea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients (Broekaert et al., 2018; Kurolap et al., 2018). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700). Clinical Features Elkadri et al. (2015) studied a male infant with severe protein-losing enteropathy, born to consanguineous parents of Afghan descent, who presented in the first weeks of life with secretory diarrhea and hematochezia, metabolic acidosis, lethargy, poor feeding, and hyponatremic seizures. Other features included bilateral colobomata, low-set ears, micrognathia, undescended testes, and mildly dysplastic kidneys. Albumin was consistently undetectable and did not respond to repeated infusions. All immunoglobulins were low or undetectable, except for IgM. He had hypothyroidism, and lipid profile showed an elevated triglyceride level, with normal cholesterol and high-density lipoprotein levels. Electron micrographs of patient duodenum showed complete lack of diaphragms in the fenestrae and caveolae of endothelial cells of all capillaries examined, resulting in plasma protein extravasation. The authors noted that plasma levels of relatively small proteins, such as albumin, ceruloplasmin, and thyroxine-binding globulin (ranging from 65 to 140 kD), were severely reduced, whereas the level of IgM (755 kD) was normal, due to selective loss of proteins based on size. The patient had recurrent respiratory tract infections, persistent anasarca, and venous thrombosis in multiple locations; he died of sepsis at age 5 months. Broekaert et al. (2018) reported a male infant, born to first-cousin parents of Turkish descent, who at the age of 9 days developed watery diarrhea and polyuria with hyponatremia, hypomagnesemia, hypocalcemia, and metabolic acidosis. His albumin level dropped from 28 to 4g/L by day 12 of life, and he also had markedly elevated gamma-GT (see 612346). Lipids and immunoglobulins were not measured. Clinical examination revealed moderate generalized edema, bilateral undescended testicles, and dysmorphic facial features, including hypoplastic supraorbital bulges, low-set ears, long flat prominent philtrum, anteverted nostrils, thin upper lip, downturned corners of the mouth, and high-arched palate. Abdominal ultrasound showed a massively dilated left ureter with kinking and a dilated left renal pelvis, and a mildly dilated ureter on the right side. Cranial ultrasound showed small plexus cysts and increased periventricular echogenicity, but he exhibited no neurologic abnormalities. On echocardiography, small apical atrial and ventricular septal defects were found, and ophthalmologic examination revealed multiple iris cysts. Despite total parenteral nutrition, diarrhea remained massive, indicative of secretory diarrhea. The patient developed portal vein thrombosis, and on day 15 he experienced hematochezia, likely due to disseminated intravascular coagulation, and died. Kurolap et al. (2018) described 2 first cousins once removed from a consanguineous Arab Muslim family with protein-losing enteropathy: a man who presented at age 22 years, and a girl who presented at age 2.5 years. Both had anasarca, severe hypoalbuminemia, and hypogammaglobulinemia, and the girl also had markedly elevated triglycerides. Neither exhibited facial dysmorphism or other congenital anomalies. Low-fat diet and middle-chain triglyceride-rich formula resulted in significant clinical and laboratory improvement, whereas exposure to high fat in their diet caused rapid recurrence of disease symptoms. Molecular Genetics In a male infant with severe protein-losing enteropathy, born to consanguineous parents of Afghan descent, Elkadri et al. (2015) performed whole-exome sequencing (WES) and identified homozygosity for a nonsense mutation in the PLVAP gene (R358X; 607647.0001). The patient died of sepsis at age 5 months. In a male infant with severe protein-losing enteropathy from a consanguineous family of Turkish descent, Broekaert et al. (2018) performed WES and identified homozygosity for a nonsense mutation in the PLVAP gene (Q330X; 607647.0002). The patient died at age 2 weeks. By WES in a 22-year-old man and a 2.5-year-old girl with protein-losing enteropathy, who were first cousins once removed from a consanguineous Arab Muslim pedigree, Kurolap et al. (2018) identified homozygosity for a missense mutation in the PLVAP gene (L34P; 607647.0003). No pathogenic variants in other protein-losing enteropathy-associated genes were found in the WES data of either patient. Noting the later-onset and milder phenotype in the 2 Arab Muslim patients, the authors suggested that it might be due to the missense nature of their pathogenic variant, compatible with residual PLVAP function. Electron microscopy of patient duodenum demonstrated preserved endothelial fenestral diaphragms, and immunostaining revealed expression of PLVAP in endothelial cells of duodenal mucosal capillaries comparable to that of age- and sex-matched controls. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Low-set ears Eyes \- Bilateral colobomas (in 1 patient) \- Multiple iris cysts (in 1 patient) Neck \- Nuchal edema CARDIOVASCULAR Heart \- Pericardial effusion \- Atrial septal defect, small \- Ventricular septal defect, small Vascular \- Thrombosis of the portal vein \- Thrombosis of multiple vessels RESPIRATORY Lung \- Pleural effusion ABDOMEN External Features \- Ascites Gastrointestinal \- Protein-losing enteropathy \- Secretory diarrhea \- Hematochezia \- Edema of stomach \- Edema of small intestine \- Duodenal inflammation \- Focal lymphangiectasia in terminal ileum GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Dilated renal pelvis \- Dysplastic kidneys, mild \- Polyuria Ureters \- Dilated ureters MUSCLE, SOFT TISSUES \- Anasarca METABOLIC FEATURES \- Metabolic acidosis ENDOCRINE FEATURES \- Hypothyroidism \- Markedly elevated thyroid-stimulating hormone (TSH) \- Undetectable free thyroxine level IMMUNOLOGY \- Hypogammaglobulinemia PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios LABORATORY ABNORMALITIES \- Hypoalbuminemia \- Low total protein \- Hypertriglyceridemia \- Hyponatremia \- Hypomagnesemia \- Hypocalcemia \- Elevated gamma-glutamyl transferase MISCELLANEOUS \- Intrafamilial variability \- Dysmorphic features may be evident prenatally \- Severe diarrhea results in death in infancy in some patients MOLECULAR BASIS: Caused by mutation in the plasmalemma vesicle-associated protein gene (PLVAP, 607647.0001 ) ▲ 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-aminobutyric 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	DIARRHEA 10, PROTEIN-LOSING ENTEROPATHY TYPE	c4014516	27,490	omim	https://www.omim.org/entry/618183	2019-09-22T15:43:13	{"omim": ["618183", "615863"], "orphanet": ["329242"], "synonyms": ["Congenital chronic diarrhea with exudative enteropathy"]}
Retinal disease that is characterized by nystagmus, sluggish or no pupillary responses, and severe vision loss or blindness Leber congenital amaurosis Other namesLeber's congenital amaurosis SpecialtyOphthalmology SymptomsVisual impairment, sensitivity to light[1] Types> 12 types[1] CausesGenetic (autosomal recessive)[1] Frequency1 in 40,000 newborns[1] Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.[2] It affects about 1 in 40,000 newborns.[1] LCA was first described by Theodor Leber in the 19th century.[3][4] It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber. One form of LCA was successfully treated with gene therapy in 2008.[5][6][7][8] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Popular culture * 6 See also * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] The term congenital refers to a condition present from birth (not acquired) and amaurosis refers to a loss of vision not associated with a lesion. However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.[9][10] LCA is typically characterized by nystagmus,[9] sluggish or absent pupillary responses,[10] and severe vision loss or blindness.[9] ## Genetics[edit] It is usually autosomal recessive; however, importantly for family planning, it is sometimes autosomal dominant. It is a disorder thought to be caused by abnormal development of photoreceptor cells.[9] OMIM currently recognizes 18 types of LCA.[9] Type OMIM Gene Locus[9] LCA1 204000 GUCY2D,[11] 17p13.1 LCA2 204100 RPE65[12] 1p31.3-p31.2 LCA3 609868 SPATA7 14q31.3 LCA4 604393 AIPL1[13][14] 17p13.2 LCA5 604537 LCA5[15] 6q14.1 LCA6 605446 RPGRIP1 14q11.2 LCA7 602225 CRX[16] 19q13.3 LCA8 604210 CRB1[16] 1q31-q32.1 LCA9 608553 NMNAT1[17][18][19][20] 1p36.22 LCA10 610142 CEP290 12q21.32 LCA11 146690 IMPDH1 7q32.1 LCA12 180040 RD3 7q32.1 LCA13 608830 RDH12 1q32.3 LCA14 604863 LRAT 14q24.1 LCA15 602280 TULP1 4q31 LCA16 603208 KCNJ13 2q37 LCA17 601147 GDF6 8q22 LCA18 179605 PRPH2 6p21 The gene CEP290 has been associated with Joubert syndrome, as well as type 10 LCA.[21] ## Diagnosis[edit] Genetic tests and related research are currently being performed at Centogene AG in Rostock, Germany; John and Marcia Carver Nonprofit Genetic Testing Laboratory in Iowa City, IA; GENESIS Center for Medical Genetics in Poznan, Poland; Miraca Genetics Laboratories in Houston, TX; Asper Biogene in Tartu, Estonia; CGC Genetics in Porto, Portugal; CEN4GEN Institute for Genomics and Molecular Diagnostics in Edmonton, Canada; and Reference Laboratory Genetics - Barcelona, Spain.[22] ## Treatment[edit] Main article: Adeno associated virus and gene therapy of the human retina One form of LCA, patients with LCA2 bearing a mutation in the RPE65 gene, has been successfully treated in clinical trials using gene therapy. The results of three early clinical trials were published in 2008 demonstrating the safety and efficacy of using adeno-associated virus to deliver gene therapy to restore vision in LCA patients. In all three clinical trials, patients recovered functional vision without apparent side-effects.