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A number sign (#) is used with this entry because of evidence that the forms of dominant intermediate Charcot-Marie-Tooth (CMT) disease and axonal CMT that map to chromosome 19p, here designated CMTDIB and CMT2M, respectively, can be caused by heterozygous mutation in the gene encoding dynamin-2 (DNM2; 602378) on chromosome 19p13. Description Charcot-Marie-Tooth disease is a clinically and genetically heterogeneous disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. ### Classification CMT neuropathy is subdivided into CMT1 (see 118200) and CMT2 (see 118210) types on the basis of electrophysiologic and neuropathologic criteria. CMT1, or hereditary motor and sensory neuropathy type I (HMSN I), is a demyelinating neuropathy, whereas CMT2, or HMSN II, is an axonal neuropathy. Most patients with CMT are classified as having CMT1 or CMT2 by use of a cut-off value of 38 m/s for the motor median nerve conduction velocity (NCV). However, in some families with CMT, patients have motor median NCVs ranging from 25 to 45 m/s. Families of this type were reported by Salisachs (1974) and Davis et al. (1978). Davis et al. (1978) proposed that this form be designated 'intermediate' CMT. Claeys et al. (2009) stated that some CMT families may have an even broader range of NCV than 25 to 45 m/s, with the lowest levels around 25 and the highest levels within the normal range (50+ m/s). They also suggested that the term 'intermediate' should not be used to describe a single NCV value, but rather the CMT subtype at the level of the family (e.g., in families with a range or combinations of NCV values). Berciano et al. (2017) provided a detailed review of the different forms of intermediate CMT, noting that diagnoses may be controversial because of variable classification issues. The authors presented an algorithm for the interpretation of electrophysiologic studies in CMT, and suggested that nerve conduction studies should be conducted on the upper arm (axilla to elbow). They noted that distal axonal degeneration can result in secondary myelination defects, which may cause significantly decreased motor NCV and CMAP values that may be misinterpreted. ### Genetic Heterogeneity of Autosomal Dominant Intermediate CMT In addition to CMTDIB, which is caused by mutation in the DNM2 gene, other forms of dominant intermediate CMT include CMTDIC (608323), caused by mutation in the YARS gene (603623) on chromosome 1p35-p34l; CMTDID (607791), caused by mutation in the MPZ gene (159440) on chromosome 1q22; CMTDIE with focal segmental glomerulosclerosis (CMTDIE; 614455), caused by mutation in the INF2 gene (610982) on chromosome 14q; CMTDIF (615185), caused by mutation in the GNB4 gene (610863) on chromosome 3q26; and CMTDIG (617882), caused by mutation in the NEFL gene (162280) on chromosome 8p21. CMTDIA (606483) has been mapped to chromosome 10q24.1-q25.1. Clinical Features Kennerson et al. (2001) described a form of CMT that they referred to as 'dominant intermediate CMT.' They used the term 'intermediate conduction velocity' to describe CMT families with nerve conduction velocities, in different affected individuals, that overlap the division between CMT1 and CMT2. Kennerson et al. (2001) reported a large Australian family in which affected members had nerve conduction velocities ranging from 24 to 54 m/s. The sural nerve biopsy in this family showed axonal degeneration, loss of large diameter fibers, rare segmental demyelination, and remyelination with onion bulb formation. Claeys et al. (2009) reviewed the phenotypic spectrum of CMT in 37 patients from 6 families with dynamin-2 mutations. Several of the families had previously been reported (see, e.g., Kennerson et al., 2001). The mean age at onset was 16 years (range, 2-50). Patients presented with a classic CMT phenotype of distal lower limb weakness and atrophy resulting in gait abnormalities and frequent falls. Electrophysiologic studies showed intermediate or axonal motor median nerve conduction velocities ranging from 26 m/s to 54 m/s; variations occurred in the same family. Sural nerve biopsy in 1 family showed diffuse loss of myelinated fibers, regenerating axons, and focal myelin thickenings without segmental demyelination. Two families had associated neutropenia, and 1 family developed early-onset cataracts. ### Axonal Charcot-Marie-Tooth Disease 2M Fabrizi et al. (2007) reported 2 unrelated families with CMT due to heterozygous mutations in the DNM2 gene (602378.0008; 602378.0009, respectively). The proband of 1 family had pes cavus, mildly ataxic gait, weakness of foot dorsiflexion, peripheral sensory neuropathy, and mild wasting of the intrinsic hand muscles. Her son had painful paresthesias, pes cavus, clawed toes, wasting of the peroneal muscles, steppage gait with sensory ataxia, and preservation of intrinsic hand muscles. Median nerve conduction velocities were normal, consistent with an axonal form of CMT. Sural nerve biopsy showed loss of large diameter fibers and rare onion bulb formations. Overall, the histology was consistent with an axonal neuropathy without detectable demyelination. Fabrizi et al. (2007) noted that the phenotype in this family was milder than that reported in other families with DNM2 mutations, and emphasized that axonal changes without demyelinating changes can be present. Gallardo et al. (2008) reported a mother and her 2 adult daughters with axonal Charcot-Marie-Tooth disease (CMT2M). The patients were ages 55, 32, and 23, and motor nerve conduction velocities were 33, 46, and 50 m/s, respectively. All had progressive gait unsteadiness and foot deformities, including pes cavus and toe clawing, in the first decade of life. All had distal muscle weakness and atrophy of the lower limbs, and the mother also had hand weakness and atrophy. Ankle reflexes were absent in all 3, and all had hypoesthesia of the lower limbs. MRI studies showed fatty infiltration of the calf muscles, particularly in the anterior compartment. The fatty infiltration increased distally and was massive in the foot musculature. Muscle edema was also present in affected muscles. In a follow-up of the family reported by Gallardo et al. (2008), Claeys et al. (2009) concluded that the phenotype was consistent with axonal CMT. Mapping By genomewide analysis of a large Australian family with dominant intermediate CMT, Kennerson et al. (2001) found strong linkage to the short arm of chromosome 19 (maximum lod score of 4.3 with a recombination fraction of 0.0 at D19S221, and maximum lod score of 5.28 with a recombination fraction of 0.0 at D19S226). Haplotype analysis performed with 14 additional markers placed the CMTDIB locus within a 16.8-cM region flanked by the markers D19S586 and D19S546. Multipoint linkage analysis suggested that the most likely location is at D19S226 (maximum multipoint lod score of 6.77) with a 10-cM confidence interval. The cytogenetic location is 19p13.2-p12. Speer et al. (2002) reduced the minimum candidate interval for CMTDI1 to a 9-cM interval spanned by markers D19S586 and D19S432. Zhu et al. (2003) performed extended haplotype analysis and clinical assessment of additional members of the family described by Kennerson et al. (2001), which together with the report of a second family linked to the CMTDI1 locus (Speer et al., 2002) enabled them to narrow the candidate region for the CMTDI1 gene to a 6-cM interval flanked by D19S558 and D19S432. Selection of positional candidate genes for screening was performed on the basis of neural expression and microarray analysis of Schwann cell differentiation in vivo. Six genes localized in the original linkage interval and 1 in the newly refined region were excluded as the cause of dominant intermediate CMT neuropathy. Molecular Genetics Zuchner et al. (2005) presented evidence that the form of dominant intermediate CMT that maps to 19p13.2-p12 is caused by mutations in the gene encoding dynamin-2 (DNM2; 602378). They refined the locus associated with DI-CMTB to 4.2 Mb and found unique mutations in DNM2 in the American family described by Speer et al. (2002), the Australian family of Kennerson et al. (2001) and Zhu et al. (2003), and in an additional multigenerational Belgian family. In the Australian and Belgian pedigrees, which carried 2 different mutations affecting the same amino acid, lys558 (602378.0002, 602378.0003), CMT cosegregated with neutropenia, which had not previously been associated with CMT neuropathies. In a mother and her 2 daughters with axonal CMT, Gallardo et al. (2008) identified a heterozygous mutation in the DNM2 gene (G358R; 602378.0012). INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes cavus NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Hyporeflexia \- Areflexia \- Distal sensory impairment \- Low to normal range of motor nerve conduction velocity (NCV) (25-54 m/s) ('intermediate' CMT, CMTDIB) \- Individuals with normal NCV values have axonal CMT (CMT2M) \- Loss of myelinated fibers on nerve biopsy \- Rare segmental demyelination/remyelination \- 'Onion' bulb formation \- Axonal degeneration MISCELLANEOUS \- Onset in first or second decade \- Begins in feet and legs (peroneal distribution) \- Features intermediate between demyelinating CMT and axonal CMT \- Some families have axonal CMT (CMT2M) \- Genetic heterogeneity (see CMTDIA, 606483 ) MOLECULAR BASIS \- Caused by mutation in the dynamin-2 gene (DNM2, 602378.0001 ) ▲ 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, DOMINANT INTERMEDIATE B	c1847902	27,300	omim	https://www.omim.org/entry/606482	2019-09-22T16:10:22	{"doid": ["0110197"], "mesh": ["C564703"], "omim": ["606482"], "orphanet": ["228179", "100044"], "synonyms": ["Alternative titles", "CHARCOT-MARIE-TOOTH NEUROPATHY, DOMINANT INTERMEDIATE B", "DI-CMTB", "CMTDI1"], "genereviews": ["NBK1358", "NBK45014"]}
Cystocele Other namesProlapsed bladder, dropped bladder,[1] anterior vaginal wall collapse[2] A cystocele protruding through the vagina in a 73-year-old woman. Pronunciation * /ˈsɪstəsiːl/ SIS-tə-seel SpecialtyUrology, gynecology[3] SymptomsTrouble starting urination, incomplete urination, urinary incontinence, frequent urination[1] ComplicationsUrinary retention [1] TypesGrade 1, 2, 3[1] Risk factorsChildbirth, constipation, chronic cough, heavy lifting, being overweight[1] Diagnostic methodBased on symptoms and examination[1] Differential diagnosisBartholin cyst, nabothian cyst, urethral diverticulum[4] TreatmentLifestyle changes, pelvic muscle exercises, vaginal pessary, surgery[1] Frequency~33% of women > 50 years old[5] A cystocele, also known as a prolapsed bladder, is a medical condition in which a woman's bladder bulges into her vagina.[1][5] Some may have no symptoms.[6] Other may have trouble starting urination, urinary incontinence, or frequent urination.[1] Complications may include recurrent urinary tract infections and urinary retention.[1][7] Cystocele and a prolapsed urethra often occur together and is called a cystourethrocele.[8] Cystocele can negatively affect quality of life.[9][10] Causes include childbirth, constipation, chronic cough, heavy lifting, hysterectomy, genetics, and being overweight.[1][2][6] The underlying mechanism involves weakening of muscles and connective tissue between the bladder and vagina.[1] Diagnosis is often based on symptoms and examination.[1] If the cystocele causes few symptoms, avoiding heavy lifting or straining may be all that is recommended.[1] In those with more significant symptoms a vaginal pessary, pelvic muscle exercises, or surgery may be recommended.[1] The type of surgery typically done is known as a colporrhaphy.[11] The condition becomes more common with age.[1] About a third of women over the age of 50 are affected to some degree.[5] ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Cause * 2.1 Risk factors * 3 Diagnosis * 3.1 Grading * 3.2 Classifications * 4 Prevention * 5 Treatment * 5.1 Non-surgical * 5.2 Surgery * 6 Epidemiology * 7 History * 8 See also * 9 References * 10 Further reading * 11 External links ## Signs and symptoms[edit] The symptoms of a cystocele may include: * a vaginal bulge * the feeling that something is falling out of the vagina * the sensation of pelvic heaviness or fullness[1][12] * difficulty starting a urine stream * a feeling of incomplete urination * frequent or urgent urination[12][1] * fecal incontinence[13] * frequent urinary tract infections[7][12] * back and pelvic pain * fatigue * painful sexual intercourse[12] * bleeding[14] A bladder that has dropped from its normal position and into the vagina can cause some forms of incontinence and incomplete emptying of the bladder.[1] ### Complications[edit] Complications may include urinary retention, recurring urinary tract infections and incontinence.[1][7] The anterior vaginal wall may actually protrude though the vaginal introitus (opening). This can interfere with sexual activity.[6] Recurrent urinary tract infections are common for those who have urinary retention.[15] In addition, though cystocele can be treated, some treatments may not alleviate troubling symptoms, and further treatment may need to be performed. Cystocele may affect the quality of life, women who have cystocele tend to avoid leaving their home and avoid social situations. The resulting incontinence puts women at risk of being placed in a nursing home or long term care facility.[medical citation needed] ## Cause[edit] A cystocele occurs when the muscles, fascia, tendons and connective tissues between a woman's bladder and vagina weaken, or detach.[2][16] The type of cystocele that can develop can be due to one, two or three vaginal wall attachment failures: the midline defect, the paravaginal defect, and the transverse defect. The midline defect is a cystocele caused by the overstretching of the vaginal wall; the paravaginal defect is the separation of the vaginal connective tissue at the arcus tendineus fascia pelvis; the transverse defect is when the pubocervical fascia becomes detached from the top (apex) of the vagina.[2] There is some pelvic prolapse in 40–60% of women who have given birth.[17][18] Muscle injuries have been identified in women with cystocele. These injuries are more likely to occur in women who have given birth than those who have not. These muscular injuries result in less support to the anterior vaginal wall.[19] Some women with connective tissue disorders are predisposed to developing anterior vaginal wall collapse. Up to one third of women with Marfan syndrome have a history of vaginal wall collapse. Ehlers-Danlos syndrome in women is associated with a rate of 3 out of 4.[6] ### Risk factors[edit] Risk factors for developing a cystocele are: * an occupation involving or history of heavy lifting * pregnancy and childbirth * chronic lung disease/smoking * family history of cystocele[20][21] * exercising incorrectly[15] * ethnicity (risk is greater for Hispanic and whites)[22] * hypoestrogenism * pelvic floor trauma * connective tissue disorders * spina bifida[6] * hysterectomy[23] * cancer treatment of pelvic organs[24] * childbirth; correlates to the number of births * forceps delivery * age * chronically high intra-abdominal pressures * chronic obstructive pulmonary disease * constipation[12] * obesity[6] Connective tissue disorders predispose women to developing cystocele and other pelvic organ prolapse. The tissues tensile strength of the vaginal wall decreases when the structure of the collagen fibers change and become weaker.[6] ## Diagnosis[edit] There are two types of cystocele. The first is distension. This is thought to be due to the overstretching of the vaginal wall and is most often associated with aging, menopause and vaginal delivery. It can be observed when the rugae are less visible or even absent. The second type is displacement. Displacement is the detachment or abnormal elongation of supportive tissue.[25] The initial assessment of cystocele can include a pelvic exam to evaluate leakage of urine when the women is asked to bear down or give a strong cough (Valsalva maneuver), and the anterior vaginal wall measured and evaluated for the appearance of a cystocele.[26][27] If a woman has difficulty emptying her bladder, the clinician may measure the amount of urine left in the woman's bladder after she urinates called the postvoid residual. This is measured by ultrasound. A voiding cystourethrogram is a test that involves taking x-rays of the bladder during urination. This x-ray shows the shape of the bladder and lets the doctor see any problems that might block the normal flow of urine.[1] A urine culture and sensitivity test will assess the presence of a urinary tract infection that may be related to urinary retention.[12] Other tests may be needed to find or rule out problems in other parts of the urinary system.[1] Differential diagnosis will be improved by identifying possible inflammation of the Skene's glands and Bartholin glands.[28] ### Grading[edit] A number of scales exist to grade the severity of a cystocele. The pelvic organ prolapse quantification (POP-Q) assessment, developed in 1996, quantifies the descent of the cystocele into the vagina.[6][13] The POP-Q provides reliable description of the support of the anterior, posterior and apical vaginal wall. It uses objective and precise measurements to the reference point, the hymen. Cystocele and prolapse of the vagina from other causes is staged using POP-Q criteria can range from good support (no descent into the vagina) reported as a POP-Q stage 0 or I to a POP-Q score of IV which includes prolapse beyond the hymen. It also used to quantifies the movement of other structures into the vaginal lumen and their descent.[6][13] The Baden–Walker Halfway Scoring System is used as the second most used system and assigns the classifications as mild (grade 1) when the bladder droops only a short way into the vagina; (grade 2) cystocele, the bladder sinks far enough to reach the opening of the vagina; and (grade 3) when the bladder bulges out through the opening of the vagina.[1][29] ### Classifications[edit] Cystocele can be further described as being apical, medial, lateral, or mediolateral. Apical cystocele is located upper third of the vagina. The structures involved are the endopelvic fascia and ligaments. The cardinal ligaments and the uterosacral ligaments suspend the upper vaginal-dome. The cystocele in this region of the vagina is thought to be due to a cardinal ligament defect.[16][25] Medial cystocele forms in the mid-vagina and is related to a defect in the suspension provided by to a sagittal suspension system defect in the uterosacral ligaments and pubocervical fascia. The pubocervical fascia may thin or tear and create the cystocele. An aid in diagnosis is the creation of a 'shiny' spot on the epithelium of the vagina. This defect can be assessed by MRI.[16][25] Lateral cystocele forms when both the pelviperineal muscle and its ligamentous–fascial develop a defect. The ligamentous– fascial creates a 'hammock-like' suspension and support for the lateral sides of the vagina. Defects in this lateral support system results in a lack of bladder support. Cystocele that develops laterally is associated with an anatomic imbalance between anterior vaginal wall and the arcus tendineus fasciae pelvis – the essential ligament structure.[16][25] ## Prevention[edit] Cystocele may be mild enough not to result in symptoms that are troubling to a woman. In this case, steps to prevent it from worsening include: * smoking cessation * losing weight * pelvic floor strengthening * treatment of a chronic cough * maintaining healthy bowel habits * eating high fiber foods * avoiding constipation and straining[22][6] ## Treatment[edit] Treatment options range from no treatment for a mild cystocele to surgery for a more extensive cystocele.[1] If a cystocele is not bothersome, the clinician may only recommend avoiding heavy lifting or straining that could cause the cystocele to worsen. If symptoms are moderately bothersome, the doctor may recommend a pessary, a device placed in the vagina to hold the bladder in place and to block protrusion.[12][23] Treatment can consist of a combination of non-surgical and surgical management. Treatment choice is also related to age, desire to have children, severity of impairment, desire to continue sexual intercourse and other diseases that a woman may have.[6] ### Non-surgical[edit] Cystocele is often treated by non-surgical means: * Pessary – This is a removable device inserted into the vagina to support the anterior vaginal wall. Pessaries come in many different shapes and sizes. There are sometimes complications with the use of a pessary.[6] * Pelvic floor muscle therapy – Pelvic floor exercises to strengthen vaginal support can be of benefit. Specialized physical therapy can be prescribed to help strengthen the pelvic floor muscles.[1][12] * Dietary changes – Ingesting high fiber foods will aid in promoting bowel movements.[1] * Estrogen – intravaginal administration helps to prevent pelvic muscle atrophy[12] ### Surgery[edit] The surgery to repair the anterior vaginal wall may be combined with other procedures that will repair the other points of pelvic organ support such as anterior-posterior repair and anterior colporrhaphy.[12] Treatment of cystocele often accompanies the more invasive hysterectomy.[30] Since the failure rate in cystocele repair remains high, additional surgery may be needed.[13] Women who have surgery to repair a cystocele have a 17% of needing another operation within the next ten years.[31] The surgical treatment of cystocele will depend on the cause of the defect and whether it occurs at the top (apex), middle, or lower part of the anterior vaginal wall. The type of surgery will also depend on the type of damage that exists between supporting structures and the vaginal wall.[2] One of the most common surgical repairs is colporrhaphy.[30] This surgical procedure consists of making a longitudinal folding of the vaginal tissue, suturing it into place and creating a stronger point of resistance to the intruding bladder wall. Surgical mesh is sometimes used to strengthen the anterior vaginal wall.[6] It has a 10–50% failure rate.[32][30] In some cases a surgeon may choose to use surgical mesh to strengthen the repair.[30] During surgery, the repair of the vaginal wall consists of folding over and then suturing the existing tissue between the vagina and bladder to strengthen it.[1][11] This tightens the layers of tissue to promote the replacement of the pelvic organs into their normal place. The surgery also provides more support for the bladder. This surgery is done by a surgeon specializing in gynecology and is performed in a hospital. Anesthesia varies according to the needs of each woman. Recovery may take four to six weeks.[1] Other surgical treatment may be performed to treat cystocele. Support for the vaginal wall is accomplished with the paravaginal defect repair. This is a surgery, usually laproscopic, that is done to the ligaments and fascia through the abdomen. The lateral ligaments and supportive structures are repaired, sometimes shortened to provide additional support to the vaginal wall.[30] Sacrocolpopexy is a procedure that stabilizes the vaginal vault (the uppermost portion of the vagina) and is often chosen as the treatment for cystocele, especially if previous surgeries were not successful. The procedure consists of attaching the vaginal vault to the sacrum. It has a success rate of 90%.[30] Some women choose not to have surgery to close the vagina. This surgery, called colpocleisis, treats cystocele by closing the vaginal opening. This can be an option for women who no longer want to have vaginal intercourse.[22] If an enterocele/sigmoidocele, or prolapse of the rectum/colon, is also present, the surgical treatment will take this concurrent condition into account while planning and performing the repairs.[2] Estrogen that is administered vaginally before surgical repair can strengthen the vaginal tissue providing a more successful outcome when mesh or sutures are used for the repair. Vaginal thickness increases after estrogen therapy.[31] Another review on the surgical management of cystocele describes a more successful treatment that more strongly attaches the ligaments and fascia to the vagina to lift and stabilize it.[33] Post surgical complications can develop. The complications following surgical treatment of cystocele are: * side effects or reactions to anesthesia * bleeding * infection * painful intercourse * Urinary incontinence * constipation[32] * bladder injuries * urethral injuries * urinary tract infection.[30][7] * vaginal erosion due to mesh[12] After surgery, a woman is instructed to restrict her activities and monitor herself for signs of infection such as an elevated temperature, discharge with a foul odor and consistent pain. Clinicians may recommend that sneezing, coughing, and constipation are to be avoided. Splinting the abdomen while coughing provides support to an incised area and decreases pain on coughing.[12] This is accomplished by applying gentle pressure to the surgical site for bracing during a cough.[34][35] Recurrent surgery on the pelvic organs may not be due to a failure of the surgery to correct the cystocele. Subsequent surgeries can be directly or indirectly relating to the primary surgery.[13] Prolapse can occur at a different site in the vagina. Further surgery after the initial repair can be to treat complications of mesh displacement, pain, or bleeding. Further surgery may be needed to treat incontinence.[13] One goal of surgical treatment is to restore the vagina and other pelvic organs to their anatomically normal positions. This may not be the outcome that is most important to the woman being treated who may only want relief of symptoms and an improvement in her quality of life. The International Urogynecological Association (IUGA) has recommended that the data collected regarding the success of cystocele and pelvic organ repairs include the presence or absence of symptoms, satisfaction and Quality of Life. Other measures of a successful outcome should include perioperative data, such as operative time and hospital stay. Standardized Healthcare Quality of Life should be part of the measure of a successful resolution of cystocele. Data regarding short- and long-term complications is included in the recommendations of the IUGA to better assess the risk–benefit ratio of each procedure.[13] Current investigations into the superiority of using biological grafting versus native tissue or surgical mesh indicates that using grafts provides better results.[36] ## Epidemiology[edit] A large study found a rate of 29% over the lifetime of a woman. Other studies indicate a recurrence rate as low as 3%.[13] In the US, greater than 200,000 surgeries are performed each year for pelvic organ prolapse and 81% of these are to correct cystocele.[14][11] Cystocele occurs most frequently compared to the prolapse of other pelvic organs and structure.[13][14] Cystocele is found to be three times as common as vaginal vault prolapse and twice as often as posterior vaginal wall defects. The incidence of cystocele is around 9 per 100 women-years. The highest incidence of symptoms occurs between ages of 70 and 79 years. Based on population growth statistics, the number of women with prolapse will increase by a minimum of 46% by the year 2050 in the US. Surgery to correct prolapse after hysterectomy is 3.6 per 1,000 women-years.[13] ## History[edit] The ancient Greek method for treating cystocele Notable is the mention of cystocele in many older cultures and locations.[37] In 1500 B.C. Egyptians wrote about the “falling of the womb”. In 400 B.C. a Greek physician documented his observations and treatments: "After the patient had been tied to a ladder-like frame, she was tipped upward so that her head was toward the bottom of the frame. The frame was then moved upward and downward more or less rapidly for approximately 3–5 min. As the patient was in an inverted position, it was thought that the prolapsing organs of the genital tract would be returned to their normal position by the force of gravity and the shaking motion."[37] Hippocrates had his own theories regarding the cause of prolapse. He thought that recent childbirth, wet feet, 'sexual excesses', exertion, and fatigue may have contributed to the condition. Polybus, Hippocrates's son-in-law, wrote: "a prolapsed uterus was treated by using local astringent lotions, a natural sponge packed into the vagina, or placement of half a pomegranate in the vagina." In 350 A.D., another practitioner named Soranus described his treatments which stated that the pomegranate should be dipped into vinegar before insertion. Success could be enhanced if the woman was on bed rest and reduced intake of fluid and food. If the treatment was still not successful, the woman's legs were tied together for three days.[37] In 1521, Berengario da Carpi performed the first surgical treatment for prolapse. This was to tie a rope around the prolapse, tighten it for two days until it was no longer viable and cut it off. Wine, aloe, and honey were then applied to the stump.[37] In the 1700s, a Swiss gynecologist, Peyer, published a description of a cystocele. He was able to describe and document both cystocele and uterine prolapse. In 1730, Halder associated cystocele with childbirth. During this same time, efforts began to standardize the terminology that is still familiar today. In the 1800s, the surgical advancements of anesthesia, suturing, suturing materials and acceptance of Joseph Lister's theories of antisepsis improved outcomes for women with cystocele. The first surgical techniques were practiced on female cadavers. In 1823, Geradin proposed that an incision and resection may provide treatment. In 1830, the first dissection of the vagina was performed by Dieffenbach on a living woman. In 1834, Mendé proposed that dissecting and repair of the edges of the tissues could be done. In 1859, Huguier proposed the amputation of the cervix was going to solve the problem for elongation.[37] In 1866, a method of correcting a cystocele was proposed that resembled current procedures. Sim subsequently developed another procedure that did not require the full-thickness dissection of the vaginal wall. In 1888, another method of treating anterior vaginal wall Manchester combined an anterior vaginal wall repair with an amputation of the cervix and a perineorrhaphy. In 1909, White noted the high rate of recurrence of cystocele repair. At this time it was proposed that reattaching the vagina to support structures was more successful and resulted in less recurrence. This same proposal was proposed again in 1976 but further studies indicated that the recurrence rate was not better.[37] In 1888, treatments were tried that entered the abdomen to make reattachments. Some did not agree with this and suggested an approach through the inguinal canal. In 1898, further abdominal approaches were proposed. No further advances have been noted until 1961 when reattachment of the anterior vaginal wall to Cooper's ligament began to be used. Unfortunately, posterior vaginal wall prolapse occurred in some patients even though the anterior repair was successful.[37] In 1955, using mesh to support pelvic structures came into use. In 1970, tissue from pigs began to be used to strengthen the anterior vaginal wall in surgery. Beginning in 1976, improvement in suturing began along with the surgical removal of the vagina being used to treat prolapse of the bladder. In 1991, assumptions about the detailed anatomy of the pelvic support structures began to be questioned regarding the existence of some pelvic structures and the non-existence of others. More recently, the use of stem cells, robot-assisted laparoscopic surgery are being used to treat cystocele.[37] ## See also[edit] * Hysterectomy * Fecal incontinence * Sigmoidocele * Urethropexy ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab "Cystocele (Prolapsed Bladder)". National Institute of Diabetes and Digestive and Kidney Diseases. March 2014. Archived from the original on 4 October 2017. Retrieved 25 October 2017. 2. ^ a b c d e f Baggish, Michael S.; Karram, Mickey M. (2016). Atlas of pelvic anatomy and gynecologic surgery (4th ed.). Philadelphia, PA: Elsevier. pp. 599–646. ISBN 9780323225526. OCLC 929893382. 3. ^ Liedl, Bernhard; Inoue, Hiromi; Sekiguchi, Yuki; Gold, Darren; Wagenlehner, Florian; Haverfield, Max; Petros, Peter (February 2017). "Update of the Integral Theory and System for Management of Pelvic Floor Dysfunction in Females". European Urology Supplements. 17 (3): 100–108. doi:10.1016/j.eursup.2017.01.001. 4. ^ Federle, Michael P.; Tublin, Mitchell E.; Raman, Siva P. (2016). ExpertDDx: Abdomen and Pelvis E-Book. Elsevier Health Sciences. p. 626. ISBN 9780323443128. Archived from the original on 2017-10-25. 5. ^ a b c Firoozi, Farzeen (2014). Female Pelvic Surgery. Springer. p. 73. ISBN 9781493915040. Archived from the original on 2017-10-25. 6. ^ a b c d e f g h i j k l m Williams, J. Whitridge (2012). Hoffman, Barbara L. (ed.). Williams gynecology (2nd ed.). New York: McGraw-Hill Medical. pp. 647–653. ISBN 9780071716727. OCLC 779244257. 7. ^ a b c d Hamid, Rizwan; Losco, Giovanni (2014-09-01). "Pelvic Organ Prolapse-Associated Cystitis". Current Bladder Dysfunction Reports. 9 (3): 175–180. doi:10.1007/s11884-014-0249-4. ISSN 1931-7212. PMC 4137160. PMID 25170365. 8. ^ "Cystoceles, Urethroceles, Enteroceles, and Rectoceles – Gynecology and Obstetrics – Merck Manuals Professional Edition". Merck Manuals Professional Edition. February 2017. Retrieved 2017-12-18. 9. ^ "Cystocele (Fallen Bladder)". www.clevelandclinic.org. Archived from the original on 2017-12-29. Retrieved 2017-12-28. 10. ^ Deng, Donna Y.; Rutman, Matthew; Rodriguez, Larissa; Raz, Shlomo (2005-09-01). "Correction of cystocele". BJU International. 96 (4): 691–709. doi:10.1111/j.1464-410x.2005.05760.x. ISSN 1464-410X. PMID 16104940. S2CID 32430707. 11. ^ a b c Halpern-Elenskaia, Ksenia; Umek, Wolfgang; Bodner-Adler, Barbara; Hanzal, Engelbert (2017-12-06). "Anterior colporrhaphy: a standard operation? Systematic review of the technical aspects of a common procedure in randomized controlled trials". International Urogynecology Journal. 29 (6): 781–788. doi:10.1007/s00192-017-3510-5. ISSN 0937-3462. PMC 5948274. PMID 29214325. 12. ^ a b c d e f g h i j k l Henry, Norma Jean E (2016). RN adult medical surgical nursing review module (10th ed.). Sitwell, KS: Assessment Technologies Institute. pp. 417–419. ISBN 9781565335653. OCLC 957778184. 13. ^ a b c d e f g h i j Barber, Matthew D.; Maher, Christopher (2013-11-01). "Epidemiology and outcome assessment of pelvic organ prolapse". International Urogynecology Journal. 24 (11): 1783–1790. doi:10.1007/s00192-013-2169-9. ISSN 0937-3462. PMID 24142054. S2CID 9305151. 14. ^ a b c "Cystocele Repair: Overview, Technique, Periprocedural Care". 2017-06-27. Archived from the original on 2018-01-05. Retrieved 2018-01-05. Cite journal requires `\|journal=` (help) 15. ^ a b Services, Department of Health & Human (April 2017). "Bladder prolapse". Victoria State Government. Archived from the original on 2018-05-07. Retrieved 2017-12-17. 16. ^ a b c d Lamblin, Géry; Delorme, Emmanuel; Cosson, Michel; Rubod, Chrystèle (2016-09-01). "Cystocele and functional anatomy of the pelvic floor: review and update of the various theories". International Urogynecology Journal. 27 (9): 1297–1305. doi:10.1007/s00192-015-2832-4. ISSN 0937-3462. PMID 26337427. S2CID 20854954. 17. ^ Robinson, Dudley; Thiagamoorthy, Gans; Cardozo, Linda (January 2018). "Review: Post-hysterectomy vaginal vault prolapse". Maturitas. 107: 39–43. doi:10.1016/j.maturitas.2017.07.011. PMID 29169578. 18. ^ "Genital prolapse fact sheet \| Women's Health Queensland Wide". womhealth.org.au. April 2011. Archived from the original on 2017-12-22. Retrieved 2017-12-17. 19. ^ Hoyte, Lennox P. John; Damaser, Margot (2016). Biomechanics of the female pelvic floor. London, UK: Elsevier Science. pp. 25–42. ISBN 9780128032282. OCLC 942975504. 20. ^ Lince SL, van Kempen LC, Vierhout ME, Kluivers KB (October 2012). "A systematic review of clinical studies on hereditary factors in pelvic organ prolapse". Int Urogynecol J. 23 (10): 1327–36. doi:10.1007/s00192-012-1704-4. PMC 3448053. PMID 22422218. 21. ^ Friedman T, Eslick GD, Dietz HP (January 2018). "Risk factors for prolapse recurrence: systematic review and meta-analysis". Int Urogynecol J. 29 (1): 13–21. doi:10.1007/s00192-017-3475-4. PMID 28921033. S2CID 195227569. 22. ^ a b c "Pelvic organ prolapse \| womenshealth.gov". womenshealth.gov. November 28, 2017. Archived from the original on May 7, 2019. Retrieved 2017-12-17. This article incorporates text from this source, which is in the public domain. 23. ^ a b "Cystocele". The Mayo Clinic. Retrieved 20 December 2017. 24. ^ Ramaseshan, Aparna S.; Felton, Jessica; Roque, Dana; Rao, Gautam; Shipper, Andrea G.; Sanses, Tatiana V. D. (2017-09-19). "Pelvic floor disorders in women with gynecologic malignancies: a systematic review". International Urogynecology Journal. 29 (4): 459–476. doi:10.1007/s00192-017-3467-4. ISSN 0937-3462. PMC 7329191. PMID 28929201. 25. ^ a b c d Walters, Mark D; Karram, Mickey M (2014). Urogynecology and Reconstructive Pelvic Surgery. Saunders. pp. 326–341. ISBN 978-0323113779. 26. ^ Zilinskas, Gwendolyn Brooke (January 2018). "Female Urinary Incontinence". Physician Assistant Clinics. 3 (1): 69–82. doi:10.1016/j.cpha.2017.08.010. 27. ^ "Anterior Colporrhaphy \| GLOWM". www.glowm.com. Archived from the original on 2017-12-28. Retrieved 2017-12-27. 28. ^ "Cystoceles, Urethroceles, Enteroceles, and Rectoceles - Gynecology and Obstetrics - Merck Manuals Professional Edition". Merck Manuals Professional Edition. Retrieved 2018-02-06. 29. ^ Persu, C; Chapple, CR; Cauni, V; Gutue, S; Geavlete, P (2011-02-15). "Pelvic Organ Prolapse Quantification System (POP–Q) – a new era in pelvic prolapse staging". Journal of Medicine and Life. 4 (1): 75–81. ISSN 1844-122X. PMC 3056425. PMID 21505577. 30. ^ a b c d e f g Williams, J. Whitridge (2012). Hoffman, Barbara L. (ed.). Williams gynecology (2nd ed.). New York: McGraw-Hill Medical. pp. 1214–1225. ISBN 9780071716727. OCLC 779244257. 31. ^ a b Rahn, David D.; Ward, Renée M.; Sanses, Tatiana V.; Carberry, Cassandra; Mamik, Mamta M.; Meriwether, Kate V.; Olivera, Cedric K.; Abed, Husam; Balk, Ethan M. (2015-01-01). "Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines". International Urogynecology Journal. 26 (1): 3–13. doi:10.1007/s00192-014-2554-z. ISSN 0937-3462. PMID 25392183. S2CID 36574083. 32. ^ a b "Colporrhaphy \| Treatment for Prolapse \| CU Urogynecology \| Denver". University of Colorado Urogynecology. Retrieved 2017-12-23. 33. ^ Liedl, Bernhard; Inoue, Hiromi; Sekiguchi, Yuki; Gold, Darren; Wagenlehner, Florian; Haverfield, Max; Petros, Peter (2018). "Update of the Integral Theory and System for Management of Pelvic Floor Dysfunction in Females". European Urology Supplements. 17 (3): 100–108. doi:10.1016/j.eursup.2017.01.001. 34. ^ "Craven & Hirnle's Nursing Procedures and Fundamentals Online". Wolters-Kluver. Retrieved 2018-01-05. 35. ^ Malone, Daniel Joseph; Lindsay, Kathy Lee Bishop (2006). Physical Therapy in Acute Care: A Clinician's Guide. SLACK Incorporated. ISBN 9781556425349. 36. ^ Maher, Christopher; Feiner, Benjamin; Baessler, Kaven; Christmann-Schmid, Corina; Haya, Nir; Brown, Julie (2016-11-30). "Surgery for women with anterior compartment prolapse". Cochrane Database of Systematic Reviews. 11: CD004014. doi:10.1002/14651858.cd004014.pub6. PMC 6464975. PMID 27901278. 37. ^ a b c d e f g h Lensen, E. J. M.; Withagen, M. I. J.; Kluivers, K. B.; Milani, A. L.; Vierhout, M. E. (2013-10-01). "Surgical treatment of pelvic organ prolapse: a historical review with emphasis on the anterior compartment". International Urogynecology Journal. 24 (10): 1593–1602. doi:10.1007/s00192-013-2074-2. ISSN 0937-3462. PMID 23494056. S2CID 11650722. ## Further reading[edit] * Using splinting to support and diminish pain while coughing, Craven and Hirnle's Fundamentals of Nursing: Human Health and Function, 6th edition ## External links[edit] * Cystocele, Pelvic Organ Prolapse Classification D * ICD-10: N81.1 * ICD-9-CM: 618.01-618.02 * MeSH: D052858 * DiseasesDB: 3391 * SNOMED CT: 40421008 * 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]: 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	Cystocele	c0010695	27,301	wikipedia	https://en.wikipedia.org/wiki/Cystocele	2021-01-18T19:04:30	{"mesh": ["D052858"], "icd-9": ["618.02", "618.01"], "icd-10": ["N81.1"], "wikidata": ["Q246085"]}
Malignant triton tumor (MTT) is a rare aggressive subtype of malignant peripheral nerve sheath tumor (MPNST; see this term) characterized histopathologically by focal rhabdomyoblastic differentiation. ## Epidemiology Incidence of malignant triton tumors is not known. MTT accounts for about 5% of all MPNSTs. There appears to be an equal sex distribution. ## Clinical description Most cases are reported in adults (mean age of about 30 years) but patients of all ages have been described. It is estimated that between 40% and 70% of cases occur in patients with neurofibromatosis type 1 (see this term), with an earlier age of onset and predominantly in male subjects. The remaining cases are sporadic and occur at a later age. MTT generally arises from a peripheral nerve in the head, neck, extremities or trunk. Rare localizations include the brain, buttock, viscera, mediastinum and retroperitoneum. Exceedingly rare intracranial MTT, not associated with a cranial nerve, has been reported. MTT is defined histologically as a malignant peripheral nerve sheath tumor with additional rhabdomyoblastic differentiation. Prognosis is generally very poor since MTT is aggressive, with a poorer prognosis than classical MPNST, and is often difficult to completely resect. Local recurrence and distant metastases are common. 5-year survival for MTT is reported to be about 10-14%. ## Etiology The pathogenesis of MTTs has not been elucidated. [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 triton tumor	c0334616	27,302	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=252212	2021-01-23T18:13:53	{"umls": ["C0334616"], "synonyms": ["MPNST with rhabdomyosarcomatous differentiation", "MTT", "Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differenciation"]}
Jackson-Weiss syndrome (JWS) is a genetic disorder characterized by specific malformations of the head and facial area and abnormalities of the feet. The range and severity of symptoms and findings may be extremely variable, and findings may include craniosynostosis; unusually flat, underdeveloped midfacial regions (midfacial hypoplasia); abnormally broad great toes; and/or malformation or fusion of certain bones within the feet. It is caused by mutations in the FGFR2 gene and is inherited in an autosomal dominant manner; in some cases, it is not inherited but results from a new mutation that occurs randomly. The treatment of JWS is typically directed toward the specific symptoms that are apparent in each individual. [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	Jackson-Weiss syndrome	c0795998	27,303	gard	https://rarediseases.info.nih.gov/diseases/6796/jackson-weiss-syndrome	2021-01-18T17:59:42	{"mesh": ["C537559"], "omim": ["123150"], "umls": ["C0795998"], "orphanet": ["1540"], "synonyms": ["JWS", "Craniosynostosis, midfacial hypoplasia, and foot abnormalities"]}
Greenberg dysplasia is a very rare lethal skeletal dysplasia characterized by fetal hydrops, short limbs and abnormal chondro-osseous calcification. The disease is characterized by early in utero lethality and affected fetuses are considered as nonviable. ## Epidemiology Less than ten cases have been published so far. ## Clinical description The main features include fetal hydrops, severe short-limbed dwarfism and a marked disorganization of chondro-osseous calcification. Unusual facial features, cystic hygroma, incomplete lung lobation, pulmonary hypoplasia, extramedullary hematopoiesis, intestinal malrotation and polydactyly may occur. ## Etiology The causative gene has been recently identified as that encoding the lamin B receptor (LBR gene), a member of the sterol reductase family. Mutations in LBR have also been reported to cause Pelger-Huët anomaly (PHA), but in this case transmission occurs in an autosomal dominant manner. PHA is characterized by hypolobulated granulocyte nuclei and abnormal chromatin structure in granulocytes. It has been suggested that homozygous LBR mutations result in distinct mild (PHA homozygosity) or severe (Greenberg skeletal dysplasia) phenotypes based on allelic heterogeneity. ## Diagnostic methods Radiologic abnormalities include a distinctive 'moth-eaten'' appearance of the long bones, marked platyspondyly with multiple abnormal ossification centers, ectopic ossification of the ribs, sternum, pelvis and epiphysis, and deficient ossification of the skull. Histological characterization shows marked disorganization of the cartilaginous architecture, with absence of cartilage column formation, nodular calcifications in cartilage and islands of cartilage surrounded by bone. Greenberg dysplasia has been shown to be associated with an abnormality of cholesterol biosynthesis. ## Differential diagnosis Greenberg dysplasia should be considered in differential diagnosis of cases with severe fetal hydrops (see this term) and phokomelia on antenatal sonography. ## Antenatal diagnosis Prenatal ultrasound diagnosis at 20 weeks of gestation will usually reveal the polyhydramnios, hydrops fetalis, severely short limbs, and cystic hygroma. Sterol profile analysis may be a useful diagnostic tool and can be used for prenatal diagnosis, as can molecular analysis if the mutation in the family is known. ## Genetic counseling It is inherited as an autosomal recessive trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Greenberg dysplasia	c2931048	27,304	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1426	2021-01-23T18:19:06	{"gard": ["8754"], "mesh": ["C537299", "C535858"], "omim": ["215140"], "umls": ["C1300226", "C2931048"], "icd-10": ["Q77.3"], "synonyms": ["HEM dysplasia", "Hydrops-ectopic calcification-motheaten syndrome", "Skeletal dysplasia, Greenberg type"]}
A number sign (#) is used with this entry because Schneckenbecken dysplasia (SHNKND) is caused by homozygous or compound heterozygous mutation in the SLC35D1 gene (610804) on chromosome 1p31. Description Schneckenbecken dysplasia is a perinatally lethal skeletal dysplasia. The German term 'Schneckenbecken' refers to the distinctive, snail-like appearance of the ilia that results from a medial bone projection from the inner iliac margin. Other hallmarks of the disorder include thoracic hypoplasia, severe flattening of the vertebral bodies, and short, thick long bones (summary by Hiraoka et al., 2007). Clinical Features In an Asian family, Knowles et al. (1986) reported a first-cousin marriage that resulted in 13 pregnancies; 4 of the offspring (2 male; 2 female) were normal and 5 were stillborn, short-limbed dwarfs; 3 pregnancies resulted in miscarriage and 1 was terminated for dwarfism detected prenatally. The radiology and histology were unique. The family was reported as probable achondrogenesis (see 200600) by Laxova et al. (1973). The vertebral bodies were hypoplastic with relatively well-preserved posterior arches. Knowles et al. (1986) commented that 'superiorly oriented orbits lend the facial roentgenograms a Mephistophilian appearance.' The authors suggested that achondrogenesis type I (see 200600) has severe shortness and bowing of limb bones with marked spur formation at the expanded metaphyseal ends and virtually unossified vertebral bodies and sacrum. Differences from achondrogenesis type II (200610) and thanatophoric dysplasia (187600) were also noted. The multiple affected sibs reported by Chemke et al. (1971) and Graff et al. (1972) as thanatophoric dysplasia were thought by Knowles et al. (1986) to have this disorder. Borochowitz et al. (1986) described the same form of neonatal lethal chondrodysplasia under the label of Schneckenbecken dysplasia, from the German for snail-pelvis, because of the radiographic configuration of the hypoplastic iliac bones. Other radiographic features were short, broad long-bones with dumbbell-like appearance, flat and hypoplastic vertebral bodies, short and wide fibula, and precocious ossification of the tarsus. Chondroosseous histology was characterized by hypervascularity, increased cellular density, and normal-sized chondrocytes with a centrally located round nucleus and absence of lacunar space. With a total of 9 cases in 4 families, autosomal recessive inheritance as well as the distinctness of the disorder seems firmly established. Camera et al. (1991) described the clinical and radiologic features of a case occurring in an Italian family. Nikkels et al. (2001) described a male fetus, with consanguineous Mediterranean parents, who presented with severe hydrops and short-limb skeletal dysplasia at 20 weeks' gestation. The pregnancy was terminated at 22 weeks. Radiographs showed typical findings of Schneckenbecken dysplasia, including platyspondyly with oval-shaped vertebral bodies, extremely short long bones with dumbbell-like appearance, and small ilia with snail-like appearance. Inheritance The transmission pattern of Schneckenbecken dysplasia in the families reported by Borochowitz et al. (1986) was consistent with autosomal recessive inheritance. Molecular Genetics Because of phenotypic similarities between the Slc35d1 knockout mouse and Schneckenbecken dysplasia, Hiraoka et al. (2007) screened 6 affected patients for SLC35D1 mutations and identified mutations in 2. One patient, who was first described by Nikkels et al. (2001), was homozygous for a 1-bp deletion (610804.0001), and the other patient was compound heterozygous for a nonsense (610804.0002) and a splice site (610804.0003) mutation. All 3 mutations were predicted to produce truncated proteins. Furuichi et al. (2009) analyzed the SLC35D1 gene in 5 unrelated patients with Schneckenbecken dysplasia and identified homozygous or compound heterozygous mutations in 3 of them (610804.0004-610804.0007, respectively); no SLC35D1 mutations were identified in the remaining 2 patients or in 15 unrelated patients with other severe spondylodysplastic dysplasias. Radiographic features common to the 3 SLC35D1 mutation-positive cases included handlebar clavicle, bell-shaped thorax, narrowing of the interpediculate distance, metaphyseal flaring, severe retardation of vertebral body ossification, relatively preserved ossification of the posterior arch, relatively preserved sacral ossification, pubic ossification, and lack of angular deformity of the humerus. Furuichi et al. (2009) noted that these features were also present in the 2 previously identified Schneckenbecken dysplasia patients with SLC35D1 mutations (Hiraoka et al., 2007). Animal Model Hiraoka et al. (2007) generated an Slc35d1-knockout mouse model. Heterozygous mice were phenotypically normal, but Slc35d1 -/- mice did not survive the neonatal period; their crown-rump length was reduced and their limbs were extremely short. Skeletal preparations showed hypoplasia of craniofacial bones, flattening of vertebral bodies, longitudinally short ilia and extremely short long bones. This severe chondrodysplasia, which resembles the phenotype of Schneckenbecken dysplasia, confirmed that Slc35d1 is crucial during prenatal skeletal development in mice. INHERITANCE \- Autosomal recessive GROWTH Height \- Dwarfism, micromelic HEAD & NECK Head \- Large head Face \- Flat midface Mouth \- Cleft palate Neck \- Short neck CHEST External Features \- Narrow chest Ribs Sternum Clavicles & Scapulae \- Short, splayed ribs \- Hook-shaped clavicles \- Hypoplastic scapulae SKELETAL Spine \- Round vertebral bodies \- Sacral stenosis Pelvis \- Snail-shaped ilia \- Flat acetabular roofs Limbs \- Dumbbell-shaped short long bones \- Metaphyseal irregularities Hands \- Brachydactyly \- Precociously ossified carpal bones Feet \- Precociously ossified tarsal bones PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios Delivery \- Stillborn or lethal in the neonatal period MISCELLANEOUS \- Stillborn or lethal in the neonatal period MOLECULAR BASIS \- Caused by mutation in the solute carrier family 35, member D1 gene (SLC25D1, 610804.0001 ) ▲ 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	SCHNECKENBECKEN DYSPLASIA	c0432194	27,305	omim	https://www.omim.org/entry/269250	2019-09-22T16:22:30	{"doid": ["0050775"], "mesh": ["C536637"], "omim": ["269250"], "orphanet": ["3144"], "synonyms": ["Alternative titles", "CHONDRODYSPLASIA, LETHAL NEONATAL, WITH SNAIL-LIKE PELVIS"]}
Intellectual disability-developmental delay-contractures syndrome is a rare, slowly progressive genetic disorder that is present at birth. It is characterized by contractures of the joints of the feet (arthrogryposis multiplex congenita), muscle degeneration (atrophy), mild intellectual disability and an impaired ability to move certain muscles of the eyes, face and tongue. Other symptoms might include spasticity and seizures. Intellectual disability-developmental delay-contractures syndrome is caused by mutations in the ZC4H2 gene and is inherited in an X-linked recessive fashion. Most people with intellectual disability-developmental delay-contractures syndrome are male; however carrier females have been reported to have mild symptoms. There is no known cure for intellectual disability-developmental delay-contractures syndrome. Treatment is symptomatic and supportive. [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	Intellectual disability-developmental delay-contractures syndrome	c0796200	27,306	gard	https://rarediseases.info.nih.gov/diseases/7890/intellectual-disability-developmental-delay-contractures-syndrome	2021-01-18T17:59:45	{"mesh": ["C536703"], "omim": ["314580"], "orphanet": ["3454"], "synonyms": ["Contractures of feet, muscle atrophy, and oculomotor apraxia", "Apraxia, oculomotor, with congenital contractures and muscle atrophy", "Wieacker Wolff syndrome", "WWS", "Wieacker syndrome"]}
Congenital short bowel syndrome is a rare intestinal disorder of neonates of unknown etiology. Patients are born with a short small bowel (less than 75 cm in length) that compromises proper intestinal absorption and leads chronic diarrhea, vomiting and failure to thrive. [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 short bowel syndrome	c2746068	27,307	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2301	2021-01-23T17:00:02	{"mesh": ["C535532"], "omim": ["300048", "615237"], "icd-10": ["Q43.8"]}
A rare acquired aplastic anemia characterized by a severe normocytic anemia with normal peripheral leukocyte and platelet counts, reticulocytopenia, high serum ferritin and transferrin saturation levels and isolated, almost complete absence of erythroblasts in the bone marrow with normal granulopoesis and megakaryopoesis. It presents with signs of severe anemia (fatigue, lethargy, pallor, intolerance of physical exercise and exertional dyspnea) in the absence of hemorrhagic symptoms. [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	Adult pure red cell aplasia	c4707560	27,308	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98872	2021-01-23T18:11:38	{"gard": ["10898"], "icd-10": ["D60.0"]}