[5][6][7][8] These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.[citation needed] The results of a phase 1 trial conducted by the University of Pennsylvania and Children’s Hospital of Philadelphia and published in 2009 showed sustained improvement in 12 subjects (ages 8 to 44) with RPE65-associated LCA after treatment with AAV2-hRPE65v2, a gene replacement therapy.[23] Early intervention was associated with better results.[23] In that study, patients were excluded based on the presence of particular antibodies to the vector AAV2 and treatment was only administered to one eye as a precaution.[23] A 2010 study testing the effect of administration of AAV2-hRPE65v2 in both eyes in animals with antibodies present suggested that immune responses may not complicate use of the treatment in both eyes.[24] On 19 December 2017, the U.S. Food and Drug Administration approved voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy for children and adults with biallelic RPE65 gene mutations responsible for retinal dystrophy, including Leber congenital amaurosis. Patients must have viable retinal cells as a prerequisite for the intraocular administration of Luxturna.[25] Retina surgeon Dr. Albert Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital.[5][26] Dr. Sue Semple-Rowland at the University of Florida has recently restored sight in an avian model using gene therapy.[27] In March 2020, doctors at the Casey Eye Institute of the Oregon Health & Science University injected a CRISPR-modified virus into a patient's eye in an attempt to treat LCA10.[28] ## Popular culture[edit] * In the episode "The Blackout in the Blizzard" (season 6, episode 16) of the television drama Bones, Dr. Jack Hodgins and his pregnant wife Angela Montenegro, who is an LCA carrier, have to wait during a citywide blackout for Hodgins's genetic test results, to see if he is also an LCA carrier. He does indeed turn out to be a carrier, giving their unborn child a 25% chance of having LCA. * In the television series ER (season 14, episode 12 named "Believe the Unseen") Dr. Abby Lockhart diagnoses a young foster girl with Leber congenital amaurosis. The girl to this point hid her condition from her foster families. The episode contains some information about symptoms, clinical diagnosis and mentions gene replacement therapy and clinical trials as hope for help in managing the condition. * In the Korean drama The King of Dramas (episode 16, "In Search Of Lost Time") Anthony Kim, played by Kim Myung-min, is diagnosed with Leber congenital amaurosis, the same disease that made his mother blind.[citation needed] * 4 year old Gavin who suffers from a form of LCA was made famous in 2013 by a YouTube video showing him using his white cane for the first time to navigate down a curb.[29] He later appeared on the TV show Little Big Shots.[citation needed] ## See also[edit] * Bleach and recycle ## References[edit] 1. ^ a b c d e "Leber congenital amaurosis". Genetics Home Reference. August 2010. Retrieved 14 May 2017. 2. ^ Stone EM (December 2007). "Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture". American Journal of Ophthalmology. 144 (6): 791–811. doi:10.1016/j.ajo.2007.08.022. PMID 17964524. 3. ^ Leber's congenital amaurosis at Who Named It? 4. ^ Leber T (1869). "Über Retinitis pigmentosa und angeborene Amaurose". Archiv für Ophthalmologie (in German). 15 (3): 1–25. doi:10.1007/BF02721213. S2CID 543893. 5. ^ a b c Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, et al. (May 2008). "Safety and efficacy of gene transfer for Leber's congenital amaurosis". The New England Journal of Medicine. 358 (21): 2240–8. doi:10.1056/NEJMoa0802315. PMC 2829748. PMID 18441370. 6. ^ a b Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, et al. (March 2010). "Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration". Molecular Therapy. 18 (3): 643–50. doi:10.1038/mt.2009.277. PMC 2839440. PMID 19953081. 7. ^ a b Cideciyan AV, Hauswirth WW, Aleman TS, Kaushal S, Schwartz SB, Boye SL, et al. (August 2009). "Vision 1 year after gene therapy for Leber's congenital amaurosis". The New England Journal of Medicine. 361 (7): 725–7. doi:10.1056/NEJMc0903652. PMC 2847775. PMID 19675341. 8. ^ a b Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, et al. (May 2008). "Effect of gene therapy on visual function in Leber's congenital amaurosis". The New England Journal of Medicine. 358 (21): 2231–9. CiteSeerX 10.1.1.574.4003. doi:10.1056/NEJMoa0802268. PMID 18441371. 9. ^ a b c d e f Online Mendelian Inheritance in Man (OMIM): LEBER CONGENITAL AMAUROSIS, TYPE I; LCA1 - 204000 10. ^ a b Weleber, R. G.; Francis, P. J.; Trzupek, K. M.; Beattie, C.; Adam, M. P.; Ardinger, H. H.; Pagon, R. A.; Wallace, S. E.; Bean LJH; Stephens, K.; Amemiya, A. (1993). "Leber Congenital Amaurosis". GeneReviews. PMID 20301475. 11. ^ Perrault I, Rozet JM, Calvas P, Gerber S, Camuzat A, Dollfus H, et al. (December 1996). "Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis". Nature Genetics. 14 (4): 461–4. doi:10.1038/ng1296-461. PMID 8944027. S2CID 21269014. 12. ^ Marlhens F, Bareil C, Griffoin JM, Zrenner E, Amalric P, Eliaou C, et al. (October 1997). "Mutations in RPE65 cause Leber's congenital amaurosis". Nature Genetics. 17 (2): 139–41. doi:10.1038/ng1097-139. PMID 9326927. S2CID 19648351. 13. ^ Yzer S, Leroy BP, De Baere E, de Ravel TJ, Zonneveld MN, Voesenek K, et al. (March 2006). "Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis". Investigative Ophthalmology & Visual Science. 47 (3): 1167–76. doi:10.1167/iovs.05-0848. PMID 16505055. 14. ^ "Inherited child blindness probed". BBC News. 2005-09-19. Retrieved 2007-09-21. 15. ^ Dharmaraj S, Li Y, Robitaille JM, Silva E, Zhu D, Mitchell TN, et al. (January 2000). "A novel locus for Leber congenital amaurosis maps to chromosome 6q". American Journal of Human Genetics. 66 (1): 319–26. doi:10.1086/302719. PMC 1288337. PMID 10631161. 16. ^ a b Preising MN, Paunescu K, Friedburg C, Lorenz B (June 2007). "[Genetic and clinical heterogeneity in LCA patients. The end of uniformity]". Der Ophthalmologe (in German). 104 (6): 490–8. doi:10.1007/s00347-007-1533-x. PMID 17525851. S2CID 46054872. 17. ^ Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, et al. (September 2012). "Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration". Nature Genetics. 44 (9): 1035–9. doi:10.1038/ng.2356. PMC 3657614. PMID 22842230. 18. ^ Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, et al. (September 2012). "NMNAT1 mutations cause Leber congenital amaurosis". Nature Genetics. 44 (9): 1040–5. doi:10.1038/ng.2361. PMC 3454532. PMID 22842227. 19. ^ Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, et al. (September 2012). "Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis". Nature Genetics. 44 (9): 972–4. doi:10.1038/ng.2370. PMID 22842231. S2CID 27501557. 20. ^ Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, et al. (September 2012). "Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy". Nature Genetics. 44 (9): 975–7. doi:10.1038/ng.2357. PMID 22842229. S2CID 205345854. 21. ^ Traboulsi EI, Koenekoop R, Stone EM (December 2006). "Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis". Ophthalmic Genetics. 27 (4): 113–5. doi:10.1080/13816810601013146. PMID 17148037. S2CID 802192. 22. ^ "GeneTests: Leber Congenital Amaurosis". Archived from the original on 2016-08-21. Retrieved 2015-08-07. 23. ^ a b c Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, et al. (November 2009). "Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial". Lancet. 374 (9701): 1597–605. doi:10.1016/S0140-6736(09)61836-5. PMC 4492302. PMID 19854499. 24. ^ Amado D, Mingozzi F, Hui D, Bennicelli JL, Wei Z, Chen Y, et al. (March 2010). "Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness". Science Translational Medicine. 2 (21): 21ra16. doi:10.1126/scitranslmed.3000659. PMC 4169124. PMID 20374996. 25. ^ "Approved Products - LUXTURNA". FDA. 2019-04-05. 26. ^ "ABC News: Miracle Cure for Nearly Blind Youth". Retrieved 2008-04-27. 27. ^ Williams ML, Coleman JE, Haire SE, Aleman TS, Cideciyan AV, Sokal I, et al. (June 2006). "Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness". PLOS Medicine. 3 (6): e201. doi:10.1371/journal.pmed.0030201. PMC 1463903. PMID 16700630. 28. ^ In A 1st, Scientists Use Revolutionary Gene-Editing Tool To Edit Inside A Patient 29. ^ "4 yr old Gavin using his white cane to navigate down a curb independently". ## Further reading[edit] * "Jocelyn Kaiser on "Gene Therapy in a New Light"". Science & Nature \| Smithsonian Magazine. p. 124. * Lewis, Ricki (2012). The Forever Fix: Gene Therapy and the Boy Who Saved It. New York: St. Martin's Press. ISBN 978-0-312-68190-6. OCLC 740628904. ## External links[edit] * GeneReview/NIH/UW entry on Leber Congenital Amaurosis Classification D * ICD-10: H35.5 * ICD-9-CM: 362.76 * OMIM: 204000 * MeSH: D057130 * DiseasesDB: 33192 External resources * GeneReviews: Leber Congenital Amaurosis * 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 * 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-aminobutyric 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	Leber congenital amaurosis	c0339527	27,491	wikipedia	https://en.wikipedia.org/wiki/Leber_congenital_amaurosis	2021-01-18T18:50:41	{"gard": ["634"], "mesh": ["D057130"], "umls": ["C0339527"], "orphanet": ["65"], "wikidata": ["Q1811132"]}
## Summary ### Clinical characteristics. Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. No other associated medical findings are present. ### Diagnosis/testing. Diagnosis of DFNB1 depends on molecular genetic testing to identify biallelic pathogenic variants in GJB2 (sequence variants as well as variants in upstream cis-regulatory elements that alter expression of the gap junction beta-2 protein [connexin 26]). ### Management. Treatment of manifestations: Hearing aids; enrollment in appropriate educational programs; consideration of cochlear implantation for individuals with profound deafness. Surveillance: Surveillance includes annual examinations and repeat audiometry to confirm stability of hearing loss. Evaluation of relatives at risk: If both pathogenic variants have been identified in an affected family member, molecular genetic testing can be used to clarify the genetic status of an at-risk relative in childhood so that appropriate early support and management can be provided. ### Genetic counseling. DFNB1 is inherited in an autosomal recessive manner. In each pregnancy, the parents of a proband have a 25% chance of having a deaf child, a 50% chance of having a hearing child who is a carrier, and a 25% chance of having a hearing child who is not a carrier. When the GJB2 pathogenic variants causing DFNB1 are detected in an affected family member, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings Nonsyndromic hearing loss and deafness caused by biallelic pathogenic GJB2 variants (DFNB1) should be suspected in individuals with the following: * Congenital, generally non-progressive sensorineural hearing impairment that is mild to profound by auditory brain stem response testing (ABR) or pure tone audiometry Note: (1) Hearing is measured in decibels (dB). The threshold or 0-dB mark for each frequency refers to the level at which normal young adults perceive a tone burst 50% of the time. Hearing is considered normal if an individual's thresholds are within 25 dB of normal thresholds. (2) Severity of hearing loss is graded as mild (26-40 dB), moderate (41-55 dB), moderately severe (56-70 dB), severe (71-90 dB), or profound (90 dB). The frequency of hearing loss is designated as low (<500Hz), middle (501-2,000 Hz), or high (>2,000 Hz) (see Hereditary Hearing Loss and Deafness Overview). * No related systemic findings identified by medical history and physical examination * A family history of nonsyndromic hearing loss consistent with autosomal recessive inheritance ### Establishing the Diagnosis The diagnosis of DFNB1 is established in a proband with mild to profound congenital, generally non-progressive sensorineural hearing impairment and identification of biallelic pathogenic variants in GJB2 (encoding connexin 26) on molecular genetic testing (see Table 1). Individuals with DFNB1 are EITHER: * Homozygous or compound heterozygous for GJB2 pathogenic variants (99%); OR * Compound heterozygous for one GJB2 pathogenic variant and one of three large deletions that includes sequences upstream of GJB2 and a portion of GJB6 (<1%). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and/or a multigene panel) and genomic testing (comprehensive genomic sequencing). Gene-targeted testing requires the clinician to determine which gene(s) are likely involved based on phenotypic data, while comprehensive genomic testing does not. Because of the overlapping phenotypes of the many causes of hereditary hearing loss and deafness, most individuals with hereditary hearing loss and deafness are diagnosed by one of two approaches: comprehensive genomic sequencing (recommended) or gene-targeted testing (to consider). #### Recommended Testing A comprehensive deafness-specific genetic panel that includes all genes implicated in nonsyndromic hearing loss and nonsyndromic hearing loss mimics (see Differential Diagnosis and Hereditary Hearing Loss and Deafness Overview) is recommended as the initial genetic test (Figure 1). #### Figure 1. Genetic diagnostic rates in 1,119 sequentially accrued persons with hearing loss. No person was excluded based on phenotype, inheritance, or previous testing. Testing resulted in identification of the underlying genetic cause for hearing loss in 440 individuals (more...) Note: (1) Genes included in available panels and the diagnostic sensitivity of the test used for each gene vary by laboratory and are likely to change over time [Shearer & Smith 2015]. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel provides the best opportunity 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. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests; detection of copy number variants must be included in hearing loss panels [Shearer et al 2014]. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Testing to Consider Single-gene testing can be considered if a deafness-specific multigene panel is not available. However, performing sequence analysis of GJB2 alone is not cost-effective unless it is limited to persons with severe-to-profound congenital nonsyndromic hearing loss. Offering single-gene testing of GJB2 reflexively to everyone with congenital hearing loss without regard to the degree of hearing loss is not evidence based and not cost effective [Jayawardena et al 2015, Shearer & Smith 2015]. Comprehensive genomic testing including exome sequencing and genome sequencing may be considered if the phenotype alone is insufficient to warrant gene-targeted testing. Both exome sequencing and genome sequencing should be complemented with appropriate genetic counseling before and after testing. 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 DFNB1 View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2, 3 Detectable by Method GJB2Sequence analysis 4> 99% Gene-targeted deletion/duplication analysis 5, 6<1% 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\. Percentages vary depending on ethnicity. Numbers in table reflect screening of a US population primarily of northern European ancestry. 4\. 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. 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\. 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 Feldmann et al [2009]) may not be detected by these methods. ## Clinical Characteristics ### Clinical Description Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital (present at birth) non-progressive sensorineural hearing impairment. Intrafamilial variability in the degree of deafness is seen. * If an affected person has severe-to-profound deafness, an affected sib with the same GJB2 pathogenic variants has a 91% chance of having severe-to-profound deafness and a 9% chance of having mild-to-moderate deafness [Tennessee Department of Health 2005]. * If an affected person has mild-to-moderate deafness, an affected sib with the same GJB2 pathogenic variants has a 66% chance of having mild-to-moderate deafness and a 34% chance of having severe-to-profound deafness [Tennessee Department of Health 2005]. * A few reports describe children with GJB2 variants who pass the newborn hearing screen and have somewhat later-onset hearing loss [Norris et al 2006, Orzan & Murgia 2007]. In a large cross-sectional analysis of GJB2 genotype and audiometric data from 1,531 individuals with autosomal recessive mild-to-profound nonsyndromic deafness (median age 8 years; 90% within age 0-26 years) from 16 countries, linear regression analysis of hearing thresholds on age in the entire study and in subsets defined by genotype did not show significant progression of hearing loss in any individual [Snoeckx et al 2005]. This finding is in concordance with prior studies [Orzan et al 1999, Löffler et al 2001]; however, progression of hearing loss cannot be excluded definitively given the cross-sectional nature of the regression analysis. Although Snoeckx et al [2005] found a slight degree of asymmetry, the difference in pure tone average at 0.5, 1.0, and 2.0 kHz between ears was less than 15 dB in 90% of individuals. Vestibular function is normal; affected infants and young children do not experience balance problems and learn to sit and walk at age-appropriate times. Except for the hearing impairment, affected individuals are healthy; life span is normal. ### Genotype-Phenotype Correlations Numerous studies have shown that it is possible to predict phenotype based on genotype. The largest study to date involved a cross-sectional analysis of GJB2 genotype and audiometric data from 1,531 persons from 16 different countries with autosomal recessive mild-to-profound nonsyndromic deafness [Snoeckx et al 2005]. Of the 83 different variants identified, 47 were predicted nontruncating (e.g., missense variants) and 36 were predicted truncating (e.g., premature stop codons). By classifying variants this way, the authors defined three genotype classes: biallelic truncating (T/T) variants, biallelic nontruncating (NT/NT) variants, and compound heterozygous truncating/nontruncating (T/NT) variants (Table 2). ### Table 2. Genotype-Phenotype Correlations by Variant Type in 1531 Persons with Biallelic GJB2 Pathogenic Variants View in own window GJB2 Genotype ClassTotal of All DFNB1Hearing Loss MildModerateSevereProfound T/T77.3% 10%-3%10%-12%25%-28%59%-64% NT/NT6.2% 253%26%8%13% T/NT16.5% 329%-37%24%-29%10%-17%24%-30% Based on Snoeckx et al [2005]. See full text, Figure 3 for scatter diagrams showing the binaural mean pure tone average (PTA) at 0.5, 1, and 2 kHz (PTA0.5,1,2kHz) for each person within each genotype class, using individuals homozygous for the c.35delG allele as a reference group. NT/NT = biallelic predicted nontruncating variants; T/NT = compound heterozygous predicted truncating/nontruncating variants; T/T = biallelic predicted truncating variants 1\. 64 different genotypes (36% of all genotypes) 2\. 42 different genoytpes (24% of all genotypes) 3\. 