A very rare mild adult type of NAGA deficiency with the features of angiokeratoma corporis diffusum and mild sensory neuropathy. ## Epidemiology Prevalence of this disorder is not known but less than 20 cases have been reported to date for NAGA deficiency. ## Clinical description This disorder is clinically heterogeneous. Some patients have been reported to have, in addition to angiokeratoma, mild intellectual impairment, but no neurologic signs. Another patient had lymphedema, cardiomegaly, corneal opacity and slight facial coarsening including thick lips, a depressed nasal bridge and an enlarged tip of the nose. Other facultative features consist of tinnitus, hearing loss and vertigo (Meniere disease) (see this term). Pathological characteristics are comprised of vacuolization seen in the blood and dermal cells including the endothelial cells of blood and lymphatic vessels, pericytes, fibrocytes, fat cells, Schwann cells, axons, arrector pili smooth muscle cells, and eccrine sweat gland cells. Vacuolization is most prominent in vascular endothelial cells and the secretory portion of sweat glands. ## Etiology Different causal homozygous mutations of the NAGA gene (22q13.2) have been described in the reported patients. These mutations lead to the dysfunction, instability and rapid degradation of the lysosomal protein, NAGA. Lack of this enzyme activity leads to impaired catabolism and accumulation of undegraded glycoconjugates in the tertiary lysosomes. ## Genetic counseling Transmission is autosomal recessive and genetic counseling is possible. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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-N-acetylgalactosaminidase deficiency type 2	c1836522	27,309	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79280	2021-01-23T18:38:02	{"gard": ["9161"], "mesh": ["C536631"], "omim": ["609242"], "umls": ["C1836522"], "icd-10": ["E77.1"], "synonyms": ["Adult-onset Alpha-N-acetylgalactosaminidase deficiency", "Kanzaki disease", "NAGA deficiency type 2", "Schindler disease type 2"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive hypohidrotic ectodermal dysplasia-10B (ECTD10B; HED/EDA) is caused by homozygous or compound heterozygous mutation in the ectodysplasin anhidrotic receptor gene (EDAR; 604095) on chromosome 2q13. Description Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011). Clinical Features Shimomura et al. (2004) reported a 24-year-old Japanese woman with autosomal recessive hypohidrotic ectodermal dysplasia. Her parents were unaffected and there was no consanguinity. She had heat intolerance, sparse hair, periorbital wrinkling, and oligodontia, and reported recurrent fevers as a child. A skin biopsy showed absence of hair follicles and hypoplastic eccrine sweat glands. Molecular analysis identified compound heterozygosity for 2 mutations in the EDAR gene (604095.0007 and 604095.0008). Naeem et al. (2005) reported 2 consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia. Affected individuals had classic features of the disorder, including sparse hair, absent eyebrows and eyelashes, missing teeth, decreased sweating, dry, thin skin, periorbital wrinkling and hyperpigmentation, prominent lips, and a saddle-shaped nose. Molecular analysis showed that affected members of each family had a homozygous mutation in the EDAR gene (see, e.g., 604095.0012). Megarbane et al. (2008) described an 18-year-old Lebanese woman, born to first-cousin parents, who had a severe form of autosomal recessive anhidrotic ectodermal dysplasia with unusual clinical manifestations including absence of breasts, a rudimentary extranumerary areola and nipple on the left side, and marked palmoplantar hyperkeratosis. Molecular analysis identified homozygosity for a mutation in the EDAR gene (604095.0013) that results in a total absence of EDAR. Inheritance A rare autosomal recessive form of anhidrotic ectodermal dysplasia was suggested by the findings of Passarge et al. (1966) in inbred people of eastern Kentucky. Phenotypically the features were indistinguishable from those in males with the X-linked form. The existence of an autosomal recessive form was further supported strongly by the report by Gorlin et al. (1970) of a female with the full-blown syndrome and by their review of reported cases in females and of parental consanguinity and by Crump and Danks (1971) who reported a boy and girl in a family with hypohidrotic ectodermal dysplasia. Kabbaj et al. (1998) reported a large consanguineous Moroccan family in which 14 individuals, both male and female, were affected. Molecular Genetics Monreal et al. (1999) identified mutations in the EDAR gene in 3 HED families displaying recessive inheritance (see, e.g., 604095.0001) and in 2 HED families with autosomal dominant inheritance (604095.0005). In an 18-year-old Lebanese woman with a severe form of autosomal recessive anhidrotic ectodermal dysplasia with unusual clinical features including absence of breasts, extranumerary areola and nipple on the left side, and marked palmoplantar hyperkeratosis, Megarbane et al. (2008) identified a novel homozygous splice site mutation in the EDAR gene (IVS9+G-A; 604095.0013). RT-PCR analysis performed on whole skin biopsies and genes known to be expressed in skin appendages indicated that the mutation severely impairs EDAR cDNA splicing, resulting in total absence of EDAR transcripts and consequently of the EDAR protein. Megarbane et al. (2008) hypothesized that the mutation leads to the loss of EDAR/NF-kappa-B signaling. They speculated that the mutation impairs Wnt (see 164820)/B-catenin (116806) downregulation, which may modify the balance between signals necessary to mammary gland development. Genotype/Phenotype Correlations Van der Hout et al. (2008) identified mutations in the EDAR gene in 5 (28%) of 18 EDA-negative probands with hypohidrotic ectodermal dysplasia. Four families showed autosomal dominant inheritance. In 1 family, 2 affected boys with a severe phenotype were compound heterozygous for 2 mutations (R89H, 604095.0002; D110A, 604095.0009). The unaffected father carried the D110A mutation. However, the mother, who was heterozygous for the R89H mutation, was mildly affected with hypohidrosis and few permanent teeth. Van der Hout et al. (2008) concluded that some presumably 'recessive' mutations may show phenotypic expression in carriers. In the study overall, patients with dominant mutations were less severely affected compared to patients with recessive mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Frontal bossing Eyes \- Periorbital wrinkles \- Periorbital hyperpigmentation Nose \- Depressed nasal bridge ('saddle nose') Mouth \- Prominent lips Teeth \- Hypodontia \- Anodontia \- Microdontia \- Misshapen teeth SKIN, NAILS, & HAIR Skin \- Hypohidrosis \- Anhidrosis Hair \- Hypotrichosis \- Sparse eyelashes and eyebrows METABOLIC FEATURES \- Intolerance to heat and fever MISCELLANEOUS \- Genetic heterogeneity (X-linked form 305100 ) \- Allelic disorder to autosomal dominant form ( 129490 ) MOLECULAR BASIS \- Caused by mutation in the ectodysplasin anhidrotic receptor gene (EDAR, 604095.0001 ) \- Caused by mutation in the EDAR-associated death domain gene (EDARADD, 606603.0001 ) ▲ 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	ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE	c1706004	27,310	omim	https://www.omim.org/entry/224900	2019-09-22T16:28:26	{"doid": ["14793"], "mesh": ["D004476"], "omim": ["224900"], "orphanet": ["238468", "248"], "synonyms": ["Alternative titles", "ECTODERMAL DYSPLASIA, HYPOHIDROTIC", "ECTODERMAL DYSPLASIA, ANHIDROTIC"], "genereviews": ["NBK1112"]}
Type of nicotine poisoning Green Tobacco Sickness (GTS) is a type of nicotine poisoning caused by the transdermal absorption of nicotine from the surface of wet tobacco plants.[1] Tobacco harvesters, whose clothings become saturated from tobacco wet with rain or morning dew, are at high risk of developing GTS. Workers can avoid getting this sickness by waiting to harvest until the tobacco leaves are dry, or by wearing a rain suit. Wet clothing that has come in contact with tobacco leaves should be removed immediately and the skin should be washed with warm soapy water. Nicotine from other sources, including nicotine gum, a nicotine patch or electronic cigarette, or other tobacco products like cigarettes or smokeless tobacco, appears to reduce the risk of GTS due to the body adapting to the intake of nicotine. Symptoms of GTS include nausea, vomiting, headache, dizziness, and severe weakness.[1] These symptoms may be accompanied by fluctuations in blood pressure or heart rate. Abdominal cramping, chills, increased sweating, salivation and difficulty breathing are also common.[1] The illness will resolve on its own within one to two days, but symptoms may be so severe as to require emergency medical treatment. Worldwide there are an estimated 33 million tobacco farm workers, with a substantial proportion living in developing countries. A recent international review reported that between 8-89% of tobacco harvesters may be affected in the course of a season (this wide variation probably being due to differences between study methodologies as well as a range of working conditions). The long-term health outcomes for individuals exposed to nicotine transdermally for extended periods of time are not known.[2] ## See also[edit] * Nicotine poisoning ## Footnotes[edit] 1. ^ a b c Schep LJ, Slaughter RJ, Beasley DM (September–October 2009). "Nicotinic plant poisoning". Clinical Toxicology. 47 (8): 771–81. doi:10.1080/15563650903252186. PMID 19778187. S2CID 28312730. 2. ^ Tobacco in Australia ## References[edit] * Recommended Practices: Green Tobacco Sickness, from National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration. * Warning to tobacco harvesters, from the National Institute for Occupational Safety and Health. * Learning About Green Tobacco Sickness, from the National Agricultural Safety Database. * Quandt SA, et al. Migrant farmworkers and Green Tobacco Sickness: New issues for understudied disease. Am J Ind Med. 2000;37:307-315. 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	Green Tobacco Sickness	None	27,311	wikipedia	https://en.wikipedia.org/wiki/Green_Tobacco_Sickness	2021-01-18T18:32:23	{"umls": ["C0238147"], "wikidata": ["Q5603286"]}
Pulmonary atresia with ventricular septal defect (PA-VSD) is a rare cyanotic congenital heart malformation characterized by underdevelopment of the right ventricular outflow tract and atresia of the pulmonary valve, ventricular septal defect (VSD) and pulmonary collateral vessels. Clinical features depend on the anatomic variability of the lesion and patients may be minimally symptomatic, severely cyanotic or may develop congestive heart failure. PA-VSD may represent a severe form of Tetralogy of Fallot (see this term). [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	Pulmonary atresia with ventricular septal defect	c0344976	27,312	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1207	2021-01-23T16:53:42	{"gard": ["4588"], "mesh": ["C562833"], "omim": ["178370"], "umls": ["C0344976"], "icd-10": ["Q25.5"]}
A number sign (#) is used with this entry because of evidence that preimplantation embryonic lethality-1 (PREMBL2) is caused by homozygous or compound heterozygous mutation in the PADI6 gene (610363) on chromosome 1p36. For a discussion of genetic heterogeneity of preimplantation embryonic lethality, see PREMBL1 (616814). Clinical Features Xu et al. (2016) studied a consanguineous Chinese family in which 3 sisters were infertile due to early embryonic arrest. The proband was a 34-year-old woman who was married at age 27 and did not conceive despite engaging in unprotected sexual intercourse twice per week on average. She had 2 older sisters, aged 44 and 46 years, who were also diagnosed with primary infertility, whereas 2 brothers and another sister had normal fertility and had children. The proband underwent 6 failed in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, during which most embryos were arrested on day 3, at the 2- to 3-cell stage. Of 3 viable embryos, 2 were transferred into the uterus at the 5- and 6-cell stage, but failed to establish pregnancy, and 1 was cultivated further but failed to form a blastocyst on day 5. Xu et al. (2016) also studied 2 additional Chinese women from 2 unrelated families, aged 34 and 35 years, who were infertile due to early embryonic arrest, with most embryos arrested on day 3 at the 2- to 5-cell stage. In the first woman, of 18 successfully fertilized oocytes over 3 cycles of IVF/ICSI, only 2 viable 5- and 6-cell embryos were present on day 3, but both failed to form a blastocyst on day 5; in the second woman, of 22 embryos with normal cleavage over 5 cycles, 4 embryos ranging from 5 to 7 cells at day 3 were implanted, but all failed to establish pregnancy. Mapping In a consanguineous Chinese family in which 3 sisters were infertile due to early embryonic arrest, Xu et al. (2016) performed homozygosity mapping and identified the strongest signals in regions on chromosome 1. Molecular Genetics In a consanguineous Chinese family in which 3 sisters were infertile due to early embryonic arrest, Xu et al. (2016) performed exome sequencing and identified homozygosity for a nonsense mutation in the PADI65 gene (Q381X; 610363.0001) that segregated with disease and was not found in 100 fertile Chinese women. A brother who was homozygous for the mutation had normal fertility. The authors performed targeted resequencing of PADI6 in an additional 36 infertile Chinese women whose embryos displayed developmental arrest in multiple IVF and ICSI attempts, and identified compound heterozygosity for truncating and missense mutations in 2 unrelated women (610363.0002-610363.0005). In both families, the parents were each heterozygous for 1 of the mutations. Significant reduction of phosphorylated RNA polymerase II (see 180660) signal and reduced expression of genes involved in cytokinesis, transcription, and RNA processing was observed in patient embryos, consistent with defective zygotic genome activation. INHERITANCE \- Autosomal recessive GENITOURINARY Internal Genitalia (Female) \- Primary infertility due to recurrent early embryonic arrest PRENATAL MANIFESTATIONS \- Recurrent early embryonic arrest MISCELLANEOUS \- Males with biallelic mutations are fertile MOLECULAR BASIS \- Caused by mutation in the peptidylarginine deiminase, type VI gene (PADI6, 610363.0001 ) ▲ 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	PREIMPLANTATION EMBRYONIC LETHALITY 2	c4310659	27,313	omim	https://www.omim.org/entry/617234	2019-09-22T15:46:24	{"omim": ["617234"]}
Extranodal NK-T-cell lymphoma Other namesAngiocentric lymphoma, Nasal-type NK lymphoma, NK/T-cell lymphoma, Polymorphic/malignant midline reticulosis SpecialtyHematology and Oncology CausesEpstein-Barr virus Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) (also termed angiocentric lymphoma, nasal-type NK lymphoma, NK/T-cell lymphoma, polymorphic/malignant midline reticulosis,[1] and lethal midline granuloma[2]) is a rare type of lymphoma that commonly involves midline areas of the nasal cavity, oral cavity, and/or pharynx[3] At these sites, the disease often takes the form of massive, necrotic, and extremely disfiguring lesions. However, ENKTCL-NT can also involve the eye, larynx, lung, gastrointestinal tract, skin, and various other tissues.[4] ENKTCL-NT mainly afflicts adults; it is relatively common in Asia and to lesser extents Mexico, Central America, and South America but is rare in Europe and North America.[5] In Korea, ENKTCL-NT often involves the skin and is reported to be the most common form of cutaneous lymphoma after mycosis fungoides.[6] ENKTCL-NT is classified as an Epstein-Barr virus-associated lymphoproliferative disease.[7] It is due to the malignant transformation of either one of two types of lymphocytes, NK cells or a T cell variant termed cytotoxic T cells, that are infected with the Epstein-Barr virus (EBV). Typically, the viral infection, which afflicts >90% of the world population, occurs years before evidence of ENKTCL-NT, is carried in cells in a latent, asymptomatic form, and for unclear reasons becomes active in causing the disease. Following the virus's activation, the infected cells acquire numerous genetic abnormalities which may play an important role in the development and/or progression of ENKTCL-NT.[8] Epstein-Barr virus-positive nodal NK/T cell lymphoma (EBV+ nodal NKTCL) was considered to be one form of ENKTCL-NT since it is a malignancy of EBV-infected NK or T cells. However, EBV+ nodal NKTCL is manifested primarily by its involvement in lymph nodes; it also has clinical, pathological, pathophysiological, and genetic features that differ significantly from those of ENKTCL-NT. The World Health Organization, 2016, therefore reclassified this lymphoma as a variant of a disease to which its features more closely resemble, peripheral T-cell lymphoma not otherwise specified.[7] While a rare disease, particularly in North America, ENKTCL-NT has recently gained much interest. Clinical studies have found that newer chemotherapeutic regimens greatly improved survival in cases of early disease. While, survival in advanced cases is still extremely poor, generally being only a few months,[9] recent studies suggest that new regimens directed at gene mutation and expression abnormalities may improve survival.[9][10] Further study of these new regimens has important implications not only for ENKTCL-NT but also for other NK/T cell malignancies. ## Contents * 1 Presentation * 2 Pathogenesis * 2.1 Disease location * 2.2 Genes * 2.2.1 EBV genes * 2.2.2 Infected cell genes * 2.2.2.1 Chromosomes * 2.2.2.2 Mutated genes * 2.2.2.3 Overexpressed genes * 2.3 Signaling pathways * 2.4 Epigenetic abnormalities * 3 Histology * 4 Diagnosis * 5 Course of ENKTCL-NT * 6 Treatment * 6.1 Experimental drugs * 7 See also * 8 References * 9 External links ## Presentation[edit] Extranodal NK/T-cell lymphoma, nasal type occurs primarily in Asians and South Americans; it is comparatively uncommon in other areas. Afflicted patients (median age 50–60 years old; males predominate) most often (~80% of cases) present with nasal bleeding, upper airway obstruction, perforation of the hard palate, and/or disfiguring, necrotic lesions of the nasal cavity, nasopharynx (including Waldeyer's tonsillar ring), paranasal sinuses, palate,[11] and/or eye socket.[12] Less often, patients present with these findings plus signs and symptoms involving extranasal sites such as the skin, upper respiratory tract, gastrointestinal tract, uterus, testes, and/or elsewhere.[13] Rarely, individuals present with evidence of involvement in the later sites without those involving the head/neck area. On further study these individuals may be found to have occult involvement in the head and neck or to develop such involvement. However, ~10 present of patients present with only skin lesions such as a solitary or multiple subcutaneous masses (which may be ulcerated) in the arms or legs[5] while another ~10% present with masses in the lower gastrointestinal tract (which may be accompanied by bleeding or obstruction), salivary glands, testes, muscles, or other organs without evidence of lesions in the head/neck areas. In these cases, there is relatively little involvement of lymph nodes except as a result of direct invasion from non-nodal sites.[12] Thirty-five to forty-five percent of patients present with a history of malaise, fever, night sweats, and/or weight loss. Most (70-75%) patients are diagnosed with early stage I or II disease while the rest have far more serious stage III or IV disease. Rarely, patients with stage III or IV disease have evidence of a life-threatening complication, hemophagocytic lymphohistiocytosis.[14] Also in rare cases, patients evidence a widespread disease that includes malignant cell infiltrations in the liver, spleen, lymph nodes, bone marrow, and/or blood. These case are, or may soon progress to, a related but potentially fatal disease, aggressive NK-cell leukemia.[12] About 45% of patients present with elevated levels of serum lactate dehydrogenase; elevation in this serum enzyme is a poor prognostic indicator.[14] Patients with ENKTCL-NT also have elevated levels of plasma EBV DNA. Quantification of these levels at diagnosis correlates with the extent of their tumor load while serially assaying these levels during treatment gives evidence of the tumors response to treatment and residual disease.[12] Rarely, patients show laboratory evidence of hemophagocytic lymphohistiocytosis such as: decreased circulating red blood cells, leukocytes, and/or platelets; increased serum levels of liver-derived enzymes, ferritin, and/or triglycerides; decreased serum levels of fibrinogen; and/or hemophagocytosis, i.e. engulfment of blood cells by tissue histiocytes in the liver, spleen, bone morrow, and/or other tissues.[15] or aggressive NK-cell leukemia (e.g. decreased circulating red blood cells, leukocytes, and/or platelets, increased circulating large, granule-containing malignant NK cells, and infiltrations of the latter cells in bone marrow and other tissues).[12] ## Pathogenesis[edit] ### Disease location[edit] ENKTCL-NT is a disease of malignant NK or, very much less often, cytotoxic T cells. Unlike most other lymphomas, which typically develop in and involve lymphatic tissues (particularly lymph nodes and spleen), ENKTCL-NT commonly develops in non-lymphatic tissues. This difference in distribution probably reflects the occupancy of the T cell and B cell precursors to most lymphomas in lymphatic tissues versus the frequent occupancy of the NK and cytotoxic T cells precursors to ENTCL-NT in non-lymphatic tissues.[12] ### Genes[edit] ENKTCL-NT is thought to arise from the expression of EBV genes in the infected NK or cytotoxic T cells and the ability of these genes to cause the cells they infect to overexpress and acquire mutations in key genes that regulate cell growth, immortalization, invasiveness, and ability to evade normal control mechanisms, particularly immune surveillance. Since these gene-related abnormalities are multiple and vary between patients, it is not clear which contribute to the development and/or progression of ENKTLC-NT. Clinical studies are therefore examining targeted therapy tactics to determine which gene abnormalities contribute to, and which drugs targeting these abnormalities are useful in treating, ENKTCL-NT.[16] #### EBV genes[edit] Infected cells carry ~10 cytosolic EBV episomes, i.e. gene-bearing viral DNA particles. In the premalignant precursor NK and cytotoxic T cells of ENKTCL-NT, these episomes express only some of their many latency genes, i.e. genes which promote the virus's latency rather than lytic phase of infectivity. EBV has three different latency phases, I, II, and III, in each of which different sets of latency genes are expressed to establish different controls on the cells which they infect. In the premalignant cells of ENKTCL-NT, EBV express latency II genes such as EBNA-1, LMP-1, LMP-2A, and LMP-2B protein-producing genes; EBER-1 and EBER-2 non-coding RNA-producing genes (see EBV non-coding RNAs); and certain BART microRNA-producing genes (see EBV microRNAs). LMP1 protein induces infected cells to overexpress genes that produce cMyc,[10] NF-κB, and BCL2 proteins which when overexpressed block these cells' apoptosis (i.e. cell death) response to injury or the host's immune system and promote their survival and proliferation;[7] LMP2A and LMP2B proteins induce infected cells to overexpress the genes that make AKT and B cell receptor proteins and to activate the NF-κ pathway[9] which when over-activated blocks these cells' apoptosis response and promotes their survival and proliferation; EBER 1 and 2 non-coding RNAs induce infected cells to overexpress the gene that makes the interleukin 10 protein which when overexpressed may promote its parent cells to proliferate and avoid the host's immune system;[7] and certain BART microRNAs may help infected cells avoid attack by the hosts immune system[8] and modify their notch signaling pathway thereby promoting their proliferation.[17] In consequence, the EBV latency II genes force infected cells to become immortal, proliferate excessively, invade tissues, and avoid attack by the hosts' immune system. Due at lease in part to these imposed factors, the infected cells may acquire other genetic abnormalities that further promote their malignant behavior.[12][16] #### Infected cell genes[edit] The rapidly proliferating and immortalized EBV-infected NK/T cells accumulate numerous changes in the expression or activity of their genes by acquisition of chromosome deletions, gene mutations, and changes in gene expression. ##### Chromosomes[edit] Deletions in the long (i.e. "q") arm at position 21-25 (notated as 6q21-25) from one of the two chromosome 6's was an early finding in occasional cases of ENKTCL-NT. This deletion removes one of the two copies of several tumor suppressor genes (i.e. genes that protect cells from becoming malignant) such as HACE1, PRDM1, FOXO3, and PTPRK. Subsequent studies showed that the disease is also occasionally associated with losses in the short arm of chromosome 8 at position 11.23 (8p11.23) which for unclear reasons are associated with a poor prognosis, and occasional losses at position 11l.2 in the q arm of chromosome 14 (14q11.2) which correlates with the ENKTCL-NT malignancy being of cytotoxic T cell origin.[10] EBV-infected NK and T cells may also occasionally develop chromosome segregation errors during mitosis and consequently divide into daughter cells which possess too few or too many chromosomes and thereby exhibit chaotic losses or increases in the expression of the genes located on these chromosomes.[10] ##### Mutated genes[edit] Second generation sequencing methods have uncovered numerous genes which are mutated in the malignant cells of ENKTCL-NT. These mutated genes and their product proteins have the following a) mutation rates in ENKTCL-NT; b) normal functions; c) gains or losses of activity; d) pro-malignant effects on EN/T cells and e) clinical impacts on the course of ENKTCL-NT: Gene Product Mutation rate Function Mutation type Influence on cell function Clinical impact on ENKTCL-NT TP53 p53 13-62% tumor suppressor gain promotes cell proliferation, survival, migration, invasiveness, and metastasis correlates with advanced stage and poor prognosis[16] DDX3X DDX3X 12-20% tumor suppressor loss lost ability to inhibit proliferation correlates with advanced stage and poor prognosis[16] STAT3 STAT3 8-26% JAK-STAT signaling pathway component gain promotes cell proliferation and survival unknown[16] STAT5B STAT5B ~2-6% JAK-STAT signaling pathway component gain promotes cell proliferation and survival unknown[16] JAK3 JAK3 0-35% JAK-STAT signaling pathway component gain promotes cell proliferation and survival unknown[16] MGA MAX dimerization protein ~8% tumor suppressor loss unknown unknown[16] MLL2 MLL2 7-80% histone methyltransferase, tumor suppressor loss reduces cellular differentiation, possibly promoting cell proliferation and survival unknown[16] BCOR BCL-6 corepressor 21-32% inhibits BCL-5, may regulate apoptosis loss may increase cell survival unknown[16] ECSIT ECSIT 19% element in TGF-β/BMP/signaling pathways gain activates NF-κB to promote cell survival and prolifaration correlates with advanced stage and poor prognosis[10] ARID1A ARID1A 4-8% a SWI/SNF protein that regulates expression of other proteins loss unknown unknown[16] MCL1 MCL1 most cases a SWI/SNF protein that regulates expression of other proteins loss unknown unknown[16] In the above table, ARID1A protein stands for AT-rich interactive domain-containing protein 1A and ECSIT protein stands for evolutionarily conserved signaling intermediate in Toll pathway; mitochondrial. A gain of function mutation in the ECSIT gene that changes the amino acid at the 140 position in its product protein from valine to alanine (i.e. V140A) is associated with a high incidence of ENKTCL-NT being complicated by the development of life-threatening Hemophagocytic lymphohistiocytosis and thereby a relatively high mortality rate.[3] Numerous other genes are rarely (i.e. ≤2% of cases) mutated in ENKTCL-NT. These include JAK1, MLL3, ARID1A, EP300, ASXL3, MSN, FAT4, NARS, IL6R, MGAM, CHPF2, (see[18]) and MIR17HG ((see[19]).[16] ##### Overexpressed genes[edit] ENKTCL-NT malignant cells overexpress NF-κB, a cellular signaling transcription factor that when up-regulated promotes these cells' proliferation and survival. They also overexpress: 1) aurora kinase A, a serine/threonine-specific protein kinase that when up-regulated in the cancer setting promotes these cells' invasiveness and to develop chromosome segregation errors during mitosis that result in daughter cells having too few or too many chromosome; 2) members of the inhibitor of apoptosis family of proteins including survivin,[10] Bcl-xL, and MCL1[20] which when up-regulated suppress programmed cell death to promote these cell's survival and resistance to attack by the host immune system;[21][22] 3) multidrug resistance protein 1, a surface membrane protein that when up-regulated causes these cells to greatly increases the export of anthracyclines such as Adriamycin and Daunomycin thereby rendering them resistant to this class of chemotherapy drugs; 4) EZH2, a histone methyltransferase that when up-regulated indirectly promotes these cells' growth; 5) runt-related transcription factor 3 that when up-regulated indirectly promotes the survival and proliferation of these cells;[10] and 6) programmed death-ligand 1 (PD-L1), that when up-regulated increases the ability of these cells to avoid attack by the host's immune system.[23] ### Signaling pathways[edit] In consequence of, or addition to the cited genetic abnormalities, ENKTCL-NT malignant cells have overly active the; JAK-STAT signaling pathway that in the cancer setting promotes cell proliferation, survival, and other pro-malignant behaviors;[12] platelet-derived growth factor signaling pathway that in the cancer setting promotes cell survival and proliferation; Notch signaling pathway that in the cancer setting promotes cellular differentiation and proliferation; and NF-κB signaling that in the cancer setting promotes cell survival and proliferation. Studies suggest that that overactive VEGF receptor and Protein kinase B signaling pathways may also play a role in the pathogenesis of ENKTCL-NT.[10]) ### Epigenetic abnormalities[edit] Studies on cultured malignant NK cells and/or patient tissue specimens find that numerous genes are hypermethylated at their promoter sites and therefore are silenced, i.e. make less or none of their protein products. This silencing has been detected in numerous proteins expressed by cultured NK cells (e.g. BCL2L11, DAPK1, PTPN6, TET2, SOCS6, PRDM1, AIM1, HACE, p15, p16, p73, MLH1, RARB, and ASNS) and the MIR146A gene for its miR-146a microRNA product. Studies conducted on the expression of microRNAs in cultured malignant NK cells have also revealed that many are either over- or under-expressed compared to non-malignant cultured NK cells. This dysregulation of thse microRNA genes may reflect the action of products expressed by certain EBV genes and/or the overexpression of the infected cells' MYC gene. In all cases, the epigenetic dysregulation of these genes requires further study to determine its significance for the development and progression of ENKTCL-NT.[10] ## Histology[edit] On microscopic examination, involved tissues show commonly show areas of necrosis and cellular infiltrates that are centered around and often injure or destroy small blood vessels. The infiltrates contain large granule-containing lymphocytes that express cell surface CD2, cytoplasmic CD3ε, and cell surface CD56 as well the cytoplasmic intracellular proteins, perforin, granzyme B, and T cell intracellular antigen-1 (TIA-1). These cells exhibit evidence of EBV infection as determined by in situ hybridization assays to detect one of the virus's latent products, typically EBER-1/2 micoRNAs.[12] Identification of the genetic abnormalities cited above in the cells may be of help in establishing the diagnoses and be of use for selecting novel therapeutic approaches to individual patients.[10] Non-malignant inflammatory white blood cells, including eosinophils, are also commonly found in these infiltrates.[12] ## Diagnosis[edit] The diagnosis of ENKTCL-NT depends on histological findings that biopsied tissue infiltrates contain lymphocytes that express CD3ε, cytotoxic molecules (granzyme B, perforin, TIA1), and EBV.[10] Bone marrow examination is recommended to determine its involvement in this disorder. Whole body PET-CT scans are recommended to determine the extent of disease at presentation as well as to follow the effects of therapeutic interventions. The tumor load of each individual's disease as well as response to therapies has also been estimated by assaying plasma levels of EBV DNA.[12] ENKTCL-NT can be mimicked by two benign diseases which involve the excessive proliferation of non-malignant NK cells in the GI tract viz., Natural killer cell enteropathy, a disease wherein NK cell infiltrative lesions occur in the intestine, colon, stomach, and/or esophagus, and lymphomatoid gastropathy, a disease wherein these cells infiltrative lesions are limited to the stomach.[24] Another lymphoproliferative disorder of the GI tract, indolent T cell lymphoproliferative disorder of the gastrointestinal tract may also mimic ENKTCL-NT. This chronic disorder involves the proliferation of CD+4, CD8+, CD4-/CD8-, or CD4+/CD8+ T cells in the mucosal layers of the GI tract to give a variety of GI tract symptoms. While generally a persistent and benign disorder, a small but significant percentage of cases have progressed to aggressive lymphomas.[25][26] Findings that differentiate these benign diseases from ENKTCL-NT are given in their Wikipedia pages. ## Course of ENKTCL-NT[edit] The course of the untreated disease is heavily dependent on its clinical stage at diagnosis. Patients presenting with highly localized stage I nasal disease usually have nasal but no other symptoms; these individuals commonly show no progression of their disease over long periods of time. Other patients with limited (i.e. stage I or II) disease involving other sites in the head area are more likely to suffer a relatively slow progression of their disease while patients with stage III or IV disease have a more rapidly progressive disease with a poor prognosis. Patients presenting with ENKTCL-NT that does not involve the head area typically have a disseminated and aggressively progressive disease with a very poor prognosis.[11] Patients with stage I or II localized disease that have been treated with the recently defined chemotherapeutic protocols have 5 year survivals of ~70-89%[9] while those with advanced stage III or IV disseminated disease treated with these protocols have 5 year survivals of 50%.[23] Patients who relapse or are resistant to these protocols have had overall survivals of just a few months.[9] Three prognostic models, NK-PI, PINK (i.e. prognostic index of natural killer lymphomas), and PINK-E) for ENKTCL-NT have evolved over the past 12 years. The latest model, PINK-E, which applies to patients treated with recently defined regimens, lists 5 risk factors (age >60, state III or IV disease, no nasal involvement, distant lymph node involvement, and detectable blood levels of EBV DNA) to define patients as low, intermediate, and high risk based on their having 0–1, 2, or 3–5 risk factors, respectively. Overall 3 year survival in these 3 respective groups were 81, 55, and 28%.[23] Patients, particularly those in the advanced poor risk groups may develop hemophagocytic lymphohistiocytosis or have their disease progress to aggressive NK-cell leukemia. Both conditions are life-threatening and far less responsive to treatment.[12] ## Treatment[edit] The treatment of ENKTCL- NT employs chemotherapy plus, where indicated, radiotherapy. Early chemotherapies relied on CHOP (i.e. cyclophosphamide, an anthracycline (primarily adriamycin), vincristine, and prednisolone) or chop-like regimens. These were only marginally successful because, as it was later discovered, the malignant NK cells in ENKTCL-NT over-express multidrug resistance protein 1. This protein exports various molecules, including anthracyclines and vincristine, from its parent cells and thereby renders these cells resistant to adriamycin[12] and vincristine[27] and therefore to CHOP and CHOP-like regimens.[12] Subsequent studies discovered that L-asparaginase[12] (NK cells do not express L-asaraginase[9]) and, to a lesser extent, platinum-based antineoplastic drugs (e.g.carboplatin)[14] were active on theses cells. Accordingly, several chemotherapeutic regimens were tested and found to give much better results than previous regimens. However, these regimens have bot undergone phase 3 clinical trials that examine their effectiveness relative to other regimens. The following regimens are recommended by many studies and the European Society for Medical Oncology Clinical Practice guidelines[14] or National Comprehensive Cancer Network:[28] * Localized stage I and 2 diseases are treated with a combination of local radiation followed by DeVIC (dexamethasone, etopoxide, ifosfamide, and carboplatin). Five-year progression-free and overall survival rates with this regimen are 70-72% and 61-63%, respectively. An alternative regimen, termed CCRT-VIDL, combines cisplatin plus radiation followed by etopoxide, ifosfamide, cisplatin, and dexamethasone to give complete response and 5 overall survival rates of 87 and 73%, respectively.[14] * Patients who have a partial response or relapse on this regimen are treated with the SMILE regimen (see below).[14] * Disseminated stage III and IV disease are treated with SMILE, i.e. dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The regimen obtains complete response and 5 year overall survival rates of 45 and 47%, respectively. In the United States, pegaspartase is used in place of L-asparaginase.[14] * Patients that have a complete or partial response to this regimen may then treated with an autologous stem-cell transplantation regimen, palliative chemotherapy, and/or experimental drugs.[14] ### Experimental drugs[edit] There are numerous regimens that use non-chemotherapeutic agents to target specific elements known or thought to be involved in the survival of the malignant cells in a significant percentage of ENKTCL-NT cases. The targets should be determined as overexpressed or present in the malignant tissues of each case before treatment.[14] The targets, therapeutic agents, and some phase 1 clinical trials (testing for appropriate dosages, safety, and side effects) and/or phase 2 clinical trials (testing for efficacy and safety) include: * PD1: Program death-ligand 1 (PD-L1) is commonly overexpressed in ENKTCL-NT as an apparent result of EBV infection. Pembrolizumab and Nivolumab are monoclonal antibody preparations that bind to the programmed cell death 1 receptor on lymphocytes thereby blocking the action of PD-L1 in suppressing the anti-cancer actions of these cells. Seven patients with refractory or relapsed ENKTCL-NT had either complete (5 patients) or partial (2 patients) responses to Pembrolizumab and three patients with relapsed ENKTCL-NT had had either complete (2 patients) or partial (1 patient) responses to Nivolumab.[23] A clinical study sponsored by the Memorial Sloan Kettering Cancer Center in New York City is recruiting individuals to study the effects of Pembrolizumab in patients with early-stage ENKTCL-NT;[29] a phase I/II clinical study sponsored by the Abramson Cancer Center of the University of Pennsylvania in Philadelphia is recruiting individuals to examine the effects of Pembrolizumab in individuals with relapsed or refractory ENKTCL-NA;[30] and a clinical phase 2 study sponsored by the University of Hong Kong is recruiting individuals to examine the effects of Pembrolizmab on ENKTCL-NT.[31] * CD30: The malignant cells in ~40% of ENKTCL-NT cases express the surface membrane protein, CD30. Two case reports have indicated that the CD30-targeted monoclonal antibody (which is conjugated to the cytoxic/antineoplastic agent auristatin E, brentuximab vedotin, was helpful in treating relapsed ENKTCL-NT.[23] A not-yet-recruiting study estimated to be finished by Sept., 2018 examines the effects of brentuxixmab vedotin on EBV-positive, CD30-positive lymphomas.[32] * CD38: CD38 is almost always expressed in the malignant cells of ENkTCL-NT. One patient with this disease, after relapsing following each of two chemotherapy courses, had a complete remission when treated with a cytotoxic antibody directed at CD38, Daratumumab.[9] A phase 2 clinical study on the effects of Daratumumab on ENTCL-NT sponsored by Janssen Research & Development, LLC is recruiting patients in China, South Korea, and Taiwan.[33] * EBV antigens: EBV-infected cells express the viral LMP1 and LMP2 proteins on their surface membranes and therefore are potential targets for attack by cytotoxic T cells (CTL). Studies have used CTL that have been engineered to attack and kill LMP1 and/or LMP2 expressing cells. Eleven patients with refractory or relapsed ENKTCL-NT were treated with their own CTL that had been engineered to kill LMP1/2-expressing cells. Nine patients had durable (>4 years) remissions, 1 patient had a complete remission which lasted only 9 months, and 2 patients show no response to the treatment. In a second study, 8 patients with localized and two with advanced disease who were in complete remission after chemotherapy (with or without radiation treatment) were given their own CTL that had been engineered to kill LMP1/2-bearing cells. One patient relapsed after 32 months while the remaining 7 patients had progression-free and overall survivals of 100 and 90%, respectively.[23] A phase I clinical trial sponsored by Baylor College of Medicine, the Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and the Methodist Hospital System is recruiting individuals to test the effects of donor CTL engineered to kill cells bearing LMP1/2, ARF, and/or EBNA-1 viral antigens.[34] A phase 2 clinical study sponsored by ViGenCell Inc. is being conducted at the Catholic University of Korea to test the effects of CTL engineered to kill EBV-infected cells on patients that are in complete remission following chemotherapy (±radiation treatment) but at high risk for recurrent disease. Patients will receive the CTL or placebo (i.e. peripheral blood mononuclear cells). The study, which begins recruitment in late Feb., 2019, seeks to determine if the CTL treatment prolongs remissions.[35] * Bcl-2 proteins: Bcl-2 proteins are a family of proteins that regulate cellular apoptosis. Venetoclax (also termed ABT-199) is a small-molecule drug that indirectly promotes the activation of two apoptosis-inducing proteins, Bcl-2-associated X protein and Bcl-2 homologous antagonist killer thereby promoting cell death. It is approved for the treatment of chronic lymphocytic leukemia.[22] Venetoclax is currently recruiting patients for a phase 2 clinical trial sponsored by the City of Hope Medical Center and the National Cancer Institute to evaluate its effects on refractory and recurrent ENKTCL-NT.[36] Small molecule inhibitors of JAK3 (e.g. tofacitinib), JAK1/JAK2 (e.g. AZD1480), STAT3 (e.g. WP1066), and DDX3X (e.g. RK-33) are being study in pre-clinical in vitro experiments as potential inhibitors of malignant NK/T cell proliferation and survival. They are in further studies to test them as potential therapeutic agents in ENKTCL-NT patients that have activating mutations or overexpression of the cited targets.[16] ## See also[edit] * Cutaneous T-cell lymphoma * Subcutaneous T-cell lymphoma * List of cutaneous conditions * Epstein-Barr virus-associated extranodal NK/T cell lymphoma, nasal type ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Li DM, Lun LD (December 2012). "Mucor irregularis infection and lethal midline granuloma: a case report and review of published literature". Mycopathologia. 174 (5–6): 429–39. doi:10.1007/s11046-012-9559-2. PMID 22744721. 3. ^ a b Yamaguchi M, Oguchi M, Suzuki R (September 2018). "Extranodal NK/T-cell lymphoma: Updates in biology and management strategies". Best Practice & Research. Clinical Haematology. 31 (3): 315–321. doi:10.1016/j.beha.2018.07.002. 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Drug Discovery Today. 22 (10): 1466–1477. doi:10.1016/j.drudis.2017.05.009. hdl:1805/15547. PMID 28577912. 22. ^ a b Kale J, Osterlund EJ, Andrews DW (January 2018). "BCL-2 family proteins: changing partners in the dance towards death". Cell Death and Differentiation. 25 (1): 65–80. doi:10.1038/cdd.2017.186. PMC 5729540. PMID 29149100. 23. ^ a b c d e f Suzuki R (February 2018). "NK/T Cell Lymphoma: Updates in Therapy". Current Hematologic Malignancy Reports. 13 (1): 7–12. doi:10.1007/s11899-018-0430-5. PMID 29368155. 24. ^ Xia D, Morgan EA, Berger D, Pinkus GS, Ferry JA, Zukerberg LR (January 2019). "NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review". American Journal of Clinical Pathology. 151 (1): 75–85. doi:10.1093/ajcp/aqy108. PMID 30212873. 25. ^ Matnani R, Ganapathi KA, Lewis SK, Green PH, Alobeid B, Bhagat G (March 2017). "Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: a review and update". Hematological Oncology. 35 (1): 3–16. doi:10.1002/hon.2317. PMID 27353398. 26. ^ Sharma A, Oishi N, Boddicker RL, Hu G, Benson HK, Ketterling RP, Greipp PT, Knutson DL, Kloft-Nelson SM, He R, Eckloff BW, Jen J, Nair AA, Davila JI, Dasari S, Lazaridis KN, Bennani NN, Wu TT, Nowakowski GS, Murray JA, Feldman AL (May 2018). "Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract". Blood. 131 (20): 2262–2266. doi:10.1182/blood-2018-01-830968. PMC 5958657. PMID 29592893. 27. ^ He SM, Li R, Kanwar JR, Zhou SF (2011). "Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)". Current Medicinal Chemistry. 18 (3): 439–81. doi:10.2174/092986711794839197. PMID 21143116. 28. ^ add NCCN ref 29. ^ https://clinicaltrials.gov/ct2/show/NCT03728972?cond=Pembrolizumab+and+NK%2FT+cell+lymphoma&rank=1 30. ^ https://clinicaltrials.gov/ct2/show/NCT03586024?cond=Pembrolizumab+and+NK%2FT+cell+lymphoma&rank=2 31. ^ https://clinicaltrials.gov/ct2/show/NCT03021057?cond=Pembrolizumab+and+NK%2FT+cell+lymphoma&rank=3 32. ^ https://clinicaltrials.gov/ct2/show/NCT02388490?term=lymphoma&cond=Brentuximab&rank=6 33. ^ https://clinicaltrials.gov/ct2/show/NCT02927925?term=NCT02927925&rank=1 34. ^ https://clinicaltrials.gov/ct2/show/NCT02287311?term=cytotoxic+T+cells&cond=lymphoma&rank=11 35. ^ https://clinicaltrials.gov/ct2/show/NCT03671850?term=cytotoxic+T+cells&cond=lymphoma&rank=20 36. ^ https://clinicaltrials.gov/ct2/show/NCT03534180?cond=NK-Cell+Lymphoma&rank=21 ## External links[edit] Classification D * ICD-10: C86.0 * ICD-O: M9719/3 * MeSH: D054391 * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias [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	Extranodal NK/T-cell lymphoma, nasal type	c0392788	27,314	wikipedia	https://en.wikipedia.org/wiki/Extranodal_NK/T-cell_lymphoma,_nasal_type	2021-01-18T19:05:12	{"gard": ["13270"], "mesh": ["D054391"], "umls": ["C0392788"], "orphanet": ["86879"], "wikidata": ["Q4763254"]}
In addition to thickening of the inner table of the frontal bone, obesity and hypertrichosis may be present. This condition affects mainly females. Knies and Le Fever (1941) reported mother and 3 children affected. Thus, the disorder may be dominant, but whether autosomal or X-linked is not known. Lieberman (1967) has observed 5 affected females in 3 generations. No case of male-to-male transmission is known. Rosatti (1972) described a family with 12 affected members (10 of them females) in 4 successive generations. Gegick et al. (1973) found elevated serum alkaline phosphatase levels in about half of patients. Pawlikowski and Komorowski (1983) found hyperostosis frontalis in 43% of women with galactorrhea as compared with a population frequency of 2.5%. (At least 2 other groups reported similar frequencies.) Since hyperprolactinemia was found in many of these cases, the authors suggested that this and other features of the syndrome such as hirsutism, diabetes, and menstrual troubles may be related to hyperprolactinemia. Skull \- Hyperostosis frontalis interna Inheritance \- Autosomal dominant Endocrine \- Galactorrhea \- Hyperprolactinemia \- Diabetes mellitus \- Menstrual irregularity Misc \- Mainly females Lab \- Hyperphosphatasemia Growth \- Obesity Skin \- Hypertrichosis ▲ 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	HYPEROSTOSIS FRONTALIS INTERNA	c0020494	27,315	omim	https://www.omim.org/entry/144800	2019-09-22T16:39:54	{"mesh": ["D006957"], "omim": ["144800"], "orphanet": ["77296"], "synonyms": ["Alternative titles", "MORGAGNI-STEWART-MOREL SYNDROME"]}
The uvula is split into two lobes by a central fissure. Meskin et al. (1965) reported that about 1% of Caucasians and 10% of American Indians and Japanese show the trait in some degree. The frequency in sibs and parents of affected persons is said to be about 18%. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Bifid uvula ▲ 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	UVULA, BIFID	c4551488	27,316	omim	https://www.omim.org/entry/192100	2019-09-22T16:32:09	{"omim": ["192100"], "synonyms": ["Alternative titles", "UVULA, CLEFT"]}
Arthralgia SpecialtyRheumatology Arthralgia (from Greek arthro-, joint + -algos, pain) literally means joint pain.[1][2] Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication.[3] According to MeSH, the term "arthralgia" should only be used when the condition is non-inflammatory, and the term "arthritis" should be used when the condition is inflammatory.[4] ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 See also * 5 References ## Causes[edit] The causes of arthralgia are varied and range, from a joints perspective, from degenerative and destructive processes such as osteoarthritis and sports injuries to inflammation of tissues surrounding the joints, such as bursitis.[5] These might be triggered by other things, such as infections or vaccinations.[6] Cause Mono- or polyarticular Speed of onset Rheumatoid arthritis Polyarticular [7] Weeks–months[8] Systemic lupus erythematosus Polyarticular[7] Months[9] Viral arthritis Polyarticular[7] Ehlers-Danlos Syndrome [10] Reactive arthritis Polyarticular[7] Rheumatic fever Polyarticular[7] Lyme disease Polyarticular[7] Gonococcal arthritis Polyarticular[7] Drug-induced arthritis Polyarticular[7] Ligamentous laxity Polyarticular[7] Osteoarthritis Monoarticular[7] Gout attack Monoarticular[7] Hours[11] Pseudogout Monoarticular[7] Behcet's Disease Monoarticular[7] Physical trauma Monoarticular[7] Immediate Septic arthritis Monoarticular[7] Hours[11] Hemarthrosis Monoarticular[7] 5HT2-antagonists[12] Henoch-Schonlein purpura[13] ## Diagnosis[edit] Diagnosis involves interviewing the patient and performing physical exams. When attempting to establish the cause of the arthralgia, the emphasis is on the interview.[2] The patient is asked questions intended to narrow the number of potential causes. Given the varied nature of these possible causes, some questions may seem irrelevant. For example, the patient may be asked about dry mouth, light sensitivity, rashes or a history of seizures.[2][14] Answering yes or no to any of these questions limits the number of possible causes and guides the physician toward the appropriate exams and lab tests. ## Treatment[edit] Treatment depends on a specific underlying cause. The underlying cause will be treated first and foremost. The treatments may include joint replacement surgery for severely damaged joints, immunosuppressants for immune system dysfunction, antibiotics when an infection is the cause, and discontinuing medication when an allergic reaction is the cause. When treating the primary cause, pain management may still play a role in treatment.[15] The extent of its role varies depending on the specific cause of the arthralgia. Pain management may include stretching exercises, over the counter pain medications, prescription pain medication, or other treatments deemed appropriate for the symptoms. Capsaicin, a substance found in chili peppers, may relieve joint pain from arthritis and other conditions. Capsaicin blocks the actions of substance P, which helps transmit pain signals, and capsaicin triggers the release of pain-blocking chemicals in the body known as endorphins. Side effects of capsaicin cream include burning or stinging in the area where it is applied. Another topical option is an arthritis cream containing the ingredient, methyl salicylate (Bengay). ## See also[edit] * Myalgia ## References[edit] 1. ^ "Arthralgia Definition". MedicineNet.com. Archived from the original on 11 October 2007. Retrieved 2007-09-20. 2. ^ a b c Joe G. Hardin. "Arthralgia". Clinical Methods - The History, Physical, and Laboratory Examinations. Retrieved 2007-09-20. 3. ^ James R Philp. "Allergic Drug Reactions - Systemic Allergic Drug Reactions". Clinical Methods - The History, Physical, and Laboratory Examinations. Retrieved 2007-09-20. 4. ^ "MeSH". Retrieved 2007-12-23. 5. ^ Joe G. Hardin. "Table 161.1. Some Common Regional Rheumatic Syndromes". Clinical Methods - The History, Physical, and Laboratory Examinations. Retrieved 2007-09-20. 6. ^ Loris McVittie. "Information from CDC and FDA on the Safety of Gardasil Vaccine". supplement to your biologics license application (BLA) for Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant (GARDASIL), to include arthralgia, myalgia, asthenia, fatigue, and malaise in the Adverse Reactions section of the package insert. Retrieved 2008-07-21. 7. ^ a b c d e f g h i j k l m n o p Table 6-8 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-7153-5. 8. ^ Diagnosis lag time of median 4 weeks, and median diagnosis lag time of 18 weeks, taken from: Chan, K. W.; Felson, D. T.; Yood, R. A.; Walker, A. M. (1994). "The lag time between onset of symptoms and diagnosis of rheumatoid arthritis". Arthritis and Rheumatism. 37 (6): 814–820. doi:10.1002/art.1780370606. PMID 8003053. 9. ^ Doria, A.; Zen, M.; Canova, M.; Bettio, S.; Bassi, N.; Nalotto, L.; Rampudda, M.; Ghirardello, A.; Iaccarino, L. (2010). "SLE diagnosis and treatment: When early is early". Autoimmunity Reviews. 10 (1): 55–60. doi:10.1016/j.autrev.2010.08.014. PMID 20813207. 10. ^ "Ehlers-Danlos syndrome - Symptoms and causes". Retrieved 10 February 2018. 11. ^ a b Page 740 (upper right of page) in: Schaider, Jeffrey; Wolfson, Allan B.; Hendey, Gregory W.; Ling, Louis; Rosen, Carlo L. (2009). Harwood-Nuss' Clinical Practice of Emergency Medicine (Clinical Practice of Emergency Medicine (Harwood-Nuss)). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-8943-1. 12. ^ Anneke Passier, Eugène van Puijenbroek (2005). "Mirtazapine-induced arthralgia". Br J Clin Pharmacol. PMID 16236049.CS1 maint: uses authors parameter (link) 13. ^ "Henoch-Schonlein purpura (video)". Khan Academy. Retrieved 2020-06-06. 14. ^ "Table 159mptomatic Extraarticular Features of the Connective Tissue Diseases and the Spondyloarthropathies". Clinical Methods - The History, Physical, and Laboratory Examinations. Retrieved 2007-09-20. 15. ^ "Pain Management". Arthritis Action UK. Arthritis Action. Archived from the original on 13 February 2016. Retrieved 16 October 2015. Classification D * ICD-10: M25.5 * ICD-9-CM: 719.4 * MeSH: D018771 * DiseasesDB: 15237 External resources * MedlinePlus: 003261 * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte * v * t * e Pain By region/system Head and neck * Headache * Neck * Odynophagia (swallowing) * Toothache Respiratory system * Sore throat * Pleurodynia Musculoskeletal * Arthralgia (joint) * Bone pain * Myalgia (muscle) * Acute * Delayed-onset Neurologic * Neuralgia * Pain asymbolia * Pain disorder * Paroxysmal extreme pain disorder * Allodynia * Chronic pain * Hyperalgesia * Hypoalgesia * Hyperpathia * Phantom pain * Referred pain * Congenital insensitivity to pain * congenital insensitivity to pain with anhidrosis * congenital insensitivity to pain with partial anhidrosis Other * Pelvic pain * Proctalgia * Back * Low back pain Measurement and testing * Pain scale * Cold pressor test * Dolorimeter * Grimace scale (animals) * Hot plate test * Tail flick test * Visual analogue scale Pathophysiology * Nociception * Anterolateral system * Posteromarginal nucleus * Substance P Management * Analgesia * Anesthesia * Cordotomy * Pain eradication Related concepts * Pain threshold * Pain tolerance * Suffering * SOCRATES * Philosophy of pain * Cancer pain * Drug-seeking behavior [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	Arthralgia	c0003862	27,317	wikipedia	https://en.wikipedia.org/wiki/Arthralgia	2021-01-18T18:48:46	{"mesh": ["D018771"], "umls": ["C0003862"], "icd-9": ["719.4"], "icd-10": ["M25.5"], "wikidata": ["Q683498"]}