71 different genotypes (40% of all genotypes) ### Nomenclature DFNB with a suffix integer is used to designate loci for autosomal recessive nonsyndromic deafness. ### Prevalence DFNB1 accounts for approximately 50% of congenital severe-to-profound autosomal recessive nonsyndromic hearing loss in the United States, France, Britain, and New Zealand/Australia [Green et al 1999, Azaiez et al 2004, Angeli 2008]. Its approximate prevalence in the general population is 14:100,000, based on the following calculation: the incidence of congenital hereditary hearing impairment is 1:2,000 neonates, of which 70% have nonsyndromic hearing loss. Seventy-five to 80% of cases of nonsyndromic hearing loss are autosomal recessive; of these, 50% result from biallelic pathogenic variants in GJB2. Thus, 5:10,000 x 0.7 x 0.8 x 0.5 = 14:100,000. Given the extreme heterogeneity of autosomal recessive nonsyndromic hearing impairment, it is not surprising that epidemiologic studies in other populations have shown that the frequency of biallelic GJB2 pathogenic variants as a cause of hearing impairment is highly variable. For example, among families segregating autosomal recessive nonsyndromic hearing impairment, GJB2 variants are causally related to congenital hereditary hearing impairment in: * 25% of Palestinian families [Shahin et al 2002] * An estimated 24% of Altaians from Siberia [Posukh et al 2005] * 18% of Han Chinese [Duan et al 2015] * 16% of the Iranian deaf population [Bazazzadegan et al 2012] * 15% of Hui people [Duan et al 2015] * 11% of Tibetan families [Duan et al 2015] ## Differential Diagnosis See Hereditary Hearing Loss and Deafness Overview for information on the genes causing nonsyndromic hereditary hearing loss and deafness. ### Table 3. Autosomal Recessive Syndromes Involving Hearing Loss View in own window SyndromeDistinctive Feature in Addition to Hearing LossGene(s)Hearing LossComments Usher syndrome type IRetinitis pigmentosa 1See footnote 2Congenital bilateral profound sensorineural hearing loss * Vestibular areflexia w/delay in motor milestones (delayed sitting & walking) * Unless fitted w/a cochlear implant, individuals w/Usher syndrome type 1 do not typically develop speech. * RP develops in adolescence, resulting in progressively constricted visual fields & impaired visual acuity Usher syndrome type IIUSH2A ADGRV1 DFNB31Congenital bilateral sensorineural hearing loss: mild-moderate in low frequencies; severe-profound in higher frequencies * Intact vestibular responses w/no delay in motor milestones * Clinical distinction between Usher syndrome types I & II: children w/type I usually delayed in walking until age 18 mos – 2 yrs (because of vestibular involvement); children w/type II usually begin walking at ~1 yr Usher syndrome type IIICLRN1Postlingual progressive sensorineural hearing loss * Late-onset RP * Variable impairment of vestibular function * Older individuals w/Usher syndrome type III may have profound hearing loss & vestibular disturbance resembling Usher syndrome type I Pendred syndromeThyroid enlargementSLC26A4 3Hearing impairment usually congenital & often severe-profound (mild-moderate progressive hearing impairment also occurs) * Bilateral dilation of the vestibular aqueduct 4 w/ or w/out cochlear hypoplasia 5 * Either an abnormal perchlorate discharge test or goiter * Thyroid abnormality variable 6 * Vestibular function usually abnormal Jervell and Lange-Nielsen syndromeCardiac conduction defects; long QTc, usually >500 msecKCNQ1 KCNE1Congenital profound bilateral sensorineural hearing loss * Long QTc is associated w/tachyarrhythmias, which may culminate in syncope or sudden death; >50% of untreated children w/JLNS die before age 15 years 7 * Classic presentation: deaf child who experiences syncopal episodes during periods of stress, exercise, or fright * Consider JLNS in any child w/congenital sensorineural deafness & negative DFNB1 testing – esp. w/a history of syncope or seizure or family history of sudden death before age 40 years 1\. Retinitis pigmentosa is a progressive bilateral symmetric degeneration of rod and cone functions of the retina. 2\. Pathogenic variants in genes at a minimum of nine different loci cause Usher syndrome type I. Genes at six of these loci – MYO7A (USH1B), USH1C, CDH23 (USH1D), PCDH15 (USH1F), USH1G, and CIB2 (USH1J) – have been identified. 3\. Pendred syndrome and DFNB4 comprise a phenotypic spectrum caused by biallelic pathogenic variants in SLC26A4 (the most common cause), or double heterozygosity in either SLC26A4 and FOXI1 or SLC26A4 and KCNJ10. 4\. Also called enlarged vestibular aqueduct (EVA) 5\. DVA with cochlear hypoplasia is known as Mondini malformation or dysplasia. 6\. Goitrous changes are typically not present at birth but do develop in early puberty (40%) or adulthood (60%). 7\. Treatment involves use of beta-adrenergic blockers, cardiac pacemakers, and implantable defibrillators as well as avoidance of drugs that cause further prolongation of the QT interval and of activities known to precipitate syncopal events. Autosomal recessive nonsyndromic hearing loss without an identifiable GJB2 variant and with progression of hearing loss: * With a dilated vestibular aqueduct on thin-cut computed tomography (CT) of the temporal bones suggests DFNB4 [Azaiez et al 2007]; * With a Mondini malformation on thin-cut CT of the temporal bones suggests Pendred syndrome. A perchlorate test and molecular genetic testing of SLC26A4 should be considered [Azaiez et al 2007]. Other causes of congenital severe-to-profound hearing loss should be considered in children who represent single cases in a family: * Congenital CMV (cytomegalovirus), the most common cause of congenital nonhereditary hearing loss * Prematurity, low birth weight, low Apgar scores, infection, and any illness requiring care in a neonatal intensive care unit ## Management ### Evaluations Following Initial Diagnosis To establish the extent of involvement and needs in an individual diagnosed with nonsyndromic hearing loss and deafness caused by biallelic pathogenic variants in GJB2 (DFNB1), the following evaluations are recommended: * Complete assessment of auditory acuity using age-appropriate tests such as ABR testing, auditory steady-state response (ASSR) testing, and pure tone audiometry * Ophthalmologic evaluation for refractive errors * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations The following are indicated: * Fitting with appropriate hearing aids * Enrollment in an appropriate educational program for the hearing impaired * Consideration of cochlear implantation (CI), an excellent habilitation option for persons with profound deafness * Recognition that, unlike with many clinical conditions, the management and treatment of severe-to-profound congenital deafness falls largely within the purview of the social welfare and educational systems rather than the medical care system [Smith et al 2005] Also see Hereditary Hearing Loss and Deafness for more detailed discussion of management issues. ### Surveillance The following are appropriate: * Annual examination by a physician familiar with hereditary hearing impairment * Repeat audiometry to confirm stability of hearing loss ### Agents/Circumstances to Avoid Individuals with hearing loss should avoid environmental exposures known to cause hearing loss. Most important among these for persons with DFNB1 and mild-to-moderate hearing loss is avoidance of repeated overexposure to loud noises. ### Evaluation of Relatives at Risk If both GJB2 pathogenic variants have been identified in the proband, it is appropriate to clarify the genetic status of at-risk sibs shortly after birth so that appropriate early support and management can be provided to the child and family. 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 information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this 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-aminobutyric 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	Nonsyndromic Hearing Loss and Deafness, DFNB1	None	27,492	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1272/	2021-01-18T21:07:39	{"synonyms": ["GJB2-Related DFNB 1 Nonsyndromic Hearing Loss and Deafness"]}
Hereditary mixed polyposis syndrome (HMPS) describes an autosomal dominantly inherited large-bowel disease characterized by the presence of a mixture of hyperplastic, atypical juvenile and adenomatous polyps that are associated with an increased risk of developing colorectal cancer if left untreated. [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-aminobutyric 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	Hereditary mixed polyposis syndrome	c1832587	27,493	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157794	2021-01-23T17:57:32	{"mesh": ["C563365"], "omim": ["601228", "610069"], "icd-10": ["D12.6"], "synonyms": ["HMPS"]}
Not to be confused with Korea or Cholera. For the ancient Greek dance, see Choreia. For other uses, see Chorea (disambiguation). Chorea SpecialtyNeurology Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term chorea is derived from the Ancient Greek: χορεία ("dance"; see choreia), as the quick movements of the feet or hands are comparable to dancing. The term hemichorea refers to chorea of one side of the body, such as chorea of one arm but not both (analogous to hemiballismus). ## Contents * 1 Presentation * 2 Causes * 2.1 Huntington's disease * 2.2 Other genetic causes * 2.3 Acquired causes * 3 Treatment * 4 History * 5 See also * 6 Notes * 7 External links ## Presentation[edit] 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: "Chorea" – news · newspapers · books · scholar · JSTOR (January 2020) (Learn how and when to remove this template message) Chorea is characterized by brief, semi-directed, irregular movements that are not repetitive or rhythmic, but appear to flow from one muscle to the next. These 'dance-like' movements of chorea often occur with athetosis, which adds twisting and writhing movements. Walking may become difficult, and include odd postures and leg movements. Unlike ataxia, which affects the quality of voluntary movements, or Parkinsonism, which is a hindrance of voluntary movements, the movements of chorea and ballism occur on their own, without conscious effort. Thus, chorea is said to be a hyperkinetic movement disorder. When chorea is serious, slight movements will become thrashing motions; this form of severe chorea is referred to as ballism, or ballismus. ## Causes[edit] ### Huntington's disease[edit] Huntington's disease is a neurodegenerative disease and most common inherited cause of chorea. The condition was formerly called Huntington's chorea but was renamed because of the important non-choreic features including cognitive decline and behavioural change.