Mandibuloacral dysplasia (MAD) is a rare genetic bone disorder characterized by growth delay, postnatal development of craniofacial anomalies including mandibular hypoplasia, progressive acral osteolysis, mottled or patchy pigmentation, skin atrophy, and partial or generalized lipodystrophy. [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	Mandibuloacral dysplasia	c0432291	27,318	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2457	2021-01-23T18:22:52	{"gard": ["11893"], "mesh": ["C535705"], "omim": ["248370", "608612"], "umls": ["C0432291"], "icd-10": ["Q87.5"], "synonyms": ["MAD"]}
Predisposition towards allergy This article is about the disease. For the philosophical use, see Atopy (philosophy). Atopy Other namesAtopic syndrome Eczema—a typical atopic manifestation Pronunciation * /ˈætəpiː/[1] SpecialtyDermatology, immunology Atopy is the tendency to produce an exaggerated IgE immune response to otherwise harmless environmental substances, while an allergic disease can be defined as the clinical manifestation of this inappropriate IgE immune response.[2] Atopy may have a hereditary component, although contact with the allergen or irritant must occur before the hypersensitivity reaction can develop.[3] Maternal psychological trauma in utero may also be a strong indicator for development of atopy.[4] The term atopy was coined by Coca and Cooke in 1923.[5][6] Many physicians and scientists use the term "atopy" for any IgE-mediated reaction (even those that are appropriate and proportional to the antigen), but many pediatricians reserve the word "atopy" for a genetically mediated predisposition to an excessive IgE reaction.[7] The term is from Greek ἀτοπία meaning "the state of being out of place", "absurdity".[8] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Causes * 3.1 Genetics * 3.2 Staphylococcus aureus * 4 Changes in prevalence * 5 Treatments * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Atopic sensitization is considered IgE positivity or prick test positivity to any common food or air born allergen.[9] Atopic conditions are considered: atopic dermatitis, allergic rhinitis (hay fever), allergic asthma. The likelihood of having asthma, rhinitis and atopic dermatitis together is 10 times higher than could be expected by chance.[10] Atopy is more common among individuals with a number of different conditions, such as eosinophilic esophagitis, non-celiac gluten sensitivity.[11][12] Allergic reactions can range from sneezing and rhinorrhoea to anaphylaxis and even death.[13] ## Pathophysiology[edit] In an allergic reaction, initial exposure to an otherwise harmless exogenous substance (known as an allergen) triggers the production of specific IgE antibodies by activated B cells.[13] These IgE antibodies bind to the surface of mast cells via high-affinity IgE receptors, a step that is not itself associated with a clinical response.[13] However, upon re-exposure, the allergen binds to membrane-bound IgE which activates the mast cells, releasing a variety of mediators.[13] This type I hypersensitivity reaction is the basis of the symptoms of allergic reactions, which range from sneezing and rhinorrhoea to anaphylaxis.[13] Allergens can be a number of different substances, for example pollen, dander, dust mites, foods. ## Causes[edit] Atopic reactions are caused by localized hypersensitivity reactions to an allergen. Atopy appears to show a strong hereditary component. One study concludes that the risk of developing atopic dermatitis (3%) or atopy in general (7%) "increases by a factor of two with each first-degree family member already suffering from atopy".[14] As well, maternal stress and perinatal programming is increasingly understood as a root cause of atopy, finding that "...trauma may be a particularly robust potentiator of the cascade of biological events that increase vulnerability to atopy and may help explain the increased risk found in low-income urban populations.” [4] Environmental factors are also thought to play a role in the development of atopy, and the 'hygiene hypothesis' is one of the models that may explain the steep rise in the incidence of atopic diseases, though this hypothesis is incomplete and in some cases, contradictory to findings.[4] This hypothesis proposes that excess 'cleanliness' in an infant's or child's environment can lead to a decline in the number of infectious stimuli that are necessary for the proper development of the immune system. The decrease in exposure to infectious stimuli may result in an imbalance between the infectious-response ("protective") elements and the allergic-response ("false alarm") elements within the immune system.[15] Some studies also suggest that the maternal diet during pregnancy may be a causal factor in atopic diseases (including asthma) in offspring, suggesting that consumption of antioxidants, certain lipids, and/or a Mediterranean diet may help to prevent atopic diseases.[16] The multicenter PARSIFAL study in 2006, involving 6630 children age 5 to 13 in 5 European countries, suggested that reduced use of antibiotics and antipyretics is associated with a reduced risk of allergic disease in children.[17] ### Genetics[edit] There is a strong genetic predisposition toward atopic allergies, especially on the maternal side. Because of the strong familial evidence, investigators have tried to map susceptibility genes for atopy.[18][19] Genes for atopy (C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1/IL18R1, TLR1/TLR6/TLR10, LPP, MYC/PVT1, IL2/ADAD1, HLA-B/MICA)[20] tend to be involved in allergic responses or other components of the immune system. C11orf30 seems to be the most relevant for atopy as it may increase susceptibility to poly-sensitization.[21] ### Staphylococcus aureus[edit] Bleach baths provide temporary control of eczema.[22] Ciprofloxacin is an allergen that may cause contact dermatitis, symptoms of which are indistinguishable from eczema.[23] Filaggrin mutations are associated with atopic eczema and may contribute to the excessive dryness of the skin and the loss of the barrier function of normal skin.[24] It may be possible that the filaggrin mutations and the loss of the normal skin barrier expose crevices that make it possible for Staphylococcus aureus to colonize the skin.[25] Atopic eczema is often associated with genetic defects in genes that control allergic responses. Thus, some investigators have proposed that atopic eczema is an allergic response to increased Staphylococcus aureus colonization of the skin.[26] A hallmark indicator of atopic eczema is a positive “wheal-and-flare” reaction to a skin test of S. aureus antigens. In addition, several studies have documented that an IgE-mediated response to S. aureus is present in people with atopic eczema.[27][28] ## Changes in prevalence[edit] In adults, the prevalence of IgE sensitization to allergens from house dust mite and cat, but not grass, seem to decrease over time as people age.[29] However, the biological reasons for these changes are not fully understood. ## Treatments[edit] The treatment of atopic disorders depends on the organ(s) involved. It can vary from local treatment options, often topical corticosteroids, to systemic treatment options with oral corticosteroids, biological treatments (e.g. Omalizumab, Mepolizumab) or allergen immunotherapy.[30][31][32] An anaphylactic reaction on the other hand is treated with adrenaline, given as an intramuscular injection.[33] ## See also[edit] * Eczema * Asthma * Rhinitis * Anaphylaxis * Allergic march ## References[edit] 1. ^ Merriam-Webster Dictionary: Atopy 2. ^ Ralston, Stuart H., Herausgeber. Penman, Ian D., Herausgeber. Strachan, Mark W. J., Herausgeber. Hobson, Richard P., Herausgeber. Britton, Robert, Illustrator. Davidson, Leybourne S. 1894-1981 Begründer des Werks. (2018-04-23). Davidson's principles and practice of medicine. ISBN 978-0-7020-7028-0. OCLC 1040673074.CS1 maint: multiple names: authors list (link) 3. ^ "Mosby's Medical Dictionary:atopy". Archived from the original on 2011-07-10. 4. ^ a b c Wright, Rosalind J; Enlow, Michelle Bosquet (2008-09-01). "Maternal stress and perinatal programming in the expression of atopy". Expert Review of Clinical Immunology. 4 (5): 535–538. doi:10.1586/1744666X.4.5.535. ISSN 1744-666X. PMC 2762209. PMID 19838310. 5. ^ Coca AF, Cooke RA. (1923) On the classification of the phenomenon of hypersensitiveness J Immunol 6. ^ Johannes Ring; Bernhard Przybilla; Thomas Ruzicka (2006). Handbook of atopic eczema. Birkhäuser. pp. 3–. ISBN 978-3-540-23133-2. Retrieved 4 May 2010. 7. ^ Ruby Pawankar; Stephen T. Holgate; Lanny J. Rosenwasser (7 April 2009). Allergy Frontiers: Classification and Pathomechanisms. Springer. pp. 33–. ISBN 978-4-431-88314-2. Retrieved 4 May 2010. 8. ^ "atopy". Online Etymology Dictionary. Douglas Harper. 2019. Retrieved 26 Sep 2019. 9. ^ Simpson, Angela; Tan, Vincent Y. F.; Winn, John; Svensén, Markus; Bishop, Christopher M.; Heckerman, David E.; Buchan, Iain; Custovic, Adnan (June 2010). "Beyond Atopy". American Journal of Respiratory and Critical Care Medicine. 181 (11): 1200–1206. doi:10.1164/rccm.200907-1101oc. ISSN 1073-449X. PMID 20167852. 10. ^ Sun, Hai-Lun; Yeh, Chih-Jung; Ku, Min-Sho; Lue, Ko-Huang (2012-01-01). "Coexistence of allergic diseases: Patterns and frequencies". Allergy and Asthma Proceedings. 33 (1): e1-4. doi:10.2500/aap.2012.33.3506. ISSN 1088-5412. PMID 22370527. 11. ^ Mansueto P, Seidita A, D'Alcamo A, Carroccio A (2014). "Non-celiac gluten sensitivity: literature review" (PDF). J Am Coll Nutr (Review). 33 (1): 39–54. doi:10.1080/07315724.2014.869996. hdl:10447/90208. PMID 24533607. S2CID 22521576. 12. ^ González-Cervera J, Arias Á, Redondo-González O, Cano-Mollinedo MM, Terreehorst I, Lucendo AJ (2017). "Association between atopic manifestations and eosinophilic esophagitis: A systematic review and meta-analysis". Ann Allergy Asthma Immunol (Systematic Review and Meta-analysis). 118 (5): 582–590.e2. doi:10.1016/j.anai.2017.02.006. PMID 28366582. 13. ^ a b c d e "Davidson's Principles and Practice of Medicine, IE Edition, 20th Ed: Medicine—Clinical Medicine". Journal of Endocrinology, Metabolism and Diabetes of South Africa. 13 (2): 75. July 2008. doi:10.1080/22201009.2008.10872174. ISSN 1608-9677. S2CID 220276722. 14. ^ Küster, W.; Petersen, M.; Christophers, E.; Goos, M.; Sterry, W. (December 12, 2004). "A family study of atopic dermatitis". Archives of Dermatological Research. 282 (2 / January, 1990): 98–102. doi:10.1007/BF00493466. PMID 2353830. S2CID 9396200. 15. ^ Grammatikos AP (2008). "The genetic and environmental basis of atopic diseases". Ann. Med. 40 (7): 482–95. doi:10.1080/07853890802082096. PMID 18608118. S2CID 188280. 16. ^ A Swedish research study titled “Atopy In Children Of Families With An Anthroposophic Lifestyle” comparing the rate of bronchial asthma, allergies, dermatitis, and other atopic diseases among Steiner school pupils and pupils in public schools originally appeared in the May 1, 1999 edition of the British medical journal The Lancet. The findings indicated that Steiner school pupils were “at a significantly lower risk of atopy” than children attending public schools. The researchers investigated a variety of factors in the lives of the Steiner school pupils that might have contributed to this lower rate of atopy, which included breastfeeding, lack of immunization, avoidance of antibiotics and medications that reduce fevers, consumption of bio-dynamic and organic foods, and other physical aspects of the children’s lives. Devereux, Graham; Seaton, A. (December 2004). "Diet as a risk factor for atopy and asthma". J Allergy Clin Immunol. 115 (6): 1109–1117. doi:10.1016/j.jaci.2004.12.1139. PMID 15940119. 17. ^ Flöistrup H, Swartz J, Bergström A; et al. (January 2006). "Allergic disease and sensitization in Steiner school children" (PDF). J. Allergy Clin. Immunol. 117 (1): 59–66. doi:10.1016/j.jaci.2005.09.039. PMID 16387585.CS1 maint: multiple names: authors list (link) 18. ^ Blumenthal MN (2005). "The Role of Genetics in the Development of Asthma and Atopy". Curr Opin Allergy Clin Immunol. 5 (141–5): 141–5. doi:10.1097/01.all.0000162306.12728.c2. PMID 15764904. S2CID 30698973. 19. ^ Hoffjan S, Nicolae D, Ober C (2003). "Association Studies for Asthma and Atopic Diseases: A Comprehensive Review of the Literature". Respir Res. 4 (14): 14748924. doi:10.1186/1465-9921-4-14. PMC 314398. PMID 14748924. 20. ^ Bønnelykke, Klaus; Matheson, Melanie C; Pers, Tune H; Granell, Raquel; Strachan, David P; Alves, Alexessander Couto; Linneberg, Allan; Curtin, John A; Warrington, Nicole M; Standl, Marie; Kerkhof, Marjan; Jonsdottir, Ingileif; Bukvic, Blazenka K; Kaakinen, Marika; Sleimann, Patrick; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Schramm, Katharina; Baltic, Svetlana; Kreiner-Møller, Eskil; Simpson, Angela; Pourcain, Beate St; Coin, Lachlan; Hui, Jennie; Walters, Eugene H; Tiesler, Carla M T; Duffy, David L; Jones, Graham; Ring, Susan M; McArdle, Wendy L; Price, Loren; Robertson, Colin F; Pekkanen, Juha; Tang, Clara S; Thiering, Elisabeth; Montgomery, Grant W; Hartikainen, Anna-Liisa; Dharmage, Shyamali C; Husemoen, Lise L; Herder, Christian; Kemp, John P; Elliot, Paul; James, Alan; Waldenberger, Melanie; Abramson, Michael J; Fairfax, Benjamin P; Knight, Julian C; Gupta, Ramneek; Thompson, Philip J; Holt, Patrick; Sly, Peter; Hirschhorn, Joel N; Blekic, Mario; Weidinger, Stephan; Hakonarsson, Hakon; Stefansson, Kari; Heinrich, Joachim; Postma, Dirkje S; Custovic, Adnan; Pennell, Craig E; Jarvelin, Marjo-Riitta; Koppelman, Gerard H; Timpson, Nicholas; Ferreira, Manuel A; Bisgaard, Hans; Henderson, A John (30 June 2013). "Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization". Nature Genetics. 45 (8): 902–906. doi:10.1038/ng.2694. PMC 4922420. PMID 23817571. 21. ^ Amaral, André F. S.; Minelli, Cosetta; Guerra, Stefano; Wjst, Matthias; Probst-Hensch, Nicole; Pin, Isabelle; Svanes, Cecilie; Janson, Christer; Heinrich, Joachim; Jarvis, Deborah L. (December 2014). "The locus increases susceptibility to poly-sensitisation" (PDF). Allergy. 70 (3): 328–333. doi:10.1111/all.12557. hdl:10044/1/21574. PMID 25546184. S2CID 25960081. 22. ^ Nguyen, T.; Zuniga, R. (2013). "Skin conditions: New drugs for managing skin disorders". FP Essentials. 407: 11–16. PMID 23600334. 23. ^ Lee, S. W.; Cheong, S. H.; Byun, J. Y.; Choi, Y. W.; Choi, H. Y. (2013). "Occupational hand eczema among nursing staffs in Korea: Self-reported hand eczema and contact sensitization of hospital nursing staffs". The Journal of Dermatology. 40 (3): 182–187. doi:10.1111/1346-8138.12036. PMID 23294332. 24. ^ O'Regan GM, Sandilands A, McLean WH, Irvine AD (2008). "Filaggrin in Atopic Dermatitis". J Allergy Clin Immunol. 122 (4): 689–93. doi:10.1016/j.jaci.2008.08.002. PMID 18774165. 25. ^ Breuer K, Kapp A, Werfel T (2001). "Bacterial Infections and Atopic Dermatitis". Allergy. 56 (11): 1034–41. doi:10.1034/j.1398-9995.2001.00146.x. PMID 11703215. S2CID 28897487.CS1 maint: multiple names: authors list (link) 26. ^ Abramson JS, Dahl MV, Walsh G, Blumenthal MN, Douglas SD, Quie PG (1982). "Antistaphylococcal IgE in Patients with Atopic Dermatitis". J Am Acad Dermatol. 7 (1): 105–110. doi:10.1016/s0190-9622(82)80017-0. PMID 7107990. 27. ^ Parish WE, Welbourn E, Champion RH (1976). "Hypersensitivity to Bacteria in Eczema. Ii. Titre and Immunoglobulin Class of Antibodies to Staphylococci and Micrococci". Br J Dermatol. 95 (3): 285–93. doi:10.1111/j.1365-2133.1976.tb07016.x. PMID 974019. S2CID 5842899. 28. ^ Motala C, Potter PC, Weinberg EG, Malherbe D, Hughes J (1986). "Anti-Staphylococcus aureus-Specific IgE in Atopic Dermatitis". J Allergy Clin Immunol. 78 (4 Pt 1): 583–9. doi:10.1016/0091-6749(86)90075-8. PMID 3771950. 29. ^ Amaral, André F.S.; Newson, Roger B.; Abramson, Michael J.; Antó, Josep M.; Bono, Roberto; Corsico, Angelo G.; de Marco, Roberto; Demoly, Pascal; Forsberg, Bertil; Gislason, Thorarinn; Heinrich, Joachim; Huerta, Ismael; Janson, Christer; Jõgi, Rain; Kim, Jeong-Lim; Maldonado, José; Martinez-Moratalla Rovira, Jesús; Neukirch, Catherine; Nowak, Dennis; Pin, Isabelle; Probst-Hensch, Nicole; Raherison-Semjen, Chantal; Svanes, Cecilie; Urrutia Landa, Isabel; van Ree, Ronald; Versteeg, Serge A.; Weyler, Joost; Zock, Jan-Paul; Burney, Peter G.J.; Jarvis, Deborah L. (November 2015). "Changes in IgE sensitization and total IgE levels over 20 years of follow-up". Journal of Allergy and Clinical Immunology. 137 (6): 1788–1795.e9. doi:10.1016/j.jaci.2015.09.037. PMC 4889785. PMID 26586040. 30. ^ Wollenberg, A.; Barbarot, S.; Bieber, T.; Christen-Zaech, S.; Deleuran, M.; Fink-Wagner, A.; Gieler, U.; Girolomoni, G.; Lau, S.; Muraro, A.; Czarnecka-Operacz, M. (May 2018). "Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I". Journal of the European Academy of Dermatology and Venereology. 32 (5): 657–682. doi:10.1111/jdv.14891. PMID 29676534. 31. ^ Reddel, Helen K.; Bateman, Eric D.; Becker, Allan; Boulet, Louis-Philippe; Cruz, Alvaro A.; Drazen, Jeffrey M.; Haahtela, Tari; Hurd, Suzanne S.; Inoue, Hiromasa; de Jongste, Johan C.; Lemanske, Robert F. (September 2015). "A summary of the new GINA strategy: a roadmap to asthma control". European Respiratory Journal. 46 (3): 622–639. doi:10.1183/13993003.00853-2015. ISSN 0903-1936. PMC 4554554. PMID 26206872. 32. ^ Klimek, Ludger; Bachert, Claus; Pfaar, Oliver; Becker, Sven; Bieber, Thomas; Brehler, Randolf; Buhl, Roland; Casper, Ingrid; Chaker, Adam; Czech, Wolfgang; Fischer, Jörg (2020-02-12). "Correction to "ARIA guideline 2019: treatment of allergic rhinitis in the German health system"". Allergo Journal International. 29 (2): 63–65. doi:10.1007/s40629-019-00115-4. ISSN 2197-0378. 33. ^ Petrides, C; Doherty, S; Patel, N (May 2019). "G462(P) Anaphylaxis nice guidelines: are we following the guidelines or is there is still a need to improve adherence". Trainees. BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health. doi:10.1136/archdischild-2019-rcpch.447. S2CID 208459511. ## External links[edit] Classification D * ICD-9-CM: 691.8 * OMIM: 147050 * DiseasesDB: 34489 * Case Studies in Environmental Medicine (CSEM): Environmental Triggers of Asthma – Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services. * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune 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	Atopy	c0392707	27,319	wikipedia	https://en.wikipedia.org/wiki/Atopy	2021-01-18T19:10:35	{"umls": ["C0392707"], "wikidata": ["Q757678"]}
A number sign (#) is used with this entry because COACH syndrome, which classically comprises cerebellar vermis hypo/aplasia, oligophrenia (mental retardation), ataxia, ocular coloboma, and hepatic fibrosis, is most commonly associated with compound heterozygous mutation in the TMEM67 gene (609884) on chromosome 8q22. Joubert syndrome-6 (JBTS6; 610688) and Meckel syndrome type 3 (MKS3; 607361) are allelic disorders with overlapping phenotypes. Less commonly, COACH syndrome is caused by mutation in other Joubert-associated genes, including CC2D2A (612013) and RPGRIP1L (610937). Description COACH syndrome is an autosomal recessive disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Other features, such as coloboma and renal cysts, may be variable. COACH syndrome is considered by some to be a subtype of Joubert syndrome (JBTS; see 213300) with congenital hepatic fibrosis. Identification of liver disease in these patients is critical because some may develop complications such as portal hypertension with fatal variceal bleeding (Brancati et al., 2009; Doherty et al., 2010). Clinical Features Verloes and Lambotte (1989) described 3 affected children in 2 sibships. In 1 of the families with an affected boy and girl, the parents were consanguineous. The features were early-onset ataxia with hypo/aplastic vermis, hepatic fibrocirrhosis, slender skeleton, peculiar face, and moderate mental retardation. Verloes and Lambotte (1989) concluded that the disorder is different from Joubert syndrome (see 213300), including the form associated with chorioretinal coloboma (243910), due to the lack of hepatic involvement in those disorders. In 2 sibs reported by Verloes and Lambotte (1989), Brancati et al. (2009) identified compound heterozygosity for 2 mutations in the TMEM67 gene (609884.0013-609884.0014). Additional clinical features included hypotonia, nystagmus, coloboma, and nephronophthisis with renal failure. Wiesner et al. (1992) described adult sibs with this disorder. Postmortem in the sister, who died at age 46, showed distorted biliary ducts and multiple small medullary renal cysts. Because changes in the liver suggested biliary ductal proliferation, a trial of ursodiol was initiated in the younger brother with benefit. Wiesner et al. (1992) suggested that biliary proliferation is a manifestation of hepatic fibrosis in this disorder. Gentile et al. (1996) reported 2 brothers of Italian descent with COACH syndrome. Clinical features included mental retardation, cerebellar ataxia with hypoplastia of the inferior vermis, visual impairment with nystagmus and oculomotor apraxia, and congenital hepatic fibrosis, with abundant bile ductules. From birth, both children showed developmental delay and hypotonia. One child required liver transplantation. Mild dysmorphic facial feature were also described, including hypertelorism, frontal bossing, anteverted nostrils, and downslanting palpebral fissures. Gentile et al. (1996) noted the phenotypic overlap with Joubert and Meckel syndromes. In the patients reported by Gentile et al. (1996), Brancati et al. (2009) identified compound heterozygosity for 2 mutations in the TMEM67 gene (609884.0016-609884.0017). Kumar and Rankin (1996) described 2 sisters, aged 23 years and 6 years, who were found to have congenital ataxia, bilateral coloboma, of the optic nerves, mental retardation, and abnormal liver function. Magnetic resonance imaging showed cerebellar vermis hypoplasia in the younger girl and liver biopsy showed hepatic fibrosis in the older sister. In addition to previously described findings typical of COACH syndrome, the older of the patients showed progressive renal insufficiency with fibrocystic changes on renal biopsy. They suggested that COACH syndrome may have been the diagnosis in the family reported by Dieterich and Straub (1980). Foell et al. (2002) described a child with profound cholestatic liver disease and COACH syndrome. At 2.5 months of age, the child was found to have cerebellar vermis hypoplasia and a unilateral optic nerve coloboma. Routine liver function testing at 5 months of age showed elevated liver enzymes. Liver biopsy at 16 months of age showed an early stage of cirrhosis with septal fibrosis and pseudolobules, inflammatory infiltrates, signs of cholestasis, and reduced numbers of intrahepatic bile ducts. There were no signs of kidney involvement. Brancati et al. (2009) defined COACH syndrome as a subtype of Joubert syndrome with congenital hepatic fibrosis. They identified 14 families with this constellation of features, including 1 of the original families with COACH syndrome reported by Verloes and Lambotte (1989). Clinical features of all families included moderate to severe mental retardation and liver disease, which varied from hepatomegaly and fluctuating liver enzymes to severe fibrosis with portal hypertension and esophageal variceal bleeding. All also had cerebellar vermis hypo- or aplasia, and all with brain MRI showed the molar tooth sign. Other features included developmental delay, hypotonia, oculomotor apraxia (75%), coloboma (42%), nystagmus, ataxia, and hyperreflexia (42%). Three patients (25%) had a severe malformation of the posterior fossa, with global cerebellar hypoplasia associated with cystic dilatation of the cisterna magna communicating with the fourth ventricle. Less common features included seizures (17%), choreodystonic movements (17%), nephronophthisis (33%), and breathing abnormalities (33%). In 1 family, a second pregnancy was terminated after prenatal ultrasound showed features consistent with Meckel syndrome, including occipital encephalocele and polydactyly. Doherty et al. (2010) reported 23 families with COACH syndrome, defined as Joubert syndrome with clinically apparent liver disease. The mean age of examination was 9 years (range 0 to 22 years). Invariant features included developmental delay, intellectual disability, hypotonia, and abnormal eye movements. Congenital hepatic fibrosis as ascertained by histology was confirmed in 18 (63%) of 26 cases. Although there were no deaths from liver disease, 4 (17%) had portal hypertension and 2 (8%) needed a liver transplant. Colobomata were present in 17 (71%) and renal disease was present in 10 (42%), including 5 with nephronophthisis and 6 with macrocystic kidney disease. Three (13%) had chronic renal insufficiency or end stage renal disease and 2 (8%) needed renal transplantation. Additional features included encephalocele (4%), abnormal respiratory control (80%), hypoplasia/agenesis of the corpus callosum (8%), ptosis (25%), and intestinal malrotation (8%). None had polydactyly or retinal dystrophy. Importantly, coloboma was not an invariant feature of COACH syndrome. Molecular Genetics In 8 (57%) of 14 families with COACH syndrome, defined as Joubert syndrome with congenital liver fibrosis, Brancati et al. (2009) identified compound heterozygous mutations in the TMEM67 gene (see, e.g., 609884.0013-609884.0017). The clinical variability of the disorder, relating to the extent and severity of liver and neurologic dysfunction as well as to the presence or absence of ocular and renal findings, was hypothesized to be due to genetic modifiers, similar to other ciliopathies, including Bardet-Biedl syndrome (BBS; 209900). The findings confirmed that COACH syndrome can be considered a distinct subtype of Joubert syndrome with congenital hepatic fibrosis. Based on the clinical features of a patient with Joubert syndrome-9 (JBTS9; 612285) associated with compound heterozygous mutations in the CC2D2A gene (612013.0004 and 612013.0006), Gorden et al. (2008) postulated that COACH syndrome, in some cases, may be a variant representing a transitional phenotype between Joubert syndrome and Meckel syndrome. The patient was a 22-year-old woman with agenesis of the corpus callosum, hydrocephalus, cerebellar vermis hypoplasia, abnormal eye movements, coloboma, mild renal disease, and hepatic fibrosis requiring liver transplant at age 10 years. Doherty et al. (2010) identified mutations in the TMEM67 gene in 19 (83%) of 23 families with COACH syndrome, defined as Joubert syndrome with liver disease. In contrast, TMEM67 mutations were only found in 2 (1%) of 209 families with Joubert syndrome without liver involvement. One patient with COACH syndrome had mutations in the CC2D2A gene (612013.0007 and 612013.0008), and 1 family had mutations in the RPGRIP1L gene (610937.0011 and 610937.0012). The findings further supported the concept that COACH syndrome is a form of Joubert syndrome with hepatic fibrosis. The proposed ciliary function for the TMEM67, CC2D2A, and RPGRIP1L genes supported a unifying underlying pathophysiology for liver disease in these disorders. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth HEAD & NECK Eyes \- Ocular coloboma \- Nystagmus \- Oculomotor apraxia \- Hypertelorism RESPIRATORY \- Abnormal breathing pattern ABDOMEN Liver \- Hepatic fibrosis, congenital \- Cirrhosis \- Ductal plate malformation \- Bile duct dilatation \- Hepatomegaly \- Portal hypertension Spleen \- Splenomegaly GENITOURINARY Kidneys \- Medullary cystic renal disease \- Nephronophthisis \- Renal failure NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation \- Hypotonia \- Ataxia \- Hyperreflexia \- Seizures (less common) \- Cerebellar vermis hypoplasia \- Molar tooth sign LABORATORY ABNORMALITIES \- Abnormal liver enzymes MISCELLANEOUS \- Onset in infancy \- Liver involvement can range from mild to severe \- Renal involvement and coloboma may not be present \- Considered to be part of the spectrum of Joubert syndrome ( 213300 ) and Meckel syndrome ( 249000 ) \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the transmembrane protein 67 gene (TMEM67, 609884.0013 ) \- Caused by mutation in the coiled-coil and C2 domains-containing protein 2A gene (CC2D2A, 612013.0006 ) \- Caused by mutation in the RPGRIP1-like gene (RPGRIP1L, 610937.0011 ) ▲ 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	COACH SYNDROME	c1857662	27,320	omim	https://www.omim.org/entry/216360	2019-09-22T16:29:31	{"mesh": ["C536430"], "omim": ["216360"], "orphanet": ["1454"], "synonyms": ["Alternative titles", "CEREBELLAR VERMIS HYPO/APLASIA, OLIGOPHRENIA, CONGENITAL ATAXIA, OCULAR COLOBOMA, AND HEPATIC FIBROSIS", "JOUBERT SYNDROME WITH CONGENITAL HEPATIC FIBROSIS"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (September 2017) STAR syndrome Other namesSyndactyly with Renal and Anogenital Malformation STAR syndrome is a rare X-linked dominant disorder. Its core features include toe syndactyly, telecanthus and anogenital and renal malformations.[1] The underlying cause is mutation in the FAM58A gene. There have currently been 10 cases reported.[2] ## References[edit] 1. ^ "Entry # 300707". OMIM. November 3, 2017. 2. ^ "STAR syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17. ## External links[edit] Classification D * OMIM: 300707 * MeSH: C567475 [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	STAR syndrome	c2678045	27,321	wikipedia	https://en.wikipedia.org/wiki/STAR_syndrome	2021-01-18T18:50:16	{"gard": ["10295"], "mesh": ["C567475"], "umls": ["C2678045"], "orphanet": ["140952"], "wikidata": ["Q39060033"]}
A number sign (#) is used with this entry because hyperekplexia-1 (HKPX1) is caused by heterozygous, homozygous, or compound heterozygous mutation in the GLRA1 gene (138491) on chromosome 5q32. Description Hyperekplexia is an early-onset neurologic disorder characterized by an exaggerated startle response to sudden, unexpected auditory or tactile stimuli. Affected individuals have brief episodes of intense, generalized hypertonia in response to stimulation. Neonates may have prolonged periods of rigidity and are at risk for sudden death from apnea or aspiration. Many affected infants have inguinal hernias. The symptoms tend to resolve after infancy, but adults may have increased startle-induced falls and/or experience nocturnal muscle jerks (summary by Ryan et al., 1992). ### Genetic Heterogeneity of Hyperekplexia See also HKPX2 (614619), caused by mutation in the GLRB gene (138492) on chromosome 4q31; HKPX3 (614618), caused by mutation in the GLYT2 gene (SLC6A5; 604159) on chromosome 11p15; and HKPX4 (618011), caused by mutation in the ATAD1 gene (614452) on chromsome 10q23. Hyperekplexia can also occur in early infantile epileptic encephalopathy-8 (EIEE8; 300607), caused by mutation in the ARHGEF9 gene (300429). See also sporadic stiff-man syndrome (184850) and the 'Jumping Frenchmen of Maine' (244100). Clinical Features Ryan et al. (1992) suggested that this disorder was first described by Kirstein and Silfverskiold (1958), who reported a 'family with emotionally precipitated drop seizures.' Suhren et al. (1966) described a family in which 25 persons spanning 5 generations with numerous instances of male-to-male transmission had transient congenital hypertonia that disappeared with sleep; hypertonia diminished during the first year of life. Later in life, affected individuals showed greatly exaggerated startle responses, which were sometimes associated with falling, markedly hyperactive brainstem reflexes (e.g., head retraction, palmomental and snout reflexes), and a momentary generalized jerking on falling asleep. The authors suggested an uninhibited nociceptive reflex pattern as a result of a defect in maturation. Barbiturate medication resulted in improvement. See also Kok and Bruyn (1962) (Kok and Suhren are the same person Went, 1974). Klein et al. (1972) reported a family in which 10 persons spanning 3 generations had a congenital form of stiff-man syndrome. Affected members had attacks of stiffness precipitated by surprise or minor physical contact and characterized by difficulty in making sudden movements; signs of myotonia or myokymia were not present. During the episodes, EMG showed continuous activity at rest with normal action potentials. The continuous electrical activity was abolished by diazepam. X-linkage could not be excluded because there was no male-to-male transmission. Sander et al. (1980) reported a large family with dominantly inherited congenital stiff-man syndrome. Affected infants were hypertonic at birth, but their tone became almost normal by 3 years of age. Stiffness reappeared at adolescence, often precipitated by sudden movement or cold. Sander et al. (1980) stated that the inherited form of the disorder is benign and that the sporadic form is more severe. Lingam et al. (1981) reported an affected family and suggested the term 'stiff-baby syndrome.' They noted that affected infants tend to look alert, frightened, and tense, and have a tendency to vomit due to hiatal hernias. In a family described by Morley et al. (1982), affected persons showed flexor hypertonia and hypokinesia during infancy. Later and throughout life, they showed an exaggerated startle reaction with involuntary myoclonus (occasionally resulting in a fall) and marked nocturnal myoclonic jerks. Morley et al. (1982) noted a high frequency of congenital dislocation of the hip and of inguinal hernia. The neurologic features could be controlled with clonazepam. Markand et al. (1984) examined 12 of 15 affected members of the family reported by Morley et al. (1982). Startles were best elicited by lightly touching the patient's nose, clapping or making other noises, or suddenly jolting the patient's chair. Electrophysiologic studies found a prominent C response 60 to 75 ms after median and peroneal nerve stimulation. The authors suggested that hyperactive long-loop reflexes may be the physiologic basis for the exaggerated startle. Saenz-Lope et al. (1984) identified the disorder, which they referred to as 'hyperekplexia,' in 5 of 7 children (3 brothers and 2 sisters) born to unrelated parents. No other members of the family were affected. Clonazepam was ineffective, whereas valproic acid, 5-hydroxytryptophan, or piracetam markedly reduced the abnormal startle. Ryan et al. (1989) identified a 5-generation kindred in which 30 of 52 persons at risk were affected with this disorder. Continuous and occasionally fatal muscular rigidity was present in infancy and electromyography showed continuous motor unit activity. An exaggerated startle response persisted throughout life; sudden, unexpected acoustic or tactile stimuli could precipitate a brief attack of intense rigidity with falling. Umbilical and inguinal hernias, presumably due to increased intraabdominal pressure, were common, as was nocturnal myoclonus. Dramatic improvement of symptoms followed treatment with clonazepam. Based on EMG findings, Ryan et al. (1989) concluded that startle disease and hereditary stiff-man syndrome are identical disorders. Hayashi et al. (1991) reported 2 unrelated Japanese families with hyperekplexia. The 9 affected members had various combinations of transient infantile hypertonia and hypokinesia, exaggerated startle response with falling episodes, nocturnal myoclonus, an easily elicited head retraction reflex, hip dislocation, and umbilical hernia. Treatment with clonazepam was effective in infants and children. Dubowitz et al. (1992) reported the case of a newborn infant with classic features of startle disease in whom the cerebrospinal fluid concentrations of gamma-aminobutyric acid (GABA) were substantially lower than normal during the first weeks of life. She improved greatly on clonazepam treatment. Dubowitz et al. (1992) suggested that the signs of this disorder may be due to a genetic defect or to delayed maturation resulting in low CSF GABA. The disorder may be confused with seizure disorder, but it does not have concomitant discharges on EEG. Milani et al. (1996) demonstrated a variable combination of clinical signs of hereditary hyperekplexia in an Italian family. The 1-year-old proband had excessive startle response, muscular hypertonia, and a continuing flexion state, whereas only startle response during early infancy was found in the mother, aged 30 years. The proband's second cousin died at the age of 45 days from apnea following myoclonic fits, and her father displayed hypertonia and muscle stiffening. No history of infantile hypertonia was recorded in the grandparents of either the proband or the affected second cousin. In affected members of this family, Milani et al. (1996) identified a mutation in the GLRA1 gene (138491.0005). Inheritance Hyperekplexia-1 shows both autosomal dominant (Shiang et al., 1993) and autosomal recessive inheritance (Rees et al., 1994). Mapping Ryan et al. (1992) studied a 5-generation family with startle disease and successfully treated 16 affected members, including 1 neonate, with clonazepam. Linkage analysis demonstrated tight linkage of the disorder with CSF1R (164770), which is located at 5q33.2-q33.3 (maximum lod of 7.10 at 3% recombination). The authors suggested that neurotransmitter receptors encoded by genes in the subtelomeric region of 5q are likely candidates for the site of the mutation in this disorder. Clonazepam acts through gamma-aminobutyric acid type A receptors; the GABRA1 gene (137160) is located at 5q34-q35 and the GABRG2 (137164) gene at 5q31.1-q33.1. In a later study, Ryan et al. (1992, 1992) performed linkage analysis in the original family and 3 additional affected pedigrees with 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid map of the region. The results provided strong evidence for genetic locus homogeneity and assigned the hyperekplexia locus to a 5.9-cM interval defined by CSF1R and D5S379, which are separated by a radiation hybrid (RH) map distance of 74 centirays (approximately 2.2-3.7 Mb). RH mapping eliminated the candidate genes GABRA1 and GABRG2 by showing that they are telomeric to the target region. Molecular Genetics In affected members of 4 families with autosomal dominant hyperekplexia, 2 of whom were reported by Ryan et al. (1992), Shiang et al. (1993) identified 2 heterozygous mutations in the GLRA1 gene (138491.0001-138491.0002). In a sporadic patient with startle disease, the offspring of a consanguineous marriage, Rees et al. (1994) identified a homozygous mutation in the GLRA1 gene (138491.0003). The phenotype was indistinguishable from that of dominant inheritance of GLRA1 mutations. In affected members of 2 consanguineous Turkish Kurd families with hyperekplexia, Siren et al. (2006) identified a large homozygous deletion, which included exons 1 to 7 of the GLRA1 gene (138491.0013). The deletion breakpoints were determined to be the same as those reported by Gilbert et al. (2004) in another affected Turkish Kurd family. Siren et al. (2006) suggested a founder effect. ### Associations Pending Confirmation For discussion of a possible role of variation in the gephyrin gene (GPHN; 603930) in hyperekplexia, see 603930.0002. Animal Model Feng et al. (1998) found that mice mutant for gephyrin (603930) exhibited a phenotype similar to that of humans with hyperekplexia. Mice homozygous for the 'spastic' (spa) mutation display a complex motor disorder with phenotypic features of hyperekplexia. In spa mice, Mulhardt et al. (1994) found aberrant splicing of the Glrb gene resulting in a truncated mRNA. The mouse mutant phenotype 'spasmodic' (spd), caused by mutation in the Glra1 gene, is inherited as a recessive and is phenotypically similar to hyperekplexia, including an altered startle response (Buckwalter et al., 1994). INHERITANCE \- Autosomal dominant \- Autosomal recessive ABDOMEN External Features \- Umbilical hernia \- Inguinal hernia SKELETAL Pelvis \- Hip dislocation NEUROLOGIC Central Nervous System \- Hypertonicity \- Hypokinesia in infancy \- Exaggerated startle response \- Myoclonus \- Nocturnal seizures \- Episodic generalized skeletal muscle contractions \- Frequent falls \- Hyperactive brainstem reflexes (head retraction, palmomental, snout) \- EMG shows continuous motor unit firing at rest \- EEG during episodes shows desynchronization Behavioral Psychiatric Manifestations \- Alert affect \- Tense affect \- Frightened expression MISCELLANEOUS \- Onset in infancy \- Infants may die from apnea or aspiration \- Good response to clonazepam \- See also adult-onset stiff person syndrome ( 184850 ) MOLECULAR BASIS \- Caused by mutation in the alpha-1 subunit of the glycine receptor gene (GLRA1, 138491.0001 ) ▲ 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	HYPEREKPLEXIA 1	c1835614	27,322	omim	https://www.omim.org/entry/149400	2019-09-22T16:39:08	{"doid": ["0060696"], "mesh": ["C538136"], "omim": ["149400"], "orphanet": ["3197"], "synonyms": ["Alternative titles", "STARTLE DISEASE, FAMILIAL", "STARTLE REACTION, EXAGGERATED", "EXAGGERATED STARTLE REACTION", "STHE", "STIFF-BABY SYNDROME", "STIFF-MAN SYNDROME, CONGENITAL", "STIFF-PERSON SYNDROME, CONGENITAL", "KOK DISEASE"], "genereviews": ["NBK1260"]}
A number sign (#) is used with this entry because of evidence that focal facial dermal dysplasia-4 (FFDD4) is caused by homozygous or compound heterozygous mutation in the CYP26C1 gene (608428) on chromosome 10q23. Description The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD4 is characterized by isolated, preauricular skin lesions (summary by Slavotinek et al., 2013). For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500). Clinical Features Prescott et al. (2006) described 3 unrelated children, a girl and 2 boys, with distinctive facial skin lesions present at birth, consisting of 2 to 3 well-circumscribed round or oval vesicular lesions, 0.5 cm to 1 cm in diameter, located along an arc on each cheek from the top of the ear to the corner of the mouth. The infant girl, born of healthy unrelated Flemish parents, had 3 skin lesions containing a small amount of fluid on each cheek as well as unilateral cleft lip and palate and a cutaneous hemangioma in the left palm. One of the infant boys, born of healthy unrelated Norwegian parents, had 2 preauricular lesions noted on both cheeks at birth; those deflated and were followed by eruption of a new, more medial, lesion on each cheek at 2 to 3 weeks of age. The lesions subsequently remained unchanged and were encircled by long, fine hairs. The other infant boy was born of healthy unrelated Dutch parents and had symmetric atrophic skin lesions on both cheeks at birth that persisted with a lanugo-like collar; he also had mildly cupped ears, a small chin, and a congenital nevus on the left foot. The girl and the Dutch boy had normal development, but the Norwegian boy had neurologic complications that were the sequelae of an unexplained left-sided intracranial perinatal hemorrhage. Microscopic examination of a biopsied lesion in the Norwegian boy showed fragmentation of elastic fibers with striation and a diffuse increase in mast cells in the dermis, consistent with nonreactive deep and superficial elastolysis. Cervantes-Barragan et al. (2011) classified the FFDD phenotype in the 3 sibs (2 boys and 1 girl) reported by Kowalski and Fenske (1992) as FFDD4. The parents were first cousins. Slavotinek et al. (2013) studied a 6-year-old girl and her 4-year-old brother who were born with bilateral blister-like lesions on the cheeks, extending from the ear down to the lateral commissures of the mouth, which filled with fluid daily during the first few years of life. Both sibs were later noted to have several intraoral polypoid lesions, measuring 1 cm to 2 cm, on the left buccal mucosa. At the time of examination, the girl's skin lesions were hypopigmented macules, whereas her brother's were rounded with a small center of cutis aplasia, bordered by a hyperpigmented rim with long thin fine hairs; the brother also had a small area of sparse hair growth in front of both ears. The remainder of the dermatologic examination was normal, except for numerous scattered dark brown nevi in the sister. She also had a history of multiple dental extractions and root canal surgery for dental caries. Their unrelated parents had normal skin and family history was negative for significant skin findings. Slavotinek et al. (2013) also studied an unrelated Belgian girl who at birth was noted to have symmetric preauricular ivory round-to-oval patches with an atrophic aspect; there were no other abnormalities, and the skin lesions remained stable after birth. Inheritance The inheritance pattern of FFDD4 in the patients reported by Slavotinek et al. (2013) was autosomal recessive. Molecular Genetics In a 6-year-old girl and her 4-year-old brother with focal facial dermal dysplasia who were negative for mutation in the TWIST2 gene (607556), Slavotinek et al. (2013) performed exome sequencing and identified compound heterozygosity for a duplication and a missense mutation in the CYP26C1 gene (608428.0001 and 608428.0002), which were maternally and paternally inherited, respectively, and were not present in 2 unaffected sibs. Analysis of the CYP26C1 gene in 12 more FFDD patients revealed 3 patients with FFDD4 who were homozygous for the duplication: 1 was a Belgian girl, and the other 2 were a Flemish girl and a Norwegian boy who had previously been reported by Prescott et al. (2006). INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Vesicular lesions, congenital bilateral, between ear and corner of mouth Mouth \- Polypoid lesions of buccal mucosa, 1 to 2 cm in diameter (in some patients) SKIN, NAILS, & HAIR Skin \- Vesicular lesions, congenital bilateral, between ear and corner of mouth \- Hyperpigmented rim with long fine hairs encircling the lesions (in some patients) Skin Histology \- Elastosis, nonreactive, deep and superficial MOLECULAR BASIS \- Caused by mutation in the cytochrome P450, subfamily XXVIC, polypeptide 1 gene (CYP26C1, 608428.0001 ) ▲ 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	FOCAL FACIAL DERMAL DYSPLASIA 4	c2936827	27,323	omim	https://www.omim.org/entry/614974	2019-09-22T15:53:31	{"mesh": ["C537068"], "omim": ["614974"], "orphanet": ["398189", "398166"], "synonyms": ["FFDD type IV", "FFDD4", "Focal facial dermal dysplasia 4", "Focal facial preauricular dysplasia"]}
Pars planitis is a disease of the eye that is characterized by inflammation of the narrowed area (pars plana) between the colored part of the eye (iris) and the choroid. This may lead to blurred vision; dark, floating spots in the vision; and progressive vision loss. As the condition advances, cataracts, retinal detachment, or macular edema (fluid within the retina) may develop. Pars planitis most often affects young men and is generally not associated with any other disease or symptoms (idiopathic); however, it can be associated with other autoimmune conditions such as multiple sclerosis and sarcoidosis. Treatment typically includes corticosteroid drugs, immunosuppressive medications, and/or 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	Pars planitis	c0030593	27,324	gard	https://rarediseases.info.nih.gov/diseases/7339/pars-planitis	2021-01-18T17:58:26	{"mesh": ["D015868"], "omim": ["606177"], "umls": ["C0030593"], "synonyms": ["Familial pars planitis (subtype)", "Intermediate uveitis", "Peripheral retinal inflammation", "Vitritis"]}
Aromatase excess syndrome Other namesHereditary prepubertal gynecomastia AEXS results when the function of aromatase is hyperactive. The aromatase protein (pictured) is responsible for the biosynthesis of estrogens like estradiol in the human body. SpecialtyEndocrinology Aromatase excess syndrome (AES or AEXS) is a rare genetic and endocrine syndrome which is characterized by an overexpression of aromatase, the enzyme responsible for the biosynthesis of the estrogen sex hormones from the androgens, in turn resulting in excessive levels of circulating estrogens and, accordingly, symptoms of hyperestrogenism. It affects both sexes, manifesting itself in males as marked or complete phenotypical feminization (with the exception of the genitalia; i.e., no pseudohermaphroditism) and in females as hyperfeminization.[1][2][3][4] To date, 30 males and 8 females with AEXS among 15 and 7 families, respectively, have been described in the medical literature.[1][2] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Society and culture * 5.1 Names * 5.2 Notable cases * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Observed physiological abnormalities of the condition include a dramatic overexpression of aromatase and, accordingly, excessive levels of estrogens including estrone and estradiol[5] and a very high rate of peripheral conversion of androgens to estrogens. In one study, cellular aromatase mRNA expression was found to be at least 10 times higher in a female patient compared to the control, and the estradiol/testosterone ratio after an injection of testosterone in a male patient was found to be 100 times greater than the control.[2] Additionally, in another study, androstenedione, testosterone, and dihydrotestosterone (DHT) were found to be either low or normal in males, and follicle-stimulating hormone (FSH) levels were very low (likely due to suppression by estrogen, which has antigonadotropic effects as a form of negative feedback inhibition on sex steroid production in sufficiently high amounts),[6] whereas luteinizing hormone (LH) levels were normal.[7] According to a recent review, estrone levels have been elevated in 17 of 18 patients (94%), while estradiol levels have been elevated only in 13 of 27 patients (48%).[1] As such, estrone is the main estrogen elevated in the condition.[1] In more than half of patients, circulating androstenedione and testosterone levels are low to subnormal.[1] The ratio of circulating estradiol to testosterone is >10 in 75% of cases.[1] FSH levels are said to be consistently low in the condition, while LH levels are in the low to normal range.[1] It is notable that gynecomastia has been observed in patients in whom estradiol levels are within the normal range.[1] This has been suggested to be due to in situ conversion of adrenal androgens into estrone and then estradiol (via local 17β-HSD) in breast tissue (where aromatase activity may be particularly high).[1] The symptoms of AEXS, in males, include heterosexual precocity (precocious puberty with phenotypically-inappropriate secondary sexual characteristics; i.e., a fully or mostly feminized appearance), severe prepubertal or peripubertal gynecomastia (development of breasts in males before or around puberty), high-pitched voice, sparse facial hair, hypogonadism (dysfunctional gonads), oligozoospermia (low sperm count), small testes, micropenis (an unusually small penis), advanced bone maturation, an earlier peak height velocity (an accelerated rate of growth in regards to height),[8] and short final stature due to early epiphyseal closure. The incidence of gynecomastia appears to be 100%, with 20 of 30 male cases opting for mastectomy according to a review.[1] In females, symptoms of AEXS include isosexual precocity (precocious puberty with phenotypically-appropriate secondary sexual characteristics), macromastia (excessively large breasts), an enlarged uterus, menstrual irregularities, and, similarly to males, accelerated bone maturation and short final height. Of seven females described in one report, three (43%) had macromastia.[2] Pubertal breast hypertrophy in association with AEXS has been described in two young girls.[9][10] Fertility, though usually affected to one degree or another—especially in males—is not always impaired significantly enough to prevent sexual reproduction, as evidenced by vertical transmission of the condition by both sexes.[2][3][4] ## Cause[edit] The root cause of AEXS is not entirely clear, but it has been elucidated that inheritable, autosomal dominant genetic mutations affecting CYP19A1, the gene which encodes aromatase, are involved in its etiology.[2][4][7] Different mutations are associated with differential severity of symptoms, such as mild to severe gynecomastia.[1][11] For example, duplications result in relatively mild gynecomastia, while deletions, resulting in chimeric genes, cause moderate or severe gynecomastia.[11] ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2017) ## Treatment[edit] Several treatments have been found to be effective in managing AEXS, including aromatase inhibitors and gonadotropin-releasing hormone analogues in both sexes, androgen replacement therapy with non-aromatizable androgens such as DHT in males, and progestogens (which, by virtue of their antigonadotropic properties at high doses, suppress estrogen levels) in females. In addition, male patients often seek bilateral mastectomy, whereas females may opt for breast reduction if warranted.[2][3][4] Medical treatment of AEXS is not absolutely necessary, but it is recommended as the condition, if left untreated, may lead to excessively large breasts (which may necessitate surgical reduction), problems with fertility, and an increased risk of endometriosis and estrogen-dependent cancers such as breast and endometrial cancers later in life.[2][12] At least one case of male breast cancer has been reported.[2] ## Society and culture[edit] ### Names[edit] AEXS has also been referred to as familial hyperestrogenism, familial gynecomastia, and familial adrenal feminization.[citation needed] ### Notable cases[edit] It has been hypothesized that the Pharaoh Akhenaten (husband of Queen Nefertiti) and other members of the 18th Dynasty of ancient Egypt may have suffered from AEXS.[13] Akhenaten and his relatives, including men and young girls, many of whom were the product of inbreeding, are described as having breasts and wide hips, and Akhenaten was described as having a "beautiful and feminine voice," unusual physical features that could be explained by AEXS or another form of hereditary hyperestrogenism.[13] However, numerous other physical abnormalities were also present in the Akhenaten family, and a variety of other conditions have been proposed to explain the observations instead.[14] Most recently, Loeys–Dietz syndrome was proposed as a probable cause, with gynecomastia and feminization possibly being caused by liver cirrhosis-induced hyperestrogenism.[14] ## See also[edit] * Androgen insensitivity syndrome * Aromatase deficiency * Congenital estrogen deficiency * Disorders of sex development * Estrogen insensitivity syndrome * Hyperestrogenism * Inborn errors of steroid metabolism ## References[edit] 1. ^ a b c d e f g h i j k Shozu, Makio; Fukami, Maki; Ogata, Tsutomu (2014). "Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis". Expert Review of Endocrinology & Metabolism. 9 (4): 397–409. doi:10.1586/17446651.2014.926810. ISSN 1744-6651. PMC 4162655. PMID 25264451. 2. ^ a b c d e f g h i Martin, Regina M.; Lin, Chin J.; Nishi, Mirian Y.; Billerbeck, Ana Elisa C.; Latronico, Ana Claudia; Russell, David W.; Mendonca, Berenice B. (2003). "Familial Hyperestrogenism in Both Sexes: Clinical, Hormonal, and Molecular Studies of Two Siblings". The Journal of Clinical Endocrinology & Metabolism. 88 (7): 3027–3034. doi:10.1210/jc.2002-021780. ISSN 0021-972X. PMID 12843139. 3. ^ a b c Stratakis CA, Vottero A, Brodie A, et al. (April 1998). "The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription". The Journal of Clinical Endocrinology and Metabolism. 83 (4): 1348–57. doi:10.1210/jc.83.4.1348. PMID 9543166. 4. ^ a b c d Gregory Makowski (22 April 2011). Advances in Clinical Chemistry. Academic Press. p. 158. ISBN 978-0-12-387025-4. Retrieved 24 May 2012. 5. ^ Binder G, Iliev DI, Dufke A, et al. (January 2005). "Dominant transmission of prepubertal gynecomastia due to serum estrone excess: hormonal, biochemical, and genetic analysis in a large kindred". The Journal of Clinical Endocrinology and Metabolism. 90 (1): 484–92. doi:10.1210/jc.2004-1566. PMID 15483104. 6. ^ de Lignières B, Silberstein S (April 2000). "Pharmacodynamics of oestrogens and progestogens". Cephalalgia: An International Journal of Headache. 20 (3): 200–7. doi:10.1046/j.1468-2982.2000.00042.x. PMID 10997774. S2CID 40392817. 7. ^ a b Fukami, Maki; Shozu, Makio; Ogata, Tsutomu (2012). "Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome". International Journal of Endocrinology. 2012: 1–8. doi:10.1155/2012/584807. ISSN 1687-8337. PMC 3272822. PMID 22319526. 8. ^ Meinhardt U, Mullis PE (2002). "The aromatase cytochrome P-450 and its clinical impact". Hormone Research. 57 (5–6): 145–52. doi:10.1159/000058374. PMID 12053085. S2CID 24115725. 9. ^ Agarwal VR, Sasano H, Takayama K, et al. Excessive levels of aromatase P450arom and its transcripts in breast adipose tissue of a girl with pubertal macromastia [Abstract P1–393]. Proceedings of the 79th Annual Meeting of the Endocrine Society; 1997 June 11–14; Minneapolis, MN, USA. Endocrine Society Press. 10. ^ Madeira J, Silva CC, Otto AP, Trarbach EB, Nishi MY, Rocha RI, Mendonca BB, Carvalho L (April 2015). "Aromatase Excess Syndrome in a 10-Year Old Girl with Gigantomastia". Endocrine Reviews. 36 (2 Suppl). 11. ^ a b Fukami M, Miyado M, Nagasaki K, Shozu M, Ogata T (2014). "Aromatase excess syndrome: a rare autosomal dominant disorder leading to pre-or peri-pubertal onset gynecomastia". Pediatric Endocrinology Reviews: PER. 11 (3): 298–305. PMID 24716396. 12. ^ Shozu, Makio; Sebastian, Siby; Takayama, Kazuto; Hsu, Wei-Tong; Schultz, Roger A.; Neely, Kirk; Bryant, Michael; Bulun, Serdar E. (2003). "Estrogen Excess Associated with Novel Gain-of-Function Mutations Affecting the Aromatase Gene". New England Journal of Medicine. 348 (19): 1855–1865. doi:10.1056/NEJMoa021559. ISSN 0028-4793. PMID 12736278. 13. ^ a b Braverman IM, Redford DB, Mackowiak PA (2009). "Akhenaten and the strange physiques of Egypt's 18th dynasty". Ann. Intern. Med. 150 (8): 556–60. doi:10.7326/0003-4819-150-8-200904210-00010. PMID 19380856. S2CID 24766974. 14. ^ a b Eshraghian, Ahad; Loeys, Bart (2012). "Loeys-Dietz syndrome: A possible solution for Akhenaten's and his family's mystery syndrome". South African Medical Journal. 102 (8): 661–4. doi:10.7196/SAMJ.5916. ISSN 2078-5135. PMID 22831939. ## External links[edit] Classification D * ICD-11: 5A92 * ICD-10: E30.1 * OMIM: 139300 * MeSH: C537436 External resources * Orphanet: 178345 * v * t * e Gonadal disorder Ovarian * Polycystic ovary syndrome * Premature ovarian failure * Estrogen insensitivity syndrome * Hyperthecosis Testicular Enzymatic * 5α-reductase deficiency * 17β-hydroxysteroid dehydrogenase deficiency * aromatase excess syndrome Androgen receptor * Androgen insensitivity syndrome * Familial male-limited precocious puberty * Partial androgen insensitivity syndrome Other * Sertoli cell-only syndrome General * Hypogonadism * Delayed puberty * Hypergonadism * Precocious puberty * Hypoandrogenism * Hypoestrogenism * Hyperandrogenism * Hyperestrogenism * Postorgasmic illness syndrome * Cytochrome P450 oxidoreductase deficiency * Cytochrome b5 deficiency * Androgen-dependent condition * Aromatase deficiency * Complete androgen insensitivity syndrome * Mild androgen insensitivity syndrome * Hypergonadotropic hypogonadism * Hypogonadotropic hypogonadism * Fertile eunuch syndrome * Estrogen-dependent condition * Premature thelarche * Gonadotropin insensitivity * Hypergonadotropic hypergonadism * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) * 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]: 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	Aromatase excess syndrome	c1970109	27,325	wikipedia	https://en.wikipedia.org/wiki/Aromatase_excess_syndrome	2021-01-18T18:28:07	{"gard": ["12949", "12494"], "mesh": ["C000591739", "C537436"], "umls": ["C1970109"], "orphanet": ["178345"], "wikidata": ["Q4795508"]}