[1] ### Other genetic causes[edit] Other genetic causes of chorea are rare. They include the classical Huntington's disease 'mimic' or phenocopy syndromes, called Huntington's disease-like syndrome types 1, 2 and 3; inherited prion disease, the spinocerebellar ataxias type 1, 3 and 17, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia, mitochondrial disease and Rett syndrome.[2] ### Acquired causes[edit] The most common acquired causes of chorea are cerebrovascular disease and, in the developing world, HIV infection—usually through its association with cryptococcal disease.[2] Sydenham's chorea occurs as a complication of streptococcal infection. Twenty percent (20%) of children and adolescents with rheumatic fever develop Sydenham's chorea as a complication. It is increasingly rare, which may be partially due to penicillin, improved social conditions, and/or a natural reduction in the bacteria ( Streptococcus ) it has stemmed from. Psychological symptoms may precede or accompany this acquired chorea and may be relapsing and remitting. The broader spectrum of paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection can cause chorea and are collectively referred to as PANDAS.[2] Chorea gravidarum refers to choreic symptoms that occur during pregnancy. If left untreated, the disease resolves in 30% of patients before delivery but, in the other 70%, it persists. The symptoms then progressively disappear in the next few days following the delivery.[2] Chorea may also be caused by drugs (commonly levodopa, anti-convulsants and anti-psychotics).[2] Other acquired causes include CSF leak,[3] systemic lupus erythematosus, antiphospholipid syndrome, thyrotoxicosis, polycythaemia rubra vera,[2] transmissible spongiform encephalopathies and coeliac disease.[4] ## Treatment[edit] There is no standard course of treatment for chorea. Treatment depends on the type of chorea and the associated disease. Although there are many drugs that can control it, no cure has yet been identified. Form Treatment Huntington's-related A common treatment is dopaminergic antagonists, although treatment is largely supportive. Tetrabenazine is the only FDA approved drug for the treatment of Huntington's disease-related chorea. Sydenham's chorea Haloperidol, carbamazepine and valproic acid. Usually involves antibiotic drugs to treat the infection, followed by drug therapy to prevent recurrence. Chorea gravidarum haloperidol,[5][6][7] chlorpromazine alone or in combination with diazepam, also pimozide can also be used. Wilson's disease Reducing levels of copper in the body using D-penicillamine, trientine hydrochloride, tetrathiomolybdate, and other chelating agents Drug-induced chorea Adjusting medication dosages. Metabolic and endocrine-related choreas Treated according to their causes. ## History[edit] Historically, choreas like Huntington disease and Sydenham's chorea were called Saint Vitus' dance, related to a series of social phenomena of the same name.[8] ## See also[edit] * Choreoathetosis * Dancing mania * Tic ## Notes[edit] 1. ^ Gillian, Bates; Sarah, Tabrizi; Lesley, Jones (2014). Huntington's disease (4th ed.). Oxford University Press. ISBN 978-0199929146. 2. ^ a b c d e f Wild, EJ; Tabrizi, SJ (November 2007). "The differential diagnosis of chorea". Practical Neurology. 7 (6): 360–73. doi:10.1136/pn.2007.134585. PMID 18024776. S2CID 31059440. 3. ^ Mokri, Bahram (December 2014). "Movement disorders associated with spontaneous CSF leaks: a case series". Cephalalgia: An International Journal of Headache. 34 (14): 1134–1141. doi:10.1177/0333102414531154. ISSN 1468-2982. PMID 24728303. S2CID 3100453. 4. ^ Bushara, Khalafalla O. (2005). "Neurologic presentation of celiac disease". Gastroenterology. 128 (4 Suppl 1): S92–7. doi:10.1053/j.gastro.2005.02.018. PMID 15825133. 5. ^ Axley, John (1972). "Rheumatic chorea controlled with haloperidol". The Journal of Pediatrics. 81 (6): 1216–7. doi:10.1016/S0022-3476(72)80272-5. PMID 4643046. 6. ^ Patterson, John F. (1979). "Treatment of Chorea Gravidarum With Haloperidol". Southern Medical Journal. 72 (9): 1220–1. doi:10.1097/00007611-197909000-00044. PMID 472859. 7. ^ Donaldson JO (March 1982). "Control of choreia gravidarum with haloperidol". Obstetrics and Gynecology. 59 (3): 381–2. PMID 7078886. 8. ^ Lawrence, David M. (2009). Huntington's Disease. Infobase Publishing. ISBN 9780791095867. ## External links[edit] * Chorea Gravidarum~clinical at eMedicine Classification D * ICD-10: G25.5 * ICD-9-CM: 333.5 * MeSH: D002819 * DiseasesDB: 16662 External resources * eMedicine: neuro/62 * Patient UK: Chorea * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral 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-aminobutyric 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	Chorea	c0393584	27,494	wikipedia	https://en.wikipedia.org/wiki/Chorea	2021-01-18T18:54:38	{"mesh": ["D002819"], "umls": ["C0393584"], "icd-9": ["333.5"], "icd-10": ["G25.525.5"], "orphanet": ["1429"], "wikidata": ["Q1076421"]}
## Summary ### Clinical characteristics. ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency. ### Diagnosis/testing. The diagnosis of ADCY5 dyskinesia is established in a proband with a hyperkinetic movement disorder (in the absence of structural brain abnormalities) and a heterozygous pathogenic variant (or, rarely, biallelic pathogenic variants) in ADCY5 identified by molecular genetic testing. ### Management. Treatment of manifestations: Management by multidisciplinary specialists, including a neurologist or neurogeneticist, cardiologist, physical therapist, social worker, speech and language pathologist, and other specialists is recommended as needed. Anecdotally, medications have had variable effect in suppressing debilitating symptoms. Treatment should be determined by the individual's physician, taking into account potential risk/benefit, other medical conditions, allergies, and potential drug-drug interactions. Response to medication is difficult to evaluate because some individuals have long periods (weeks) of remission of the dyskinesia. Physical and occupational therapy may help maintain mobility and function. Speech and language therapy for dysarthria may include alternative communication methods. Cognitive impairment and psychiatric manifestations are managed per standard practice. Surveillance: Routine follow up of neurologic involvement, dysarthria, oculomotor involvement, musculoskeletal involvement, activities of daily living, cognitive impairment, and psychiatric manifestations. Pregnancy management: Potential teratogenic effects of medications given for treatment of ADCY5 dyskinesia should be discussed with affected women of childbearing age, ideally prior to conception. ### Genetic counseling. ADCY5 dyskinesia is typically inherited in an autosomal dominant (AD) manner. Autosomal recessive (AR) inheritance has been reported in two families. AD inheritance: The majority of individuals diagnosed with ADCY5 dyskinesia represent simplex cases (i.e., a single affected family member) and have the disorder as the result of a de novo pathogenic variant. Each child of an individual with ADCY5 dyskinesia has a 50% chance of inheriting the pathogenic variant. Both AD and AR inheritance: Once the ADCY5 pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for ADCY5 dyskinesia are possible. ## Diagnosis No consensus diagnostic guidelines for ADCY5 dyskinesia have been published. ### Suggestive Findings Diagnosis of ADCY5 dyskinesia should be suspected in individuals with the following clinical findings, neuroimaging, and family history. Clinical findings * Infantile to late-adolescent onset of choreiform, myoclonic, and/or dystonic movements that involve the limbs, neck, and/or face * Familial benign chorea * Alternating hemiplegia in childhood * Myoclonus-dystonia * Focal dystonia and tremor * Spasticity and dystonia * Sleep-related motor and behavior disorder Neuroimaging. Brain MRI shows no evidence of structural abnormalities. Family history is consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations) or, rarely, autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis. ### Establishing the Diagnosis The diagnosis of ADCY5 dyskinesia is established in a proband with a hyperkinetic movement disorder (in the absence of structural brain abnormalities) and a heterozygous pathogenic variant (or, rarely, biallelic pathogenic variants) in ADCY5 identified by molecular genetic testing (see Table 1). Note: Identification of a heterozygous ADCY5 variant of uncertain significance does not establish or rule out the diagnosis of this disorder. 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) 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 findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of ADCY5 dyskinesia has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 Single-gene testing. Sequence analysis of ADCY5 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step typically is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications; however, because ADCY5 dyskinesia occurs through a gain-of-pathogenic-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. Mosaicism of pathogenic variants has been reported. A movement disorder multigene panel that includes ADCY5 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. #### Option 2 Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; 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 ADCY5 Dyskinesia View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method ADCY5Sequence analysis 3100% 4, 5 Gene-targeted deletion/duplication analysis 6None reported 7 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on 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\. Chen et al [2012], Chen et al [2014], Chen et al [2015], Zech et al [2017], and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017] 5\. In a simplex case (i.e., a single occurrence in a family), germline mosaicism for the pathogenic variant may complicate interpretation of sequencing results. 6\. 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. 7\. Because ADCY5 dyskinesia occurs through a gain-of-pathogenic-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. ## Clinical Characteristics ### Clinical Description The hallmark of ADCY5 dyskinesia is infantile to late-adolescent onset of a hyperkinetic movement disorder characterized by chorea, athetosis, dystonia, myoclonus, or a combination which tends to be more prominent in the face and arms than the legs [Chen et al 2015]. Affected individuals identified to date have overlapping but not identical clinical manifestations with wide-ranging clinical severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal bouts of exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors have included emotional stress, intercurrent illness, sneezing, or caffeine [Vijiaratnam et al 2019]. In other affected individuals, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays [Carecchio et al 2017]. The phenotypic spectrum of this disorder is still being elucidated. ADCY dyskinesia was first identified in a single multigenerational family [Chen et al 2012]. Following that publication, more than 40 individuals representing simplex cases (i.e., a single occurrence in a family) and members of more than ten families with ADCY5 dyskinesia have been reported [Chen et al 2015, Vijiaratnam et al 2019]. The following description of the phenotypic features associated with this condition is based on these reports. ### Table 2. ADCY5 Dyskinesia: Frequency of Select Features View in own window FeatureFrequencyComment Nearly allCommonInfrequent Dyskinesia● Axial hypotonia●In children presenting in infancy Spasticity● Intellectual disability● Epilepsy● Psychiatric disease● Cardiomyopathy● #### Neurologic Manifestations All affected individuals reported to date have had episodes of choreiform, myoclonic, and/or dystonic movements that primarily affect the limbs, face, and/or neck. Typically the abnormal movements first appear during infancy, childhood, or early adolescence (range: neonatal period to age 19 years) [Chen et al 2015]. In those with milder manifestations, the abnormal movements involve the face and distal limbs (although minimally affecting function) and are socially debilitating. Some affected individuals may be described as "excessively clumsy." In more severely affected infants, the earliest manifestations can include severe axial hypotonia resulting in developmental delays that lead to impairment in the ability to ambulate, requiring use of wheelchairs. The abnormal movements are continual during waking hours, and have been noted to persist during sleep, particularly in infancy. Several affected individuals have noted severe, sleep-disrupting movements [Chen et al 2014, Chen et al 2015] that occurred during stages N2 and N3 of sleep, and were not associated with epileptiform discharges in one individual [Chen et al 2014]. A curious feature observed in some individuals is the occurrence of long periods (days to weeks) of remission. The movements are often exacerbated by anxiety or stress and with drowsiness or sleep (although not by startle or alcohol). Less common triggers include intercurrent illness, fatigue, excitement, or caffeine, although one individual showed improvement with caffeine and other individuals have reported benefit [J Friedman, personal observation]. One woman reported that her choreiform movements were precipitated by enforced inactivity (e.g., as during a road trip), and could often be alleviated by voluntary movement. Facial "twitches" (previously thought to be myokymia) involving the periorbital and/or perioral muscles may also be present. Twitches were also documented in limb muscles in one individual [Fernandez et al 2001]. Dysarthria and hypotonia have been reported in some affected individuals [Chen et al 2014, Chen et al 2015, Mencacci et al 2015]. Intellect and life span are usually normal. In severely affected individuals with onset in early childhood, intellectual disability may be present. Neurologic examination can vary widely between individuals and in the same individual over time. Examination may reveal: * A mixed movement disorder that may include prominent choreiform movements usually affecting the hands and/or feet, often characterized as piano playing movements [Vijiaratnam et al 2019]; * Myoclonic and dystonic movements [Friedman et al 2016]; * Non-myokymic facial twitching, hyperreflexia of the lower limbs, and intermittent head or limb tremors [Chen et al 2014]; * Axial hypotonia with limb and axial weakness including severe neck weakness [Chen et al 2014, Chen et al 2015]; * Alternating hemiplegia of childhood [Westenberger et al 2017]; * Progressive spasticity and dystonia with hyperreflexia [Dean et al 2019, Waalkens et al 2018]. Somatic mosaicism has been demonstrated in 43% of individuals with a de novo pathogenic variant [Raskind et al 2017] and in the founders of two multigenerational families, including one individual shown to be mosaic for the p.Met1029Lys variant who demonstrated considerable improvement during adulthood [Chen et al 2015]. Another individual, thought to be mosaic for p.Arg418Trp, exhibited significantly milder phenotypic features: fewer facial twitches, milder chorea, and no dysarthria [Mencacci et al 2015]. The natural history varies. In most, the abnormal movements are static or slowly progressive with increased severity and frequency. In some instances, choreiform movements have been more constant, and less paroxysmal, from the onset [Mencacci et al 2015]. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals. #### Cardiac Complications Chen et al [2011] reported that five individuals in a family with ADCY5 dyskinesia also had congestive heart failure. Because ADCY5 encodes a specific adenylyl cyclase that is highly expressed in both striatum and myocardium [Ho et al 2010], these observations suggest that pathogenic variants in ADCY5 could contribute to cardiac pathology; further study is required. #### Studies Needle electromyogram (EMG) studies in two individuals with facial muscle twitching suggested centrally driven irregular muscle movements that were also observed in other muscles, including the orbicularis oculi, tongue, frontalis, and dorsal interosseous muscles. No fibrillations, fasciculations, myokymia, or myotonia were noted on EMG. Brain imaging (MRI, CT) is normal. Neuropathology. Gross pathology is normal. Detailed immunohistochemical analysis in one individual with molecularly confirmed ADCY5 dyskinesia revealed increased immunoreactivity for ADCY5 in multiple brain regions as well as tau deposits in deep cortical sulci, the midbrain and hippocampus. Lewy bodies and amyloid pathology were absent [Chen et al 2019]. ### Genotype-Phenotype Correlations In general, the number of individuals and families tested to date is too small to make reliable predictions of phenotypic features based on genotype; however, one missense variant, p.Ala726Thr, has been associated with a milder phenotype [Vijiaratnam et al 2019] (see Table 7). ### Penetrance In molecularly confirmed ADCY5 dyskinesia, penetrance has been 100% in both men and women. ### Nomenclature ADCY5 dyskinesia has been previously described as: * A variant of familial essential ("benign") chorea. Although the term "benign" was used to distinguish the movement disorder from progressive, neurodegenerative forms of chorea such as Huntington disease, ADCY5 dyskinesia can be disabling and in some instances progressive, and, thus, use of the term "benign hereditary chorea" should be avoided. * "Familial dyskinesia facial myokymia" because the prominent facial twitching was originally thought to be myokymia (see Clinical Description); however, more recently EMG studies of affected individuals have revealed that these twitches are not myokymia. DYT-ADCY5 may be an appropriate designation because dystonia is often a prominent feature [Marras et al 2012]. ### Prevalence No data are available for the prevalence of ADCY5 dyskinesia. It is likely underdiagnosed because of the variability in the clinical presentation and age of onset, and because of the high rate of de novo variants resulting in simplex cases (i.e., a single occurrence in a family) [Vijiaratnam et al 2019]. ## Differential Diagnosis ### Hereditary Disorders ### Table 3. Genes of Interest in the Differential Diagnosis of ADCY5 Dyskinesia View in own window Gene(s)DisorderMOIClinical Characteristics of Differential Diagnosis Overlapping w/ADCY5 DyskinesiaDistinguishing from ADCY5 Dyskinesia ANO3DYT-ANO3 (See Hereditary Dystonia Overview.)ADFocal dystonia & tremorAffects neck, laryngeal muscles, and arms ATP1A3Alternating hemiplegia of childhood (See ATP1A3 Neurologic Disorders.)ADAlternating hemiplegiaEpisodic hemiplegia assoc w/movement disorder CHRNA2 CHRNA4 CHRNB2 CRH DEPDC5 KCNT1AD nocturnal frontal lobe epilepsyADSleep-related motor & behavioral disordersOn video-EEG: focal interictal epileptiform discharges arising from the frontal lobe; seizures recorded GCH1GTP cyclohydrolase 1-deficient dopa-responsive dystoniaADDystoniaDramatic response to treatment w/L-dopa HTTHuntington diseaseADChorea * Mean onset age: 35-44 yrs * Choreiform movements become constant over time. NKX2-1Benign hereditary chorea (See NKX2-1 Disorders.)ADPresents before age 5 yrs * Manifestations often