## Summary ### Clinical characteristics. Primary congenital glaucoma (PCG) is characterized by elevated intraocular pressure (IOP), enlargement of the globe (buphthalmos), edema, and opacification of the cornea with rupture of Descemet's membrane (Haab’s striae), thinning of the anterior sclera and iris atrophy, anomalously deep anterior chamber, and structurally normal posterior segment except for progressive glaucomatous optic atrophy. Symptoms include photophobia, blepharospasm, and excessive tearing. Typically, the diagnosis is made in the first year of life. Depending on when treatment is instituted, visual acuity may be reduced and/or visual fields may be restricted. In untreated individuals, blindness invariably occurs. ### Diagnosis/testing. The diagnosis of PCG is based on clinical criteria including: elevated IOP in a child typically before age one year, enlargement of the globe, increased corneal diameter, cloudy corneas, breaks in Decsemet’s membrane (Haab’s striae) and anomalously deep anterior chamber. Identification of biallelic pathogenic variants in CYP1B1 or LTBP2 or identification of a heterozygous pathogenic variant in TEK confirms the diagnosis if clinical features are inconclusive. ### Management. Treatment of manifestations: Surgery (goniotomy, trabeculotomy, trabeculectomy, or deep sclerectomy) as early as possible; use of drainage implants or cyclodestruction if surgery fails; medication preoperatively and postoperatively to help control IOP; routine treatment of refractive errors and amblyopia. Prevention of secondary complications: Discontinuation of medications such as Phospholine Iodide® (echothiophate) before surgery to prevent prolonged apnea. Surveillance: Lifelong monitoring to ensure control of IOP. Agents/circumstances to avoid: Alpha-2 agonists because of risk for apnea and bradycardia. Evaluation of relatives at risk: If the pathogenic variant(s) have been identified in the family, molecular genetic testing of at-risk sibs as soon as possible after birth in order to avoid repeated examinations under anesthesia in young children who do not have the pathogenic variant(s). ### Genetic counseling. PCG caused by biallelic pathogenic variants in CYP1B1 or LTBP2 is inherited in an autosomal recessive manner. PCG caused by a heterozygous pathogenic variant in TEK is inherited in an autosomal dominant manner. * Autosomal recessive inheritance: 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. Heterozygotes (carriers) are asymptomatic; carrier testing for at-risk family members is possible if the pathogenic variants in the family are known. * Autosomal dominant inheritance: Each child of an individual with TEK-related PCG has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the PCG-causing pathogenic variant(s) in the family are known. ## Diagnosis ### Suggestive Findings Primary congenital glaucoma (PCG) should be suspected in infants or children with the following clinical features: * Photophobia, blepharospasm, and excessive tearing * Edema and opacification of the cornea with rupture of Descemet's membrane, known as Haab's striae * Thinning of the anterior sclera and atrophy of the iris * Structurally normal posterior segment except for progressive optic atrophy * Absence of structural changes in the anterior chamber that are consistent with a diagnosis of anterior segment dysgenesis or associated systemic disease. ### Establishing the Diagnosis The diagnosis of PCG is established in a proband by the following clinical criteria: * Elevated intraocular pressure (IOP) in an infant or child typically (but not always) before age one year. An IOP greater than 21 mm Hg (mercury) in one or both eyes as measured by applanation tonometry, I-care tonometry™, or pneumotonometry on at least two occasions is considered abnormally elevated. In general, normal intraocular pressure in children is 12.02 ± 3.74 mm Hg [Sihota et al 2006]. * Enlargement of the (infantile) globe (buphthalmos) * Increased corneal diameter and cloudy corneas * Breaks in Decsemet’s membrane (Haab’s striae) * Anomalously deep anterior chamber * Bilateral or unilateral findings Identification of biallelic pathogenic variants in CYP1B1 or LTBP2 or a heterozygous TEK pathogenic variant on molecular genetic testing (see Table 1) confirms the diagnosis if clinical features are inconclusive. Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Serial single-gene testing. Perform sequence analysis of CYP1B1, followed by deletion/duplication analysis if only one or no pathogenic variant is found. If no CYP1B1 pathogenic variants are identified, consider sequence analysis of LTBP2. Sequence analysis and gene-targeted deletion/duplication analysis of TEK can be considered next if one or no pathogenic has been identified. Targeted analysis for CYP1B1 pathogenic variant p.Glu387Lys may be performed first in individuals of Rom Slovakian ancestry. CYP1B1 pathogenic variant p.Gly61Glu may be performed first in individuals of Saudi Arabian ancestry. * A multigene panel that includes CYP1B1, LTBP2, TEK, and other genes of interest (see Differential Diagnosis) may also be considered. 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; thus, clinicians need to determine which multigene panel 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. (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. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). 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 Primary Congenital Glaucoma View in own window Gene 1Proportion of PGC Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method Sequence analysis 3Gene-targeted deletion/duplication analysis 4 CYP1B120%-100% of familial cases 5 10%-15% of simplex cases 6~ 90%-95%~5%-10% 7 LTBP2≤40% 8~100%Unknown 9 TEK10 families 109/10 families1 family Unknown 11, 12NA 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. 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. 5\. The probability of identifying pathogenic variants in CYP1B1 increases with the presence of: positive family history, parental consanguinity, and bilateral and severe disease. Differences in the number of individuals studied, the methods of ascertainment (familial vs. simplex cases, unilateral vs. bilateral disease), and the molecular genetic testing methods used make accurate estimates of variant detection frequency difficult. 6\. Mashima et al [2001], Stoilov et al [2002], Curry et al [2004] 7\. At least five CYP1B1 alleles with gross deletions, sometimes including the entire CYP1B1 along with adjacent genes, have been reported. Additionally, gross duplications and a complex mutational event are known. For details see Molecular Genetics, Table A, Locus-Specific Databases and HGMD. 8\. Ali et al [2009], Narooie-Nejad et al [2009], Micheal et al [2016] 9\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 10\. Heterozygous TEK pathogenic variants were identified in affected individuals from 10/189 unrelated families with PCG [Souma et al 2016]. 11\. Kaur et al [2005] presented evidence in a single individual that the combination of a heterozygous pathogenic variant in MYOC and a heterozygous pathogenic variant in CYP1B1 was associated with PCG, suggesting digenic inheritance. A report of a Chinese family segregating both primary congenital open-angle glaucoma (POAG) and PCG suggested that homozygous MYOC variants may cause PCG [Zhuo et al 2006]. 12\. Two additional loci, GLC3B on 1p36 [Akarsu et al 1996] and GLC3C on 14q24.3 [Stoilov & Sarfarazi 2002], have been linked to PCG; however, the genes at these loci are not known. One additional locus linked to PCG, on 14q24.2-q24.3, does not appear to overlap the GLC3C critical region [Firasat et al 2008]. ## Clinical Characteristics ### Clinical Description Primary congenital glaucoma (PCG) is characterized by developmental defect(s) of the trabecular meshwork and anterior chamber angle that prevent adequate drainage of aqueous humor, resulting in elevated intraocular pressure (IOP) and stretching of the sclera that produces an enlarged globe (buphthalmos). The following information comes from the detailed clinical papers on PCG of deLuise & Anderson [1983] and Ho & Walton [2004] unless otherwise noted. By definition, congenital glaucoma is present at birth; it is typically diagnosed in the first year of life. PCG is more common in males (65%) and is bilateral in 70% of individuals. The clinical signs and symptoms depend primarily on the age of onset and the severity of the disease. The classic symptoms include tearing, photophobia, and irritability. Occasionally, parents may notice cloudy and/or unusually large corneas in their child caused by corneal edema; the corneal enlargement generally occurs before age three years. The most severe clinical features are typically seen in the newborn, who may present with corneal opacity, increased corneal diameter, increased IOP, and an enlarged globe [Walton 1998]. In 35 newborns with PCG, corneal edema was present in 100% of the eyes, either as diffuse (90%) or localized (10%) opacity [Walton 1998]. Early detection and appropriate treatment of congenital glaucoma can improve visual outcome. In contrast to the permanent optic nerve cupping and visual field loss seen in adults with adult-onset glaucoma, the pressure-induced optic nerve cupping in infants and young children with PCG is reversible, particularly in the early stages of the disease. This favorable outcome is believed to be a result of the highly elastic nature of the tissues of the optic nerves of infants and young children [Allingham et al 2005]. A delay in treatment can result in reduced visual acuity and/or restricted visual fields. In untreated individuals, blindness invariably occurs. The ultimate visual outcome depends on the severity of the disease at diagnosis, the presence of other associated ocular abnormalities, response to surgical treatment, and success in controlling IOP on follow up. The earlier the onset of clinical manifestations of glaucoma, the worse the prognosis. Despite early treatment and multiple surgical interventions, some individuals with severe disease evident at birth develop significant visual impairment from corneal opacification, advanced glaucomatous damage, or amblyopia, and may eventually become legally blind. Individuals with milder forms of disease who present later in childhood often do well with a single surgical procedure and have an excellent visual prognosis later in life. The IOP is a significant prognostic factor for postoperative visual function, with substantially better vision observed in individuals with IOP <19 mm Hg. ### Phenotype Correlations by Gene CYP1B1. Individuals with CYP1B1 pathogenic variants needed significantly more surgical procedures to control intraocular pressure than individuals with congenital glaucoma of unknown cause, when both eyes of an individual were evaluated (P=0.003) or the worst eye was evaluated (P=0.011) [Della Paolera et al 2010]. The correlations with genotype have been inconsistent. Individuals with CYP1B1 pathogenic variants tend to have a higher operative success rate than individuals without identified CYP1B1 pathogenic variants in terms of better intraocular pressure control effect. Together, the presence or absence of pathogenic variants in CYP1B1 and the preoperative corneal opacity score can partially predict the outcome of PCG surgery [Chen et al 2014b]. Individuals with CYP1B1 pathogenic variants had higher last postoperative visit indices in terms of postoperative haze and the need for anti-glaucoma medications than individuals without pathogenic variants in CYP1B1 [Abu-Amero et al 2011]. LTBP2. Individuals with LTBP2-related PCG had clinical features not seen in individuals with pathogenic variants in CYP1B1 or TEK; these features included ectopia lentis, high arched palate, and mild-to-moderate osteopenia [Ali et al 2009]. TEK. Individuals with TEK-related congenital glaucoma exhibit a clinical phenotype that is variable in severity and age of onset [Souma et al 2016]. ### Genotype-Phenotype Correlations Walton and colleagues have shown that the phenotype can vary significantly in the same individual (one eye being more severely affected than the other) [Walton 1998]. CYP1B1. No consistent genotype-phenotype correlation has been observed for CYP1B1 pathogenic variants. Intra- and interfamilial variability is reported among individuals with identical CYP1B1 pathogenic variants [Berraho et al 2015, de Melo et al 2015]. No information is available on correlation between the CYP1B1 pathogenic variants and the success of surgical therapy. LTBP2. No genotype-phenotype correlation has been observed for LTBP2 pathogenic variants. TEK. No genotype-phenotype correlation has been observed for TEK pathogenic variants. ### Prevalence CYP1B1. The prevalence of CYP1B1 pathogenic variants in individuals with PCG varies: 20% in Japanese [Plásilová et al 1999], 33.3% in Indonesians [Sitorus et al 2003], 44% among Indians [Chakrabarti et al 2010], 50% among Brazilians [Stoilov et al 2002], 70% in Iranians [Chitsazian et al 2007], and 80%-100% among Saudi Arabians [Bejjani et al 2000, Abu-Amero et al 2011] and the Rom Slovakian population [Plásilová et al 1999]. The relatively higher prevalence of these pathogenic variants in the latter two populations could be attributed to consanguinity. Some pathogenic variants are more common in specific ethnic groups. For example: * p.Glu387Lys accounts for all the pathogenic variants in the Rom Slovakian population. * p.Gly61Glu accounts for 72% of the pathogenic variants in Saudi Arabians [Bejjani et al 1998]. Additional pathogenic variants have been associated (although with lesser frequencies) with other specific ethnic groups [Belmouden et al 2002, Panicker et al 2002, Chakrabarti et al 2006]. PCG occurs in all ethnic groups. The birth prevalence, however, varies worldwide: * 1:5,000-22,000 in western countries * 1:2,500 in the Middle East * 1:1,250 in the Rom population of Slovakia [Plásilová et al 1998] * 1:3,300 in the Indian state of Andhra Pradesh, where the disease accounts for approximately 4.2% of all childhood blindness [Dandona et al 2001] In Saudi Arabia and in the Rom population of Slovakia, PCG is the most common cause of childhood blindness [Plásilová et al 1998, Bejjani et al 2000]. ## Differential Diagnosis A number of congenital ocular conditions can mimic PCG and must be considered by the clinician [Khan 2011]. For example, the nonspecific findings of tearing and redness of the eyes may mimic more common conditions such as conjunctivitis or congenital nasolacrimal duct obstruction; ocular irritation with photophobia and redness may mimic the more frequent problem of corneal abrasion. Congenital glaucoma can be subcategorized by age of onset into the following three types: * Primary "newborn"-type congenital glaucoma. The most severe type; clinically apparent between birth and age one month * Primary "infantile" glaucoma (or infantile PCG) as described by Walton & Katsavounidou [2005]. Clinically recognized between age one month and two years * "Juvenile" ("late-recognized") primary infantile glaucoma. Onset clinically apparent after age two years The types do not correlate with a specific genetic cause, although primary "newborn"-type congenital glaucoma is more likely to be caused by mutation of CYP1B1 than the other types of congenital glaucoma in some populations. In the older child with juvenile onset, or in less severely affected individuals, the increase in intraocular pressure (IOP) is gradual; thus, corneal edema and opacity may be less obvious than in the newborn type. Progressive enlargement of the globe or "buphthalmos" usually does not occur after age three to four years [Ho & Walton 2004, Allingham et al 2005]. Conditions/syndromes associated with infantile glaucoma. A number of well-recognized conditions and syndromes may present with infantile glaucoma, along with other ocular and/or systemic findings. Some conditions may not be compatible with life (e.g., trisomy 13, trisomy 18, Walker-Warburg syndrome, and Zellweger Syndrome); others may be less severe or confined only to the eye. It is important to establish the diagnosis of an associated syndrome because of the implications for genetic counseling and treatment (see Table 2). ### Table 2. Conditions/Syndromes Associated with Infantile Glaucoma View in own window DisorderGene(s)MOIClinical Features Eye FindingsOther AniridiaPAX6 WT1 1AD * Complete or partial iris hypoplasia w/associated foveal hypoplasia, resulting in reduced visual acuity & nystagmus * Presents in early infancy * Frequently associated w/other ocular abnormalities, often of later onset, incl cataract, glaucoma, & corneal opacification& vascularization May occur either as an isolated ocular abnormality w/out systemic involvement or as part of WAGR syndrome 1 Anterior segment dysgenesis syndromes (e.g., Peters Plus syndrome)See footnote 2Phenotypically & genotypically distinct from PCG in general, but severe or advanced PCG can be difficult to distinguish clinically from some of the anterior segment dysgenesis syndromes; e.g., Peters anomalyPeters Plus syndrome: developmental delay, mild to severe ID, cleft lip, cleft palate Axenfeld-Rieger anomaly (anterior segment disorder)FOXC1 PITX2AD * Presents w/posterior embryotoxon & (variably) iris strands adherent to Schwalbe's line, iris hypoplasia, focal iris atrophy, & ectropion uveae. * Glaucoma develops in ~50% of affected individuals but is more common in those w/central iris changes & marked anterior iris insertion * Always bilateral, but may be distinctly asymmetric May occur in the setting of Axenfeld-Rieger syndrome (OMIM 180500): dysmorphic features, dental anomalies, sensorineural hearing loss, cardiac malformations, endocrine & orthopedic abnormalities MicrocorneaUnknown 3 * Corneal diameter <10 mm * Can be associated w/glaucoma & other ocular anomalies incl congenital cataracts, sclerocornea, & corneal plana May be a feature of systemic syndromes Congenital hereditary endothelial dystrophy (CHED; OMIM 217700)SLC4A11AR * Bilateral corneal opacification * May be difficult to distinguish from microcornea, but corneal diameter & IOP are usually normal in CHED * The primary defect in the corneal endothelium leads to corneal edema & opacification. * CHED & CG are known to coexist; exact incidence unknown 4 Sensorineural hearing loss Lowe syndromeOCRLXL * Dense congenital cataracts are found in all affected boys, infantile glaucoma in ~50% * All boys have impaired vision; corrected acuity rarely >20/100 * Almost all affected males have some ID Congenital hypotonia, delayed development, proximal renal tubular dysfunction (renal Fanconi type), progressive chronic renal failure and ESRD after age 10-20 yrs Neurofibromatosis type 1NF1AD * Iris Lisch nodules * CG rarely observed Multiple café au lait spots, axillary & inguinal freckling, cutaneous neurofibromas, learning disabilities in ≥50% of individuals Nance-Horan syndrome (OMIM 302350)NHSXLCataract and microcorneaSkeletal features Sturge-Weber syndrome (OMIM 185300)GNAQSee footnote 5CG w/associated angle anomalies in ≤60% of affected individualsNevus flammeus of the face, angioma of the meninges AD = autosomal dominant; AR = autosomal recessive; CG = congenital glaucoma; ESRD = end-stage renal disease; ID = intellectual disability; MOI = mode of inheritance; WAGR = Wilms tumor-aniridia-genital anomalies-retardation; XL = X-linked 1\. Pathogenic variants or deletions in PAX6 or its control elements are associated with isolated aniridia. Contiguous gene deletions including PAX6 and WT1 are associated with aniridia and the risk of one or more additional manifestations of WAGR. 2\. Anterior segment dysgenesis syndromes are a heterogeneous group of disorders that are usually inherited in an autosomal dominant manner with reduced penetrance. 3\. Huang et al [2015] 4\. Ramamurthy et al [2007] 5\. Somatic mosaic pathogenic variants in GNAQ have been reported in individuals with Sturge-Weber syndrome. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with primary congenital glaucoma (PCG), examination under anesthesia or sedation is warranted to make a complete assessment of both eyes. The examination includes the following: * Measurement of intraocular pressure (IOP) within the first few minutes of anesthesia * Measurement of corneal diameter * Examination of the anterior segment * Direct gonioscopy to rule out secondary glaucoma * Dilated fundus examination to evaluate for optic nerve damage * If the cornea is opaque, ultrasound biomicroscopy or optical coherence tomography to aid in evaluating the anterior segment structures * Measurement of axial length If the child is examined under anesthesia, consent may be obtained to perform the appropriate surgical procedure after evaluation under anesthesia. Consultation with a clinical geneticist and/or genetic counselor is recommended. ### Treatment of Manifestations The primary goal of treatment is to decrease IOP to prevent vision-threatening complications including corneal opacification and glaucomatous optic atrophy. Early treatment to control IOP will reverse some of these complications in children. A Cochcrane review analyzed the literature that addressed the surgical management of congenital glaucoma but could not draw any conclusions from the analysis [Ghate & Wang 2015]. Surgical treatment. The following approach is based on the work of deLuise & Anderson [1983], Ho & Walton [2004], Bowman et al [2011], Sharaawy & Bhartiya [2011], and Al-Obeidan et al [2014]. PCG is almost always managed surgically. The primary goal of surgery is to eliminate the resistance to aqueous outflow caused by the structural abnormalities in the anterior chamber angle. This goal may be accomplished through an internal approach (goniotomy) or an external approach (trabeculotomy or trabeculectomy). In goniotomy, the surgeon visualizes the anterior chamber structures through a special lens (goniolens) to create openings in the trabecular meshwork. The goal of the procedure is to eliminate any resistance imposed by the abnormal trabecular meshwork. A clear cornea is necessary for direct visualization of the anterior chamber structures during this procedure. In trabeculotomy, the trabecular meshwork is incised by cannulating Schlemm's canal with a metal probe or suture via an external opening in the sclera. In trabeculectomy, a section of trabecular meshwork and Schlemm's canal is removed under a partial thickness sclera flap to create a wound fistula [Morales et al 2013, Chen et al 2014a]. In deep sclerectomy the dissection of a deep scleral flap, deroofing of Schlemm's canal, and preserving the structural integrity of the trabecular meshwork results in improved aqueous outflow outside the anterior chamber. Note: In contrast to goniotomy, deep sclerectomy, trabeculotomy, and trabeculectomy can be performed in individuals with advanced glaucoma and cloudy corneas. Glaucoma drainage implants or cyclodestruction may be used to control IOP when initial surgical procedures have failed. More than one surgical intervention may be necessary to control IOP; thus, significant morbidity is associated with both PCG and the currently available surgical treatment options. Individuals with milder forms of disease who present later in childhood often do well with a single surgical procedure and have an excellent visual prognosis later in life. Clarity of the cornea and other ocular media, control of the ocular dimensions (corneal diameters and axial lengths), and optic nerve damage are important indicators of the course of the disease following surgery. Reported success rates for each (initial) procedure are approximately 80%. Infants with elevated IOP and cloudy corneas at birth have the poorest prognosis. The most favorable outcome is seen in infants in whom surgery is performed between the second and eighth month of life. With increasing age, surgery is less effective in preserving vision. Medications. Beta-blockers (e.g., timolol), parasympathomimetics (e.g., pilocarpine), sympathomimetics (e.g., adrenergic agonists and alpha-2 adrenergic receptor agonists), carbonic anhydrase inhibitors, and prostaglandin agonists have all been used. These medications, particularly the alpha-2 adrenergic receptor agonists, may have severe side effects and must be used with caution in infants and children [Maris et al 2005, Papadopoulos & Khaw 2007]. Surgery should not be delayed in an attempt to achieve medical control of IOP. Medication may be used preoperatively to lower the IOP to prevent optic nerve damage, to reduce the risk of sudden decompression of the globe, and to clear the cornea for better visualization during examination and surgery. Postoperatively, medication may help control IOP until the success of the surgical procedure is established. Medical therapy is also used when surgery may be life threatening or has led to incomplete control of the glaucoma [deLuise & Anderson 1983]. Treatment of refractive errors. Amblyopia from uncorrected refractive errors often associated with PCG must be treated to obtain optimal visual function. ### Prevention of Secondary Complications Medications such as Phospholine Iodide® (echothiophate) need to be discontinued before surgery, especially if succinylcholine is used because of the danger of prolonged apnea. ### Surveillance Lifelong monitoring is necessary to ensure control of IOP to preserve remaining vision and to prevent further loss of vision; the intervals at which monitoring needs to be performed vary depending on the severity of disease and control of IOP. Once IOP is controlled and the child is visually rehabilitated, follow up is typically every three months to keep IOP at the "target" level, which depends on the severity of the glaucomatous optic nerve damage and the age of the individual. Standard clinical follow-up tests include optic nerve photography and visual field testing. The complete ophthalmic evaluation often requires examination under anesthesia or sedation in infants and in young and uncooperative children. This process may be challenging to the individual, the family, and the treating physician [deLuise & Anderson 1983, Ho & Walton 2004]. ### Agents/Circumstances to Avoid Alpha-2 agonists should be avoided in children in the treatment of elevated IOP because of the risk for apnea and bradycardia. ### Evaluation of Relatives at Risk Testing at-risk sibs in the neonatal period may be helpful in establishing the diagnosis of PCG early and in avoiding repeated examinations under anesthesia in at-risk young children. * Molecular genetic testing alone is appropriate in sibs of affected individuals in whom the pathogenic variant(s) have been identified. * If the PCG-related pathogenic variant(s) have not been identified in an affected family member (i.e., no definitive exclusion of the disease is possible by molecular genetic testing), screening including IOP measurements under anesthesia/sedation may be necessary. Note: The literature is unclear as to timing of the onset of glaucoma, especially in families in whom pathogenic variants have been identified. In this high-risk group, it may be appropriate to perform yearly glaucoma screening into young adulthood. 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	Primary Congenital Glaucoma	c1533041	27,326	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1135/	2021-01-18T21:02:35	{"synonyms": []}
Trench fever Other namesWolhynia fever, shin bone fever, Meuse fever, His disease and His–Werner disease SpecialtyInfectious disease Symptomsfever Duration5 days Causesinfected insect bite Preventionbody hygiene MedicationTetracycline-group antibiotics DeathsRare Trench fever (also known as "five-day fever", "quintan fever" (Latin: febris quintana), and "urban trench fever"[1]) is a moderately serious disease transmitted by body lice. It infected armies in Flanders, France, Poland, Galicia, Italy, Salonika, Macedonia, Mesopotamia, Russia and Egypt in World War I.[2][3] Three noted sufferers during WWI were the authors J. R. R. Tolkien,[4] A. A. Milne,[5] and C. S. Lewis.[6] From 1915 to 1918 between one-fifth and one-third of all British troops reported ill had trench fever while about one-fifth of ill German and Austrian troops had the disease.[2] The disease persists among the homeless.[7] Outbreaks have been documented, for example, in Seattle[8] and Baltimore in the United States among injection drug users[9] and in Marseille, France,[8] and Burundi.[10] Trench fever is also called Wolhynia fever, shin bone fever, Meuse fever, His disease and His–Werner disease or Werner-His disease (after Wilhelm His Jr. and Heinrich Werner). The disease is caused by the bacterium Bartonella quintana (older names: Rochalimea quintana, Rickettsia quintana), found in the stomach walls of the body louse.[3] Bartonella quintana is closely related to Bartonella henselae, the agent of cat scratch fever and bacillary angiomatosis. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] The disease is classically a five-day fever of the relapsing type, rarely exhibiting a continuous course. The incubation period is relatively long, at about two weeks. The onset of symptoms is usually sudden, with high fever, severe headache, pain on moving the eyeballs, soreness of the muscles of the legs and back, and frequently hyperaesthesia of the shins. The initial fever is usually followed in a few days by a single, short rise but there may be many relapses between periods without fever.[11] The most constant symptom is pain in the legs.[3] Recovery takes a month or more. Lethal cases are rare, but in a few cases "the persistent fever might lead to heart failure".[4][11] Aftereffects may include neurasthenia, cardiac disturbances and myalgia.[11] ## Pathophysiology[edit] Bartonella quintana is transmitted by contamination of a skin abrasion or louse-bite wound with the faeces of an infected body louse (Pediculus humanus corporis). There have also been reports of an infected louse bite passing on the infection.[3][11] ## Diagnosis[edit] Serological testing is typically used to obtain a definitive diagnosis. Most serological tests would succeed only after a certain period of time past the symptom onset (usually a week). The differential diagnosis list includes typhus, ehrlichiosis, leptospirosis, Lyme disease, and virus-caused exanthema (measles or rubella).[citation needed] ## Treatment[edit] Tetracycline-group antibiotics (doxycycline, tetracycline) are commonly used. Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver disease, kidney dysfunction, in children under nine years and in pregnant women. The medication is administered for seven to ten days. ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1095. ISBN 978-1-4160-2999-1. 2. ^ a b Justina Hamilton Hill (1942). Silent Enemies: The Story of the Diseases of War and Their Control. G. P. Putnam's Sons. 3. ^ a b c d Francis Timoney; William Arthur Hagan (1973). Hagan and Bruner's Microbiology and Infectious Diseases of Domestic Animals. Cornell University Press. 4. ^ a b John Garth (2003). Tolkien and the Great War: The Threshold of Middle-earth. HarperCollins Publishers. 5. ^ Humphrey Carpenter; Mari Prichard (1984). The Oxford companion to children's literature. Oxford University Press. p. 351. ISBN 9780192115829. 6. ^ C. S. Lewis (1955). Surprised By Joy. Harcourt. 7. ^ Sarah Perloff (17 January 2020). "Trench Fever". EMedicine. 8. ^ a b Ohl, M. E.; Spach, D. H. (1 July 2000). "Bartonella quintana and Urban Trench Fever". Clinical Infectious Diseases. 31 (1): 131–135. doi:10.1086/313890. PMID 10913410. 9. ^ Comer, James A. (25 November 1996). "Antibodies to Bartonella Species in Inner-city Intravenous Drug Users in Baltimore, Md". Archives of Internal Medicine. 156 (21): 2491–5. doi:10.1001/archinte.1996.00440200111014. PMID 8944742. 10. ^ Raoult, D; Ndihokubwayo, JB; Tissot-Dupont, H; Roux, V; Faugere, B; Abegbinni, R; Birtles, RJ (1998). "Outbreak of epidemic typhus associated with trench fever in Burundi". The Lancet. 352 (9125): 353–358. doi:10.1016/S0140-6736(97)12433-3. PMID 9717922. S2CID 25814472. 11. ^ a b c d Edward Rhodes Stitt (1922). The Diagnostics and treatment of tropical diseases. P. Blakiston's Son & Co. ## External links[edit] Classification D * ICD-10: A79.0 * ICD-9-CM: 083.1 * MeSH: D014205 * DiseasesDB: 29814 External resources * eMedicine: med/2303 * Orphanet: 64694 * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis [v]: 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	Trench fever	c0040830	27,327	wikipedia	https://en.wikipedia.org/wiki/Trench_fever	2021-01-18T18:58:49	{"mesh": ["D014205"], "umls": ["C0040830"], "icd-9": ["083.1083.1"], "icd-10": ["A79.079.0"], "orphanet": ["64694"], "wikidata": ["Q393477"]}
Personality disorder characterized by unstable relationships, impulsivity, and strong emotional reactions Borderline personality disorder Other names * Emotionally unstable personality disorder – impulsive or borderline type[1] * Emotional intensity disorder[2] Idealization is seen in Edvard Munch's The Brooch. Eva Mudocci (1903)[3] SpecialtyPsychiatry SymptomsUnstable relationships, sense of self, and emotions; impulsivity; recurrent suicidal behavior and self-harm; fear of abandonment; chronic feeling of emptiness; inappropriate anger; feeling detached from reality[4][5] ComplicationsSuicide[4] Usual onsetEarly adulthood[5] DurationLong term[4] CausesUnclear[6] Risk factorsFamily history, trauma, abuse[4][7] Diagnostic methodBased on reported symptoms[4] Differential diagnosisIdentity disorder, mood disorders, post traumatic stress disorder, cptsd, substance use disorders, histrionic, narcissistic, or antisocial personality disorder[5][8] TreatmentBehavioral therapy[4] PrognosisImproves over time[5] Frequency1.6% of people in a given year[4] Personality disorders Cluster A (odd) * Paranoid * Schizoid * Schizotypal Cluster B (dramatic) * Antisocial * Borderline * Histrionic * Narcissistic Cluster C (anxious) * Avoidant * Dependent * Obsessive–compulsive Not specified * Depressive * Haltlose * Immature * Passive–aggressive * Cyclothymic * Psychopathy * v * t * e Borderline personality disorder (BPD), also known as emotionally unstable personality disorder (EUPD),[9] is a mental illness characterized by a long-term pattern of unstable relationships, distorted sense of self, and strong emotional reactions.[4][5][10] Those affected often engage in self-harm and other dangerous behavior.[4] They may also struggle with a feeling of emptiness, fear of abandonment, and detachment from reality.[4] Symptoms of BPD may be triggered by events considered normal to others.[4] BPD typically begins by early adulthood and occurs across a variety of situations.[5] Substance abuse, depression, and eating disorders are commonly associated with BPD.[4] Approximately 10% of people affected with the disorder die by suicide.[4][5] The disorder is often stigmatized in both the media and the psychiatric field.[11] The causes of BPD are unclear but seem to involve genetic, neurological, environmental, and social factors.[4][6] It occurs about five times more often in a person who has an affected close relative.[4] Adverse life events appear to also play a role.[7] The underlying mechanism appears to involve the frontolimbic network of neurons.[7] BPD is recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a personality disorder, along with nine other such disorders.[5] The condition must be differentiated from an identity problem or substance use disorders, among other possibilities.[5] BPD is typically treated with therapy, such as cognitive behavioral therapy (CBT) or dialectical behavior therapy (DBT).[4] DBT may reduce the risk of suicide in the disorder.[4] Therapy for BPD can occur one-on-one or in a group.[4] While medications cannot cure BPD, they may be used to help with the associated symptoms.[4] Severe cases of the disorder may require hospital care.[4] About 1.6% of people have BPD in a given year, with some estimates as high as 6%.[4][5] Women are diagnosed about three times as often as men.[5] The disorder appears to become less common among older people.[5] Up to half of those with BPD improve over a ten-year period.[5] Those affected typically use a high amount of healthcare resources.[5] There is an ongoing debate about the naming of the disorder, especially the suitability of the word borderline.[4] ## Contents * 1 Signs and symptoms * 1.1 Emotions * 1.2 Interpersonal relationships * 1.3 Behavior * 1.4 Self-harm and suicide * 1.5 Sense of self * 1.6 Cognitions * 1.7 Psychotic symptoms * 1.8 Disability * 2 Causes * 2.1 Genetics * 2.2 Brain abnormalities * 2.2.1 Neurobiology * 2.2.2 Hypothalamic-pituitary-adrenal axis * 2.2.3 Estrogen * 2.3 Developmental factors * 2.3.1 Childhood trauma * 2.4 Neurological patterns * 2.5 Mediating and moderating factors * 2.5.1 Executive function * 2.5.2 Family environment * 2.5.3 Self-complexity * 2.5.4 Thought suppression * 2.6 Developmental theories * 3 Diagnosis * 3.1 Diagnostic and Statistical Manual * 3.2 International Classification of Disease * 3.2.1 F60.30 Impulsive type * 3.2.2 F60.31 Borderline type * 3.3 Millon's subtypes * 3.4 Misdiagnosis * 3.5 Family members * 3.6 Adolescence * 3.7 Differential diagnosis and comorbidity * 3.7.1 Comorbid Axis I disorders * 3.7.1.1 Mood disorders * 3.7.1.2 Premenstrual dysphoric disorder * 3.7.2 Comorbid Axis II disorders * 4 Management * 4.1 Psychotherapy * 4.2 Medications * 4.3 Services * 5 Prognosis * 6 Epidemiology * 7 History * 7.1 Etymology * 8 Controversies * 8.1 Credibility and validity of testimony * 8.1.1 Dissociation * 8.1.2 Lying as a feature * 8.2 Gender * 8.3 Manipulative behavior * 8.4 Stigma * 8.4.1 Physical violence * 8.4.2 Mental health care providers * 8.5 Terminology * 9 Society and culture * 9.1 Fiction * 9.2 Awareness * 10 See also * 11 References * 12 Bibliography * 13 External links ## Signs and symptoms[edit] One of the symptoms of BPD is fear of abandonment BPD is characterized by the following signs and symptoms: * Markedly disturbed sense of identity * Frantic efforts to avoid real or imagined abandonment, and extreme reactions to such * Splitting ("black-and-white" thinking) * Impulsive or reckless behaviors (e.g., impulsive or uncontrollable spending, unsafe sex, substance abuse, reckless driving, binge eating)[12] * Intense or uncontrollable emotional reactions that are disproportionate to the event or situation * Unstable and chaotic interpersonal relationships * Self-damaging behavior * Distorted self-image[4] * Dissociation * Frequently accompanied by depression, anxiety, anger, substance abuse, or rage Overall, the most distinguishing symptoms of BPD are marked sensitivity to minor rejection or criticism;[13] alternating between extremes of idealization and devaluation of others, along with varying moods and difficulty regulating strong emotional reactions. Dangerous and impulsive behavior are also correlated with the disorder. Other symptoms may include feeling unsure of one's personal identity, morals, and values; having paranoid thoughts when feeling stressed; depersonalization; and, in moderate to severe cases, stress-induced breaks with reality or psychotic episodes. ### Emotions[edit] People with BPD may feel emotions with greater ease and depth and for a longer time than others do.[14][15] A core characteristic of BPD is affective instability, which generally manifests as unusually intense emotional responses to environmental triggers, with a slower return to a baseline emotional state.[16][17] According to Marsha Linehan, the sensitivity, intensity, and duration with which people with BPD feel emotions have both positive and negative effects.[17] People with BPD are often exceptionally enthusiastic, idealistic, joyful, and loving,[18] but may feel overwhelmed by negative emotions (anxiety, depression, guilt/shame, worry, anger, etc.), experiencing intense grief instead of sadness, shame and humiliation instead of mild embarrassment, rage instead of annoyance, and panic instead of nervousness.[18] People with BPD are also especially sensitive to feelings of rejection, criticism, isolation, and perceived failure.[19] Before learning other coping mechanisms, their efforts to manage or escape from their very negative emotions may lead to emotional isolation, self-injury or suicidal behavior.[20] They are often aware of the intensity of their negative emotional reactions and, since they cannot regulate them, shut them down entirely since awareness would only cause further distress.[17] This can be harmful since negative emotions alert people to the presence of a problematic situation and move them to address it.[17] While people with BPD feel euphoria (ephemeral or occasional intense joy), they are especially prone to dysphoria (a profound state of unease or dissatisfaction), depression, and/or feelings of mental and emotional distress. Zanarini et al. recognized four categories of dysphoria typical of this condition: extreme emotions, destructiveness or self-destructiveness, feeling fragmented or lacking identity, and feelings of victimization.[21] Within these categories, a BPD diagnosis is strongly associated with a combination of three specific states: feeling betrayed, feeling out of control, and "feeling like hurting myself".[21] Since there is great variety in the types of dysphoria people with BPD experience, the amplitude of the distress is a helpful indicator.[21] In addition to intense emotions, people with BPD experience emotional "lability" (changeability, or fluctuation). Although that term suggests rapid changes between depression and elation, mood swings in people with BPD more frequently involve anxiety, with fluctuations between anger and anxiety and between depression and anxiety.[22] ### Interpersonal relationships[edit] People with BPD can be very sensitive to the way others treat them, by feeling intense joy and gratitude at perceived expressions of kindness, and intense sadness or anger at perceived criticism or hurtfulness.[23] People with BPD often engage in idealization and devaluation of others, alternating between high positive regard for people and great disappointment in them.[24] Their feelings about others often shift from admiration or love to anger or dislike after a disappointment, a threat of losing someone, or a perceived loss of esteem in the eyes of someone they value. This phenomenon is sometimes called splitting.[25] Combined with mood disturbances, idealization and devaluation can undermine relationships with family, friends, and co-workers.[26] While strongly desiring intimacy, people with BPD tend toward insecure, avoidant or ambivalent, or fearfully preoccupied attachment patterns in relationships,[27] and often view the world as dangerous and malevolent.[23] Like other personality disorders, BPD is linked to increased levels of chronic stress and conflict in romantic relationships, decreased satisfaction of romantic partners, abuse, and unwanted pregnancy.[28] ### Behavior[edit] Impulsive behavior is common, including substance or alcohol abuse, eating in excess, unprotected sex or indiscriminate sex with multiple partners, reckless spending, and reckless driving.[29] Impulsive behavior may also include leaving jobs or relationships, running away, and self-injury.[30] People with BPD might do this because it gives them the feeling of immediate relief from their emotional pain,[30] but in the long term they feel increased shame and guilt over the inevitable consequences of continuing this behavior.[30] A cycle often begins in which people with BPD feel emotional pain, engage in impulsive behavior to relieve that pain, feel shame and guilt over their actions, feel emotional pain from the shame and guilt, and then experience stronger urges to engage in impulsive behavior to relieve the new pain.[30] As time goes on, impulsive behavior may become an automatic response to emotional pain.[30] ### Self-harm and suicide[edit] Scarring as a result of self-harm, which is a common sign in borderline personality disorder.[4] Self-harming or suicidal behavior is one of the core diagnostic criteria in the DSM-5.[5] Self-harm occurs in 50 to 80% of people with BPD. The most frequent method of self-harm is cutting.[31] Bruising, burning, head banging or biting are not uncommon with BPD.[31] People with BPD may feel emotional relief after cutting themselves.[32] The lifetime risk of suicide among people with BPD is between 3% and 10%.[13][33] There is evidence that men diagnosed with BPD are approximately twice as likely to die by suicide as women diagnosed with BPD.[34] There is also evidence that a considerable percentage of men who die by suicide may have undiagnosed BPD.[35] The reported reasons for self-harm differ from the reasons for suicide attempts.[20] Nearly 70% of people with BPD self-harm without trying to end their life.[36] Reasons for self-harm include expressing anger, self-punishment, generating normal feelings (often in response to dissociation), and distracting oneself from emotional pain or difficult circumstances.[20] In contrast, suicide attempts typically reflect a belief that others will be better off following the suicide.[20] Both suicide and self-harm are a response to feeling negative emotions.[20] Sexual abuse can be a particular trigger for suicidal behavior in adolescents with BPD tendencies.[37] ### Sense of self[edit] People with BPD tend to have trouble seeing their identity clearly. In particular, they tend to have difficulty knowing what they value, believe, prefer, and enjoy.[38] They are often unsure about their long-term goals for relationships and jobs. This can cause people with BPD to feel "empty" and "lost".[38] Self-image can also change rapidly from healthy to unhealthy. ### Cognitions[edit] The often intense emotions people with BPD experience can make it difficult for them to concentrate.[38] They may also tend to dissociate, which can be thought of as an intense form of "zoning out".[39] Others can sometimes tell when someone with BPD is dissociating because their facial or vocal expressions may become flat or expressionless, or they may appear distracted.[39] Dissociation often occurs in response to a painful event (or something that triggers the memory of a painful event). It involves the mind automatically redirecting attention away from that event—presumably to protect against intense emotion and unwanted behavioral impulses that such emotion might trigger.[39] The mind's habit of blocking out intense painful emotions may provide temporary relief, but it can also have the side effect of blocking or blunting ordinary emotions, reducing the access of people with BPD to the information those emotions provide, information that helps guide effective decision-making in daily life.[39] ### Psychotic symptoms[edit] Though BPD is primarily seen as a disorder of emotional regulation, psychotic symptoms are fairly common, with an estimated 21-54% prevalence in clinical BPD populations.[40] These symptoms are sometimes referred to as “pseudo-psychotic” or “psychotic-like,” terms that suggest a distinction from those seen in primary psychotic disorders. Recent research, however, has indicated that there is more similarity between pseudo-psychotic symptoms in BPD and “true” psychosis than originally thought.[40][41] Some researchers critique the concept of pseudo-psychosis for, on top of weak construct validity, the implication that it’s “not true” or “less severe,” which could trivialize distress and serve as a barrier to diagnosis and treatment. Some researchers have suggested classifying these BPD symptoms as “true” psychosis, or even eliminating the distinction between pseudo-psychosis and true psychosis altogether.[40][42] The DSM-5 recognizes transient paranoia that worsens in response to stress as a symptom of BPD.[5] Studies have documented both hallucinations and delusions in BPD patients who lack another diagnosis that would better account those symptoms.[41] Phenomenologically, research suggests that auditory verbal hallucinations found in patients with BPD cannot be reliably distinguished from those seen in schizophrenia.[41][42] Some researchers suggest there may be a common etiology underlying hallucinations in BPD and those in other conditions like psychotic and affective disorders.[41] ### Disability[edit] Many people with BPD are able to work if they find appropriate jobs and their condition is not too severe. People with BPD may be found to have a disability in the workplace if the condition is severe enough that the behaviors of sabotaging relationships, engaging in risky behaviors or intense anger prevent the person from functioning in their job role.[43] ## Causes[edit] As is the case with other mental disorders, the causes of BPD are complex and not fully agreed upon.[44] Evidence suggests that BPD and post-traumatic stress disorder (PTSD) may be related in some way.[45] Most researchers agree that a history of childhood trauma can be a contributing factor,[46] but less attention has historically been paid to investigating the causal roles played by congenital brain abnormalities, genetics, neurobiological factors, and environmental factors other than trauma.[44][47] Social factors include how people interact in their early development with their family, friends, and other children.[48][unreliable medical source?] Psychological factors include the individual's personality and temperament, shaped by their environment and learned coping skills that deal with stress.