improve by late adolescence. * Pulmonary dysfunction & endocrine abnormalities, most commonly hypothyroidism (Note: Non-neurologic manifestations are rare in ADCY5 dyskinesia.) PDE10AInfantile-onset limb & orofacial dyskinesia (OMIM 616921)ARChildhood onset chorea * Diurnal fluctuation * Striatal lesions on brain MRI PDE2APDE10A childhood-onset chorea 1Childhood onset choreaStriatal lesions on brain MRI PNKDFamilial paroxysmal nonkinesigenic dyskinesiaAD * Unilateral or bilateral involuntary movements * Attacks are spontaneous or precipitated; involve dystonic posturing w/choreic & ballistic mvmts; may be accompanied by preceding aura; occur while awake; are not assoc w/seizures. Consumption of alcohol or caffeine may precipitate attacks PRRT2Paroxysmal kinesigenic dyskinesia (PKD) (See PRRT2 Paroxysmal Movement Disorders.)AD * Unilateral or bilateral involuntary mvmts precipitated by other sudden mvmts (e.g., standing up from sitting position; being startled; changes in velocity). * Attacks incl combinations of dystonia, choreoathetosis, & ballism; are sometimes preceded by an aura; do not involve loss of consciousness. PKD is more common in men & is precipitated by voluntary movement. SGCESGCE myoclonus-dystoniaADMyoclonus-dystoniaImproves w/alcohol consumption; psychiatric manifestations are more common. SLC2A1Paroxysmal choreoathetosis w/spasticity (See Glucose Transporter Type 1 Deficiency Syndrome.)AD (AR)Presents w/dystonic paroxysms affecting toes, legs, & arms; dysarthria; & changes in perioral sensationNo distinguishing clinical characteristics AD = autosomal dominant; AR = autosomal recessive; DYT = dystonia; MOI = mode of inheritance 1\. Mencacci et al [2016] Mitochondrial disorders can present with dystonia or other abnormal movements. ### Drug-Induced and Acquired Disorders Tardive dyskinesia, a hyperkinetic movement disorder associated with long-term use of specific dopamine receptor blocking agents (including neuroleptics and certain antiemetics) [Aquino & Lang 2014], is often precipitated by a recent dose reduction or a change to a less potent drug. Sydenham chorea, a manifestation of acute rheumatic fever, is the most common cause of acquired chorea in childhood, and typically presents between ages five and 12 years. Although carditis and arthritis are other manifestations of rheumatic fever, chorea may be the only clinical sign. Antistreptolysin O (ASO) titers are elevated in a significant proportion of affected individuals. Multiple sclerosis can cause continuous facial myokymia in individuals with lesions impinging on the facial nerve as it courses in the dorsolateral pontine tegmentum. Other features – particularly abnormalities on brain MRI, which are disseminated in space and time – should assist in making the correct diagnosis. Note: The hyperkinetic movements of ADCY5 dyskinesia may be mistakenly thought to be epileptiform; however, normal EEGs, lack of impaired consciousness, and/or lack of response to antiepileptic medication distinguish epilepsy from ADCY5 dyskinesia. ## Management Consensus clinical management recommendations for ADCY5 dyskinesia have not been published. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ADCY5 dyskinesia, 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 ADCY5 Dyskinesia View in own window System/ConcernEvaluationComment Neurologic involvementBy a neurologistAssess: * Neurologic findings incl spasticity, dystonic posturing, sleep-related movements; * Response or lack of response to medications. Oculomotor involvementComplete ophthalmologic examinationAssess best corrected visual acuity; nystagmus, saccades & smooth pursuit; vertical & horizontal gaze limitation; ptosis. MusculoskeletalOrthopedics / physical medicine & rehabilitation / PT/OT evaluationTo incl assessment of: * Gross motor & fine motor skills * Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills) * Mobility, self-help skills, activities of daily living, & need for adaptive devices DD / Cognitive impairmentDevelopmental behavioral pediatrician, neurologist, or geneticistChildren: To incl motor, adaptive, cognitive, & speech/language eval; eval for early intervention / special education Clinical psychologistAdults: Assess for deficits in spatial working & episodic memory DysarthriaSpeech & language assessmentRelated to abnormal tongue & facial movements Psychiatric manifestations * Child psychiatrist * Clinical psychologist Depression, psychosis w/delusions & auditory hallucinations, obsessive-compulsive symptoms, autistic-like behavior Cardiac involvementECG, echocardiogram, cardiology evalDilated cardiomyopathy may be a manifestation. Genetic counselingBy genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of ADCY5 dyskinesia in order to facilitate medical & personal decision-making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support; * Need for home nursing referral. Disease severity may qualify some persons for disability &/or social security benefits. DD = developmental delay; MOI= mode of inheritance 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations Management by multidisciplinary specialists, including a neurologist, or neurogeneticist, cardiologist, physical therapist, social worker, speech and language pathologist, and other specialists is recommended as needed. Medication has been variably effective in suppressing debilitating manifestations. Treatment should be determined by the individual's physician, taking into account potential risk/benefit, other medical conditions, allergies, and potential drug-drug interactions. Response to medication is difficult to evaluate in an individual because some have long periods (weeks) of remission of the dyskinesia [Vijiaratnam et al 2019]. ### Table 5. Treatment of Manifestations in Individuals with ADCY5 Dyskinesia View in own window Manifestation/ ConcernTreatmentConsiderations/Other Chorea & dyskinesiaAcetazolamideUp to 30 mg/kg/day Other potentially beneficial medications * Trihexyphenidyl * Tetrabenazine * Clonazepam * Propranolol * Levocarnitine * Levetirracetam * Methylphenidate Medications that may worsen manifestationsAny of the above Deep brain stimulationImproves movement disorder in some persons refractory to medical treatment 1 Sleep-related movementsClonazepamImproves nocturnal dystonia & axial hypotonia in some Other potentially beneficial medicationsMelatonin DysarthriaSpeech/language evalConsider alternative communication methods as needed (e.g., writing pads & digital devices). Oculomotor involvementPer treating ophthalmologist MusculoskeletalOrthopedics / physical medicine & rehabilitation / PT / OT * To help maintain mobility & function * Walking aids incl canes or walkers when appropriate * Durable medical equipment & positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers) * Home adaptations for safety & function * Consider disability parking placard for care-givers. Developmental delaySee Developmental Delay / Intellectual Disability Management Issues. Cognitive impairment * Developmental eval * Individualized education plan To identify degree of disability & provide resources for learning Psychiatric manifestations * Cognitive behavioral therapy * Medication * Mental health professionals Family support/ resourcesEnsure appropriate social work involvement to: * Connect families w/local resources, respite, & support; * Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies. 1\. Reported in fewer than five individuals with overall beneficial effects [Dy et al 2016, Meijer et al 2017] #### Developmental Disability / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual 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 as well as infant mental health services, special educators, and sensory impairment specialists. 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; for children too medically unstable to attend, home-based services are provided. 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. * 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 6. Recommended Surveillance for Individuals with ADCY5 Dyskinesia View in own window System/ConcernEvaluationFrequency Neurologic involvementAssess for new manifestations incl changes in tone, scoliosis, & movement disorders.Annually DysarthriaSpeech & language eval incl need for alternative communication methodsAt each visit Oculomotor involvementPer treating ophthalmologistAs clinically indicated Musculoskeletal / Activities of daily livingPT/OT evalAt each visit Developmental delayMonitor developmental progress & educational needs. Cognitive impairmentNeuropsychological testing; developmental eval Psychiatric manifestationsAssess for changes in mood, attention, psychosis, or obsessive-compulsive disorder. Cardiac involvementECG, echocardiogram, cardiac MRIAs clinically indicated OT = occupational therapy; PT = physical therapy ### Agents/Circumstances to Avoid The only exacerbating factor that is observed consistently across affected individuals is the presence of anxiety and exposure to typical life stressors. Further investigation is needed to determine whether stress management techniques or limitation of stressful activities may reduce the number and frequency of movements. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Potential teratogenic effects of medications given for treatment of ADCY5 dyskinesia should be discussed with affected women of childbearing age, ideally prior to conception. See MotherToBaby for further information on medication use during pregnancy. ### 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-aminobutyric 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	ADCY5 Dyskinesia	None	27,495	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK263441/	2021-01-18T21:45:33	{"synonyms": []}
Cholesterolosis of gallbladder Micrograph of cholesterolosis of the gallbladder, with an annotated foam cell. H&E stain. SpecialtyGastroenterology In surgical pathology, strawberry gallbladder, more formally cholesterolosis of the gallbladder and gallbladder cholesterolosis, is a change in the gallbladder wall due to excess cholesterol.