[48][unreliable medical source?] These different factors together suggest that there are multiple factors that may contribute to the disorder.[49] ### Genetics[edit] The heritability of BPD is estimated to be between 37% to 69%.[50] That is, 37% to 69% of the variability in liability underlying BPD in the population can be explained by genetic differences. Twin studies may overestimate the effect of genes on variability in personality disorders due to the complicating factor of a shared family environment.[51] Even so, the researchers of one study concluded that personality disorders "seem to be more strongly influenced by genetic effects than almost any Axis I disorder [e.g., depression, eating disorders], and more than most broad personality dimensions".[52] Moreover, the study found that BPD was estimated to be the third most-heritable personality disorder out of the 10 personality disorders reviewed.[52] Twin, sibling, and other family studies indicate partial heritability for impulsive aggression, but studies of serotonin-related genes have suggested only modest contributions to behavior.[53] Families with twins in the Netherlands were participants of an ongoing study by Trull and colleagues, in which 711 pairs of siblings and 561 parents were examined to identify the location of genetic traits that influenced the development of BPD.[54] Research collaborators found that genetic material on chromosome 9 was linked to BPD features.[54] The researchers concluded that "genetic factors play a major role in individual differences of borderline personality disorder features".[54] These same researchers had earlier concluded in a previous study that 42% of variation in BPD features was attributable to genetic influences and 58% was attributable to environmental influences.[54] Genes under investigation as of 2012[update] include the 7-repeat polymorphism of the dopamine D4 receptor (DRD4) on chromosome 11, which has been linked to disorganized attachment, whilst the combined effect of the 7-repeat polymorphism and the 10/10 dopamine transporter (DAT) genotype has been linked to abnormalities in inhibitory control, both noted features of BPD.[55] There is a possible connection to chromosome 5.[56] ### Brain abnormalities[edit] A number of neuroimaging studies in BPD have reported findings of reductions in regions of the brain involved in the regulation of stress responses and emotion, affecting the hippocampus, the orbitofrontal cortex, and the amygdala, amongst other areas.[55] A smaller number of studies have used magnetic resonance spectroscopy to explore changes in the concentrations of neurometabolites in certain brain regions of BPD patients, looking specifically at neurometabolites such as N-acetylaspartate, creatine, glutamate-related compounds, and choline-containing compounds.[55] Some studies have identified increased gray matter in areas such as the bilateral supplementary motor area, dentate gyrus, and bilateral precuneus, which extends to the bilateral posterior cingulate cortex (PCC).[57] The hippocampus tends to be smaller in people with BPD, as it is in people with post-traumatic stress disorder (PTSD). However, in BPD, unlike PTSD, the amygdala also tends to be smaller.[58] This unusually strong activity may explain the unusual strength and longevity of fear, sadness, anger, and shame experienced by people with BPD, as well as their heightened sensitivity to displays of these emotions in others.[58] Given its role in regulating emotional arousal, the relative inactivity of the prefrontal cortex might explain the difficulties people with BPD experience in regulating their emotions and responses to stress.[59] #### Neurobiology[edit] Borderline personality disorder has previously been strongly associated with the occurrence of childhood trauma. While many psychiatric diagnoses are believed to be associated with traumatic experiences occurring during critical periods of childhood, specific neurobiological factors have been identified within patients diagnosed with BPD. Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol levels have been intensively studied in individuals who have experienced childhood traumas and have been formally diagnosed with BPD. The HPA axis functions to maintain homeostasis when the body is exposed to stressors but has been found to be dysregulated among individuals with a history of childhood abuse. When the body is exposed to stress, the hypothalamus, specifically the paraventricular nucleus (PVN) releases peptides arginine vasopressin (AVP) and corticotropin-releasing factor (CRF). When these peptides travel through the body, they stimulate corticotrophic cells, resulting in the release of adrenocorticotropic hormone (ACTH). ACTH binds to receptors in the adrenal cortex, which stimulates the release of cortisol. Intracellular glucocorticoid receptor subtypes of mineralocorticoid receptor (MR) and low-affinity type receptor (GR) have been found to mediate the effects of cortisol on different areas of the body. While MRs have high affinity for cortisol and are highly saturated in response to stress, GRs have low affinity for cortisol and bind cortisol at high concentrations when an individual is exposed to a stressor.[60] There have also been associations identified with FKBP5 polymorphisms, rs4713902 and rs9470079 in individuals with BPD. For those with BPD who have experienced childhood trauma, rs3798347-T and rs10947563-A have been associated, specifically in individuals with both BPD diagnosis and a history of childhood physical abuse and emotional neglect.[60] #### Hypothalamic-pituitary-adrenal axis[edit] The hypothalamic-pituitary-adrenal axis (HPA axis) regulates cortisol production, which is released in response to stress. Cortisol production tends to be elevated in people with BPD, indicating a hyperactive HPA axis in these individuals.[61] This causes them to experience a greater biological stress response, which might explain their greater vulnerability to irritability.[62] Since traumatic events can increase cortisol production and HPA axis activity, one possibility is that the prevalence of higher than average activity in the HPA axis of people with BPD may simply be a reflection of the higher than average prevalence of traumatic childhood and maturational events among people with BPD.[62] #### Estrogen[edit] Individual differences in women's estrogen cycles may be related to the expression of BPD symptoms in female patients.[63] A 2003 study found that women's BPD symptoms were predicted by changes in estrogen levels throughout their menstrual cycles, an effect that remained significant when the results were controlled for a general increase in negative affect.[64] ### Developmental factors[edit] #### Childhood trauma[edit] There is a strong correlation between child abuse, especially child sexual abuse, and development of BPD.[65][66][67] Many individuals with BPD report a history of abuse and neglect as young children, but causation is still debated.[68] Patients with BPD have been found to be significantly more likely to report having been verbally, emotionally, physically, or sexually abused by caregivers of either sex.[69] They also report a high incidence of incest and loss of caregivers in early childhood.[70] Individuals with BPD were also likely to report having caregivers of both sexes deny the validity of their thoughts and feelings. Caregivers were also reported to have failed to provide needed protection and to have neglected their child's physical care. Parents of both sexes were typically reported to have withdrawn from the child emotionally and to have treated the child inconsistently.[70] Additionally, women with BPD who reported a previous history of neglect by a female caregiver and abuse by a male caregiver were significantly more likely to have experienced sexual abuse by a non-caregiver.[70] It has been suggested that children who experience chronic early maltreatment and attachment difficulties may go on to develop borderline personality disorder.[71] Writing in the psychoanalytic tradition, Otto Kernberg argues that a child's failure to achieve the developmental task of psychic clarification of self and other and failure to overcome splitting might increase the risk of developing a borderline personality.[72] ### Neurological patterns[edit] The intensity and reactivity of a person's negative affectivity, or tendency to feel negative emotions, predicts BPD symptoms more strongly than does childhood sexual abuse.[73] This finding, differences in brain structure (see Brain abnormalities), and the fact that some patients with BPD do not report a traumatic history[74] suggest that BPD is distinct from the post-traumatic stress disorder which frequently accompanies it. Thus, researchers examine developmental causes in addition to childhood trauma. Research published in January 2013 by Anthony Ruocco at the University of Toronto has highlighted two patterns of brain activity that may underlie the dysregulation of emotion indicated in this disorder: (1) increased activity in the brain circuits responsible for the experience of heightened emotional pain, coupled with (2) reduced activation of the brain circuits that normally regulate or suppress these generated painful emotions. These two neural networks are seen to be dysfunctionally operative in the limbic system, but the specific regions vary widely in individuals, which calls for the analysis of more neuroimaging studies.[75] Also (contrary to the results of earlier studies) sufferers of BPD showed less activation in the amygdala in situations of increased negative emotionality than the control group. John Krystal, editor of the journal Biological Psychiatry, wrote that these results "[added] to the impression that people with borderline personality disorder are 'set-up' by their brains to have stormy emotional lives, although not necessarily unhappy or unproductive lives".[75] Their emotional instability has been found to correlate with differences in several brain regions.[76] ### Mediating and moderating factors[edit] #### Executive function[edit] While high rejection sensitivity is associated with stronger symptoms of borderline personality disorder, executive function appears to mediate the relationship between rejection sensitivity and BPD symptoms.[77] That is, a group of cognitive processes that include planning, working memory, attention, and problem-solving might be the mechanism through which rejection sensitivity impacts BPD symptoms. A 2008 study found that the relationship between a person's rejection sensitivity and BPD symptoms was stronger when executive function was lower and that the relationship was weaker when executive function was higher.[77] This suggests that high executive function might help protect people with high rejection sensitivity against symptoms of BPD.[77] A 2012 study found that problems in working memory might contribute to greater impulsivity in people with BPD.[78] #### Family environment[edit] Family environment mediates the effect of child sexual abuse on the development of BPD. An unstable family environment predicts the development of the disorder, while a stable family environment predicts a lower risk. One possible explanation is that a stable environment buffers against its development.[79] #### Self-complexity[edit] Self-complexity, or considering one's self to have many different characteristics, may lessen the apparent discrepancy between an actual self and a desired self-image. Higher self-complexity may lead a person to desire more characteristics instead of better characteristics; if there is any belief that characteristics should have been acquired, these may be more likely to have been experienced as examples rather than considered as abstract qualities. The concept of a norm does not necessarily involve the description of the attributes that represent the norm: cognition of the norm may only involve the understanding of "being like", a concrete relation and not an attribute.[80] #### Thought suppression[edit] A 2005 study found that thought suppression, or conscious attempts to avoid thinking certain thoughts, mediates the relationship between emotional vulnerability and BPD symptoms.[73] A later study found that the relationship between emotional vulnerability and BPD symptoms is not necessarily mediated by thought suppression. However, this study did find that thought suppression mediates the relationship between an invalidating environment and BPD symptoms.[81] ### Developmental theories[edit] Marsha Linehan's biosocial developmental theory of borderline personality disorder suggests that BPD emerges from the combination of an emotionally vulnerable child, and an invalidating environment. Emotional vulnerability may consist of biological, inherited factors that affect a child's temperament. Invalidating environments may include contexts where a child's emotions and needs are neglected, ridiculed, dismissed, or discouraged, or may include contexts of trauma and abuse. Linehan’s theory was modified by Sheila Crowell, who proposed that impulsivity also plays an important role in the development of BPD. Crowell found that children who are emotionally vulnerable and are exposed to invalidating environments are much more likely to develop BPD if they are also highly impulsive.[82] Both theories describe an interplay between a child’s inherited personality traits and their environment. For example, an emotionally sensitive or impulsive child may be difficult to parent, exacerbating the invalidating environment; conversely, invalidation can make an emotionally sensitive child more reactive and distressed. ## Diagnosis[edit] Diagnosis of borderline personality disorder is based on a clinical assessment by a mental health professional. The best method is to present the criteria of the disorder to a person and to ask them if they feel that these characteristics accurately describe them.[13] Actively involving people with BPD in determining their diagnosis can help them become more willing to accept it.[13] Some clinicians prefer not to tell people with BPD what their diagnosis is, either from concern about the stigma attached to this condition or because BPD used to be considered untreatable; it is usually helpful for the person with BPD to know their diagnosis.[13] This helps them know that others have had similar experiences and can point them toward effective treatments.[13] In general, the psychological evaluation includes asking the patient about the beginning and severity of symptoms, as well as other questions about how symptoms impact the patient's quality of life. Issues of particular note are suicidal ideations, experiences with self-harm, and thoughts about harming others.[83] Diagnosis is based both on the person's report of their symptoms and on the clinician's own observations.[83] Additional tests for BPD can include a physical exam and laboratory tests to rule out other possible triggers for symptoms, such as thyroid conditions or substance abuse.[83] The ICD-10 manual refers to the disorder as emotionally unstable personality disorder and has similar diagnostic criteria. In the DSM-5, the name of the disorder remains the same as in the previous editions.[5] ### Diagnostic and Statistical Manual[edit] The Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) has removed the multiaxial system. Consequently, all disorders, including personality disorders, are listed in Section II of the manual. A person must meet 5 of 9 criteria to receive a diagnosis of borderline personality disorder.[84] The DSM-5 defines the main features of BPD as a pervasive pattern of instability in interpersonal relationships, self-image, and affect, as well as markedly impulsive behavior.[84] In addition, the DSM-5 proposes alternative diagnostic criteria for BPD in section III, "Alternative DSM-5 Model for Personality Disorders". These alternative criteria are based on trait research and include specifying at least four of seven maladaptive traits.[85] According to Marsha Linehan, many mental health professionals find it challenging to diagnose BPD using the DSM criteria, since these criteria describe such a wide variety of behaviors.[86] To address this issue, Linehan has grouped the symptoms of BPD under five main areas of dysregulation: emotions, behavior, interpersonal relationships, sense of self, and cognition.[86] ### International Classification of Disease[edit] The World Health Organization's ICD-10 defines a disorder that is conceptually similar to BPD, called (F60.3) Emotionally unstable personality disorder. Its two subtypes are described below.[87] #### F60.30 Impulsive type[edit] At least three of the following must be present, one of which must be (2): 1. marked tendency to act unexpectedly and without consideration of the consequences; 2. marked tendency to engage in quarrelsome behavior and to have conflicts with others, especially when impulsive acts are thwarted or criticized; 3. liability to outbursts of anger or violence, with inability to control the resulting behavioral explosions; 4. difficulty in maintaining any course of action that offers no immediate reward; 5. unstable and capricious (impulsive, whimsical) mood. #### F60.31 Borderline type[edit] At least three of the symptoms mentioned in F60.30 Impulsive type must be present [see above], with at least two of the following in addition: 1. disturbances in and uncertainty about self-image, aims, and internal preferences; 2. liability to become involved in intense and unstable relationships, often leading to emotional crisis; 3. excessive efforts to avoid abandonment; 4. recurrent threats or acts of self-harm; 5. chronic feelings of emptiness; 6. demonstrates impulsive behavior, e.g., speeding in a car or substance abuse.[88] The ICD-10 also describes some general criteria that define what is considered a personality disorder. ### Millon's subtypes[edit] Theodore Millon has proposed four subtypes of BPD. He suggests that an individual diagnosed with BPD may exhibit none, one, or multiple of the following:[89] Subtype Features Discouraged borderline (including avoidant and dependent features) Pliant, submissive, loyal, humble; feels vulnerable and in constant jeopardy; feels hopeless, depressed, helpless, and powerless. Petulant borderline (including negativistic features) Negativistic, impatient, restless, as well as stubborn, defiant, sullen, pessimistic, and resentful; easily feels "slighted" and quickly disillusioned. Impulsive borderline (including histrionic or antisocial features) Captivating, capricious, superficial, flighty, distractable, frenetic, and seductive; fearing loss, the individual becomes agitated; gloomy and irritable; and potentially suicidal. Self-destructive borderline (including depressive or masochistic features) Inward-turning, intropunitive (self-punishing), angry; conforming, deferential, and ingratiating behaviors have deteriorated; increasingly high-strung and moody; possible suicide. ### Misdiagnosis[edit] Main article: Misdiagnosis of borderline personality disorder People with BPD may be misdiagnosed for a variety of reasons. One reason for misdiagnosis is BPD has symptoms that coexist (comorbidity) with other disorders such as depression, posttraumatic stress disorder (PTSD), and bipolar disorder.[90][91] ### Family members[edit] People with BPD are prone to feeling angry at members of their family and alienated from them. On their part, family members often feel angry and helpless at how their BPD family members relate to them.[13] Parents of adults with BPD are often both over-involved and under-involved in family interactions.[92] In romantic relationships, BPD is linked to increased levels of chronic stress and conflict, decreased satisfaction of romantic partners, domestic abuse, and unwanted pregnancy. However, these links may apply to personality disorders in general.[28] ### Adolescence[edit] Onset of symptoms typically occurs during adolescence or young adulthood, although symptoms suggestive of this disorder can sometimes be observed in children.[93] Symptoms among adolescents that predict the development of BPD in adulthood may include problems with body-image, extreme sensitivity to rejection, behavioral problems, non-suicidal self-injury, attempts to find exclusive relationships, and severe shame.[13] Many adolescents experience these symptoms without going on to develop BPD, but those who experience them are 9 times as likely as their peers to develop BPD. They are also more likely to develop other forms of long-term social disabilities.[13] BPD is recognised as a valid and stable diagnosis during adolescence.[94][95][96][97] The diagnosis of BPD (also described as "personality disorder: borderline pattern qualifier") in adolescents is supported in recent updates to the international diagnostic and psychiatric classification tools including the DSM-5 and ICD-11.[98][99][100] Early diagnosis of BPD has been recognised as instrumental to the early intervention and effective treatment for BPD in young people.[96][101][102] Accordingly, national treatment guidelines recommend the diagnosis and treatment of BPD among adolescents in many countries including Australia, the United Kingdom, Spain, and Switzerland.[103][104][105][106] The diagnosis of BPD during adolescence has been controversial.[96][107][108] Early clinical guidelines encouraged caution when diagnosing BPD during adolescence.[109][110][111] Perceived barriers to the diagnosis of BPD during adolescence included concerns about the validity of a diagnosis in young people, the misdiagnosis normal adolescent behaviour as symptoms of BPD, the stigmatising effect of a diagnosis for adolescents, and whether personality during adolescence was sufficiently stable for a valid diagnosis of BPD.[96] Psychiatric research has since shown BPD to be a valid, stable and clinically useful diagnosis in adolescent populations.[94][95][96][97] However, ongoing misconceptions about the diagnosis of BPD in adolescence remain prevalent among mental health professionals.[112][113][114] Clinical reluctance to diagnose BPD as a key barrier to the provision of effective treatment in adolescent populations.[112][115][116] A BPD diagnosis in adolescence might predict that the disorder will continue into adulthood.[109][117] Among individuals diagnosed with BPD during adolescence, there appears to be one group in which the disorder remains stable over time and another group in which the individuals move in and out of the diagnosis.[118] Earlier diagnoses may be helpful in creating a more effective treatment plan for the adolescent.[109][117] Family therapy is considered a helpful component of treatment for adolescents with BPD.[119] ### Differential diagnosis and comorbidity[edit] Lifetime comorbid (co-occurring) conditions are common in BPD. Compared to those diagnosed with other personality disorders, people with BPD showed a higher rate of also meeting criteria for[120] * mood disorders, including major depression and bipolar disorder * anxiety disorders, including panic disorder, social anxiety disorder, and post-traumatic stress disorder (PTSD) * other personality disorders, including schizotypal, antisocial and dependent personality disorder * substance abuse * eating disorders, including anorexia nervosa and bulimia * attention deficit hyperactivity disorder[121][non-primary source needed] * somatic symptom disorders (formerly known as somatoform disorders: a category of mental disorders included in a number of diagnostic schemes of mental illness) * dissociative disorders A diagnosis of a personality disorder should not be made during an untreated mood episode/disorder, unless the lifetime history supports the presence of a personality disorder. #### Comorbid Axis I disorders[edit] Sex differences in Axis I lifetime comorbid diagnosis, 2008[122] and 1998[120] Axis I diagnosis Overall (%) Male (%) Female (%) Mood disorders 75.0 68.7 80.2 Major depressive disorder 32.1 27.2 36.1 Dysthymia 09.7 07.1 11.9 Bipolar I disorder 31.8 30.6 32.7 Bipolar II disorder 07.7 06.7 08.5 Anxiety disorders 74.2 66.1 81.1 Panic disorder with agoraphobia 11.5 07.7 14.6 Panic disorder without agoraphobia 18.8 16.2 20.9 Social phobia 29.3 25.2 32.7 Specific phobia 37.5 26.6 46.6 PTSD 39.2 29.5 47.2 Generalized anxiety disorder 35.1 27.3 41.6 Obsessive-compulsive disorder 15.6 \--- \--- Substance use disorders 72.9 80.9 66.2 Any alcohol use disorder 57.3 71.2 45.6 Any drug use disorder 36.2 44.0 29.8 Eating disorders 53.0 20.5 62.2 Anorexia nervosa** 20.8 07 * 25 * Bulimia nervosa** 25.6 10 * 30 * Eating disorder not otherwise specified 26.1 10.8 30.4 Somatoform disorders 10.3 10 * 10 * Somatization disorder 04.2 \--- \--- Hypochondriasis 04.7 \--- \--- Somatoform pain disorder 04.2 \--- \--- Psychotic disorders 01.3 01 * 01 * * Approximate values ** Values from 1998 study[120] \--- Value not provided by study A 2008 study found that at some point in their lives, 75% of people with BPD meet criteria for mood disorders, especially major depression and bipolar I, and nearly 75% meet criteria for an anxiety disorder.[122] Nearly 73% meet criteria for substance abuse or dependency, and about 40% for PTSD.[122] It is noteworthy that less than half of the participants with BPD in this study presented with PTSD, a prevalence similar to that reported in an earlier study.[120] The finding that less than half of patients with BPD experience PTSD during their lives challenges the theory that BPD and PTSD are the same disorder.[120] There are marked sex differences in the types of comorbid conditions a person with BPD is likely to have[120] – a higher percentage of males with BPD meet criteria for substance-use disorders, while a higher percentage of females with BPD meet criteria for PTSD and eating disorders.[120][122][123] In one study, 38% of participants with BPD met the criteria for a diagnosis of ADHD.[121] In another study, 6 of 41 participants (15%) met the criteria for an autism spectrum disorder (a subgroup that had significantly more frequent suicide attempts).[124] Regardless that it is an infradiagnosed disorder, a few studies have shown that the "lower expressions" of it might lead to wrong diagnoses. The many and shifting Axis I disorders in people with BPD can sometimes cause clinicians to miss the presence of the underlying personality disorder. However, since a complex pattern of Axis I diagnoses has been found to strongly predict the presence of BPD, clinicians can use the feature of a complex pattern of comorbidity as a clue that BPD might be present.[120] ##### Mood disorders[edit] Many people with borderline personality disorder also have mood disorders, such as major depressive disorder or a bipolar disorder.[26] Some characteristics of BPD are similar to those of mood disorders, which can complicate the diagnosis.[125][126][127] It is especially common for people to be misdiagnosed with bipolar disorder when they have borderline personality disorder or vice versa.[128] For someone with bipolar disorder, behavior suggestive of BPD might appear while experiencing an episode of major depression or mania, only to disappear once mood has stabilized.[129] For this reason, it is ideal to wait until mood has stabilized before attempting to make a diagnosis.[129] At face value, the affective lability of BPD and the rapid mood cycling of bipolar disorders can seem very similar.[130] It can be difficult even for experienced clinicians, if they are unfamiliar with BPD, to differentiate between the mood swings of these two conditions.[131] However, there are some clear differences.[128] First, the mood swings of BPD and bipolar disorder tend to have different durations. In some people with bipolar disorder, episodes of depression or mania last for at least two weeks at a time, which is much longer than moods last in people with BPD.[128] Even among those who experience bipolar disorder with more rapid mood shifts, their moods usually last for days, while the moods of people with BPD can change in minutes or hours.[131] So while euphoria and impulsivity in someone with BPD might resemble a manic episode, the experience would be too brief to qualify as a manic episode.[129][131] Second, the moods of bipolar disorder do not respond to changes in the environment, while the moods of BPD do respond to changes in the environment.[129] That is, a positive event would not lift the depressed mood caused by bipolar disorder, but a positive event would potentially lift the depressed mood of someone with BPD. Similarly, an undesirable event would not dampen the euphoria caused by bipolar disorder, but an undesirable event would dampen the euphoria of someone with borderline personality disorder.[129] Third, when people with BPD experience euphoria, it is usually without the racing thoughts and decreased need for sleep that are typical of hypomania,[129] though a later 2013 study of data collected in 2004 found that borderline personality disorder diagnosis and symptoms were associated with chronic sleep disturbances, including difficulty initiating sleep, difficulty maintaining sleep, and waking earlier than desired, as well as with the consequences of poor sleep, and noted that "[f]ew studies have examined the experience of chronic sleep disturbances in those with borderline personality disorder".[132] Because the two conditions have a number of similar symptoms, BPD was once considered to be a mild form of bipolar disorder[133][134] or to exist on the bipolar spectrum. However, this would require that the underlying mechanism causing these symptoms be the same for both conditions. Differences in phenomenology, family history, longitudinal course, and responses to treatment suggest that this is not the case.[135] Researchers have found "only a modest association" between bipolar disorder and borderline personality disorder, with "a strong spectrum relationship with [BPD and] bipolar disorder extremely unlikely".[136] Benazzi et al. suggest that the DSM-IV BPD diagnosis combines two unrelated characteristics: an affective instability dimension related to bipolar II and an impulsivity dimension not related to bipolar II.[137] ##### Premenstrual dysphoric disorder[edit] Premenstrual dysphoric disorder (PMDD) occurs in 3–8% of women.[138] Symptoms begin during the luteal phase of the menstrual cycle, and end during menstruation.[139] Symptoms may include marked mood swings, irritability, depressed mood, feeling hopeless or suicidal, a subjective sense of being overwhelmed or out of control, anxiety, binge eating, difficulty concentrating, and substantial impairment of interpersonal relationships.[140][141] People with PMDD typically begin to experience symptoms in their early twenties, although many do not seek treatment until their early thirties.[140] Although some of the symptoms of PMDD and BPD are similar, they are different disorders. They are distinguishable by the timing and duration of symptoms, which are markedly different: the symptoms of PMDD occur only during the luteal phase of the menstrual cycle,[140] whereas BPD symptoms occur persistently at all stages of the menstrual cycle. In addition, the symptoms of PMDD do not include impulsivity.[140] #### Comorbid Axis II disorders[edit] Percentage of people with BPD and a lifetime comorbid Axis II diagnosis, 2008[122] Axis II diagnosis Overall (%) Male (%) Female (%) Any cluster A 50.4 49.5 51.1 Paranoid 21.3 16.5 25.4 Schizoid 12.4 11.1 13.5 Schizotypal 36.7 38.9 34.9 Any other cluster B 49.2 57.8 42.1 Antisocial 13.7 19.4 9.0 Histrionic 10.3 10.3 10.3 Narcissistic 38.9 47.0 32.2 Any cluster C 29.9 27.0 32.3 Avoidant 13.4 10.8 15.6 Dependent 3.1 2.6 3.5 Obsessive-compulsive 22.7 21.7 23.6 About three-fourths of people diagnosed with BPD also meet the criteria for another Axis II personality disorder at some point in their lives. (In a major 2008 study – see adjacent table – the rate was 73.9%.)[122] The Cluster A disorders, paranoid, schizoid, and schizotypal, are broadly the most common. The Cluster as a whole affects about half, with schizotypal alone affecting one third.[122] BPD is itself a Cluster B disorder. The other Cluster B disorders, antisocial, histrionic, and narcissistic, similarly affect about half of BPD patients (lifetime incidence), with again narcissistic affecting one third or more.[122] Cluster C, avoidant, dependent, and obsessive-compulsive, showed the least overlap, slightly under one third.[122] ## Management[edit] Main article: Management of borderline personality disorder Psychotherapy is the primary treatment for borderline personality disorder.[7] Treatments should be based on the needs of the individual, rather than upon the general diagnosis of BPD. Medications are useful for treating comorbid disorders, such as depression and anxiety.[142] Short-term hospitalization has not been found to be more effective than community care for improving outcomes or long-term prevention of suicidal behavior in those with BPD.[143] ### Psychotherapy[edit] Long-term psychotherapy is currently the treatment of choice for BPD.[144] While psychotherapy, in particular dialectical behavior therapy and psychodynamic approaches, is effective, the effects are slow: many people have to put in years of work to be effective.[145] More rigorous treatments are not substantially better than less rigorous treatments.[146] There are six such treatments available: dynamic deconstructive psychotherapy (DDP),[147] mentalization-based treatment (MBT), transference-focused psychotherapy, dialectical behavior therapy (DBT), general psychiatric management, and schema-focused therapy.[13] While DBT is the therapy that has been studied the most,[148] all these treatments appear effective for treating BPD, except for schema-focused therapy.[13][ambiguous] Long-term therapy of any kind, including schema-focused therapy, is better than no treatment, especially in reducing urges to self-injure.[144] Transference-focused therapy aims to break away from absolute thinking. In this, it gets the people to articulate their social interpretations and their emotions in order to turn their views into less rigid categories. The therapist addresses the individual's feelings and goes over situations, real or realistic, that could happen as well as how to approach them.[149] Dialectical behavior therapy (DBT) has similar components to CBT, adding in practices such as meditation. In doing this, it helps the individual with BPD gain skills to manage symptoms. These skills include emotion regulation, mindfulness, and stress hardiness.[149] Since those diagnosed with BPD have such intense emotions, learning to regulate them is a huge step in the therapeutic process. Some components of DBT are working long-term with patients, building skills to understand and regulate emotions, homework assignments, and strong availability of therapist to their client. [150] Patients with borderline personality disorder also must take time in DBT to work with their therapist to learn how to get through situations surrounded by intense emotions or stress as well as learning how to better their interpersonal relationships. The stages used in dialectical behavior therapy Cognitive behavioral therapy (CBT) is also a type of psychotherapy used for treatment of BPD. This type of therapy relies on changing people's behaviors and beliefs by identifying problems from the disorder. CBT is known to reduce some anxiety and mood symptoms as well as reduce suicidal thoughts and self-harming behaviors.[4] Mentalization-based therapy and transference-focused psychotherapy are based on psychodynamic principles, and dialectical behavior therapy is based on cognitive-behavioral principles and mindfulness.[144] General psychiatric management combines the core principles from each of these treatments, and it is considered easier to learn and less intensive.[13] Randomized controlled trials have shown that DBT and MBT may be the most effective, and the two share many similarities.[151][152] Researchers are interested in developing shorter versions of these therapies to increase accessibility, to relieve the financial burden on patients, and to relieve the resource burden on treatment providers.[144][152] Some research indicates that mindfulness meditation may bring about favorable structural changes in the brain, including changes in brain structures that are associated with BPD.[153][154][155] Mindfulness-based interventions also appear to bring about an improvement in symptoms characteristic of BPD, and some clients who underwent mindfulness-based treatment no longer met a minimum of five of the DSM-IV-TR diagnostic criteria for BPD.[155][156] ### Medications[edit] A 2010 review by the Cochrane collaboration found that no medications show promise for "the core BPD symptoms of chronic feelings of emptiness, identity disturbance, and abandonment". However, the authors found that some medications may impact isolated symptoms associated with BPD or the symptoms of comorbid conditions.[157] A 2017 review examined evidence published since the 2010 Cochrane review and found that "evidence of effectiveness of medication for BPD remains very mixed and is still highly compromised by suboptimal study design".[158] Of the typical antipsychotics studied in relation to BPD, haloperidol may reduce anger and flupenthixol may reduce the likelihood of suicidal behavior. Among the atypical antipsychotics, one trial found that aripiprazole may reduce interpersonal problems and impulsivity.[157] Olanzapine, as well as quetiapine, may decrease affective instability, anger, psychotic paranoid symptoms, and anxiety, but a placebo had a greater benefit on suicidal ideation than olanzapine did. The effect of ziprasidone was not significant.[157][158] Of the mood stabilizers studied, valproate semisodium may ameliorate depression, impulsivity, interpersonal problems, and anger. Lamotrigine may reduce impulsivity and anger; topiramate may ameliorate interpersonal problems, impulsivity, anxiety, anger, and general psychiatric pathology. The effect of carbamazepine was not significant. Of the antidepressants, amitriptyline may reduce depression, but mianserin, fluoxetine, fluvoxamine, and phenelzine sulfate showed no effect. Omega-3 fatty acid may ameliorate suicidality and improve depression. As of 2017[update], trials with these medications had not been replicated and the effect of long-term use had not been assessed.[157][158] Because of weak evidence and the potential for serious side effects from some of these medications, the United Kingdom (UK) National Institute for Health and Clinical Excellence (NICE) 2009 clinical guideline for the treatment and management of BPD recommends, "Drug treatment should not be used specifically for borderline personality disorder or for the individual symptoms or behavior associated with the disorder." However, "drug treatment may be considered in the overall treatment of comorbid conditions". They suggest a "review of the treatment of people with borderline personality disorder who do not have a diagnosed comorbid mental or physical illness and who are currently being prescribed drugs, with the aim of reducing and stopping unnecessary drug treatment".[159] ### Services[edit] There is a significant difference between the number of those who would benefit from treatment and the number of those who are treated. The so-called "treatment gap" is a function of the disinclination of the afflicted to submit for treatment, an underdiagnosing of the disorder by healthcare providers, and the limited availability and access to state-of-the-art treatments.[160] Nonetheless, individuals with BPD accounted for about 20% of psychiatric hospitalizations in one survey.[161] The majority of individuals with BPD who are in treatment continue to use outpatient treatment in a sustained manner for several years, but the number using the more restrictive and costly forms of treatment, such as inpatient admission, declines with time.[162] Experience of services varies.[163] Assessing suicide risk can be a challenge for clinicians, and patients themselves tend to underestimate the lethality of self-injurious behaviors. People with BPD typically have a chronically elevated risk of suicide much above that of the general population and a history of multiple attempts when in crisis.[164] Approximately half the individuals who commit suicide meet criteria for a personality disorder. Borderline personality disorder remains the most commonly associated personality disorder with suicide.[165] After a patient suffering from BPD died, The National Health Service (NHS) in England was criticized by a coroner in 2014 for the lack of commissioned services to support those with BPD. Evidence was given that 45% of female patients had BPD and there was no provision or priority for therapeutic psychological services. At the time, there were only a total of 60 specialized inpatient beds in England, all of them located in London or the northeast region.[166] ## Prognosis[edit] With treatment, the majority of people with BPD can find relief from distressing symptoms and achieve remission, defined as a consistent relief from symptoms for at least two years.[167][168] A longitudinal study tracking the symptoms of people with BPD found that 34.5% achieved remission within two years from the beginning of the study. Within four years, 49.4% had achieved remission, and within six years, 68.6% had achieved remission. By the end of the study, 73.5% of participants were found to be in remission.[167] Moreover, of those who achieved recovery from symptoms, only 5.9% experienced recurrences. A later study found that ten years from baseline (during a hospitalization), 86% of patients had sustained a stable recovery from symptoms.[169] Patient personality can play an important role during the therapeutic process, leading to better clinical outcomes. Recent research has shown that BPD patients undergoing dialectical behavior therapy (DBT) exhibit better clinical outcomes correlated with higher levels of the trait of agreeableness in the patient, compared to patients either low in agreeableness or not being treated with DBT. This association was mediated through the strength of a working alliance between patient and therapist; that is, more agreeable patients developed stronger working alliances with their therapists, which in turn, led to better clinical outcomes.[170] In addition to recovering from distressing symptoms, people with BPD also achieve high levels of psychosocial functioning. A longitudinal study tracking the social and work abilities of participants with BPD found that six years after diagnosis, 56% of participants had good function in work and social environments, compared to 26% of participants when they were first diagnosed. Vocational achievement was generally more limited, even compared to those with other personality disorders. However, those whose symptoms had remitted were significantly more likely to have good relationships with a romantic partner and at least one parent, good performance at work and school, a sustained work and school history, and good psychosocial functioning overall.[171] ## Epidemiology[edit] The prevalence of BPD was initially[when?] estimated to be 1–2% of the general population[168] and to occur three times more often in women than in men.[172][173] However, the lifetime prevalence of BPD, as defined in the DSM-IV, in a 2008 study was found to be 5.9% of the American population, occurring in 5.6% of men and 6.2% of women.[122] The difference in rates between men and women in this study was not found to be statistically significant.[122] Borderline personality disorder is estimated to contribute to 20% of psychiatric hospitalizations and to occur among 10% of outpatients.[174] 29.5% of new inmates in the U.S. state of Iowa fit a diagnosis of borderline personality disorder in 2007,[175] and the overall prevalence of BPD in the U.S. prison population is thought to be 17%.[174] These high numbers may be related to the high frequency of substance abuse and substance use disorders among people with BPD, which is estimated at 38%.[174] ## History[edit] Devaluation in Edvard Munch's Salome (1903). Idealization and devaluation of others in personal relations is a common trait in BPD. The painter Edvard Munch depicted his new friend, the violinist Eva Mudocci, in both ways within days. First as "a woman seen by a man in love", then as "a bloodthirsty and cannibalistic Salome".[3] In modern times, Munch has been diagnosed as having had BPD.[176][177] The coexistence of intense, divergent moods within an individual was recognized by Homer, Hippocrates, and Aretaeus, the latter describing the vacillating presence of impulsive anger, melancholia, and mania within a single person. The concept was revived by Swiss physician Théophile Bonet in 1684 who, using the term folie maniaco-mélancolique,[178] described the phenomenon of unstable moods that followed an unpredictable course. Other writers noted the same pattern, including the American psychiatrist Charles H. Hughes in 1884 and J. C. Rosse in 1890, who called the disorder "borderline insanity".[179] In 1921, Kraepelin identified an "excitable personality" that closely parallels the borderline features outlined in the current concept of BPD.[180] The first significant psychoanalytic work to use the term "borderline" was written by Adolf Stern in 1938.[181][182] It described a group of patients suffering from what he thought to be a mild form of schizophrenia, on the borderline between neurosis and psychosis. The 1960s and 1970s saw a shift from thinking of the condition as borderline schizophrenia to thinking of it as a borderline affective disorder (mood disorder), on the fringes of bipolar disorder, cyclothymia, and dysthymia. In the DSM-II, stressing the intensity and variability of moods, it was called cyclothymic personality (affective personality).[109] While the term "borderline" was evolving to refer to a distinct category of disorder, psychoanalysts such as Otto Kernberg were using it to refer to a broad spectrum of issues, describing an intermediate level of personality organization[180] between neurosis and psychosis.[183] After standardized criteria were developed[184] to distinguish it from mood disorders and other Axis I disorders, BPD became a personality disorder diagnosis in 1980 with the publication of the DSM-III.[168] The diagnosis was distinguished from sub-syndromal schizophrenia, which was termed "schizotypal personality disorder".[183] The DSM-IV Axis II Work Group of the American Psychiatric Association finally decided on the name "borderline personality disorder", which is still in use by the DSM-5 today.[5] However, the term "borderline" has been described as uniquely inadequate for describing the symptoms characteristic of this disorder.[185] ### Etymology[edit] Earlier versions of the DSM, prior to the multiaxial diagnosis system, classified most people with mental health problems into two categories, the psychotics and the neurotics. Clinicians noted a certain class of neurotics who, when in crisis, appeared to straddle the borderline into psychosis.[186] The term "borderline personality disorder" was coined in American psychiatry in the 1960s. It became the preferred term over a number of competing names, such as "emotionally unstable character disorder" and "borderline schizophrenia" during the 1970s.[187][188] Borderline personality disorder was included in DSM-III (1980) despite not being universally recognized as a valid diagnosis.[189] ## Controversies[edit] ### Credibility and validity of testimony[edit] The credibility of individuals with personality disorders has been questioned at least since the 1960s.[190]:2 Two concerns are the incidence of dissociation episodes among people with BPD and the belief that lying is a key component of this condition. #### Dissociation[edit] Researchers disagree about whether dissociation, or a sense of detachment from emotions and physical experiences, impacts the ability of people with BPD to recall the specifics of past events. A 1999 study reported that the specificity of autobiographical memory was decreased in BPD patients.[191] The researchers found that decreased ability to recall specifics was correlated with patients' levels of dissociation.[191] #### Lying as a feature[edit] Some theorists argue that patients with BPD often lie.[192] However, others write that they have rarely seen lying among patients with BPD in clinical practice.[192] ### Gender[edit] Since BPD can be a stigmatizing diagnosis even within the mental health community, some survivors of childhood abuse who are diagnosed with BPD are re-traumatized by the negative responses they receive from healthcare providers.[193] One camp argues that it would be better to diagnose these men or women with post-traumatic stress disorder, as this would acknowledge the impact of abuse on their behavior. Critics of the PTSD diagnosis argue that it medicalizes abuse rather than addressing the root causes in society.[194] Regardless, a diagnosis of PTSD does not encompass all aspects of the disorder (see brain abnormalities and terminology). Joel Paris states that "In the clinic ... Up to 80% of patients are women. That may not be true in the community."[195] He offers the following explanations regarding these sex discrepancies: > The most probable explanation for gender differences in clinical samples is that women are more likely to develop the kind of symptoms that bring patients in for treatment. Twice as many women as men in the community suffer from depression (Weissman & Klerman, 1985). In contrast, there is a preponderance of men meeting criteria for substance abuse and psychopathy (Robins & Regier, 1991), and males with these disorders do not necessarily present in the mental health system. Men and women with similar psychological problems may express distress differently. Men tend to drink more and carry out more crimes. Women tend to turn their anger on themselves, leading to depression as well as the cutting and overdosing that characterize BPD. Thus, anti-social personality disorder (ASPD) and borderline personality disorders might derive from similar underlying pathology but present with symptoms strongly influenced by gender (Paris, 1997a; Looper & Paris, 2000). We have even more specific evidence that men with BPD may not seek help. In a study of completed suicides among people aged 18 to 35 years (Lesage et al., 1994), 30% of the suicides involved individuals with BPD (as confirmed by psychological autopsy, in which symptoms were assessed by interviews with family members). Most of the suicide completers were men, and very few were in treatment. Similar findings emerged from a later study conducted by our own research group (McGirr, Paris, Lesage, Renaud, & Turecki, 2007).[35] In short, men are less likely to seek or accept appropriate treatment, more likely to be treated for symptoms of BPD such as substance abuse rather than BPD itself (the symptoms of BPD and ASPD possibly deriving from a similar underlying etiology), possibly more likely to wind up in the correctional system due to criminal behavior, and possibly more likely to commit suicide prior to diagnosis. Among men diagnosed with BPD there is also evidence of a higher suicide rate: "men are more than twice as likely as women—18 percent versus 8 percent"—to die by suicide.[34] There are also sex differences in borderline personality disorders.[196] Men with BPD are more likely to abuse substances, have explosive temper, high levels of novelty seeking and have anti-social, narcissistic, passive-aggressive or sadistic personality traits.[196] Women with BPD are more likely to have eating disorders, mood disorders, anxiety and post-traumatic stress.[196] ### Manipulative behavior[edit] Manipulative behavior to obtain nurturance is considered by the DSM-IV-TR and many mental health professionals to be a defining characteristic of borderline personality disorder.[197] However, Marsha Linehan notes that doing so relies upon the assumption that people with BPD who communicate intense pain, or who engage in self-harm and suicidal behavior, do so with the intention of influencing the behavior of others.[198] The impact of such behavior on others—often an intense emotional reaction in concerned friends, family members, and therapists—is thus assumed to have been the person's intention.[198] However, their frequent expressions of intense pain, self-harming, or suicidal behavior may instead represent a method of mood regulation or an escape mechanism from situations that feel unbearable.[199] ### Stigma[edit] The features of BPD include emotional instability; intense, unstable interpersonal relationships; a need for intimacy; and a fear of rejection. As a result, people with BPD often evoke intense emotions in those around them. Pejorative terms to describe people with BPD, such as "difficult", "treatment resistant", "manipulative", "demanding", and "attention seeking", are often used and may become a self-fulfilling prophecy, as the negative treatment of these individuals triggers further self-destructive behavior.[200] #### Physical violence[edit] The stigma surrounding borderline personality disorder includes the belief that people with BPD are prone to violence toward others.[201] While movies and visual media often sensationalize people with BPD by portraying them as violent, the majority of researchers agree that people with BPD are unlikely to physically harm others.[201] Although people with BPD often struggle with experiences of intense anger, a defining characteristic of BPD is that they direct it inward toward themselves.[202] One of the key differences between BPD and antisocial personality disorder (ASPD) is that people with BPD tend to internalize anger by hurting themselves, while people with ASPD tend to externalize it by hurting others.[202] In addition, adults with BPD have often experienced abuse in childhood, so many people with BPD adopt a "no-tolerance" policy toward expressions of anger of any kind.[202] Their extreme aversion to violence can cause many people with BPD to overcompensate and experience difficulties being assertive and expressing their needs.[202] This is one way in which people with BPD choose to harm themselves over potentially causing harm to others.[202] Another way in which people with BPD avoid expressing their anger through violence is by causing physical damage to themselves, such as engaging in non-suicidal self-injury.[20][201] #### Mental health care providers[edit] People with BPD are considered to be among the most challenging groups of patients to work with in therapy, requiring a high level of skill and training for the psychiatrists, therapists, and nurses involved in their treatment.[203] A majority of psychiatric staff report finding individuals with BPD moderately to extremely difficult to work with and more difficult than other client groups.[204] This largely negative view of BPD can result in people with BPD being terminated from treatment early, being provided harmful treatment, not being informed of their diagnosis of BPD, or being misdiagnosed.[205] With healthcare providers contributing to the stigma of a BPD diagnosis, seeking treatment can often result in the perpetuation of BPD features. [205] Efforts are ongoing to improve public and staff attitudes toward people with BPD.