[1] The name strawberry gallbladder comes from the typically stippled appearance of the mucosal surface on gross examination, which resembles a strawberry. Cholesterolosis results from abnormal deposits of cholesterol esters in macrophages within the lamina propria (foam cells) and in mucosal epithelium. The gallbladder may be affected in a patchy localized form or in a diffuse form. The diffuse form macroscopically appears as a bright red mucosa with yellow mottling (due to lipid), hence the term strawberry gallbladder. It is not tied to cholelithiasis (gallstones) or cholecystitis (inflammation of the gallbladder).[2] ## Contents * 1 Additional images * 2 See also * 3 References * 4 Further reading * 5 External links ## Additional images[edit] * Cholesterolosis of the gallbladder (gross image) * Micrograph of cholesterolosis of the gallbladder * Micrograph of cholesterolosis of the gallbladder * Micrograph of cholesterolosis of the gallbladder ## See also[edit] * Cholecystectomy * Rokitansky-Aschoff sinuses ## References[edit] 1. ^ Strawberry gallbladder \- cancerweb.ncl.ac.uk. 2. ^ "Cholesterolosis of the Gall Bladder". ## Further reading[edit] * Izzo L, Boschetto A, Brachini G, et al. (2001). "["Strawberry" gallbladder: review of the literature and our experience]". Il Giornale di Chirurgia (in Italian). 22 (1–2): 33–6. PMID 11272434. ## External links[edit] Classification D * ICD-10: K82.4 * ICD-9-CM: 575.6 * DiseasesDB: 31524 * 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-aminobutyric 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	Cholesterolosis of gallbladder	c0152456	27,496	wikipedia	https://en.wikipedia.org/wiki/Cholesterolosis_of_gallbladder	2021-01-18T18:34:57	{"umls": ["C0152456"], "icd-10": ["K82.4"], "wikidata": ["Q1075909"]}
A number sign (#) is used with this entry because of evidence that a variant of the CFH gene (134370) influences the development of basal laminar drusen. Clinical Features Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. ('Drusen' is the plural for 'Druse,' German for 'nodule' or 'crystal.') 'Basal laminar drusen' refers to an early adult-onset drusen phenotype that shows a pattern of uniform small (25- to 75-micrometer), slightly raised yellow subretinal nodules randomly scattered in the macula (Boon et al., 2008). The term 'basal laminar drusen' is widely used but may be a misnomer because these deposits do not appear to correspond with nodular or diffuse thickening of the Bruch membrane. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. On fluorescein angiography, a typical 'stars in the sky' appearance may be observed. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss. Deutman and Jansen (1970) described a family in which 8 persons in 5 sibships had confirmed multiple drusen of Bruch membrane. There was no instance of male-to-male transmission but an affected male had 2 daughters who were negative by examination. They observed concordant monozygotic twins and affected boys 12 and 14 years old. They concluded that the family with 'crystalline retinal degeneration' reported by Evans (1950) had this condition. The authors also concluded that Doyne honeycomb choroiditis (126600) is the same condition. Round or oval lesions in almost grape-like clusters are concentrated in the posterior polar region. Pigmentary disturbances with secondary calcifications occur. The macula is almost always involved and may appear edematous or hemorrhagic. Loss of vision occurs during the progressive stages. This is considered a form of fleck retina disease (see 228980). One form of autosomal dominant drusen, malattia leventinese, or Doyne honeycomb degeneration of retina (126600), has been mapped to 2p. There may be other causes of hereditary drusen. Bok (2002) stated that there was widespread agreement among ophthalmologists that numerous large drusen, when present in both eyes, represent a significant risk factor for the evolution of early age-related macular dystrophy (ARMD1; 603075) into more advanced ARMD, with loss of central vision. Biochemical Features To understand the molecular basis of drusen formation, Crabb et al. (2002) developed a method for isolating microgram quantities of drusen and Bruch membrane for proteome analysis. They found oxidative protein modifications in drusen, supporting the hypothesis that oxidative injury contributes to the pathogenesis of ARMD and that these modifications may have a critical role in drusen formation. Molecular Genetics In 30 probands with a diagnosis of basal laminar drusen maculopathy, Boon et al. (2008) found the tyr402-to-his variant of the CFH gene, encoding complement factor H (134370.0008), in 48% of alleles. They found compound heterozygosity in affected members of 5 families for Y402H and another CFH mutation. Boon et al. (2008) concluded that their findings strongly supported a recessive disease model in a subgroup of patients with basal laminar drusen. In these families, individuals develop drusen when they carry a CFH mutation on 1 allele and the Y402H variant on the other. The presence of a CFH mutation in the absence of the Y402H variant, however, might contribute to the development of age-related macular degeneration at a later age. Eyes \- Multiple drusen of Bruch membrane \- Round or oval grape-like lesions of posterior polar retina \- Pigmentary disturbances with secondary calcifications \- Progressive loss of vision Inheritance \- Autosomal dominant \- also a recessive form, fleck retina disease (see 228980) ▲ 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-aminobutyric 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	BASAL LAMINAR DRUSEN	c1832174	27,497	omim	https://www.omim.org/entry/126700	2019-09-22T16:42:14	{"doid": ["0060746"], "mesh": ["C535602"], "omim": ["126700"], "orphanet": ["75376"], "synonyms": ["Alternative titles", "DRUSEN OF BRUCH MEMBRANE", "DRUSEN, CUTICULAR", "DRUSEN, EARLY ADULT-ONSET, GROUPED"]}
A number sign (#) is used with this entry because this form of juvenile hemochromatosis (HFE2B) is caused by homozygous mutation in the HAMP gene (606464) on chromosome 19q13. For a general phenotypic description and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200. Description Juvenile, or type 2, hemochromatosis is an autosomal recessive inborn error of iron metabolism that leads to severe iron loading and organ failure before 30 years of age (summary by Roetto et al., 1999). HFE2B is caused by mutation in the HAMP gene (606464). HFE2 is genetically heterogeneous (see HFE2A, 602390). Clinical Features Papanikolaou et al. (2002) reported a single inbred pedigree with juvenile hemochromatosis that was not linked to 1q. The 2 affected daughters of third-cousin parents had a typical JH phenotype. Molecular Genetics Roetto et al. (2003) studied 2 families with juvenile hemochromatosis not linked to 1q, including the one studied by Papanikolaou et al. (2002). Using microsatellite markers encompassing a region of 2.7 cM on 19q13 in one family, they identified a region of homozygosity in both probands. They then sequenced the coding region of the HAMP gene (606464), exon-intron boundaries, and 5- and 3-prime untranslated regions in this family and a second family (one studied by Camaschella et al. (1997)) and identified 2 mutations (606464.0001, 606464.0002). All affected individuals were less than 30 years at onset of clinical symptoms and had severe iron overload with liver fibrosis or cirrhosis and hypogonadism, meeting the diagnostic criteria for juvenile hereditary hemochromatosis (De Gobbi et al., 2002). One affected individual also had cardiomyopathy. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Heart failure \- Cardiomyopathy ABDOMEN Liver \- Fibrosis \- Cirrhosis \- Hepatomegaly Spleen \- Splenomegaly GENITOURINARY External Genitalia (Male) \- Hypogonadism External Genitalia (Female) \- Hypogonadism SKIN, NAILS, & HAIR Skin \- Hyperpigmentation HEMATOLOGY \- Anemia LABORATORY ABNORMALITIES \- Increased serum iron \- Increased serum ferritin \- Increased transaminases \- Increased or complete (100%) transferrin saturation MISCELLANEOUS \- Onset is usually before 30 years of age MOLECULAR BASIS \- Caused by mutation in the hepcidin antimicrobial peptide gene (HAMP, 606464.0001 ) ▲ 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-aminobutyric 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	HEMOCHROMATOSIS, TYPE 2B	c0268060	27,498	omim	https://www.omim.org/entry/613313	2019-09-22T15:59:04	{"doid": ["0111032"], "mesh": ["C537247"], "omim": ["613313"], "orphanet": ["79230"], "genereviews": ["NBK1170"]}
Takayasu arteritis is a condition that causes inflammation of the main blood vessel that carries blood from the heart to the rest of the body (aorta) and its associated branched blood vessels. As a result of the inflammation, the blood vessel walls become thick and make it difficult for blood to flow. Over time, impaired blood flow causes damage to the heart and various other organs of the body. Although the cause remains unknown, Takayasu arteritis appears to be an autoimmune condition, in which cells that fight infection and disease are wrongly targeted against the body's own tissues. [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-aminobutyric 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	Takayasu arteritis	c0039263	27,499	gard	https://rarediseases.info.nih.gov/diseases/7730/takayasu-arteritis	2021-01-18T17:57:26	{"mesh": ["D013625"], "omim": ["207600"], "orphanet": ["3287"], "synonyms": ["TA", "Young female arteritis", "Takayasu disease", "Pulseless disease", "Aortic arch syndrome"]}

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