[206][207] In psychoanalytic theory, the stigmatization among mental health care providers may be thought to reflect countertransference (when a therapist projects his or her own feelings on to a client). Thus, a diagnosis of BPD often says more about the clinician's negative reaction to the patient than it does about the patient and explains away the breakdown in empathy between the therapist and the patient and becomes an institutional epithet in the guise of pseudoscientific jargon.[183] This inadvertent countertransference can give rise to inappropriate clinical responses, including excessive use of medication, inappropriate mothering, and punitive use of limit setting and interpretation.[208] Some clients feel the diagnosis is helpful, allowing them to understand that they are not alone and to connect with others with BPD who have developed helpful coping mechanisms. However, others experience the term "borderline personality disorder" as a pejorative label rather than an informative diagnosis. They report concerns that their self-destructive behavior is incorrectly perceived as manipulative and that the stigma surrounding this disorder limits their access to health care.[209][non-primary source needed] Indeed, mental health professionals frequently refuse to provide services to those who have received a BPD diagnosis.[210] ### Terminology[edit] Because of concerns around stigma, and because of a move away from the original theoretical basis for the term (see history), there is ongoing debate about renaming borderline personality disorder. While some clinicians agree with the current name, others argue that it should be changed,[211] since many who are labelled with borderline personality disorder find the name unhelpful, stigmatizing, or inaccurate.[211][212] Valerie Porr, president of Treatment and Research Advancement Association for Personality Disorders states that "the name BPD is confusing, imparts no relevant or descriptive information, and reinforces existing stigma".[213] Alternative suggestions for names include emotional regulation disorder or emotional dysregulation disorder. Impulse disorder and interpersonal regulatory disorder are other valid alternatives, according to John G. Gunderson of McLean Hospital in the United States.[214] Another term suggested by psychiatrist Carolyn Quadrio is post traumatic personality disorganization (PTPD), reflecting the condition's status as (often) both a form of chronic post traumatic stress disorder (PTSD) as well as a personality disorder.[67] However, although many with BPD do have traumatic histories, some do not report any kind of traumatic event, which suggests that BPD is not necessarily a trauma spectrum disorder.[74] The Treatment and Research Advancements National Association for Personality Disorders (TARA-APD) campaigned unsuccessfully to change the name and designation of BPD in DSM-5, published in May 2013, in which the name "borderline personality disorder" remains unchanged and it is not considered a trauma- and stressor-related disorder.[215] ## Society and culture[edit] ### Fiction[edit] Films and television shows have portrayed characters either explicitly diagnosed with or exhibiting traits suggestive of BPD. These may be misleading if they are thought to depict this disorder accurately.[201] The majority of researchers agree that in reality, people with BPD are unlikely to physically harm others, but rather most likely to harm themselves.[201] Robert O. Friedel has suggested that the behavior of Theresa Dunn, the leading character of Looking for Mr. Goodbar (1975) is consistent with a diagnosis of borderline personality disorder.[216] The films Play Misty for Me (1971)[217] and Girl, Interrupted (1999, based on the memoir of the same name) both suggest the emotional instability of the disorder.[218] The film Single White Female (1992), like the first example, also suggests characteristics, some of which are actually atypical of the disorder: the character Hedy had markedly disturbed sense of identity and reacts drastically to abandonment.[217]:235 In a review of the film Shame (2011) for the British journal The Art of Psychiatry, another psychiatrist, Abby Seltzer, praises Carey Mulligan's portrayal of a character with the disorder even though it is never mentioned onscreen.[219] Films attempting to depict characters with the disorder include A Thin Line Between Love and Hate (1996), Filth (2013), Fatal Attraction (1987), The Crush (1993), Mad Love (1995), Malicious (1995), Interiors (1978), The Cable Guy (1996), Mr. Nobody (2009), Moksha (2001), Margot at the Wedding (2007), Cracks (2009),[220] and Welcome to Me (2014).[221][222] Psychiatrists Eric Bui and Rachel Rodgers argue that the Anakin Skywalker/Darth Vader character in the Star Wars films meets six of the nine diagnostic criteria; Bui also found Anakin a useful example to explain BPD to medical students. In particular, Bui points to the character's abandonment issues, uncertainty over his identity, and dissociative episodes.[223] On television, The CW show Crazy Ex-Girlfriend portrays a main character with borderline personality disorder,[224] and Emma Stone's character in the Netflix miniseries Maniac is diagnosed with the disorder.[225] Additionally, incestuous twins Cersei and Jaime Lannister, in George R. R. Martin's A Song of Ice and Fire series and its television adaptation, Game of Thrones, have traits of borderline and narcissistic personality disorders.[226] ### Awareness[edit] In early 2008, the United States House of Representatives declared the month of May Borderline Personality Disorder Awareness Month.[227][228] In 2020, South Korean singer-songwriter Lee Sunmi spoke out about her struggle with borderline personality disorder on the show Running Mates, having been diagnosed 5 years prior. 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Retrieved 1 November 2010. ## External links[edit] Wikimedia Commons has media related to Borderline personality disorder. * Borderline personality disorder at Curlie * "Borderline personality disorder". National Institute of Mental Health. * APA DSM 5 Definition of Borderline personality disorder * APA Division 12 treatment page for Borderline personality disorder * ICD-10 definition of EUPD by the World Health Organization * NHS Classification D * ICD-10: F60.3 * ICD-9-CM: 301.83 * MeSH: D001883 * SNOMED CT: 20010003 External resources * MedlinePlus: 000935 * eMedicine: article/913575 * Patient UK: Borderline personality disorder * v * t * e Borderline personality disorder General * Dimensional models of personality disorders * Impulse control disorders * Trauma model of mental disorders * Misdiagnosis of borderline personality disorder Symptoms and behaviors * Dissociation * Eating disorders * Emotional dysregulation * Feelings of emptiness * Hypersexuality * Idealization and devaluation * Impulsivity * Mood swings * Projection * Self-harm * Splitting * Suicidal ideation Management * Dialectical behavior therapy * Dynamic deconstructive psychotherapy * McLean Hospital * Mentalization-based treatment * Schema therapy * Social psychiatry * Transference focused psychotherapy Family challenges * BPDFamily (support group) * Codependency * Complex PTSD * Emotional blackmail * Family estrangement * Personal boundaries * v * t * e DSM personality disorders DSM-III-R only * Sadistic * Self-defeating (masochistic) DSM-IV only Personality disorder not otherwise specified Appendix B (proposed) * Depressive * Negativistic (passive–aggressive) DSM-5 (Categorical model) Cluster A (odd) * Paranoid * Schizoid * Schizotypal Cluster B (dramatic) * Antisocial * Borderline * Histrionic * Narcissistic Cluster C (anxious) * Avoidant * Dependent * Obsessive-compulsive DSM-5 Alternative hybrid categorical and dimensional model in Section III included to stimulate further research * v * t * e Personality disorders Schizotypal * Schizotypal Specific * Anankastic * Anxious (avoidant) * Dependent * Dissocial * Emotionally unstable * Histrionic * Paranoid * Schizoid * Other * Eccentric * Haltlose * Immature * Narcissistic * Passive–aggressive * Psychoneurotic Organic * Organic Unspecified * Unspecified Authority control * GND: 4007720-2 * NKC: ph135781 [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	Borderline personality disorder	c0006012	27,328	wikipedia	https://en.wikipedia.org/wiki/Borderline_personality_disorder	2021-01-18T18:29:58	{"mesh": ["D001883"], "umls": ["C0006012"], "icd-10": ["F60.3"], "wikidata": ["Q208166"]}
A number sign (#) is used with this entry because of evidence that isolated partial growth hormone (GH; 139350) deficiency (GHDP) is caused by heterozygous, compound heterozygous, or homozygous mutation in the growth hormone secretagogue receptor gene (GHSR; 601898) on chromosome 3q26. Molecular Genetics Pantel et al. (2006) screened for mutations in the GHSR gene in 41 probands with idiopathic short stature and 51 probands with isolated growth hormone deficiency and identified the same mutation (A204E; 601898.0001) in 2 probands of unrelated Moroccan families. No mutations in the GH1 (139250) or GHRHR (139191) genes were identified in the probands. In family 1, which was consanguineous, the proband was homozygous for the mutation; 2 affected sibs and the affected parents were all heterozygous for the mutation, as was an unaffected sib whose height was in the low range of normal (-1.1 SD below the mean). In family 2, the proband and her affected father were both heterozygous for the mutation, as were 2 unaffected sibs, 1 of normal height and the other in the low range of normal (-1.2 SD below the mean), consistent with incomplete penetrance and variable expressivity. Pantel et al. (2006) noted that 2 of the affected children had a phenotype compatible with idiopathic short stature, whereas the other 2 had isolated growth hormone deficiency confirmed by testing. The mutation was not found in 100 Moroccan controls. Functional studies showed that the mutation results in decreased cell surface expression of the receptor and selectively impairs the constitutive activity of GHSR, while preserving its ability to respond to ghrelin. The authors suggested autosomal dominant inheritance of growth failure in these families. In a 17.4-year-old male proband with short stature and endocrine analysis consistent with partial IGHD, Pantel et al. (2009) analyzed 3 candidate genes, GH1, GHRHR, and GHSR, and identified compound heterozygosity for a nonsense and a missense mutation in the GHSR gene (W2X, 601898.0002 and R237W, 601898.0003). The proband initially presented at 5 years of age with episodic abdominal pain, vomiting, hypoglycemia, and ketosis in the context of postnatal growth delay. He had markedly low levels of IGF1 (147440) and a low GH response to provocative tests without other pituitary hormone deficiency. His pituitary gland was subnormal in size by MRI. He responded to treatment with GH and had delayed puberty starting at 15 years of age; unexplained recurrent episodes of abdominal pain, vomiting, and ketosis continued while on GH therapy, but without hypoglycemia. His unaffected mother and an unaffected brother were heterozygous for the missense mutation; his father, who had normal stature but was reported to have had delayed puberty, was heterozygous for the nonsense mutation. His mother had a first cousin who had very short stature (adult height, 138 cm). In vitro expression experiments showed that the R237W mutation would result in a partial loss of constitutive activity of the receptor, whereas both its ability to respond to ghrelin and its cell surface expression are preserved. INHERITANCE \- Autosomal dominant \- Autosomal recessive GROWTH Height \- Short stature Other \- Postnatal growth delay SKELETAL \- Delayed bone age (in some patients) NEUROLOGIC Central Nervous System \- Subnormal-size pituitary (in some patients) ENDOCRINE FEATURES \- Partial isolated growth hormone deficiency (IGHD) \- Low levels of insulin-like growth factor I (in most patients) \- Low growth hormone response MISCELLANEOUS \- Patients with homozygous, compound heterozygous, and heterozygous mutation have been reported \- Incompletely penetrant phenotype in heterozygotes \- Positive response to treatment with growth hormone MOLECULAR BASIS \- Caused by mutation in the growth hormone secretagogue receptor gene (GSHR, 601898.0001 ) ▲ 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	GROWTH HORMONE DEFICIENCY, ISOLATED PARTIAL	c1858656	27,329	omim	https://www.omim.org/entry/615925	2019-09-22T15:50:33	{"mesh": ["C565805"], "omim": ["615925"], "orphanet": ["314811"], "synonyms": ["Ghrelin receptor deficiency", "Short stature due to growth hormone secretagogue receptor deficiency"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive congenital ichthyosis-11 (ARCI11) is caused by homozygous mutation in the ST14 gene (606797), which encodes type II transmembrane serine protease matriptase, on chromosome 11q24. Description Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300). Clinical Features Lestringant et al. (1998) reported the cases of 5 Emirati sibs (3 girls and 2 boys), aged 4 to 18 years, with normal stature, diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse nonscarring hypotrichosis, and marked hypohidrosis. Ichthyosis was present at birth; there were no babies collodion babies. The scaling was diffuse and involved the great flexures and scalp, but spared the face, elbows, knees, hands, and feet. The follicular atrophoderma, also present at birth, involved pronounced follicular pitting on the dorsal aspects of the wrists, hands, and first phalanges of the fingers. In all patients, there were ill-defined pits on facial skin, giving a vermiculate or 'orange peel' appearance. On the dorsum of the wrists and around the elbows and knees there was a zone where ichthyosis progressively transformed into follicular atrophoderma. Sweating was assessed only clinically, with very few droplets present in the eyebrows and on the nose. Steroid sulfatase activity was normal. Electron microscopic studies of ichthyotic skin showed no specific abnormality. The first-cousin parents were of Bedouin ancestry and had normal stature, normal sweating, and no skin or hair lesions. Lestringant et al. (1998) noted that follicular atrophoderma, which is a rare anomaly observed mainly as a feature of the X-linked dominant form of chondrodysplasia punctata (302960) and in the X-linked dominant Bazex syndrome (301845), had not previously been reported in association with diffuse ichthyosis; they concluded that the disorder in this family represented a new autosomal recessive genodermatosis. Tursen et al. (2002) reported an isolated case, a 17-year-old Turkish girl from a consanguineous family who exhibited ichthyosis, hypotrichosis, and follicular atrophoderma. Ichthyosis was present at birth, and she had almost no scalp hair until 4 months of age; she stated that her scalp hair had improved and straightened with age. Examination revealed diffuse ichthyosiform scaling sparing the major flexures and face; the ichthyotic skin was hypohidrotic, but the axillae, palms, and soles sweated normally. Follicular atrophoderma was observed on the backs of her hands. She had diffuse and patchy nonscarring hypotrichosis with a receding anterior hairline. Her hair, which the authors characterized as 'woolly,' was light brown, coarse, curly, and unruly, in contrast to the straight black hair of family members. Eyelashes and particularly eyebrows were sparse. Hair microscopy was normal apart from curling, and skin biopsy of ichthyotic skin showed orthokeratosis with focal hypogranulosis; electron microscopy showed normal tonofilaments. There was no family history of similar skin problems; her parents and paternal grandparents were first cousins. Basel-Vanagaite et al. (2007) described a consanguineous Israeli Arab family with autosomal recessive ichthyosis with hypotrichosis. Among the offspring of first-cousin parents, 3 sibs were affected and 5 unaffected. Ichthyosis and abnormal hair were present at birth. Two of the affected sibs had a vernix-like layer covering the entire body, which was progressively shed during the first month of life. Hypotrichosis was generalized and diffuse. Scaling was diffuse, including on the scalp, but the face was unaffected. The hair of all patients appeared curly, sparse, fragile, brittle, dry, and lusterless, and showed slow growth. Light microscopy and scanning electron microscopy of hair obtained from affected sibs disclosed a number of abnormalities, including dysplastic hair, pili torti, pili bifurcati, and central pili mono-bifurcati. Over time, scalp hair growth and appearance improved, and the scalp hair darkened with age. Follicular atrophoderma was not seen and sweating was normal. All 3 affected sibs had photophobia and 1 had corneal opacities. Another had pingueculum from 11 years of age. In addition, 2 of the 3 affected sibs had abnormal dentition, with notching/pitting in 1 and conical primary teeth in the other. Four of the 8 sibs had Hirschsprung disease; however, only 1 of these 4 had ichthyosis. Avrahami et al. (2008) reported a 2.5-year-old Turkish girl with congenital ichthyosis, light brown, curly, sparse hair, and generalized hypotrichosis with sparse body hair, eyebrows, and eyelashes. She did not have photophobia or corneal opacities, but did have blepharitis. Her nails, teeth, and sweating were normal. The phenotype of this patient closely resembled that of the family reported by Basel-Vanagaite et al. (2007), but was less severe. Alef et al. (2009) restudied the Emirati Bedouin family originally reported by Lestringant et al. (1998), noting that the hypotrichosis appeared to improve with age. At the time of first examination, the younger sibs had sparse, unruly, and lusterless hair on the scalp, with bald patches and a receding anterior hairline, whereas the 2 oldest sibs had nearly normal scalp hair with only a receding hairline. Similarly, eyebrows that were at first wiry and limited to the most medial part, progressively straightened and extended outward, and eyelashes, initially sparse and limited to the upper eyelids, progressively grew on the lower lids. Facial and body hair were absent in the 3 younger sibs, whereas the 2 oldest had exhibited some lip and armpit hair. Examination 8 years after initial presentation in the 2 affected brothers showed fully developed pingueculum and photophobia in the 19-year-old, who also had normal-appearing scalp hair, whereas the 22-year-old had marked photophobia and corneal opacities, and had developed ichthyosis in place of prior follicular atrophoderma on the dorsum of his right hand and his knees. Histopathology of skin biopsies from 1 of the Emirati Bedouin patients and from the Turkish woman originally reported by Tursen et al. (2002) showed an epidermis of normal thickness with regular differentiation of keratinocytes in the spinous layer. The granular layer was thinned, and the stratum corneum showed orthohyperkeratosis. The hair follicle epithelium was thinned, and hair infundibulum showed hyperkeratosis and a very thin stratum granulosum. Electron microscopy confirmed the very thin stratum granulosum, and the lower lamellae of the stratum corneum appeared only loosely connected laterally and contained deposits that appeared to be lamellar bodies. Alef et al. (2009) noted that the ultrastructural findings were similar in patients from both families. Mapping By homozygosity mapping in a consanguineous Israeli Arab family segregating autosomal recessive congenital ichthyosis with hypotrichosis, Basel-Vanagaite et al. (2007) mapped the disorder to chromosome 11q24.3-q25, in a region containing 22 known or predicted genes. Alef et al. (2009) performed genomewide microsatellite analysis in 5 affected and 3 unaffected sibs from a large Emirati Bedouin pedigree with ichthyosis, follicular atrophoderma, and hypotrichosis, originally described by Lestringant et al. (1998), and obtained maximum 2-point lod scores of 3.6 and 3.4 at D11S910 and D2S1363, respectively. Analysis of a Turkish pedigree with a similar phenotype, previously reported by Tursen et al. (2002), was only compatible with linkage to the region on chromosome 11. Refined mapping confirmed the locus with a combined lod score of 4.0 at D11S4131 and D11S910. Haplotype analysis defined an approximately 10.9-cM (4.1-Mb) candidate interval on chromosome 11q24, between markers D11S4150 and M11TA01. Molecular Genetics By sequencing candidate genes in a consanguineous Israeli Arab family with autosomal recessive congenital ichthyosis with hypotrichosis mapping to chromosome 11q24.3-q25, Basel-Vanagaite et al. (2007) identified homozygosity for a missense mutation in the ST14 gene (G827R; 606797.0001) that segregated with disease and was not found in 434 Arab control chromosomes. In a 2.5-year-old Turkish girl with ARCI and hypotrichosis, Avrahami et al. (2008) identified a homozygous mutation in the ST14 gene (M1I; 606797.0002). In a large Emirati Bedouin pedigree and a Turkish woman with ARCI, hypotrichosis, and follicular atrophoderma mapping to chromosome 11q24, originally described by Lestringant et al. (1998) and Tursen et al. (2002), respectively, Alef et al. (2009) analyzed the candidate gene ST14 and identified homozygosity for a splice site mutation (606797.0003) and a 1-bp deletion (606797.0004). INHERITANCE \- Autosomal recessive GROWTH Weight \- Normal birth weight HEAD & NECK Eyes \- Sparse eyebrows \- Long, curly dark upper eyelashes (in some patients) \- Sparse eyelashes, more severe in lower lashes (in some patients) \- Photophobia \- Corneal opacity \- Pingueculum \- Blepharitis Teeth \- Conical primary teeth (rare) \- Notched teeth (rare) \- Pitted teeth (rare) SKIN, NAILS, & HAIR Skin \- Ichthyosis, congenital \- Vernix-like skin covering, present at birth, shed during first month of life (in some patients) \- Follicular atrophoderma (in some patients) \- Hypohidrosis (in some patients) Skin Histology \- Marked acanthosis \- Thickened stratum corneum \- Orthohyperkeratosis in stratum corneum \- Thinned hair follicle epithelium \- Hyperkeratosis of hair infundibulum \- Very thin stratum granulosum of hair infundibulum Electron Microscopy \- Thin stratum granulosum \- Persistence of corneodesmosomes in stratum corneum \- Lamellar body-like deposits in stratum corneum Nails \- Normal nails Hair \- Sparse eyebrows \- Long, curly dark upper eyelashes (in some patients) \- Sparse eyelashes, more severe in lower lashes (in some patients) \- Hypotrichosis (improves with age in some patients) \- Sparse hair \- Curly hair \- Fragile hair \- Dysplastic hair \- Pili torti \- Pili bifurcati \- Central pili mono bifurcati MOLECULAR BASIS \- Caused by mutation in the suppression of tumorigenicity 14 gene (ST14, 606797.0001 ) ▲ 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	ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 11	c1835851	27,330	omim	https://www.omim.org/entry/602400	2019-09-22T16:13:51	{"doid": ["0060720"], "mesh": ["C536273"], "omim": ["602400"], "orphanet": ["91132"], "synonyms": ["Alternative titles", "ICHTHYOSIS WITH HYPOTRICHOSIS, AUTOSOMAL RECESSIVE", "ICHTHYOSIS AND FOLLICULAR ATROPHODERMA WITH HYPOTRICHOSIS AND HYPOHIDROSIS"]}
Dopamine transporter deficiency syndrome (DTDS) is a rare movement disorder that causes progressive (worsening) dystonia and parkinsonism. It usually begins in infancy ('classic DTDS') and for this reason, it is also known as 'infantile parkinsonism dystonia.' However, some people with DTDS may not develop symptoms until childhood or later (which is known as 'atypical DTDS'). The dystonia in DTDS is characterized by uncontrollable (involuntary), long-lasting muscle contractions and cramps that involve many different muscles. Dystonia causes difficulty with daily activities and impairs the ability to talk, eat, drink, pick up objects, and walk. Parkinsonism develops as the disorder progresses and is characterized by tremor (shaking), slowed movements (bradykinesia), rigidity (stiffness), and impaired balance and coordination. Additional symptoms that may be present include abnormal eye movements, reduced facial expressions, irritability, sleeping problems, digestive problems (such as reflux or constipation), and recurrent pneumonia which can be life-threatening. Classic DTDS is associated with a poor outlook (prognosis), and death may occur in the teenage years due to unexplained sudden causes or respiratory complications. Those with atypical DTDS may have milder symptoms and a longer lifespan, but the long-term outlook for this form is not well-known. DTDS is caused by mutations in the SLC6A3 gene and inheritance is autosomal recessive. There is no cure for DTDS; treatment aims to relieve symptoms and increase quality of life. Treatment may include medicines to control involuntary movements (such as tetrabenazine and benzodiazepines), medicines to control dystonia (such as pramipexole and ropinirole), and physical therapy to reduce the risk of contractures from muscle rigidity. [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	Dopamine transporter deficiency syndrome	c2751067	27,331	gard	https://rarediseases.info.nih.gov/diseases/10484/dopamine-transporter-deficiency-syndrome	2021-01-18T18:00:49	{"mesh": ["C567730"], "omim": ["613135"], "umls": ["C2751067"], "orphanet": ["238455"], "synonyms": ["Parkinsonism-dystonia infantile", "Infantile Parkinsonism-dystonia", "DTDS", "PKDYS", "SLC6A3-Related Dopamine Transporter Deficiency Syndrome", "DAT Deficiency"]}
Hereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may fail to grow and gain weight at the expected rate (failure to thrive). Repeated ingestion of fructose-containing foods can lead to liver and kidney damage. The liver damage can result in a yellowing of the skin and whites of the eyes (jaundice), an enlarged liver (hepatomegaly), and chronic liver disease (cirrhosis). Continued exposure to fructose may result in seizures, coma, and ultimately death from liver and kidney failure. Due to the severity of symptoms experienced when fructose is ingested, most people with hereditary fructose intolerance develop a dislike for fruits, juices, and other foods containing fructose. Hereditary fructose intolerance should not be confused with a condition called fructose malabsorption. In people with fructose malabsorption, the cells of the intestine cannot absorb fructose normally, leading to bloating, diarrhea or constipation, flatulence, and stomach pain. Fructose malabsorption is thought to affect approximately 40 percent of individuals in the Western hemisphere; its cause is unknown. ## Frequency The incidence of hereditary fructose intolerance is estimated to be 1 in 20,000 to 30,000 individuals each year worldwide. ## Causes Mutations in the ALDOB gene cause hereditary fructose intolerance. The ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is found primarily in the liver and is involved in the breakdown (metabolism) of fructose so this sugar can be used as energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into other molecules called glyceraldehyde and dihydroxyacetone phosphate. ALDOB gene mutations reduce the function of the enzyme, impairing its ability to metabolize fructose. A lack of functional aldolase B results in an accumulation of fructose-1-phosphate in liver cells. This buildup is toxic, resulting in the death of liver cells over time. Additionally, the breakdown products of fructose-1-phosphase are needed in the body to produce energy and to maintain blood sugar levels. The combination of decreased cellular energy, low blood sugar, and liver cell death leads to the features of hereditary fructose intolerance. ### Learn more about the gene associated with Hereditary fructose intolerance * ALDOB ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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 fructose intolerance	c0016751	27,332	medlineplus	https://medlineplus.gov/genetics/condition/hereditary-fructose-intolerance/	2021-01-27T08:25:01	{"gard": ["6622"], "mesh": ["D005633"], "omim": ["229600"], "synonyms": []}
Photophthalmia ( pho·toph·thal·mia (fōt″of-thal´me-ah) ) is ophthalmia or inflammation of the eye, especially of the cornea and conjunctiva due to exposure to intense light of short wavelength (as ultraviolet light), as in snow blindness.[1] It involves occurrence of multiple epithelial erosions due to the effect of ultraviolet rays, especially between 311 and 290 nm. Snow blindness occurs due to reflection of ultraviolet rays from snow surface. Photoretinitis is another form that can occur due to infra-red rays (eclipse burn of retina). ## Contents * 1 Presentation * 2 Prevention * 3 Treatment * 4 References ## Presentation[edit] It can present with the following:[2] * severe burning pain * lacrimation * photophobia * blepharospasm * swelling of palpebral conjunctiva * retrotarsal folds Usually the effect of UV exposure is felt after 6-8 hours from exposure. With severe irritation, the eyes become blood red. In minor cases, avoid rubbing and wash the eyes thoroughly with water until the irritation subdues. Always consult an eye specialist as soon as possible. Medications (for minor erosion of cornea) usually involve eye drop such as Hydroxypropyl Methycellulose Ophthalmic solution USP sold under the trade name GenTeal®. (February 2019) ## Prevention[edit] Crooke’s glass[3] is a prophylactic aid consisting of a spectacle lens combined with metallic oxides[4] to absorb ultraviolet or infrared rays[5] and should be used by those who are prone to exposure e.g. Welding workers, cinema operators. ## Treatment[edit] The following may provide relief:[6] * Cold compresses * Pad and bandage with antibiotics drops for 24 hours, heals most of the cases * anaesthetic drops should not be used * Oral analgesics if pain is intolerable * Single dose of tranquilizers ## References[edit] 1. ^ "photophthalmia". Merriam-Webster. 2. ^ H. V. Nema; Nitin Nema (1 December 2011). Textbook of Ophthalmology. JP Medical Ltd. p. 157. ISBN 978-93-5025-507-0. 3. ^ "Colorless crookes glass US 1634182 A". Google Patents. Retrieved 26 April 2015. 4. ^ William Hodson Brock (2008). William Crookes (1832-1919) and the Commercialization of Science. Ashgate Publishing, Ltd. p. 464. ISBN 978-0-7546-6322-5. 5. ^ "Crookes glass". medilexicon.com. Archived from the original on 2016-08-06. Retrieved 2015-04-26. 6. ^ Ilkka Kunnamo (4 March 2005). Evidence-Based Medicine Guidelines. John Wiley & Sons. p. 1211. ISBN 978-0-470-01184-3. [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	Photophthalmia	c1397694	27,333	wikipedia	https://en.wikipedia.org/wiki/Photophthalmia	2021-01-18T18:35:05	{"wikidata": ["Q2247373"]}
Pseudoathetosis SpecialtyNeurology Pseudoathetosis is abnormal writhing movements, usually of the fingers, caused by a failure of joint position sense (proprioception)[1] and indicates disruption of the proprioceptive pathway, from nerve to parietal cortex. ## Contents * 1 Presentation * 2 Variants * 3 Diagnosis * 3.1 Differential diagnosis * 4 References * 5 External links ## Presentation[edit] Analogous to Romberg's sign, the abnormal posturing is most pronounced when the eyes are closed as visual inputs are unavailable to guide corrective movements. Paradoxically, eye closure may decrease the amount of movement as the visual cues probably trigger corrective movements which return the limb to the desired "baseline" allowing a new phase of involuntary drift before a subsequent corrective phase occurs.[citation needed] ## Variants[edit] Hemipseudaoathetosis refers to pseudoathetosis on one side of the body, usually the upper limb and is most commonly caused by a lesion affecting the cuneate tract or cuneate nucleus in the cervical spine or lower brainstem (medulla) respectively.[2][3] ## Diagnosis[edit] ### Differential diagnosis[edit] It may be mistaken for choreoathetosis, however, these abnormal movements are relatively constant irrespective of whether the eyes are open or closed and occur in the absence of proprioceptive loss. ## References[edit] 1. ^ Spitz M, Costa Machado AA, Carvalho Rdo C, et al. (2006). "Pseudoathetosis: report of three patients". Mov. Disord. 21 (9): 1520–2. doi:10.1002/mds.21014. PMID 16817195. S2CID 43471025. 2. ^ Gotkine M, Gomori JM (2007). "Hemipseudoathetosis due to a hemorrhage at the cervicomedullary junction". Neurology. 69 (15): 1551. doi:10.1212/01.wnl.0000285506.04246.c2. PMID 17923617. 3. ^ Ghika J, Bogousslavsky J (1997). "Spinal pseudoathetosis: a rare, forgotten syndrome, with a review of old and recent descriptions". Neurology. 49 (2): 432–7. doi:10.1212/wnl.49.2.432. PMID 9270573. S2CID 28064301. ## External links[edit] Classification D * DiseasesDB: 30711 * SNOMED CT: 299952008 * Hemipseudoathetosis video clip [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	Pseudoathetosis	c0576705	27,334	wikipedia	https://en.wikipedia.org/wiki/Pseudoathetosis	2021-01-18T18:57:01	{"umls": ["C0576705"], "wikidata": ["Q7254518"]}
Albinism is a group of inherited disorders that results in little or no production of the pigment melanin, which determines the color of the skin, hair and eyes. Melanin also plays a role in the development of certain optical nerves, so all forms of albinism cause problems with the development and function of the eyes. Other symptoms can include light skin or changes in skin color; very white to brown hair; very light blue to brown eye color that may appear red in some light and may change with age; sensitivity to sun exposure; and increased risk of developing skin cancer. Albinism is caused by mutations in one of several genes, and most types are inherited in an autosomal recessive manner. Although there's no cure, people with the disorder can take steps to improve vision and avoid too much sun exposure. [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	Albinism	c0001916	27,335	gard	https://rarediseases.info.nih.gov/diseases/5768/albinism	2021-01-18T18:02:13	{"mesh": ["D000417"], "umls": ["C0001916"], "synonyms": []}
A number sign (#) is used with this entry because Vici syndrome (VICIS) is caused by homozygous or compound heterozygous mutation in the EPG5 gene (615068) on chromosome 18q. Description Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum (ACC), cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012). Clinical Features Dionisi Vici et al. (1988) described 2 brothers with a malformation syndrome consisting of agenesis of the corpus callosum, cutaneous hypopigmentation, bilateral cataract, cleft lip and palate, and combined immunodeficiency. The sibs suffered from severe psychomotor retardation, seizures, recurrent severe respiratory infections, and chronic mucocutaneous candidiasis. They died of bronchopneumonia at ages 2 and 3 years. In the 1 sib studied, skin anergy to recall antigens, profound depletion of T4-positive lymphocytes, and deficiency of serum IgG2 were demonstrated. Autopsy showed agenesis of the corpus callosum, hypoplasia of the cerebellar vermis, and profound hypoplasia of the thymus and of the peripheral lymphoid tissue. No precisely similar cases were found. Del Campo et al. (1999) reported 4 more cases (including 2 sibs, a male and a female) of this disorder. Their patients had agenesis of the corpus callosum, oculocutaneous albinism, repeated infections suggestive of an immunodeficiency, cardiomyopathy, postnatal growth retardation, microcephaly, and profound developmental delay. The authors suggested that these cases confirmed the existence of this disorder, which they called Vici syndrome. Their finding of affected sibs of both sexes born to unaffected parents supported autosomal recessive inheritance. Autosomal recessive inheritance was supported by the report of Chiyonobu et al. (2002), who described a sister and brother with agenesis of the corpus callosum, albinism, and recurrent infections. Both also had cataracts and cardiomyopathy and were born to healthy and unrelated parents. They showed postnatal growth retardation, profound developmental delay, and hypotonia. The sister had recurrent infections and died of progressive heart failure at age 19 months. The brother was alive at age 6 months with mild cardiomyopathy, and had a single episode of acute bronchitis at age 3 months. McClelland et al. (2010) reported an infant with Vici syndrome who presented at birth with hypotonia, feeble cry, and feeding difficulties. Examination showed microcephaly, hypertrophic cardiomyopathy, hypopigmentation, and dysmorphic facial features, such as broad nose, full lips, and long philtrum. He also had nystagmus, cataracts, profound sensorineural hearing loss, decreased lymphocytes, and recurrent infections. He died at age 3 months of cardiac failure. Brain MRI showed agenesis of the corpus callosum and septum pellucidum, and pontocerebellar hypoplasia. Skeletal muscle biopsy showed wide variation in fiber size, centralized nuclei, and small fibers with high glycogen content. Electron microscopy showed redundant basal lamina with small areas of debris between the layers, suggesting exocytosis. There were also several enlarged abnormal mitochondria with abnormal cristae. The case expanded the clinical features of Vici syndrome to include myopathy. Al-Owain et al. (2010) reported a male infant, born of distantly related Saudi parents, with Vici syndrome. At birth, he had poor sucking and feeding, with poor weight gain. Physical features included inverted triangular face, hypotonia with open mouth, mild ptosis, epicanthal folds, micrognathia, and high-arched palate. He also had axial hypotonia with mildly increased limb tone, bilateral cataracts, and optic neuropathy. Brain MRI showed agenesis of the corpus callosum, cerebellar and pontine hypoplasia, and delayed myelination. He had severe global developmental delay. He developed frequent recurrent infections, particularly with Pseudomonas and Klebsiella, associated with lymphopenia, although he had normal immunologic reactions to vaccination. Electrophysiologic studies showed severely reduced compound muscle action potentials and a myopathic pattern with pseudomyotonic discharges. Muscle biopsy showed marked variation in myofiber size, rare degenerative and regenerative fibers, internal nuclei, and vacuoles. Some small fibers were angular, suggesting a neurogenic component. The results of muscle studies were consistent with a myopathy due to a possible metabolic abnormality. Other features included left lung hypoplasia and left ventricular hypertrophy. The patient died of sepsis at age 9 months. The parents had 3 other children who died of a similar disorder, suggesting autosomal recessive inheritance. Finocchi et al. (2012) reported a 2-year-old Italian boy, born of unrelated patients, with Vici syndrome. He developed respiratory distress and sepsis of unknown origin on the second day of life. He had profound cervicoaxial hypotonia, nystagmus, sucking difficulties with frequent regurgitation, failure to thrive, pharyngomalacia, and hypopigmentation of the hair. Brain imaging showed agenesis of the corpus callosum. Muscle biopsy showed hypoplastic fibers with about 10% internal nuclei. Many fibers showed increased fucsinophilic material in addition to increased oxidative stain, and there were abnormally shaped and enlarged mitochondria with osmiophilic inclusions. Other features included cataracts, unilateral hearing loss, seizures, and progressive systolic cardiac dysfunction. He had recurrent infections, and immunologic workup showed progressive leukopenia. T cell mitogen response was normal, but he had a humoral defect with low immunoglobulins and defective antibody response. Treatment with intravenous immunoglobulin resulted in marked improvement of general clinical conditions and no infectious episodes. Said et al. (2012) reported a girl, born of unrelated Maltese parents, with Vici syndrome. Her neonatal period was uneventful and she was noted to have hypotonia, right-sided cataract, and fine, fair hair at age 6 weeks. By age 8 weeks, developmental delay was apparent. She did not smile, fix, or follow, and had head lag. She had poor growth, microcephaly, and dysmorphic features, including depressed nasal bridge, a high palate, micrognathia, and low-set ears with poorly developed ear lobes. She had truncal hypertonia and hypertonia in the lower limbs with general hyperreflexia. At 11 weeks of age, she showed sudden neurologic deterioration, developed recurrent infections, and had poor growth, necessitating hospitalization. She died of severe infection at age 15 months. Initial laboratory studies showed granulocytopenia, which corrected spontaneously, and a persisting low total lymphocyte and low T cell count; immunoglobulins were normal. Echocardiography showed an initial left ventricular hypertrophy in the first 3 months which resolved by 9 months of age, and liver enzymes were elevated until age 9 months. Brain imaging showed complete agenesis of the corpus callosum and a cyst in septum pellucidum. Electromyography at 3.5 months showed evidence of widespread denervation without clear involvement of peripheral nerves. Muscle biopsy showed abnormal variation in fiber size associated with clusters of small fibers and internal and central nuclei in atrophic fibers. Said et al. (2012) concluded that the patient's disease course was consistent with neurologic deterioration together with muscular involvement and transient hepatic and cardiac dysfunction. Cullup et al. (2013) reported 18 affected children from 13 families with Vici syndrome. Nine of the patients had previously been reported. Clinical features were homogeneous, including agenesis of the corpus callosum, hypopigmentation, immunodeficiency, cardiomyopathy, and cataracts. Some patients had additional central nervous system abnormalities, such as cerebellar and pontine hypoplasia, paucity of white matter and ventricular dilatation, heterotopias, abnormalities of the septum pellucidum, and schizencephaly. Cardiomyopathy was dilated or hypertrophic. Other more variable features included coarse facial features in older children, retinal hypopigmentation, microcephaly, seizures, nystagmus, cleft palate, and failure to thrive. None achieved independent ambulation. The condition was severe, with only half of the patients still alive at the time of the study. The most common causes of death were progressive cardiac failure and recurrent infections. Ehmke et al. (2014) reported a male infant, born of consanguineous Iranian parents, with Vici syndrome. The patient presented at age 2 months with hypotonia and poor feeding, and was noted to have hypopigmentation of the skin and hair compared to his parents. He had delayed development and spasticity. Dysmorphic features included microcephaly (-2 SD), depressed nasal bridge, micrognathia, and macular atrophy. Laboratory and radiographic investigations showed mild neutropenia, mild hypertrophic cardiomyopathy, complete agenesis of the corpus callosum, and cerebellar atrophy. He died of respiratory failure at age 3.5 months. Ehmke et al. (2014) reviewed the clinical features of all 27 reported patients with VICIS, including their own. All had severely delayed psychomotor development, agenesis of the corpus callosum, and pigmentary abnormalities. Most had additional brain abnormalities, such as cerebellar hypoplasia, as well as immunodeficiency, cardiomyopathy, and growth abnormalities. Maillard et al. (2017) reported a 2-year-old girl, born of unrelated parents, with Vici syndrome. Routine ultrasonography at 22 plus 6 weeks' gestation showed agenesis of the corpus callosum. MRI at 32 weeks' gestation showed ACC with abnormal gyration suggestive of polymicrogyria. She was born at term with normal weight and head circumference. She had severe developmental delay, failure to thrive, hypopigmentation, progressive microcephaly, neurologic symptoms including axial hypotonia with peripheral hypertonia, adducted thumbs, and opisthotonic posture. She had mild dysmorphic features including prominent epicanthic folds, anteverted nostrils, bitemporal narrowing, and fine fair hair. She had hypopigmented fundi but no cataract. Echocardiography and CPK were normal. She had recurrent aspiration pneumonia but normal hematologic investigations including T-cell subsets, T-cell proliferative responses, immunoglobulin levels, and antibody responses. Postnatal MRIs showed ACC, underoperculization of both Sylvian fissures, frontoparietal polymicrogyria, absent supratentorial myelination, and pontocerebellar atrophy. Other Features Miyata et al. (2007) reported 2 sibs with Vici syndrome. Both developed cardiomyopathy with elevated serum B-type natriuretic peptide (NPPB; 600295) and partial response to beta-blockers. Both patients also developed renal tubular acidosis, a previously undocumented potential complication of the disorder. A sleep study including polysomnography indicated functional brainstem involvement. Although both patients had recurrent infections, neither had serologic evidence of immunodeficiency. Miyata et al. (2014) reported the postmortem findings of one of these sibs, who died at 8 months of age. The heart showed dilation of the left ventricle with vacuole formation in the mammillary muscles of the endocardium and immunoreactivity for the autophagy marker p62 (SQSTM1; 601530); the brain showed hypoplasia of the cerebellum and brainstem, and absence of the corpus callosum. Purkinje cells and granule cells were well-preserved, but there was axonal and dendritic swelling. Miyata et al. (2014) noted that Vici syndrome is often described as a malformation syndrome, but it is also characterized by degenerative changes likely resulting from impaired autophagy. Inheritance The transmission pattern of Vici syndrome is most consistent with autosomal recessive inheritance (Chiyonobu et al., 2002; Al-Owain et al., 2010). Molecular Genetics In 16 patients from 13 unrelated families with Vici syndrome, Cullup et al. (2013) identified homozygous or compound heterozygous mutations in the EPG5 gene (see, e.g., 615068.0001-615068.0005). Nine of the patients had previously been reported, including the 2 sibs originally reported by Dionisi Vici et al. (1988). All of the mutations were truncating or splice site mutations, except for 2 that were missense mutations. The first mutations were identified by exome sequencing of 4 patients from 3 families, and the rest of the mutations were identified by screening of the EPG5 gene in 12 additional families. Two families with the disorder did not have EPG5 mutation, suggesting genetic heterogeneity for the disorder. In a male infant, born of consanguineous Iranian parents, with Vici syndrome, Ehmke et al. (2014) identified a homozygous truncating mutation in the penultimate exon (exon 43) of the EPG5 gene (R2483X; 615068.0006). By whole-exome sequencing in a 2-year-old girl, born of unrelated parents, with Vici syndrome, Maillard et al. (2017) identified compound heterozygosity for a missense (G1336E; 615068.0007) and a frameshift (615068.0008) mutation in the EPG5 gene. Each parent carried one of the mutations. Pathogenesis The identification of loss-of-function mutations in the EPG5 gene, which is involved in autophagy, suggested to Cullup et al. (2013) that Vici syndrome results from defective autophagy. Patient skeletal muscle tissue showed fiber-type disproportion with type 1 atrophy and numerous vacuole-like areas. Immunofluorescence studies of skeletal muscle from 2 patients showed upregulation of the sarcomere-associated autophagy proteins SQSTM1 and NBR1 (166945) with numerous puncta, indicating accumulation of autophagosomes in EPG5-deficient cells. Treatment of patient and control cells with autophagy inducers and inhibitors suggested that patient cells had a severe deficit in autophagosomal clearance and impaired fusion to lysosomes. The findings were consistent with histopathologic features of defective autophagy, including storage of abnormal material and secondary mitochondrial abnormalities in skeletal muscle, as well as multisystem defects in the heart, immune system, skin pigmentation, and central nervous system, implicating defective autophagy in various tissues. Animal Model Zhao et al. (2013) found that Epg5-null mice developed progressive neurologic symptoms with hind limb paralysis around 4 months of age, resulting in death at 10 to 12 months. Autophagy flux was impaired, resulting in the accumulation of SQSTM1 aggregates in only certain neuronal populations in the central nervous system, including anterior horn cells of the spinal cord but not Purkinje cells in the cerebellum. Mutant mice also had severe muscle atrophy and muscle denervation, reminiscent of amyotrophic lateral sclerosis (ALS; 105400). The mice showed only some features of Vici syndrome, including thin corpus callosum and muscle atrophy, but other core features, such as growth retardation, dysmorphic facial features, cataract, hypopigmentation, and immunodeficiency, were not present. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive \- Post natal growth retardation HEAD & NECK Head \- Microcephaly Face \- Hypertelorism Ears \- Low-set ears \- Sensorineural hearing loss (in some patients) Eyes \- Bilateral cataracts \- Ocular albinism \- Retinal hypopigmentation \- Nystagmus Mouth \- Cleft lip \- Cleft palate \- Micrognathia CARDIOVASCULAR Heart \- Cardiomyopathy, dilated \- Left ventricular hypertrophy \- Systolic dysfunction \- Heart failure RESPIRATORY Airways \- Recurrent respiratory tract infections GENITOURINARY External Genitalia (Male) \- Hypospadias, penile Kidneys \- Renal tubular acidosis (2 sibs) SKIN, NAILS, & HAIR Skin \- Skin hypopigmentation \- Cutaneous albinism \- Chronic mucocutaneous candidiasis Hair \- Hair hypopigmentation MUSCLE, SOFT TISSUES \- Hypotonia \- Myopathy \- Variation in fiber size \- Internal nuclei \- Abnormal mitochondria \- Numerous vacuole-like areas \- Redundancy of basal lamina with accumulated debris NEUROLOGIC Central Nervous System \- Hypotonia \- Abnormal posturing \- Corpus callosum agenesis \- Cerebellar vermis hypoplasia \- Profound psychomotor retardation \- White matter neuronal heterotopia \- Bilateral schizencephaly \- Seizures IMMUNOLOGY \- Recurrent bacterial, viral, and fungal infections \- Skin anergy to recall antigens \- Profound depletion of T4+ lymphocytes \- Thymic hypoplasia \- Lack of delayed skin hypersensitivity reaction \- Decreased serum immunoglobulins \- Defective humoral response LABORATORY ABNORMALITIES \- Reduced IgG levels, particularly IgG2 subclass \- Normal IgA levels \- Normal IgM levels MISCELLANEOUS \- Onset at birth \- Early death often occurs from cardiac failure or infection \- Immunologic defects are variable MOLECULAR BASIS \- Caused by mutation in the ectopic P-granules autophagy protein 5 homolog gene (EPG5, 615068.0001 ) ▲ 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	VICI SYNDROME	c1855772	27,336	omim	https://www.omim.org/entry/242840	2019-09-22T16:26:22	{"doid": ["0060356"], "mesh": ["C535566"], "omim": ["242840"], "orphanet": ["1493"], "synonyms": ["Alternative titles", "IMMUNODEFICIENCY WITH CLEFT LIP/PALATE, CATARACT, HYPOPIGMENTATION, AND ABSENT CORPUS CALLOSUM"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4) is caused by compound heterozygous mutation in the DGUOK gene (601465) on chromosome 2p13. Biallelic mutation in the DGUOK gene can also cause the more severe disorder mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880). Description Autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4) is an autosomal recessive disorder characterized by adult onset of eye muscle weakness and proximal limb muscle weakness associated with deletions of mtDNA on skeletal muscle biopsy, which results from defective mtDNA replication in post-mitotic muscle tissue. Additional features are more variable (summary by Ronchi et al., 2012). For a discussion of genetic heterogeneity of autosomal recessive PEO, see PEOB1 (258450). Clinical Features Ronchi et al. (2012) reported 6 patients, including 2 sibs, with adult-onset mitochondrial myopathy. Three patients and the 2 sibs presented between 40 and 69 years of age with slowly progressive external ophthalmoplegia (in 2 patients) and/or limb muscle weakness. Three patients had proximal muscle weakness primarily affecting the lower limbs. Some patients had dysphagia and/or dysphonia; 1 had cataracts and diabetes. EMG studies showed a myopathic pattern, and serum creatine kinase and lactate were mildly increased. Muscle biopsies showed fiber size variability, ragged-red fibers, and COX-negative fibers. All patients had multiple mtDNA deletions in skeletal muscle, without evidence of mtDNA depletion (mtDNA copy number was normal). There was some phenotypic variability: the sibs had distal muscle weakness and atrophy associated with signs of a distal neuropathy, including fasciculations, decreased nerve conduction velocities, hyporeflexia, and neurogenic signs on EMG. Sural nerve biopsy in 1 sib showed a severe axonal neuropathy and demyelination. The sibs also had sensorineural hearing loss and mild cortical atrophy on brain imaging. Another patient (patient 4) had a more severe disorder with features of MTDPS3. She presented in infancy with liver failure and underwent liver transplant at age 9 months. She was then well until age 20 years, when she experienced 2 episodes of acute mitochondrial myopathy with proximal muscle weakness, increased serum creatine kinase, and rhabdomyolysis possibly triggered by infection. Muscle biopsy showed severe COX deficiency and ragged-red fibers. Inheritance The transmission pattern of PEOB4 in the families reported by Ronchi et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 patients, including 2 sibs, with adult-onset PEOB4, Ronchi et al. (2012) identified compound heterozygous mutations in the DGUOK gene (601465.0008; 601465.0010-601465.0015). The mutations, which were found by targeted exome sequencing and confirmed by standard sequencing, included both missense and truncating mutations. Skeletal muscle from patients showed mtDNA deletions as well as decreased protein levels and activity of DGUOK. The findings expanded the phenotype associated with DGUOK mutations. In this study, DGUOK mutations accounted for 5.6% of 90 probands with mtDNA deletions in skeletal muscle. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural deafness (family A) Eyes \- Progressive external ophthalmoplegia (in most patients) \- Ptosis (in most patients) ABDOMEN Gastrointestinal \- Dysphagia (in some patients) MUSCLE, SOFT TISSUES \- Mitochondrial myopathy \- Muscle weakness, proximal \- Weakness primarily affects lower limbs \- Upper limbs may show muscle weakness \- Muscle weakness, distal (family A) \- Muscle atrophy \- Muscle biopsy shows fiber size variability \- Ragged-red fibers \- COX-negative fibers \- MtDNA deletions \- Myopathic changes seen on EMG NEUROLOGIC Central Nervous System \- Cognitive impairment (family A) \- Cortical atrophy (family A) Peripheral Nervous System \- Axonal neuropathy (family A) \- Hyporeflexia (family A) VOICE \- Dysphonia LABORATORY ABNORMALITIES \- Increased serum creatine kinase, mild \- Increased serum lactate, mild MISCELLANEOUS \- Onset in adulthood \- Variable presentation and phenotype MOLECULAR BASIS \- Caused by mutation in the deoxyguanosine kinase gene (DGUOK, 601465.0008 ) ▲ 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	PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4	c4310733	27,337	omim	https://www.omim.org/entry/617070	2019-09-22T15:46:58	{"omim": ["617070"], "orphanet": ["329314"], "synonyms": ["Adult-onset multiple mtDNA deletion syndrome due to DGUOK deficiency", "Alternative titles", "PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL RECESSIVE 4"]}
Fusariosis SpecialtyDermatology, infectious disease Fusariosis is an infection seen in neutropenic patients, and is a significant opportunistic pathogen in patients with hematologic malignancy.[1]:330 It is associated with infections with Fusarium species, such as Fusarium proliferatum.[2] ## See also[edit] * Skin lesion ## 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. ^ Neuburger S, Massenkeil G, Seibold M, et al. (July 2008). "Successful salvage treatment of disseminated cutaneous fusariosis with liposomal amphotericin B and terbinafine after allogeneic stem cell transplantation". Transpl Infect Dis. 10 (4): 290–3. doi:10.1111/j.1399-3062.2007.00296.x. PMID 18194367. ## External links[edit] Classification D * ICD-10: B48.7 * MeSH: D060585 External resources * Orphanet: 228119 This infection-related 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	Fusariosis	c0276758	27,338	wikipedia	https://en.wikipedia.org/wiki/Fusariosis	2021-01-18T18:45:07	{"mesh": ["D060585"], "umls": ["C0276758"], "orphanet": ["228119"], "wikidata": ["Q18928476"]}
Prominent glabella – microcephaly – hypogenitalism is a very rare syndrome described in two sibs and characterized by prenatal onset of growth deficiency, microcephaly, hypoplastic genitalia, and birth onset of convulsions. [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	Prominent glabella-microcephaly-hypogenitalism syndrome	c0796024	27,339	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2083	2021-01-23T18:28:43	{"gard": ["144"], "mesh": ["C537714"], "omim": ["247990"], "umls": ["C0796024"], "icd-10": ["Q87.8"], "synonyms": ["MacDermot-Winter syndrome"]}
Wise-Rein disease SpecialtyDermatology Lichen ruber moniliformis is a rare skin disease named for Fred Wise and Charles R. Rein.[1][2] It is one of several diseases also known as Kaposi's disease, based on its characterization in 1886 by Moritz Kaposi.[1][3] It is thought to be a rare variety of lichen planus.[citation needed]It is also known as "Morbus moniliformis lichenoides".[4] ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Presentation[edit] The disease causes numerous whitish punctiform papules and brownish macules arranged in a necklace-like pattern.[citation needed] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (September 2017) ## See also[edit] * Lichen planus * List of cutaneous conditions ## References[edit] 1. ^ a b synd/1213 at Who Named It? \- entry on Kaposi's disease I 2. ^ F. Wise, C. R. Rein. Lichen ruber moniliformis (morbus moniliformis lichenoides). Report of a case and description of a hitherto unrecorded histologic structure. Archives of Dermatology and Syphilology, Chicago, 1936, 34: 830-849. 3. ^ M. Kaposi. Lichen ruber moniliformis. Vierteljahrsschrift für Dermatologie und Syphilis, Wien, 1886, 13: 571-582. 4. ^ Mumford PB, Barber HW (April 1943). "Lichen Ruber Moniliformis (Morbus Moniliformis Lichenoides; Myxoedema Moniliforme.)". Proc. R. Soc. Med. 36 (6): 286–287. PMC 1998513. PMID 19992630. ## External links[edit] Classification D * ICD-10: L44.3 * ICD-9-CM: 697.8 * DiseasesDB: 32214 * 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 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	Lichen ruber moniliformis	c0263375	27,340	wikipedia	https://en.wikipedia.org/wiki/Lichen_ruber_moniliformis	2021-01-18T19:08:21	{"umls": ["C0263375"], "icd-9": ["697.8"], "icd-10": ["L44.3"], "wikidata": ["Q6543211"]}
Reif-Lehrer (1976) reported that 25% of persons develop the 'Chinese restaurant syndrome' on exposure to monosodium glutamate (MSG) used as a flavor enhancer. Its heavy use in soy sauce is the reason for association of its effects with Chinese restaurants. He suggested that sensitive individuals may have an inborn error of metabolism. Symptoms of the Chinese restaurant syndrome include tightness in the back of the neck, pressure behind the eyes, frontal or temporal headache, facial flushing, nausea, etc. Family and twin studies are needed. 'Hot dog' headache (Henderson and Raskin, 1972) and diet-induced migraine (Youdim et al., 1971; Sandler et al., 1974) may be similar examples. HEENT \- Headache, monosodium glutamate (MSG) induced \- Pressure behind the eyes \- Frontal headache \- Temporal headache \- Facial flushing Neck \- Tightness in back of neck GI \- Nausea Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	MONOSODIUM GLUTAMATE SENSITIVITY	c0008127	27,341	omim	https://www.omim.org/entry/231630	2019-09-22T16:27:34	{"mesh": ["C562377"], "omim": ["231630"], "synonyms": ["Alternative titles", "CHINESE RESTAURANT SYNDROME"]}
Pyruvate dehydrogenase complex deficiency SpecialtyEndocrinology Pyruvate dehydrogenase deficiency (also known as pyruvate dehydrogenase complex deficiency or PDCD) is a rare neurodegenerative disorders associated with abnormal mitochondrial metabolism. PDCD is a genetic disease resulting from mutations in one of the components of the pyruvate dehydrogenase complex (PDC).[1] The PDC is a multi-enzyme complex that plays a vital role as a key regulatory step in the central pathways of energy metabolism in the mitochondria.[2] The disorder shows heterogeneous characteristics in both clinical presentation and biochemical abnormality.[3] ## Contents * 1 Biochemistry & Genetics * 2 Epidemiology * 3 Signs and symptoms * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment & Monitoring * 6 See also * 7 References * 8 External links ## Biochemistry & Genetics[edit] Aerobic respiration is the process of converting energy in the form of glucose into ATP, the primary currency of energy used by cells to fuel biochemical processes and support growth. The first phase of respiration is glycolysis, a series of ten biochemical reactions in the cytoplasm that convert glucose into pyruvate. Pyruvate is then transported into mitochondria, where it is converted by the pyruvate dehydrogenase complex into acetyl-CoA, the starting substrate of the Krebs cycle. When PDC activity is reduced or abolished by mutation, pyruvate levels rise. Excess pyruvate is then converted into lactic acid by lactate dehydrogenase. Lactic acid enters the blood stream, causing acidification in a condition known as lactic acidosis. Glycolysis Citric acid cycle with aconitate 2 The most commonly seen form of PDCD is caused by mutations in the X-linked E1 alpha gene, PDHA1,[4] and is approximately equally prevalent in both males and females. However, males are more severely affected than heterozygous females. This can be explained by x-inactivation, as females carry one normal and one mutant gene. Cells with a normal allele active can metabolize the lactic acid that is released by the PDH deficient cells. They cannot, however, supply ATP to these cells and, therefore, phenotype depends largely on the nature/severity of the mutation.[5][6] More rarely, mutations occur in the E2 (dihydrolipoyl transacetylase) or the E3 (dihydrolipoyl dehydrogenase) subunits of the PDC enzymatic complex, DLAT and DLD genes respectively. In these cases, PDCD displays autosomal recessive inheritance, affecting males and females equally.[7] In cases where PDHD is a result of a mutation in a gene other than PDHA1, it is most commonly known to be due to mutations in the following four genes, PDHB, DLAT, PDHX and PDP1. All of these genes, like the PDHA1 gene are responsible for coding for a specific subunit of the pyruvate dehydrogenase complex. The PDHB gene is responsible for the coding of the E1 beta subunit of the pyruvate dehydrogenase complex. The DLAT gene is responsible for the coding of the E2 subunit, and the PDP1 is responsible for producing the PDH phosphatase catalytic subunit that catalyzes PDH dephosphorylation. This dephosphorylation activates the complex. The final gene that could be responsible for this disease is the PDHX gene, which codes for the E3 binding protein which is responsible for binding E3 dimers to the E2 subunit of the complex [8] ## Epidemiology[edit] Pyruvate dehydrogenase deficiency is extremely rare, with ~500 reported cases in the medical literature. Due to the rarity and unfamiliarity of the disease, it is likely underdiagnosed[9] (Shin et al., 2017). ## Signs and symptoms[edit] Microcephaly and a normal head size PDCD is generally presented in one of two forms. The metabolic form appears as lactic acidosis. The neurological form of PDCD contributes to hypotonia, poor feeding, lethargy and structural abnormalities in the brain.[10] Patients may develop seizures and/or neuropathological spasms. These presentations of the disease usually progress to mental retardation, microcephaly, blindness, and spasticity.[5][11][9] Females with residual pyruvate dehydrogenase activity will have no uncontrollable systemic lactic acidosis and few, if any, neurological symptoms. Conversely, females with little to no enzyme activity will have major structural brain abnormalities and atrophy. Males with mutations that abolish, or almost abolish, enzyme activity presumably die in utero because brain cells are not able to generate enough ATP to be functionally viable. It is expected that most cases will be of mild severity and have a clinical presentation involving lactic acidosis.[6] Male infants that reach full term display more severe symptoms than females, and exhibit high mortality within the first few years of life [12][9] Prenatal onset may present with non-specific signs such as low Apgar scores and small for gestational age. These cases display hydrocephalus, and thinning of the cerebral tissue.[9] Metabolic disturbances may also be considered with poor feeding and lethargy out of proportion to a mild viral illness, and especially after bacterial infection has been ruled out.[5] PDH activity may be enhanced by exercise, phenylbutyrate and dichloroacetate.[citation needed] The clinical presentation of congenital PDH deficiency is typically characterized by heterogenous neurological features that usually appear within the first year of life. In addition, patients usually show severe hyperventillation due to profound metabolic acidosis mostly related to lactic acidosis. Metabolic acidosis in these patients is usually refractory to correction with bicarbonate.[13] The following table lists common symptoms of pyruvate dehydrogenase deficiency.[3] Symptoms Definition/Explanation Lactic Acidosis High levels of lactate in the blood; can cause nausea, vomiting, breathing problems, abnormal heartbeats In less severe cases, signs of lactic acidosis can include ataxia and episodes may only occur when ill, under stress, or after consuming high amounts of carbohydrates. Hyperammonemia High levels of ammonia in the blood; can cause confusion, weakness, fatigue Facial Deformities Narrow head, prominent forehead, wide nasal bridge, flared nostrils Neurological Impairments Developmental delays, intellectual impairments, seizures, lethargy (lack of energy), abnormal eye movements, blindness, microcephaly, poor coordination, difficulty walking Abnormal Brain Structure Underdeveloped corpus callosum, atrophy of the cerebral cortex, lesions on some parts of the brain Muscular Abnormalities Hypotonia (weak muscle tone), spasticity (tight muscles), ataxia (abnormal muscle movements) Abnormalities at Infancy Low APGAR scores (scores measuring a baby’s health after birth), low birth weight, difficulty nursing Breathing Difficulties Tachypnea (rapid breathing) Fetal Abnormalities Poor fetal weight gain, low levels of estriol in the mother’s urine ## Diagnosis[edit] MRI of head(brain)- cerebral atrophy can be detected by such a method[14] Pyruvate dehydrogenase deficiency can be diagnosed via the following methods:[14] Blood test (Lactate and pyruvate levels) * Urine analysis * Magnetic resonance spectroscopy * MRI ### Differential diagnosis[edit] The differential diagnosis of pyruvate dehydrogenase deficiency can consist of either D-Lactic acidosis or abnormalities associated with gluconeogenesis.[14] ## Treatment & Monitoring[edit] Direct treatment that stimulates the pyruvate dehydrogenase complex (PDC), provides alternative fuels, and prevents acute worsening of the syndrome.[15] However, some correction of acidosis does not reverse all the symptoms. CNS damage is common and limits a full recovery.[9] Ketogenic diets, with high fat and low carbohydrate intake have been used to control or minimize lactic acidosis and anecdotal evidence shows successful control of the disease, slowing progress and often showing rapid improvement.[16] Ketogenic baby formulas such as Nutricia KetoCal are available.[17] With the ketogenic diet, ATP is synthesized by the catabolism of fatty acids rather than glucose, which produces the ketone bodies, 3-beta-hydroxybutyrate, acetoacetate, and acetone. Ketone bodies serve as an alternate source of energy for the body and the brain.[16] Preliminary data from PDHD patients on the ketogenic diet indicate that in milder cases, there is a reduction in the frequency of seizures, abnormal EEG readings, ataxia and abnormal sleeping patterns, and extension of remission periods. More severe cases are less responsive to the ketogenic diet, but have displayed modest improvement of gross and fine motor skills, speech and language development and development of social skills.[16] The ketogenic diet has several long term drawbacks, including pancreatitis, sialorrhea and obstipation to vomiting. Patients must be monitored regularly for blood lactate levels, transaminase and plasma ketone levels.[16] There is some evidence that dichloroacetate reduces the inhibitory phosphorylation of pyruvate dehydrogenase complex and thereby activates any residual functioning complex. Resolution of lactic acidosis is observed in patients with E1 alpha enzyme subunit mutations that reduce enzyme stability. However, treatment with dichloroacetate does not improve neurological damage.[5] Oral citrate is often used to treat acidosis.[18] Clinical trials to improve scientific and medical understanding of PDCD are underway. More information is located at ClinicalTrials.gov.[19] ## See also[edit] * Citric acid cycle * Branched-chain alpha-keto acid dehydrogenase complex * Anti-mitochondrial antibody ## References[edit] 1. ^ Brown, G K; Otero, L J; LeGris, M; Brown, R M (November 1994). "Pyruvate dehydrogenase deficiency". Journal of Medical Genetics. 31 (11): 875–879. doi:10.1136/jmg.31.11.875. ISSN 0022-2593. PMC 1016663. PMID 7853374. 2. ^ Patel, Mulchand S.; Nemeria, Natalia S.; Furey, William; Jordan, Frank (2014-06-13). "The Pyruvate Dehydrogenase Complexes: Structure-based Function and Regulation". Journal of Biological Chemistry. 289 (24): 16615–16623. doi:10.1074/jbc.R114.563148. ISSN 0021-9258. PMC 4059105. PMID 24798336. 3. ^ a b Reference, Genetics Home. "pyruvate dehydrogenase deficiency". Genetics Home Reference. Retrieved 2016-11-08. 4. ^ Imbard, A.; Boutron, A.; Vequaud, C.; Zater, M.; de Lonlay, P.; de Baulny, H. Ogier; Barnerias, C.; Miné, M.; Marsac, C.; Saudubray, J.-M.; Brivet, M. (December 2011). "Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein". Molecular Genetics and Metabolism. 104 (4): 507–516. doi:10.1016/j.ymgme.2011.08.008. ISSN 1096-7206. PMID 21914562. 5. ^ a b c d G K Brown; L J Otero; M LeGris; R M Brown (November 1994). "Pyruvate dehydrogenase deficiency". J Med Genet. 31 (11): 875–879. doi:10.1136/jmg.31.11.875. PMC 1016663. PMID 7853374. 6. ^ a b H H Dahl (March 1995). "Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again". Am J Hum Genet. 56 (3): 553–557. PMC 1801181. PMID 7887408. 7. ^ Kerr, D. S.; Wexler, I. D.; Tripatara, A.; Patel, M. S. (1996), Patel, Mulchand S.; Roche, Thomas E.; Harris, Robert A. (eds.), "Human defects of the pyruvate dehydrogenase complex", Alpha-Keto Acid Dehydrogenase Complexes, MCBU Molecular and Cell Biology Updates, Birkhäuser, pp. 249–269, doi:10.1007/978-3-0348-8981-0_18, ISBN 978-3-0348-8981-0 8. ^ (GeneCards - Human Genes \| Gene Database \| Gene Search, n.d.) 9. ^ a b c d e Shin, Ha Kyung; Grahame, George; McCandless, Shawn E.; Kerr, Douglas S.; Bedoyan, Jirair K. (2017-11-01). "Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency". Molecular Genetics and Metabolism. 122 (3): 61–66. doi:10.1016/j.ymgme.2017.09.001. ISSN 1096-7192. PMC 5722699. PMID 28918066. 10. ^ Cassandra L. Kniffin (28 October 2014). "pyruvate dehydrogenase E1-alpha deficiency; PDHAD". Online Mendelian Inheritance in Man. Johns Hopkins University. Entry # 312170. Retrieved 2016-11-09. 11. ^ Patel, Kavi P.; O'Brien, Thomas W.; Subramony, Sankarasubramon H.; Shuster, Jonathan; Stacpoole, Peter W. (January 2012). "The Spectrum of Pyruvate Dehydrogenase Complex Deficiency: Clinical, Biochemical and Genetic Features in 371 Patients". Molecular Genetics and Metabolism. 105 (1): 34–43. doi:10.1016/j.ymgme.2011.09.032. ISSN 1096-7192. PMC 3754811. PMID 22079328. 12. ^ Natarajan, Niranjana; Tully, Hannah M.; Chapman, Teresa (2016-08-01). "Prenatal presentation of pyruvate dehydrogenase complex deficiency". Pediatric Radiology. 46 (9): 1354–1357. doi:10.1007/s00247-016-3585-z. ISSN 1432-1998. PMC 6383724. PMID 27026023. 13. ^ Mitochondrion. 14. ^ a b c "Pyruvate Dehydrogenase Complex Deficiency Workup: Laboratory Studies, Imaging Studies, Histologic Findings". emedicine.medscape.com. Retrieved 8 November 2016. 15. ^ Garry Brown, ed. (April 2012). "Pyruvate dehydrogenase deficiency". Orphanet. ORPHA765. Retrieved 8 November 2016. 16. ^ a b c d Sofou, Kalliopi; Dahlin, Maria; Hallböök, Tove; Lindefeldt, Marie; Viggedal, Gerd; Darin, Niklas (2017). "Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes". Journal of Inherited Metabolic Disease. 40 (2): 237–245. doi:10.1007/s10545-016-0011-5. ISSN 1573-2665. PMC 5306430. PMID 28101805. 17. ^ "KetoCal family of ketogenic medical foods (ketogenic formulas)". www.myketocal.com. Retrieved 2020-05-06. 18. ^ "Metabolic Acidosis Treatment & Management: Approach Considerations, Type 1 Renal Tubular Acidosis, Type 2 Renal Tubular Acidosis". 2019-11-11. Cite journal requires `\|journal=` (help) 19. ^ "Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-05-06. ## External links[edit] Classification D * ICD-10: E74.4 * ICD-9-CM: 271.8 * OMIM: 312170 * MeSH: D015325 * DiseasesDB: 30060 External resources * eMedicine: ped/1969 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * 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[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	Pyruvate dehydrogenase deficiency	c1839413	27,342	wikipedia	https://en.wikipedia.org/wiki/Pyruvate_dehydrogenase_deficiency	2021-01-18T19:01:42	{"gard": ["7513", "4620"], "mesh": ["D015325", "C564071"], "umls": ["C1839413"], "orphanet": ["765", "79243"], "wikidata": ["Q7263801"]}
Non-freezing cold injury to the foot Trench foot Other namesimmersion foot Trench foot as seen on an unidentified soldier during World War I SpecialtyEmergency medicine Symptoms * Tingling, itch and numbness or pain in feet Complications * Infection Causes * Prolonged exposure of feet to damp Treatment * Keep feet dry * Surgical debridement Trench foot is a type of foot damage due to moisture.[1] Initial symptoms often include tingling or itching which can progress to numbness.[1][2] The feet may become red or bluish in color.[1] As the condition worsens the feet can start to swell and smell of decay.[1] Complications may include skin breakdown or infection.[1] Trench foot occurs due to prolonged exposure of the feet to cold, damp, and often unsanitary conditions.[1] Unlike frostbite, trench foot usually occurs at temperatures above freezing.[1] Onset can be as rapid as 10 hours.[1] Risk factors include overly tight boots and not moving.[3] The underlying mechanism is believed to involve constriction of blood vessels resulting in not enough blood flow to the feet.[1] Diagnosis is based on symptoms and examination.[1] Prevention involves keeping the feet warm, dry, and clean.[1] After the condition has occurred, pain medications may be required during the gradual rewarming process.[1] Pain may persist for months following treatment.[3] Surgery to remove damaged tissue or amputation may be necessary.[1] Those in the military are most commonly affected, though cases may also occur in the homeless.[1] The condition was first described during Napoleon Bonaparte's retreat from Russia in the winter of 1812.[1] The word trench in the name is a reference to trench warfare, mainly associated with World War I.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Evaluation * 4 Prevention * 5 Treatment * 6 History * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Trench foot Trench foot frequently begins with the feeling of tingling and an itch in affected feet, and subsequently progresses to numbness or pain.[1][2] The feet may become red or blue as a result of poor blood supply.[1] Later, as the condition worsens feet can start to swell and smell of decay as muscle and tissue become macerated. The feet often feel warm to touch.[1][4] Advanced trench foot often involves blisters and open sores, which lead to fungal infections; this is sometimes called tropical ulcer (jungle rot). It is marked by severe short-term pain when feeling returns.[3] ## Causes[edit] Unlike frostbite, trench foot does not require freezing temperatures; it can occur in temperatures up to 16 °C (61 °F) and within as little as 13 hours. Exposure to these environmental conditions causes deterioration and destruction of the capillaries, and leads to damage of the surrounding flesh.[4] Excessive sweating (hyperhidrosis) has long been regarded as a contributory cause; unsanitary, cold, and wet conditions can also cause trench foot.[5] ## Evaluation[edit] The diagnosis of trench foot does not usually require any investigations unless an underlying infection of bone is suspected, when an x-ray is performed. A full blood count might show a high white blood cell count if infection is present and inflammatory markers such as an erythrocyte sedimentation rate or C-reactive protein (CRP) might highlight severity.[1] ## Prevention[edit] Trench foot can be prevented by keeping the feet clean, warm, and dry.[1] ## Treatment[edit] Keeping the feet dry is the first line treatment. The initial aim is to protect undamaged tissue of the feet and prevent any further destruction of the feet.[3][4] Applying emollient helps.[4] The mainstay of treatment, like the treatment of gangrene, is surgical debridement, and often includes amputation.[1] Self-treatment consists of changing socks two or three times a day and usage of plenty of talcum powder. Whenever possible, shoes and socks should be taken off, the feet bathed for five minutes and patted dry, talcum powder applied, and feet elevated to let air get to them.[1] ## History[edit] Office of War Information - WW2 Trench foot was first reported in 1812 by the French army surgeon Dominique Jean Larrey when Napoleon’s army was retreating from Russia.[1][6] It was also a problem for soldiers engaged in trench warfare during the winters of World War I (hence the name).[1][2] It was also discovered in World War I that a key preventive measure was regular foot inspections; soldiers would be paired and each partner made responsible for the feet of the other, and they would generally apply whale oil to prevent trench foot. If left to their own devices, soldiers might neglect to take off their own boots and socks to dry their feet each day, but when it was made the responsibility of another, this became less likely.[7] The condition has been documented in survivors of shipwrecks and downed aeroplanes.[4] Trench foot made a reappearance in the British Army during the Falklands War, in 1982.[1][8] The condition was reported at the 1998 and 2007 Glastonbury Festivals.[9][10] ## See also[edit] * Chilblains * Trench fever ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Bush, Jeffrey S.; Lofgran, Trevor; Watson, Simon (2020), Trench Foot, StatPearls Publishing, PMID 29493986 2. ^ a b c Atenstaedt, Robert L. (1 December 2006). "Trench Foot: The Medical Response in the First World War 1914–18". Wilderness & Environmental Medicine. 17 (4): 282–289. doi:10.1580/06-WEME-LH-027R.1. ISSN 1080-6032. PMID 17219792. 3. ^ a b c d Ackerman, Bret T.; Wedmore, Ian S. (2008). "11. Operational Medicine Environmental Considerations". In Schwartz, Richard B.; McManus, John G.; Swienton, Raymond E. (eds.). Tactical Emergency Medicine. LWW medical book collection. Philadelphia: Lippincott Williams & Wilkins. pp. 78–80. ISBN 978-0-7817-7332-4. 4. ^ a b c d e Linklater, James M.; Read, John W.; Hayter, Catherine L. (2013), "3. Imaging of the foot and ankle", in Saltzman, Charles L.; Saltzman, Charles L.; Anderson, Robert (eds.), Mann's Surgery of the Foot and Ankle, 1 (9th ed.), Philadelphia: Elsevier Saunders, p. 738, ISBN 978-0-323-07242-7 5. ^ Redisch, Walter; Brandman, Otto; Rainone, Salvatore (1 May 1951). "Chronic trench foot: a study of 100 cases". Annals of Internal Medicine. 34 (5): 1163–1168. doi:10.7326/0003-4819-34-5-1163. ISSN 0003-4819. 6. ^ Régnier C (2004). "Etiological argument about the Trench Foot". Histoire des sciences médicales (in French). 38 (3): 315–32. PMID 15617178. 7. ^ David, Saul (presenter) (February 2012). Bullets, Boots and Bandages (episode 1/3). BBC Four. 8. ^ Thompson, Julian (18 September 2014). "Falklands Conflict Gallery By Major General Julian Thompson". BBC. Retrieved 10 March 2018. 9. ^ Sully, Andy (23 June 2008). "I got trench foot at Glastonbury". BBC News. Retrieved 26 May 2010. 10. ^ Reid, Fiona (2017). Medicine in First World War Europe: Soldiers, Medics, Pacifists. Bloomsbury Academic. p. 51-55. ISBN 978-1-4725-1324-3. ## External links[edit] Classification D * ICD-10: T69.0 * ICD-9-CM: 991.4 * DiseasesDB: 31219 * Media related to Trench foot at Wikimedia Commons * v * t * e Consequences of external causes Temperature Elevated Hyperthermia Heat syncope Reduced Hypothermia Immersion foot syndromes Trench foot Tropical immersion foot Warm water immersion foot Chilblains Frostbite Aerosol burn Cold intolerance Acrocyanosis Erythrocyanosis crurum Radiation Radiation poisoning Radiation burn Chronic radiation keratosis Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy Radiation acne Radiation-induced cancer Radiation recall reaction Radiation-induced erythema multiforme Radiation-induced hypertrophic scar Radiation-induced keloid Radiation-induced morphea Air * Hypoxia/Asphyxia * Barotrauma * Aerosinusitis * Decompression sickness * High altitude * Altitude sickness * Chronic mountain sickness * Death zone * HAPE * HACE Food * Starvation Maltreatment * Physical abuse * Sexual abuse * Psychological abuse Travel * Motion sickness * Seasickness * Airsickness * Space adaptation syndrome Adverse effect * Hypersensitivity * Anaphylaxis * Angioedema * Allergy * Arthus reaction * Adverse drug reaction Other * Electrical injury * Drowning * Lightning injuries Ungrouped skin conditions resulting from physical factors * Dermatosis neglecta * Pinch mark * Pseudoverrucous papules and nodules * Sclerosing lymphangitis * Tropical anhidrotic asthenia * UV-sensitive syndrome environmental skin conditions Electrical burn frictional/traumatic/sports Black heel and palm Equestrian perniosis Jogger's nipple Pulling boat hands Runner's rump Surfer's knots Tennis toe Vibration white finger Weathering nodule of ear Wrestler's ear Coral cut Painful fat herniation Uranium dermatosis iv use Skin pop scar Skin track Slap mark Pseudoacanthosis nigricans Narcotic dermopathy [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	Trench foot	c0040831	27,343	wikipedia	https://en.wikipedia.org/wiki/Trench_foot	2021-01-18T19:02:12	{"mesh": ["D007102"], "icd-9": ["991.4"], "icd-10": ["T69.0"], "wikidata": ["Q1660072"]}
Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head." Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal. MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed. People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems. ## Frequency The prevalence of all forms of microcephaly that are present from birth (primary microcephaly) ranges from 1 in 30,000 to 1 in 250,000 newborns worldwide. About 200 families with MCPH have been reported in the medical literature. This condition is more common in several specific populations, such as in northern Pakistan, where it affects an estimated 1 in 10,000 newborns. ## Causes MCPH can result from mutations in at least seven genes. Mutations in the ASPM gene are the most common cause of the disorder, accounting for about half of all cases. The genes associated with MCPH play important roles in early brain development, particularly in determining brain size. Studies suggest that the proteins produced from many of these genes help regulate cell division in the developing brain. Mutations in any of the genes associated with MCPH impair early brain development. As a result, affected infants have fewer nerve cells (neurons) than normal and are born with an unusually small brain. The reduced brain size underlies the small head size, intellectual disability, and developmental delays seen in many affected individuals. ### Learn more about the gene associated with Autosomal recessive primary microcephaly * ASPM Additional Information from NCBI Gene: * CDK5RAP2 * CENPJ * CEP152 * KNL1 * MCPH1 * STIL * WDR62 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	Autosomal recessive primary microcephaly	c1855081	27,344	medlineplus	https://medlineplus.gov/genetics/condition/autosomal-recessive-primary-microcephaly/	2021-01-27T08:24:51	{"gard": ["12117"], "mesh": ["C565384"], "omim": ["251200", "604317", "604804", "604321", "608716", "608393", "612703"], "synonyms": []}
## Clinical Features Mir et al. (2005) reported a consanguineous Pakistani family in which 9 members had a prelingual, nonsyndromic form of profound neurosensory deafness. Mapping By genomewide linkage analysis followed by fine mapping in a consanguineous Pakistani family with nonsyndromic deafness, Mir et al. (2005) identified a 17.6-cM candidate disease locus, termed DFNB46, on chromosome 18p11.32-p11.31 between markers D18S59 and D18S391 (maximum multipoint lod score of 3.8 at markers D18S481 and D18S1370). INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness, neurosensory \- Profound deafness MISCELLANEOUS \- Prelingual 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	DEAFNESS, AUTOSOMAL RECESSIVE 46	c1864815	27,345	omim	https://www.omim.org/entry/609647	2019-09-22T16:05:43	{"doid": ["0110503"], "mesh": ["C566459"], "omim": ["609647"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
A type of ALCL, a rare and aggressive peripheral T-cell non-Hodgkin lymphoma affecting lymph nodes and extranodal sites, which is characterized by the expression of a protein called anaplastic lymphoma kinase (ALK). ## Epidemiology The prevalence of ALK+ ALCL is unknown. This subtype usually affects children and young adults. ## Clinical description ALK+ ALCL is characterized by peripheral, mediastinal, or abdominal lymph node involvement. It manifests with the development of painless, enlarged lymph nodes, especially in the neck or armpit (axillary lymph nodes). General symptoms include loss of appetite and fatigue as well as fever, weight loss, and night sweats (B symptoms). Mediastinal involvement manifests as cough, dypsnea and/or edema. ALK+ ALCL can also extend to extranodal sites such as the bones, bone marrow, subcutaneous tissue, lungs, spleen and liver. The 5-year survival rate of ALK-positive patients is 70-80%. ## Etiology In ALK+ ALCL, the anaplastic lymphoma receptor tyrosine kinase ALK>/i> gene is overexpressed due to a t(2;5) (p23;q35) 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	ALK-positive anaplastic large cell lymphoma	c1332079	27,346	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=300895	2021-01-23T17:56:07	{"icd-10": ["C84.6"], "synonyms": ["ALK+ ALCL", "ALK+ anaplastic large cell lymphoma"]}
A rare large, multinodular, usually benign, tumor that is generally located in the posterior part of the scalp in aged women (over 50 years). It first appears as a painless nodule that later grows into a solid or partially cystic tumor that is mobile over the underlying subcutaneous tissues. It can present ulceration, inflammation or even bleeding and can cause necrosis of the adjacent 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	Proliferating trichilemmal cyst	c0345992	27,347	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=492	2021-01-23T16:55:30	{"gard": ["4509"], "icd-10": ["L72.1"]}
An X-linked intellectual disability syndrome (XLMR) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome. ## Epidemiology The prevalence is unknown. It has been reported in a family with 2 brothers and their 2 maternal uncles who presented with severe intellectual deficiency. ## Clinical description Marked facial characteristics (abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, small mouth, and micrognathia), cleft or highly arched palate, and atrial septal defects were observed. Three out of four patients died in infancy or early childhood. Hamel cerebro-palato-cardiac syndrome represents the more severe phenotypic variant. ## Etiology The syndrome is caused by mutations in the PQBP1 gene. Expansions or reductions in the DR/ER repeat in the polar-amino-acid-rich domain (PRD) are responsible for a truncated protein that is thought to disrupt polyglutamine binding. ## Genetic counseling Hamel cerebro-palato-cardiac syndrome follows an X-linked recessive pattern of inheritance. Genetic testing is possible to identify carrier females and to inform them of the risk of passing on the gene to their offspring. [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	Hamel cerebro-palato-cardiac syndrome	None	27,348	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93946	2021-01-23T18:35:01	{}
Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. This condition is characterized by low levels of a fat-like substance called cholesterol in the blood. The severity of signs and symptoms experienced by people with FHBL vary widely. The most mildly affected individuals have few problems with absorbing fats from the diet and no related signs and symptoms. Many individuals with FHBL develop an abnormal buildup of fats in the liver called hepatic steatosis or fatty liver. In more severely affected individuals, fatty liver may progress to chronic liver disease (cirrhosis). Individuals with severe FHBL have greater difficulty absorbing fats as well as fat-soluble vitamins such as vitamin E and vitamin A. This difficulty in fat absorption leads to excess fat in the feces (steatorrhea). In childhood, these digestive problems can result in an inability to grow or gain weight at the expected rate (failure to thrive). ## Frequency FHBL is estimated to occur in 1 in 1,000 to 3,000 individuals. ## Causes Most cases of FHBL are caused by mutations in the APOB gene. This gene provides instructions for making two versions of the apolipoprotein B protein: a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which transport fats and cholesterol in the blood. Most APOB gene mutations that lead to FHBL cause both versions of apolipoprotein B to be abnormally short. The severity of the condition largely depends on the length of these two versions of apolipoprotein B. Severely shortened versions cannot partner with lipoproteins and transport fats and cholesterol. Proteins that are only slightly shortened retain some function but partner less effectively with lipoproteins. Generally, the signs and symptoms of FHBL are worse if both versions of apolipoprotein B are severely shortened. Mild or no signs and symptoms result when the proteins are only slightly shortened. All of these protein changes lead to a reduction of functional apolipoprotein B. As a result, the transportation of dietary fats and cholesterol is decreased or absent. A decrease in fat transport reduces the body's ability to absorb fats and fat-soluble vitamins from the diet. Although APOB gene mutations are responsible for most cases of FHBL, mutations in a few other genes account for a small number of cases. Some people with FHBL do not have identified mutations in any of these genes. Changes in other, unidentified genes are likely involved in this condition. ### Learn more about the genes associated with Familial hypobetalipoproteinemia * APOB * PCSK9 Additional Information from NCBI Gene: * ANGPTL3 ## Inheritance Pattern This condition is inherited in an autosomal codominant pattern. Codominance means that copies of the gene from both parents are active (expressed), and both copies influence the genetic trait. In FHBL, a change in one copy of the APOB gene in each cell can cause the condition, but changes in both copies of the gene cause more severe health problems. [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	Familial hypobetalipoproteinemia	c1862596	27,349	medlineplus	https://medlineplus.gov/genetics/condition/familial-hypobetalipoproteinemia/	2021-01-27T08:25:16	{"gard": ["2876"], "mesh": ["C566267"], "omim": ["615558", "605019"], "synonyms": []}
Nakamura et al. (2003) examined a newborn who had no bile and pancreatic ducts. Hydrops was evident after 29 weeks of gestation, and she died shortly after birth. One of her sibs, a male, had died of hydrops at about 6 months of gestation, and there were 2 more miscarriages of unknown causes. The newborn had 2 healthy but small sisters, who were 4 years and 1 year of age, respectively. The parents were not consanguineous. The presumed occurrence in at least 2 sibs, a brother and sister, suggested a genetic basis. At autopsy on the newborn, the liver had an abnormally round shape and the pancreas was not in the normal position. There was an ectopic small pancreas with normally developed islets. Histologic analysis showed complete absence of extra- and intrahepatic bile and pancreatic ducts. Immunostaining of these tissues showed no positive bile duct marker staining using epithelial membrane antigen (158340) and cytokeratin-19 (148020) in the liver. Albumin (103600) and alpha-fetoprotein (104150) staining was positive in the liver, and insulin (176730) and glucagon (138030) staining was positive in the remaining islets of the pancreas. Nakamura et al. (2003) noted that, in animal studies, Pdx1 (600733) deficiency and Hlxb9 (142994) deficiency lead to agenesis of the pancreas and/or ectopic pancreas, and, in humans, PDX1 deficiency has manifestations ranging from agenesis of the pancreas to maturity-onset diabetes of the young-4 (MODY4; 606392). However, pancreatic ducts are not affected in either PDX1 deficiency or HLXB9 deficiency. Patients with Alagille syndrome (see 118450) have paucity or absence of intrahepatic bile ducts, but congenital absence of the interlobular bile ducts has not been noted, and pancreatic ducts are normal. One feature of Meckel syndrome (249000) is hepatic ductal dysplasia, but complete defects of both bile and pancreatic ducts has not been described. Nakamura et al. (2003) concluded that the complete absence of bile and pancreatic ducts represents a novel entity related to a gene involved in bile and pancreatic duct development. [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	BILE AND PANCREATIC DUCTS, COMPLETE ABSENCE OF	c1842614	27,350	omim	https://www.omim.org/entry/608063	2019-09-22T16:08:25	{"mesh": ["C564298"], "omim": ["608063"]}
A rare developmental disorder involving the lung and characterized by pulmonary subpleural, interlobar, perivascular, and peribronchial lymphatic dilatation. ## Epidemiology The prevalence is unknown. ## Clinical description Congenital pulmonary lymphangiectasia (PL) presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth. ## Etiology Most reported cases are sporadic and the etiology is not completely understood. It has been suggested that PL lymphatic channels of the fetal lung do not undergo the normal regression process at 20 weeks of gestation. Secondary PL may be caused by a cardiac lesion. ## Diagnostic methods The diagnostic approach includes obtaining a complete family and obstetric history, conventional radiologic studies, ultrasound and magnetic resonance studies, lymphoscintigraphy, lung functionality tests, lung biopsy, bronchoscopy, and pleural effusion examination. ## Differential diagnosis During the prenatal period, all causes leading to hydrops fetalis should be considered in the diagnosis of PL. ## Antenatal diagnosis Fetal ultrasound evaluation plays a key role in the antenatal diagnosis of PL. ## Management and treatment At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated with prolonged pleural drainage. ## Prognosis Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy, present medical problems which are characteristic of chronic lung 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	Congenital pulmonary lymphangiectasia	c1849554	27,351	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2414	2021-01-23T17:00:28	{"gard": ["9900"], "mesh": ["C537727"], "omim": ["265300"], "umls": ["C0265800", "C1849554"], "icd-10": ["Q33.8"], "synonyms": ["Pulmonary lymphangiomatosis"]}
## Summary ### Clinical characteristics. Ornithine transcarbamylase (OTC) deficiency can occur as a severe neonatal-onset disease in males (but rarely in females) and as a post-neonatal-onset (partial deficiency) disease in males and females. Males with severe neonatal-onset OTC deficiency are typically normal at birth but become symptomatic from hyperammonemia on day two to three of life and are usually catastrophically ill by the time they come to medical attention. After successful treatment of neonatal hyperammonemic coma these infants can easily become hyperammonemic again despite appropriate treatment; they typically require liver transplant by age six months to improve quality of life. Males and heterozygous females with post-neonatal-onset (partial) OTC deficiency can present from infancy to later childhood, adolescence, or adulthood. No matter how mild the disease, a hyperammonemic crisis can be precipitated by stressors and become a life-threatening event at any age and in any situation in life. For all individuals with OTC deficiency, typical neuropsychological complications include developmental delay, learning disabilities, intellectual disability, attention deficit hyperactivity disorder (ADHD), and executive function deficits. ### Diagnosis/testing. The diagnosis of OTC deficiency is established in a male proband with suggestive clinical and laboratory findings and/or at least ONE of the following: * A hemizygous pathogenic variant in OTC by molecular genetic testing * A markedly abnormal increase of orotic acid excretion after an allopurinol challenge test * Decreased OTC enzyme activity in liver The diagnosis of OTC deficiency is usually established in a female proband with the suggestive clinical and laboratory findings and/or with at least ONE of the following: * A heterozygous pathogenic variant in OTC by molecular genetic testing * A markedly abnormal increase of orotic acid excretion after an allopurinol challenge test Measurement of OTC enzyme activity in liver is not a reliable means of diagnosis in females. ### Management. Treatment of manifestations: Treatment is best provided by a clinical geneticist and a nutritionist experienced in the treatment of metabolic disease; treatment of hyperammonemic coma should be provided by a team coordinated by a metabolic specialist in a tertiary care center experienced in the management of OTC deficiency. The mainstays of treatment of the acute phase are rapid lowering of the plasma ammonia level to ≤200 μmol/L (if necessary, with renal replacement therapy); use of ammonia scavenger treatment to allow excretion of excess nitrogen via alternative pathways; reversal of catabolism; and reducing the risk of neurologic damage. The goals of long-term treatment are to promote growth and development and to prevent hyperammonemic episodes. In severe, neonatal-onset urea cycle disorders, liver transplantation is typically performed by age six months to prevent further hyperammonemic crises and neurodevelopmental deterioration. In females and males with partial OTC deficiency liver transplant is typically considered in those who have frequent hyperammonemic episodes. Complications of OTC deficiency, including ADHD and learning disability/intellectual disability, are treated according to the standard of care for these conditions while monitoring for signs of liver disease. Prevention of primary manifestations: If neonatal-onset OTC deficiency is diagnosed prenatally, intravenous (IV) treatment with ammonia scavengers within a few hours of birth (before the ammonia level rises) can prevent a hyperammonemic crisis and coma. For preventive measures after the neonatal period see Treatment of manifestations. Prevention of secondary complications: Avoid overrestriction of protein/amino acids; use gastrostomy tube feedings as needed to help avoid malnutrition; practice careful hand hygiene among all who have contact with the affected individual to minimize risk of infection; give immunizations on the usual schedule, including annual flu vaccine; provide multivitamin and vitamin D supplementation; and use antipyretics appropriately (e.g., ibuprofen is preferred over acetaminophen because of the potential for liver toxicity). Surveillance: At the start of therapy, routine measurement of plasma ammonia and plasma amino acids. Assess liver function (depending on symptoms) every three to six months or more often when previously abnormal. Perform neuropsychological testing at the time of expected significant developmental milestones. Agents/circumstances to avoid: Valproate, haloperidol, systemic corticosteroids, fasting, and physical and psychological stress. Evaluation of relatives at risk: If the pathogenic variant in the family is known and if prenatal testing has not been performed, it is appropriate to perform biochemical and molecular genetic testing on at-risk newborns (males and females) as soon after birth as possible so that the appropriate treatment or surveillance (for those with the family-specific pathogenic variant) can be promptly established. If the pathogenic variant in the family is NOT known, biochemical analysis (plasma amino acid analysis, ammonia level), an allopurinol challenge test (in older individuals), and/or OTC enzyme activity measurement in liver (males only) can be performed. Preventive measures at birth should be instituted until such a time as the diagnosis can be ruled out. Pregnancy management: Heterozygous females are at risk of becoming catabolic during pregnancy and especially in the postpartum period. Those who are symptomatic need to be treated throughout pregnancy as necessary; those who are asymptomatic need to avoid catabolism in the peripartum and postpartum periods and should be treated as needed. ### Genetic counseling. OTC deficiency is inherited in an X-linked manner. If an affected male reproduces, none of his sons will be affected and all of his daughters will inherit the pathogenic variant and may or may not develop clinical symptoms related to the disorder. Heterozygous females have a 50% chance of transmitting the pathogenic variant with each pregnancy: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant may or may not develop clinical findings related to the disorder. Carrier testing for females at risk of being heterozygous and prenatal testing for pregnancies at increased risk are possible if the OTC pathogenic variant has been identified in an affected family member. ## Diagnosis Diagnostic criteria for ornithine transcarbamylase (OTC) deficiency have been set forth by the Urea Cycle Disorders Consortium of the Rare Disease Clinical Research Network [Tuchman et al 2008]. ### Suggestive Findings OTC deficiency should be suspected in an individual with the following clinical features (by sex/age), family history, and supportive laboratory findings: #### Clinical Features Term newborn male * Normal at birth * Development of reduced oral intake with poor latching and suck * Acute neonatal encephalopathy (lethargy, somnolence) with hyperventilation and low body temperature Child, adolescent, or adult (male or female) * Encephalopathic or psychotic episodes (i.e., episodes of altered mental status), including erratic behavior, clouded consciousness, and delirium * A recent stress that could be regarded as a precipitating event (e.g., significant change in diet, significant medical problem including illness or accident, delivery, systemic use of corticosteroids or valproate) * History of recurrent vomiting * Migraine headaches * Reye-like syndrome * Seizures * History of true protein avoidance (avoidance of not only red meat but also of milk, eggs, other high-protein foods) * Unexplained "cerebral palsy" #### Family History Death of newborn males (related through females in a manner consistent with X-linked inheritance) in the first week of life from "sepsis" or with unexplained somnolence, refusal to feed, tachypnea, and catastrophic illness is suggestive of OTC deficiency. Note: Absence of a family history of individuals with similar episodes does not preclude the diagnosis. #### Supportive Laboratory Findings Newborn screening (NBS). OTC deficiency is universally screened for in eight states and likely to be detected in three additional states (www.newsteps.org). See Baby's First Test to search by state. * The sensitivity and specificity of a low citrulline level as a marker for OTC deficiency in NBS has been questioned; however, the false positive rate in Minnesota has matched the average performance of primary analytes for conditions detected by tandem mass spectroscopy (MS/MS) on NBS [Hall et al 2014]. * The detection of OTC deficiency on NBS may be improved by using the Collaborative Laboratory Integrated Reports (CLIR), an interactive web tool that includes glutamine, glutamate, and amino acid ratios (e.g., citrulline-to-glycine ratio) in the analysis. Plasma ammonia concentration. During acute encephalopathy, ammonia levels are typically above 200 μmol/L and often above 500-1,000 μmol/L. Note: The plasma ammonia concentration at which an individual becomes symptomatic varies but is generally above 100 μmol/L; in stage 2 coma [Plum & Posner 1982] the plasma concentration may be between 200 and 400 μmol/L; and in stage 3 to 4 coma, above 500 μmol/L. These levels are approximations and a wider range of elevated ammonia levels may be observed. Plasma amino acid analysis. A high glutamine concentration (generally >800 μmol/L) and a (very) low citrulline concentration (e.g., single digits, with or without elevated plasma ammonia concentration) is suggestive of a proximal urea cycle defect, such as N-acetylglutamate synthetase (NAGS) deficiency, carbamoyl phosphate synthetase I (CPSI) deficiency, or OTC deficiency. Urine organic acid (UOA) analysis. Orotic acid concentration is elevated in a random urine sample (e.g., >20 μmol/mmol creatinine if the laboratory provides quantitative values). Blood gases * Respiratory alkalosis in an encephalopathic individual who is hyperventilating is pathognomonic of urea cycle disorders [Maestri et al 1999]. * In a terminally ill individual who has been in a coma for days, acidosis may develop. ### Establishing the Diagnosis Male proband. The diagnosis of OTC deficiency is established in a male proband with the above clinical and laboratory findings and/or with at least ONE of the following: * A hemizygous pathogenic variant in OTC by molecular genetic testing (see Table 1) * A markedly abnormal increase of orotic acid excretion after an allopurinol challenge test (see Allopurinol challenge test below) with or without a family history of OTC deficiency [Tuchman et al 2008] * Decreased OTC enzyme activity in liver (see OTC enzyme activity in liver below) Female proband. The diagnosis of OTC deficiency is usually established in a female proband with the above clinical features and supportive laboratory findings and/or with at least ONE of the following: a heterozygous pathogenic variant in OTC by molecular genetic testing (see Table 1) or a markedly abnormal increase of orotic acid excretion after an allopurinol challenge test (see Allopurinol challenge test) with or without a family history of OTC deficiency. Note: Liver biopsy is not recommended to establish the diagnosis in females (see OTC enzyme activity in liver). Molecular genetic testing approaches can include single-gene testing and use of a multigene panel. Single-gene testing. Sequence analysis of OTC is performed first. * In a male, lack of amplification by PCR prior to sequence analysis should prompt gene-targeted deletion/duplication analysis. * In a female in whom sequence analysis does not reveal a pathogenic variant, gene-targeted deletion/duplication should be performed next. A multigene panel that includes OTC and other genes of interest (see Differential Diagnosis) may also be considered. Note: 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. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in Ornithine Transcarbamylase (OTC) Deficiency View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method OTCSequence analysis 3, 4, 560%-80% 6, 7 Gene-targeted deletion/duplication analysis & complex rearrangements 85%-10% 9, 10, 11 Unknown 12NA 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\. 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. 5\. Sequencing of OTC regulatory regions can be used to screen for pathogenic variants in the OTC promoter and enhancer [Luksan et al 2010]. See Molecular Genetics. 6\. In individuals with biochemically confirmed OTC deficiency (i.e., elevated urinary orotate, a positive allopurinol test, reduced OTC enzyme activity in liver biopsy, or a combination of these findings) [Caldovic et al 2015] 7\. Bailly et al [2015], Choi et al [2015], Mohamed et al [2015], Prasun et al [2015] 8\. 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. 9\. When sequence analysis was followed by deletion/duplication analysis a molecular defect was detected in 80%-90% of affected individuals with biochemically confirmed OTC deficiency [Tuchman et al 1998, Shchelochkov et al 2009, Caldovic et al 2015]. 10\. Large deletions, duplications, and chromosomal rearrangements that encompass parts or all of OTC as well as neighboring genes have been detected using cytogenetic and molecular genetic techniques (see Genetically Related Disorders and Molecular Genetics) [Caldovic et al 2015, Choi et al 2015, Di Stefano et al 2015, Gallant et al 2015]. 11\. Synthesis and sequencing of OTC cDNA from illegitimate transcripts isolated from fibroblasts or from transcripts isolated from liver biopsy specimens has been used to detect pathogenic variants that create novel splice sites leading to aberrant OTC transcripts [Häberle & Koch 2003, Engel et al 2008]. 12\. Because an estimated 10%-20% of affected individuals have no detectable pathogenic variant, locus heterogeneity cannot be excluded. Allopurinol challenge test. In males and females suspected of having partial OTC deficiency who have normal molecular genetic testing and normal or borderline urinary orotic acid concentration under normal conditions, an allopurinol challenge test should be performed. A markedly abnormal increase of orotic acid excretion after administering allopurinol is diagnostic [Burlina et al 1992, Oexle 2006a, Oexle 2006b, Grünewald et al 2004]. The test consists of taking a single dose of allopurinol and immediately thereafter starting to collect urine during four six-hour periods for a total of 24 hours. Aliquots from each six-hour period are analyzed for orotic acid concentration. OTC enzyme activity in liver. Previously the gold standard for diagnosing OTC deficiency [Tuchman et al 1989], analysis of OTC enzyme activity in liver requires a liver biopsy, and thus is currently used only when an OTC pathogenic variant is not found in a male with a high clinical suspicion of OTC deficiency or if an allopurinol challenge is inconclusive. * Males. In severely affected males, OTC enzyme activity is typically less than 20% of the control value. In milder OTC deficiency, enzymatic activity may be as high as 30% of the control value. * Females. Results of enzyme activity analysis in a liver biopsy may not represent the true total OTC activity in a heterozygous female because of the X-chromosome inactivation pattern (previously known as lyonization) in the biopsy specimen (see Clinical Description, Heterozygous Females). ## Clinical Characteristics ### Clinical Description Ornithine transcarbamylase (OTC) deficiency can occur as a severe neonatal-onset disease in males and as a post-neonatal-onset (partial deficiency) disease in males and females. Neonatal-onset disease in females is very rare. Although neonatal-onset ornithine transcarbamylase (OTC) deficiency accounted for approximately 60% of all OTC deficiency in the older literature [Matsuda et al 1991], the longitudinal study of the Urea Cycle Disorders Consortium (UCDC) of the NICHD-supported Rare Disease Clinical Research Network (RDCRN) has enrolled to date a substantially smaller proportion of individuals with neonatal-onset OTC deficiency than with post-neonatal-onset OTC deficiency. Of 260 individuals who had symptomatic OTC deficiency, 47 (18%) had neonatal-onset disease (42 males and 5 females) and 213 (82%) had post-neonatal onset disease (154 females and 59 males) [Batshaw et al 2014]. #### Neonatal-Onset OTC Deficiency Males with severe OTC deficiency are typically normal at birth, but become symptomatic on the second to third day of life with poor suck, reduced intake, and hypotonia, followed by lethargy progressing to somnolence and coma. They hyperventilate, and may have seizures. By the time neonates with OTC deficiency come to medical attention they typically are catastrophically ill with low body temperature (hypothermia), severe encephalopathy, and respiratory alkalosis. When clinical and laboratory findings support the diagnosis of a urea cycle disorder, rescue therapy is begun immediately (see Management, Treatment of Manifestations). The prognosis of a newborn in hyperammonemic coma depends on the duration of elevated ammonia level, not the height of the ammonia level or the presence or absence of seizures [Msall et al 1984]. After successful rescue from neonatal hyperammonemic coma, infants with severe neonatal-onset OTC deficiency can easily become hyperammonemic again despite a low-protein diet and treatment with an oral ammonia scavenger. Even on maximum ammonia scavenger therapy a neonate with severe OTC deficiency may only tolerate 1.5 g/kg/day of protein (the minimum amount needed to grow), and growth may be along the third percentile for length. After neonatal rescue therapy, a child with severe neonatal-onset disease can also experience a "honeymoon" period in which the protein tolerance is so high, due to rapid growth, that the child is metabolically stable for some months before experiencing frequent hyperammonemic episodes. Typically by age six months (if not sooner) a liver transplant is needed because of the effect of recurrent hyperammonemia on the brain and of prolonged hospitalizations on quality of life. The overall outcome depends on the severity of brain damage during the initial hyperammonemic crisis and during subsequent hyperammonemic crises, as well as on the success of long-term treatment in maintaining metabolic balance and treating complications of the disease. #### Post-Neonatal-Onset (Partial) OTC Deficiency Hemizygous males and heterozygous females with partial OTC deficiency can present from infancy to later childhood, adolescence, or adulthood [Ahrens et al 1996, Ausems et al 1997, McCullough et al 2000]. Often they first become symptomatic in infancy when switched from breast milk to formula or whole milk (breast milk contains less protein than infant formulas manufactured in the US). Infants may show episodic vomiting, lethargy, irritability, failure to thrive, and developmental delay. They show true protein avoidance, which can be documented by a detailed assessment of their dietary intake. When forced to eat high-protein-content food, they may become symptomatic. A stressor can cause an individual with partial OTC deficiency to become symptomatic at any age. In general the milder the disease, the later the onset and the stronger the stressor required to precipitate symptoms. Adults with very mild disease have become symptomatic after crush injury, post-operatively [Chiong et al 2007, Hu et al 2007], when on a high-protein diet (e.g., Atkins diet [Ben-Ari et al 2010]), during the postpartum period (see Pregnancy Management), during cancer therapy, after prolonged fasting [Marcus et al 2008], when treated with high-dose systemic corticosteroids [Lipskind et al 2011], or after a febrile illness [Panlaqui et al 2008]. Treatment with valproate [Morgan et al 1987, Arn et al 1990, Honeycutt et al 1992] or haloperidol has been associated with hyperammonemic crises in persons with OTC deficiency [Rubenstein et al 1990, Leão 1995, Oechsner et al 1998, Thakur et al 2006]. When children, adolescents, or adults with post-neonatal-onset disease become encephalopathic they may reach stage 2 coma [Plum & Posner 1982] with erratic behavior, combativeness, and delirium (e.g., not recognizing family members around them, unintelligible speech). They may come to medical attention if these behavioral abnormalities lead to an emergency medical or psychiatric evaluation. #### Heterozygous Females The phenotype of a heterozygous female can range from asymptomatic to significant symptoms with recurrent hyperammonemia and neurologic compromise depending on favorable vs non-favorable X-chromosome inactivation. The amount of OTC enzyme activity in the liver of a heterozygous female depends on the pattern of X-chromosome inactivation in her liver [Yorifuji et al 1998]. Thus, a heterozygous female can manifest symptoms of OTC deficiency if X-chromosome inactivation in her liver cells is skewed such that the X chromosome with the pathogenic OTC allele is active in more hepatocytes than the X chromosome with the wild type OTC allele [Ricciuti et al 1976, McCullough et al 2000, Yamaguchi et al 2006]. Previously, approximately 15% of heterozygous females were thought to become symptomatic during their lifetime [Batshaw et al 1986]. Many heterozygous females exhibit mild symptoms, self-restrict protein intake, and are never diagnosed as being symptomatic. The diagnosis may only be revealed when a more severely affected child is born, prompting molecular genetic testing in the mother. Thus, the percent of symptomatic females may be higher than previously thought. When a male has post-neonatal-onset disease, the risk for symptoms in heterozygous females in his family is much lower than in families in which a male has neonatal-onset severe disease [McCullough et al 2000]. #### Complications of Neonatal-Onset and Post-Neonatal-Onset Disease Neuropsychological. Typical neuropsychological complications include developmental delay, learning disabilities, intellectual disability [Rowe et al 1986], attention deficit hyperactivity disorder (ADHD), and executive function deficits [Gyato et al 2004, Krivitzky et al 2009]. * Attention deficit hyperactivity disorder and executive function deficits can greatly affect (school) performance even when intellectual ability is in the normal range [Gyato et al 2004, Krivitzky et al 2009]. * Impulsivity and immaturity can lead to inappropriate behavior and problems in peer relationships especially for preteens and adolescents. * In adulthood, problems with private and professional relationships may persist, leading to problems in interpersonal relationships and frequent job changes. Even asymptomatic heterozygous females were shown to have mild cognitive impairments and executive function deficits on neuropsychological testing [Nagata et al 1991, Gyato et al 2004]. Neurologic. During hyperammonemic coma electroencephalogram (EEG) shows low voltage with slow waves and may include a burst suppression pattern in which the duration of the interburst interval correlates with the height of the ammonia levels [Clancy & Chung 1991]. Seizures are common during hyperammonemic coma and may only be detected on EEG. They do not indicate a poor prognosis. However, persons with urea cycle disorders may also be prone to having seizures independent of hyperammonemic episodes [Zecavati et al 2008]. Neuroimaging studies reveal, during a crisis, cerebral edema with small ventricles, flattening of cerebral gyri, and low density of white matter [Kendall et al 1983]. Neonates who survived after prolonged coma may have ventriculomegaly, diffuse brain atrophy (not affecting the cerebellum), low-density white matter defects, and injury to the bilateral lentiform nuclei and the deep sulci of the insular and perirolandic regions [Kendall et al 1983, Yamanouchi et al 2002, Takanashi et al 2003, Majoie et al 2004]. Although metabolic strokes (involving the caudate and putamen and resulting in extrapyramidal syndromes) have been described in OTC deficiency and CPS1 deficiency (see Urea Cycle Disorders Overview) [Keegan et al 2003, Takanashi et al 2003], they are not typical for urea cycle disorders. Note: For more information regarding MR spectroscopy research results in OTC deficiency see Pathophysiology (pdf). Neuropathology in those children who died after prolonged coma included cortical atrophy with ventriculomegaly, prominent cortical neuronal loss, and spongiform changes at the gray-white interface and in the basal ganglia and thalamus [Dolman et al 1988]. Better neurologic outcomes are seen in infants with neonatal-onset disease who were treated soon after the onset of coma. Gastrointestinal * During a hyperammonemic crisis liver enzymes are typically moderately elevated and PT and PTT may be prolonged. * Severe elevations of liver enzyme and coagulopathy consistent with acute liver failure are more typically seen in individuals with OTC deficiency after the neonatal period [Mustafa & Clarke 2006]. * Prolonged PT and PTT as well as mildly increased direct bilirubin are also observed in persons with a urea cycle disorder during long-term follow up when ammonia levels are normal and the individual is asymptomatic. Liver cell carcinoma has recently been described in a few older individuals (e.g., in a symptomatic heterozygous female age 66 years [Wilson et al 2012]), suggesting that OTC deficiency may be associated with an increased risk for liver cancer. However, data are currently insufficient to support such a conclusion. ### Pathophysiology For more information about the pathophysiology of OTC, click here. ### Genotype-Phenotype Correlations While the following genotype-phenotype correlations do in general exist, it is well established that significant medical problems (e.g., neonatal sepsis or other causes of newborn catabolism) can cause a severe, early presentation in an individual with an OTC pathogenic variant typically associated with mild disease, making it appear that the pathogenic variant is associated with severe neonatal-onset disease. Likewise, individuals with pathogenic variants associated with mild, late-onset disease (including females heterozygous for a milder pathogenic variant and skewed X-chromosome inactivation) may experience severe life-threatening hyperammonemia at any time in their life when they are exposed to strong environmental stressors. In general: * Pathogenic missense variants that affect residues essential for catalysis, substrate binding, and folding severely impair or completely abolish OTC enzyme activity and result in neonatal-onset disease in hemizygous males [Caldovic et al 2015]. * Pathogenic nonsense variants, insertions, and deletions that cause frameshift of the open reading frame and single-nucleotide variants in canonical intronic splice sites result in complete absence of functional OTC and neonatal-onset disease in hemizygous males [Caldovic et al 2015]. * Females heterozygous for a pathogenic variant can develop symptoms of OTC deficiency later in life if X-chromosome inactivation in their hepatocytes is skewed in favor of the X chromosome with the pathogenic allele [McCullough et al 2000, Caldovic et al 2015]. * Amino acid substitutions that decrease OTC enzyme activity or stability may result in a post-neonatal-onset phenotype in hemizygous males [Caldovic et al 2015] and heterozygous females [Pinner et al 2010]. * Although one would only expect pathogenic variants that cause severe neonatal-onset disease in hemizygous males to be associated with disease manifestation in heterozygous females, symptoms of OTC deficency in two females heterozygous for a hypomorphic OTC pathogenic variant were reported [Pinner et al 2010]. ### Penetrance Penetrance for OTC deficiency is complete in hemizygous males. The following observations, which may erroneously be interpreted as evidence of incomplete penetrance, are in fact explained by X-chromosome inactivation and environmental factors: * Heterozygous females who become symptomatic (the result of skewed X-chromosome inactivation) * Hemizygous males with the same mild pathogenic variant, only some of whom develop symptoms (the result of differences in environmental stressors) ### Prevalence OTC deficiency is thought to be the most common urea cycle defect (see Urea Cycle Disorders Overview). Estimated prevalence of OTC deficiency was one in 14,000 live births [Brusilow & Maestri 1996]. However, other surveys of incidence of OTC deficiency in Italy, Finland, and New South Wales, Australia, revealed a lower prevalence of one in 70,000, one in 62,000, and one in 77,000 live births, respectively [Dionisi-Vici et al 2002, Keskinen et al 2008, Balasubramaniam et al 2010]. Given that males and females with partial OTC deficiency may manifest symptoms at any age, prevalence numbers are biased toward the earliest and most severe presentations. ## Differential Diagnosis Neonatal-onset urea cycle disorders (UCDs) – N-acetylglutamate synthase (NAGS) deficiency, severe carbamyl phosphate synthetase I (CPSI) deficiency, argininosuccinate synthetase (ASS) deficiency (citrullinemia type I), and argininosuccinate lyase (ASL) deficiency (argininosuccinic aciduria [ASA]) – show the same clinical symptoms at presentation as severe OTC deficiency. See Urea Cycle Disorders Overview. Respiratory alkalosis is a typical finding in UCD [Maestri et al 1999] and its presence clearly distinguishes a UCD from an organic acidemia presenting with hyperammonemia and ketoacidosis. However, when a child who has been in a coma for days becomes terminally ill, acidosis rather than respiratory alkalosis may be present. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ornithine transcarbamylase (OTC) deficiency, the following evaluations are recommended if they have not already been completed: * Plasma ammonia concentration * Plasma amino acid analysis * Laboratory values that reflect nutritional status (e.g., vitamin D level, ferritin, pre-albumin) * Liver function tests (liver enzymes, bilirubin, albumin) * PT/PTT and fibrinogen * Developmental/neuropsychological/psychological evaluation * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Treatment is best provided by a clinical geneticist and a nutritionist experienced in the treatment of metabolic disease. #### Care of Hyperammonemic Coma Care should be provided by a team coordinated by a metabolic specialist in a tertiary care center experienced in the management of individuals with OTC deficiency. In the acute phase, the mainstays of treatment are the following. Rapid lowering of the plasma ammonia * Level should be 200 μmol/L or lower even if a diagnosis has not yet been established because of the severely toxic effect of an elevated ammonia level on the brain. * The fastest method for lowering the ammonia level is hemodialysis [Tuchman 1992, McBryde et al 2004]: * A neonate should not be hemodialysed longer than four hours and should then be switched to hemofiltration for stabilization to prevent a rebound of the ammonia level. * An older individual can be dialysed longer and should also be switched to hemofiltration for stabilization. * Depending on the height of the ammonia level (≤1500 μmol/L), one can also start with high flow hemofiltration methods to achieve a similarly speedy reduction of the ammonia level and then switch to regular hemofiltration for stabilization to prevent a rebound of the ammonia level. Note: Peritoneal dialysis is ineffective for management of acute hyperammonemia and is not recommended. Ammonia scavenger therapy * Treatment allows an alternative pathway for the excretion of excess nitrogen (see Table 2). * Nitrogen scavenger therapy is available as an intravenous infusion of a mixture of sodium phenylacetate and sodium benzoate for acute management and as an oral preparation of phenylbutyrate or sodium benzoate for long-term maintenance therapy. * Citrulline is supplemented at 170 mg/kg/day or 3.8g/m2/day (enterally). ### Table 2. Intravenous (IV) Ammonia Scavenger Therapy Protocol Used in OTC Deficiency and Carbamyl Phosphate Synthetase I (CPSI) Deficiency View in own window Patient WeightComponents of Infusion SolutionLoading 1 and Maintenance Dose 2, 3 Sodium phenylacetate & sodium benzoate 4Arginine HCl injection, 10%Sodium phenylacetateSodium benzoateArginine HCl 5 <25 kgUndiluted: 2.5 mL (contains 250 mg of each) Dilute 1:10 42.0 mL at 100 mg/mL250 mg/kg250 mg/kg200 mg/kg ≥25 kgUndiluted: 55 mL (contains 5,500 mg of each) Dilute 1:10 440 mL at 100 mg/mL5,500 mg/m25,500 mg/m24,000 mg/m2 Batshaw et al [2001] 1\. Loading dose given over 90 to 120 minutes 2\. Maintenance dose given over 24 hours 3\. If an affected individual has symptomatic hyperammonemia and has not received a full dose of ammonia scavenger in the previous 12 hours, the affected person should first receive an IV bolus directly followed by maintenance infusion. 4\. Sodium phenylacetate/sodium benzoate must be diluted with sterile 10% dextrose before administration. The typical dilution is 1:10. 5\. Arginine infusion not to exceed 150mg/kg/h Reversal of catabolism * Provide calories from glucose and fat, and resume protein intake (in the form of natural protein and an essential amino acid mix) no later than 24 hours after protein intake was discontinued Note: Persons on hemodialysis or hemofiltration in particular need adequate nutrition to overcome catabolism because nutrients are removed by these procedures. Discontinuation of protein intake should not exceed 24 hours because deficiency of essential amino acids results in muscle breakdown and uncontrolled nitrogen release. Daily quantitative plasma amino acid analysis should guide nutritional therapy, the goal of which is to keep essential amino acid levels in the normal range. * Use of a high glucose infusion rate supported by continuous insulin infusion to maintain high set point normoglycemia (140 mg/dL) as needed. For a newborn in crisis the goal is to deliver at least 100 kcal/kg/day, mostly from glucose and fat. Reducing the risk of neurologic damage * Affected individuals who are intubated and sedated may not show clinical signs of seizures, which are prevalent in acute hyperammonemia. EEG surveillance is thus highly recommended to allow electroencephalographic detection and subsequent treatment of seizures. Note: Phenobarbital is removed by dialysis and valproic acid is contraindicated in urea cycle disorders. * The use of hypothermia for neuroprotection in hyperammonemia has long been proposed [Vaquero & Butterworth 2007] but has yet to be proven efficacious. A pilot study showed feasibility and safety (see Therapies Under Investigation). * No other interventions (besides lowering the ammonia level) have proven efficacy for neuroprotection in hyperammonemic coma due to a urea cycle disorder or other conditions. #### Long-Term Treatment Long-term treatment (including restriction of protein intake, use of nitrogen scavengers, and in some cases liver transplantation) is aimed at promoting growth and development and preventing hyperammonemic episodes. Protein intake should be restricted to the required dietary allowance (RDA) for protein or the minimum amount necessary to allow growth and prevent catabolism depending on the severity of the disease. Use of an essential amino acid mixture is generally necessary to maintain normal essential amino acid levels in those on significant protein restriction, even persons with partial OTC deficiency. The diet should also provide vitamins, minerals, and trace elements, either in a calorie-rich, protein-free formula or in the form of supplements. Although protein restriction is the mainstay of therapy, when protein intake is too low, catabolism can cause chronic hyperammonemia just as high protein intake does. Careful monitoring of plasma amino acid concentrations is necessary to detect essential amino acid deficiencies. High glutamine concentrations are interpreted as evidence of poor metabolic control and chronic hyperammonemia. Nitrogen scavengers provide alternative routes for nitrogen disposal and allow more protein intake [Batshaw et al 2001, Berry & Steiner 2001]. Although it removes only half as much nitrogen as phenylbutyrate, oral sodium benzoate is the ammonia scavenger of choice in European countries and Australia rather than phenylbutyrate because it is felt to have fewer side effects. Phenylbutyrate causes menstrual dysfunction and body odor, and appears to deplete branched chain amino acids; sodium benzoate causes hypokalemia due to increased renal losses of potassium [Scaglia et al 2004, Häberle et al 2012]. Recommendations for ammonia scavenger therapy: * Long-term ammonia scavenger treatment may consist of 450-600 mg/kg/day of sodium phenylbutyrate and 170 mg/kg/day of L-citrulline in children <25 kg, and 9.9-13.0 g/m2/day of sodium phenylbutyrate and 3.8 g/m2/day of L-citrulline in individuals weighing ≥25 kg. Treatment should be accompanied by an appropriate low-protein diet [Batshaw et al 2001]. Note: (1) Citrulline offers the advantage over arginine of incorporating aspartate into the pathway thus pulling one additional nitrogen molecule into the urea cycle. (2) Sodium benzoate is being used instead of sodium phenylbutyrate in conjunction with L-citrulline. The recommended dose is ≤250 mg/kg/d in children <25 kg and a maximum of 12 g/d [Häberle et al 2012]. * Glycerol phenylbutyrate, which is significantly more palatable than sodium phenylbutyrate, is another treatment option. It has the same mechanism of action as sodium phenylbutyrate. Liver transplantation. No matter how mild OTC deficiency appears to be, stressors can at any age precipitate a hyperammonemic crisis that becomes life threatening. The fear of such an event, along with the restrictions on daily living imposed by the dietary therapy, prompt many families to consider liver transplantation even if the disease has been manageable up to that point with diet and medication. * In severe, neonatal-onset urea cycle disorders, liver transplantation remains the most effective means of preventing further hyperammonemic crises and neurodevelopmental deterioration [Leonard & McKiernan 2004]. It is typically performed by age six months. * Females and males with partial OTC deficiency can, after diagnosis, be maintained on a low-protein diet and oral ammonia scavenger treatment for life; the need for liver transplant depends on the individual and is typically considered when an affected individual is unstable and has frequent hyperammonemic episodes. * Living related donor livers are often considered for partial liver transplantation (LT) in individuals with a urea cycle disorder. The suitability of a heterozygous mother as a donor has been discussed [Wong 2012]. According to Wakiya et al [2012], enzyme activity measurement in a liver biopsy sample is useful in determining the suitability of a heterozygous mother as a donor. However, this approach is problematic for several reasons: * A liver biopsy sample may not adequately represent the enzyme activity in the liver of a heterozygous female. It can thus not be known whether a transplanted lobe contains enough enzyme activity to prevent symptoms in the recipient. * After partial hepatectomy the liver of the donor mother will regenerate. Since the X-chromosome inactivation pattern in the regenerated liver in the donor cannot be predicted, it is also impossible to predict whether the overall enzyme activity in the donor mother will remain adequate to prevent symptoms in her. * Likewise, the lobe that is transplanted into the recipient child will undergo changes after transplantation; thus, the enzyme activity in the donated lobe cannot be accurately determined at the time of transplantation, since additional post-transplantation changes could make the final enzyme activity in the recipient even more unpredictable. Note: The efficacy of hepatocyte transfer for providing sufficient enzyme activity to bridge the time to liver transplantation in unstable individuals with neonatal-onset disease is currently under investigation (see Therapies Under Investigation). Attention deficit/hyperactivity disorder (ADHD). Instruction in small classroom settings to minimize distraction and extra support to manage executive function deficits are often required and necessary to maximize success in school. Monotherapy or combination therapy with non-stimulant or stimulant medication is often necessary for the treatment of ADHD (at least during times of learning) [Gyato et al 2004, Krivitzky et al 2009]. However, these medications negatively affect appetite and their use warrants even closer monitoring of intake and body weight to avoid a catabolic state that could lead to hyperammonemia. Seizure disorders. Valproic acid is contraindicated for treatment of seizures in urea cycle disorders because it can cause a hyperammonemic crisis. Learning disability/intellectual disability. Brain damage from an initial hyperammonemic coma, frequent hyperammonemic episodes with moderate to severe hyperammonemia, and chronic hyperammonemia can lead to learning disabilities and intellectual disability. Appropriate support services are necessary to optimize intellectual outcome in these individuals. Also see Urea Cycle Disorders Overview. ### Prevention of Primary Manifestations In neonatal-onset OTC deficiency diagnosed prenatally, prospective intravenous (IV) treatment with ammonia scavengers within a few hours of birth (before the ammonia level rises) can prevent a hyperammonemic crisis and coma. Later on, prevention of hyperammonemic episodes is focused on restriction of dietary protein through low-protein diet and administration of oral nitrogen scavenging drugs balanced with supplementation of essential amino acids (see Treatment of Manifestations). ### Prevention of Secondary Complications The following are recommended: * Avoid overrestriction of protein/amino acids, a common cause of hyperammonemia and poor growth. Gastrostomy tube feedings help avoid malnutrition in affected individuals who self-restrict protein intake and object to the taste of the essential amino acid formulas used for the treatment of urea cycle disorders. * Minimize risk of respiratory and gastrointestinal illnesses through hand hygiene. * Give immunizations on the usual schedule, including annual flu vaccine. * Provide multivitamin and vitamin D supplementation. * Use antipyretics appropriately. Note: Ibuprofen is preferred in the home setting over acetaminophen because of the potential liver toxicity of acetaminophen. See also Therapies Under Investigation regarding the use of hypothermia as neuroprotective therapy to prevent intellectual disability, a complication of hyperammonemia. ### Surveillance The following are appropriate: * At the start of therapy, measure plasma ammonia concentration at least every two weeks (or more often depending on the stability of the affected individual), then slowly extend to every month, every two months, every three months, and every four months, as possible. * At the start of therapy, perform plasma amino acid (PAA) analysis at least every two weeks (or more often depending on the stability of the affected individual), then slowly extend to every month, every two months, every three months, and every four months. * Perform liver function tests depending on symptoms every three to six months or more often if they have been previously elevated. * Perform neuropsychological testing at the time that significant developmental milestones are expected to be achieved (e.g., at 6-9 months, 18 months, 3 years) ### Agents/Circumstances to Avoid Avoid the following: * Valproate * Haloperidol * Fasting * Stress, especially physical stress; potentially also psychological stress * Systemic corticosteroids because they cause catabolism, which can trigger a hyperammonemic crisis Note: If systemic corticosteroids need to be administered as a life-saving therapy (e.g., during a severe asthma attack or an anaphylactic reaction), a metabolic specialist should be consulted; at the same time, preemptive measures (e.g., increased calorie intake) should be instituted to prevent catabolism. ### Evaluation of Relatives at Risk It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives (both male and female) of an affected individual in order to identify as early as possible those who would benefit from initiation of treatment and/or preventive measures. Evaluations can include: * Molecular genetic testing if the OTC pathogenic variant in the family is known; * If prenatal testing has not been performed, it is appropriate to perform biochemical (plasma amino acid analysis, ammonia level) and molecular genetic testing on at-risk newborns (males and females) as soon after birth as possible to clarify their disease status so that the appropriate treatment or surveillance of those with the family-specific pathogenic variant can be promptly established before the child experiences a metabolic crisis. * Biochemical analysis (plasma amino acid analysis, ammonia level), an allopurinol challenge test (in older individuals), and/or OTC enzyme activity measurement in liver (males only) if the OTC pathogenic variant in the family is not known. In general for children with neonatal-onset disease, such testing cannot be performed rapidly enough to prevent a metabolic crisis. Therefore, preventive measures at birth should be instituted until such a time as the diagnosis can be ruled out (see the description of prospective treatment in Prevention of Primary Manifestations). See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Heterozygous females are at risk of becoming catabolic during pregnancy and (especially) post partum [Redonnet-Vernhet et al 2000, Mendez-Figueroa et al 2010, Celik et al 2011, Lipskind et al 2011, Ituk et al 2012]. * A symptomatic heterozygous female needs to be treated throughout pregnancy according to her pre-pregnancy protocol with adaptation for her needs during pregnancy. In the peripartum and immediate postpartum periods proactive measures to prevent catabolism include, for example, administration of a 10% dextrose solution with appropriate electrolytes at 1.5 times maintenance and addition of intralipids as needed to meet caloric requirements during these periods. * In an asymptomatic female known to be heterozygous, precautions should be taken in the peripartum and postpartum period to prevent catabolism; in addition, measurement of ammonia levels and administration of dextrose should be considered as heterozygous females have become symptomatic for the first time in the peripartum period. ### Therapies Under Investigation The use of hypothermia for neuroprotection in hyperammonemia has long been proposed [Vaquero & Butterworth 2007]. Two case reports were published about its use in UCD [Whitelaw et al 2001, Vargha et al 2012]. Whole-body therapeutic hypothermia (TH) may decrease ammonia production through an overall slowing of metabolism. Decreased ammonia production was indicated in acute liver failure studies by lower arterial ammonia levels with cooling. The success of hemodialysis in lowering the ammonia level depends on whether the amount of ammonia removed by dialysis exceeds the amount of ammonia produced. If TH reduces ammonia production, dialysis will be more effective. In addition to its direct effect on ammonia metabolism TH may have a neuroprotective effect, at least in part due to reduced brain uptake of ammonia, reduced brain glutamine production, normal osmolyte levels, reduced intracranial pressure and cerebral blood flow, and improved cerebral perfusion [Jalan et al 1999, Jalan et al 2004]. Results of a pilot study assessing the feasibility and safety of whole-body therapeutic hypothermia during neonatal hyperammonemic coma have been published [ClinicalTrials.gov, Lichter-Konecki et al 2013]. While the study was not able to determine if the treatment was efficacious, the authors concluded that it was feasible and could be conducted safely. The efficacy of hepatocyte transfer for providing sufficient enzyme activity is under investigation (see ClinicalTrials.gov). In September 2009 a meeting in London assessed the "state of the art" of hepatocyte transplantation and limits to its success; according to Puppi et al [2012] the participating experts agreed that, "to obtain sufficient levels of repopulation of the liver with donor cells in patients with metabolic liver disease, some form of liver preconditioning would likely be required to enhance the engraftment and/or proliferation of donor cells. It was reported that clinical protocols for preconditioning by hepatic irradiation, portal vein embolization, and surgical resection had been developed." Use of human induced pluripotent stem (iPS) cells is under consideration. The principal concept is the use of an affected individual's somatic cells to generate pluripotent stem cells that are then induced to become hepatocytes. Gene therapy could be performed on those hepatocytes in vitro, and the ‘corrected' hepatocytes could then be used for liver regeneration in the same person without the need for immune suppression [Soto-Gutierrez et al 2011]. Current gene therapy approach. An adeno-associated virus (AAV) vector construct harboring the OTC cDNA has been developed; its efficient delivery to the liver of animal models has been accomplished [Wang et al 2010, Wang et al 2012a, Wang et al 2012b]. However, most recent efforts have focused on AAV-mediated gene correction using the CRISPR-Cas9 system [Yang et al 2016]. 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. [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	Ornithine Transcarbamylase Deficiency	c0268542	27,352	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK154378/	2021-01-18T21:06:28	{"mesh": ["D020163"], "synonyms": ["Ornithine Carbamoyltransferase Deficiency", "OTC Deficiency"]}
Pneumosinus dilatans Lateral view paranasal sinus Pneumosinus dilatans is a condition consisting of abnormal expansion or dilatation of one or more paranasal sinuses. It most often affects the frontal sinus, and can cause damage to vision due to pressure on the nearby optic nerve. The preferred treatment is endoscopic surgery to deflate the sinus. ## Sources[edit] * Hsu, Wen-Ming; et al. (2002). "Pneumosinus dilatans Associated with Orbital Neurilemmoma" (PDF). Chinese Medical Journal. Archived from the original (PDF) on 2006-01-05. Retrieved 2006-06-28. * Carta, A.; et al. (June 1999). "Neuro-ophthalmological presentation of pneumosinus dilatans". Neuro-Ophthalmology. Retrieved 2006-06-28. ## External links[edit] * MR/CT scans of pneumosinus dilatans from MedPix [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	Pneumosinus dilatans	None	27,353	wikipedia	https://en.wikipedia.org/wiki/Pneumosinus_dilatans	2021-01-18T18:30:46	{"wikidata": ["Q7206010"]}
A number sign (#) is used with this entry because HARP syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration) is caused by mutation in the gene encoding pantothenate kinase-2 (PANK2; 606157). Only 2 unrelated genetically confirmed patients have been reported. Pantothenate kinase-associated neurodegeneration (PKAN, NBIA1; 234200), also known as Hallervorden-Spatz disease, is a more severe disorder also caused by mutation in the PANK2 gene. Clinical Features Higgins et al. (1992) described a woman with the combination of hyperprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration. She had demonstrated severe spasticity and dystonia since early childhood. At age 10, she was shown on funduscopic examination to have pigmentary retinopathy and the 'eye of the tiger' sign on brain MRI. A peripheral blood smear and electron microscopy demonstrated marked acanthocytosis that was not due to an intrinsic erythrocyte protein defect. On high-resolution lipoprotein electrophoresis, she demonstrated absence of the pre-beta fraction, with normal blood levels of cholesterol, triglycerides, high and low density lipoprotein cholesterol, and apolipoproteins A, B, and C. Orrell et al. (1995) described a second case of HARP syndrome in an 18-year-old woman who presented with longstanding intellectual subnormality, night blindness, and a 2-year history of orobuccolingual dystonia causing dysarthria and dysphagia. Investigation showed 53% acanthocytosis and hypoprebetalipoproteinemia, and ERG was typical of tapetoretinal degeneration. MRI showed the 'eye of the tiger' sign. The patient's sister and mother had a similar lipid disorder and acanthocytosis, but no neurologic or retinal disease. The authors noted that HARP syndrome shares many clinical and radiographic features with PKAN, including the 'eye of the tiger' sign, but is distinguished by a specific lipoprotein abnormality. Molecular Genetics Ching et al. (2002) studied the original patient reported by Higgins et al. (1992) and identified an arg371-to-ter (R371X) mutation in the PANK2 gene (606157.0011). This finding established that HARP is part of the PKAN disease spectrum. In a patient with HARP syndrome initially reported by Orrell et al. (1995), Houlden et al. (2003) identified compound heterozygosity for mutations in the PANK2 gene: a met327-to-thr substitution (M327T; 606157.0012) and a splice site mutation (606157.0013). The patient's mother and sister, both of whom had acanthocytosis and hypoprebetalipoproteinemia without neurologic abnormalities, were heterozygous for the splice site mutation, whereas her unaffected father was heterozygous for the M327T mutation. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinitis pigmentosa NEUROLOGIC Central Nervous System \- Dystonia \- Spasticity \- Orofacial dyskinesia \- Progressive dementia \- Dysarthria \- Dysphagia \- Pallidal degeneration \- Iron deposition in pallidal nuclei \- MRI shows decreased signal intensity in the pallidal nuclei with central hyperintensity ('eye of the tiger' sign) HEMATOLOGY \- Acanthocytes LABORATORY ABNORMALITIES \- Hypoprebetalipoproteinemia MISCELLANEOUS \- Two unrelated patients have been reported \- Onset in first or second decade \- Slowly progressive \- In 1 family, heterozygous mutations were associated with hypobetalipoproteinemia and acanthocytes without neurologic abnormalities \- Allelic to the more severe pantothenate kinase-associated neurodegeneration (NBIA1, 234200 ) \- Distinguished from NBIA1 by the presence of hypobetalipoproteinemia and acanthocytosis MOLECULAR BASIS \- Caused by mutation in the pantothenate kinase-2 gene (PANK2, 607157.0011 ) ▲ 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	HYPOPREBETALIPOPROTEINEMIA, ACANTHOCYTOSIS, RETINITIS PIGMENTOSA, AND PALLIDAL DEGENERATION	c1846582	27,354	omim	https://www.omim.org/entry/607236	2019-09-22T16:09:33	{"mesh": ["C564603"], "omim": ["607236"], "orphanet": ["157855"], "synonyms": ["Alternative titles", "HARP SYNDROME"], "genereviews": ["NBK1490"]}
Hapnes et al. (1980) described large subcutaneous angiolipomata around the wrists, knees and ankles of a 16-year-old boy (his 8-year-old sister was similarly affected). The tumors extended deeply between muscles, tendons and joint capsules, without infiltration of these structures. (Infiltrating angiolipoma is distinct. The tumors appear in early adulthood. They are not multiple. No familial clustering is observed.) The tumors recurred after subtotal excision. Muscular hypotrophy and deformation of bones near the affected joints were noted. Klem (1949) reported 2 affected sibs whose deceased father was said to have been identically affected. Hapnes et al. (1980) provided follow-up on Klem's family: 1 sib had no children, the other had 2 unaffected children and 2 unaffected grandchildren. Thus, the inheritance in this case also may have been recessive. Starting from the histologic slides of 102 cases of angiolipomata with microthrombi, Koudstaal (1974) obtained information from 65 patients of whom 4 males and 4 females reported familial occurrence. Two of the 4 women turned out to be sisters, who reported lipomata in another sister, a brother, and their father. The third woman reported similar tumors in her mother and the fourth woman mentioned fatty tumors in her father, a brother and her son. The 4 males reported fatty tumors in, respectively, a son, a brother, a mother and a cousin (or nephew; in Dutch the word 'neef' can have both meanings). In the view of ten Kate (1983), who called Koudstaal's paper to my attention, the separation of familial angiolipomatosis and familial lipomatosis (151900) is not certain. According to the description of Koudstaal (1974), the head and neck and the palms and soles are spared; the tumors cause only slight discomfort, e.g., mild pain on pressure, and they do not regress spontaneously. Limbs \- Subcutaneous tumors at wrists, knees and ankles \- Bone deformity near affected joints Misc \- Early adult onset Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	ANGIOLIPOMATOSIS, FAMILIAL	c1859784	27,355	omim	https://www.omim.org/entry/206550	2019-09-22T16:31:04	{"mesh": ["C565951"], "omim": ["206550"], "orphanet": ["199279"], "synonyms": ["Alternative titles", "ANGIOLIPOMA MICROTHROMBOTICUM"]}
A number sign (#) is used with this entry because of evidence that distal arthrogryposis type 5 (DA5) is caused by heterozygous mutation in the PIEZO2 gene (613629) on chromosome 18p11. Biallelic mutation in the PIEZO2 gene causes distal arthrogryposis with impaired proprioception and touch (DAIPT; 617146). Description Distal arthrogryposis type 5 is distinguished from other forms of DA by the presence of ocular abnormalities, typically ptosis, ophthalmoplegia, and/or strabismus, in addition to contractures of the skeletal muscles. Some cases have been reported to have pulmonary hypertension as a result of restrictive lung disease (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA5 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 3 (DA3, or Gordon syndrome; 114300) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of cleft palate and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders might represent variable expressivity of the same condition. For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). ### Genetic Heterogeneity of Distal Arthrogryposis 5 A subtype of DA5 due to mutation in the ECEL1 gene (605896) on chromosome 2q36 has been designated DA5D (615065). See NOMENCLATURE. Clinical Features Altman and Davidson (1939) reported a 9-year-old boy with what they termed 'amyoplasia congenita,' or arthrogryposis multiplex congenita, which they appear to have considered a synonymous designation. The boy had contractures of the fingers, toes, wrist, ankles, knees, and elbows with a lack of interphalangeal creases. Although the authors described bilateral ptosis, they did not report frank ophthalmoplegia. The patient subsequently had 3 children, one of whom likewise had distal contractures and ptosis. Friedman and Heidenreich (1995) provided follow-up of the father at age 63 years and the affected son at age 30 years. Both had distal joint contractures, ptosis, and limitation of extraocular movements. The son had a number of conical-shaped teeth, especially prominent in the lateral incisors; dentition could not be evaluated in the father because all secondary teeth had been extracted. Both the father and the son had an unusual pattern of hair loss with thinning over the parietotemporal areas. Hall et al. (1982) reported 3 patients, 2 of whom were mother and daughter, with a unique form of distal arthrogryposis. In addition to the characteristic features of camptodactyly, ulnar deviation, and foot deformities, all patients had short stature and ptosis. Other features included epicanthal folds, keratoconus, prominent ears, and decreased facial expression. Hall et al. (1982) noted that similar features had been described by Krieger and Espiritu (1972) and Aase and Smith (1968); see 114300 and 147800. Lai et al. (1991) reported a 27-year-old man with congenital distal arthrogryposis and ophthalmoplegia. He was born with bilateral clubfeet necessitating several operations. As an adult, he had a stiff trunk, mild pectus deformity, and limited movement of his knees, hips, and shoulders. He had internal rotation of the arms with overlapping fingers and wrist flexion. Eye movement was restricted both vertically and horizontally, and abnormal responses on electroretinogram (ERG) suggested tapetoretinal degeneration. An affected son was born with contractures of the hands and feet, stiff hands with long fingers, and internally rotated shoulders. At 1 year of age, he had increased chest diameter with widely spaced nipples, stiff trunk, camptodactyly, and limited wrist extension. Schrander-Stumpel et al. (1993) described an isolated case of arthrogryposis, ophthalmoplegia, and retinopathy in a Dutch family. The patient had rigid fingers and bilateral clubfeet at birth. Deep set eyes, a triangular face, and prominent ears were evident from an early age. At age 17, he had limited horizontal and vertical eye movements, a rigid back, stiff walk, anteverted, hunched shoulders, and pectus excavatum. The fingers were long, phalangeal creases were totally absent, and flexion was limited to about 30 degrees. Abnormal pigmentation was present in both retinal maculas. Gripp et al. (1996) reported a mother and son with multiple congenital contractures, expressionless face, blepharophimosis, microstomia, arachnodactyly, and short stature. The mother had sensorineural hearing loss. Although neither patient had ophthalmoplegia, the authors suggested that the disorder most closely resembled distal arthrogryposis type IIb, as classified by Hall et al. (1982). Pallotta et al. (2000) described a family with DA5 spanning 3 generations. The proband was born with congenital flexion contractures at the elbows, hips, knees, fingers, and toes. At 9 years of age, she showed decreased facial expression, triangular face, ptosis, limitation of gaze, strabismus, high-arched palate, camptodactyly, lack of the distal interphalangeal flexion creases, clinodactyly of the toes, and a firm feel to the muscles. The patient's mother and brother had similar features. The proband also had Dandy-Walker anomaly, which raised the question of whether this anomaly is part of the spectrum of distal arthrogryposis type 5 or whether the Aase-Smith syndrome (147800), which has Dandy-Walker anomaly as a conspicuous feature, belongs to the distal arthrogryposis spectrum. Sahni et al. (2004) described 4 members spanning 3 generations of a Caucasian family with distal arthrogryposis type 5. All patients had a degree of ophthalmoplegia, ptosis, astigmatism, and strabismus. Other findings included keratoconus in the index patient, which was associated with abnormal electron microscopy of the affected cornea and increased thickness of the central cornea, small axial length of the globe, and, in other members of the family, choroidal folds. Beals and Weleber (2004) reported a 4-generation family with DA5. Ocular findings included ptosis, epicanthal folds, astigmatism, keratoglobus, pigmentary maculopathy, macular retinal folds, and dysplastic optic nerve heads. All had restrictive limitations involving all ocular muscles, which the authors attributed to fibrosis and contracture. The limb muscles felt firm, and some patients had scoliosis and/or restrictive lung function. Beals and Weleber (2004) commented that ophthalmoplegia in DA5 is a misleading term because the ocular movement abnormalities are not neurologic in origin. Williams et al. (2007) described 4 affected members in 3 generations of a family with DA5 and an apparent autosomal dominant pattern of inheritance. In addition to the typical features of DA5, the propositus had pulmonary hypertension attributed to chronic hypoxia from severe restrictive chest disease (forced vital capacity and total lung capacity were 30% and 51% of predicted, respectively) and alveolar hypoventilation, exacerbated by residence at high altitude. Her affected brother and son demonstrated active use of accessory muscles of respiration and had evidence of limited chest excursion strongly suggestive of restrictive chest disease, but declined further evaluation. Her mother died at 50 years of age from congestive heart failure that was diagnosed at age 23; she reportedly had the same pattern of contractures as other affected members of the family. Williams et al. (2007) concluded that restrictive chest disease is a component of DA5. Castori et al. (2009) reported a 19-year-old man who presented with restricted forearm pronation/supination and juvenile macular dystrophy, in whom examination revealed short stature, firm muscles, stiff spine with lumbar hyperlordosis, generalized mild limitation of the large joints, external rotation of the hips, unilateral ptosis, exophoria, and abnormal photopic and scotopic responses on ERG. Examination of the proband's father and paternal grandfather revealed restricted range of movement of the small joints together with ulnar deviation of the fingers, consistent with DA5. Castori et al. (2009) suggested that DA5 may have a very mild musculoskeletal phenotype and that it should be considered in the differential diagnosis of congenital contracture syndromes even in the absence of obvious distal joint involvement. Coste et al. (2013) studied a mother and son and an unrelated woman who had generalized arthrogryposis associated with ptosis and ophthalmoplegia as well as restrictive lung disease. In addition, the mother had recurrent knee subluxations due to absence of the anterior cruciate ligament (ACL) bilaterally, and her son exhibited similarly unstable knees compatible with absence of the ACL. Other features present in all 3 patients included reduced ability to open the mouth, hypermetropia, hypermobile first metacarpophalangeal joint, and weak or absent tendon reflexes in the knees and ankles. Coste et al. (2013) noted that absence of the ACL had previously been reported in a father and son with arthrogryposis by Kwan and Ross (2009); no eye involvement or restrictive lung disease was reported in the father or son, however. Molecular Genetics In a woman with generalized arthrogryposis associated with ptosis and ophthalmoplegia as well as restrictive lung disease and absence of the anterior cruciate ligament, Coste et al. (2013) performed whole-exome sequencing and identified heterozygosity for a de novo missense mutation in the PIEZO2 gene (I802F; 613629.0001). The mutation was confirmed by Sanger sequencing in the patient and her similarly affected son. Independently, Coste et al. (2013) performed whole-genome sequencing in an unrelated woman with generalized arthrogryposis associated with ptosis, ophthalmoplegia, and restrictive lung disease, and identified heterozygosity for an in-frame 3-bp deletion in PIEZO2 (613629.0002). Functional analyses demonstrated that both mutations cause changes in kinetics that result in increased channel activity in response to a given mechanical stimulus, suggesting that DA5 is caused by PIEZO2 gain-of-function mutations. McMillin et al. (2014) used molecular inversion probes and Sanger sequencing to screen the PIEZO2 gene in 29 families with a diagnosis of DA5, and identified heterozygous mutations in affected individuals from 24 (83%) of the families (see, e.g., 613629.0006-613629.0009), including the families originally reported by Altman and Davidson (1939), Lai et al. (1991), and Sahni et al. (2004). Ten (42%) of the 24 mutation-positive families carried the same recurrent 3-bp deletion (Glu2727del; 613629.0002), including the families originally reported by Pallotta et al. (2000) and Williams et al. (2007). In the Dutch patient described by Schrander-Stumpel et al. (1993) and another patient diagnosed with DA5, McMillin et al. (2014) identified heterozygosity for a recurrent DA3-associated mutation in the PIEZO2 gene, R2686H (613629.0003), and suggested that the correct diagnosis in those patients was DA3 (Gordon syndrome). Noting that 3 syndromes with overlapping features, DA3, DA5, and MWKS, are all caused by heterozygous mutation in the PIEZO2 gene, McMillin et al. (2014) proposed that they share a common developmental mechanism and may represent variable expressivity of the same condition. Nomenclature In a revised classification scheme of the distal arthrogryposes, Bamshad et al. (1996) renamed the disorder referred to as DAIIB by Hall et al. (1982) as DA5. This disorder is distinct from DA2B (601680). Bamshad et al. (2009) stated that 2 DA5 families had been found to have mutations in the MYH2 (160740) and MYH13 (603487) genes. McMillin et al. (2011) stated that based on linkage results and screening of candidate genes, they had 'tentatively' divided DA5 into various subtypes, with MYH2-associated DA5 being designated as 'DA5A,' MYH13-associated DA5 as 'DA5B,' and DA5 mapping to chromosome 11 as 'DA5C;' thus they designated a new autosomal recessive form of DA5 as 'DA5D' (615065). However, no supporting evidence regarding MYH2-, MYH13-, or chromosome 11-associated DA5 subtypes was provided by Bamshad et al. (2009) or McMillin et al. (2011). INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Triangular face \- Decreased facial expression Ears \- Prominent ears Eyes \- Ophthalmoplegia \- Deep-set eyes \- Epicanthal folds \- Abnormal electroretinogram \- Blepharophimosis \- Hypermetropia (in some patients) \- Ptosis \- Duane anomaly \- Abnormal retinal pigmentation \- Strabismus \- Astigmatism \- Macular retinal folds \- Keratoglobus \- Keratoconus Mouth \- High-arched palate \- Reduced ability to open mouth (in some patients) RESPIRATORY Lung \- Restrictive lung disease CHEST External Features \- Hunched, anteverted shoulders Ribs Sternum Clavicles & Scapulae \- Pectus excavatum SKELETAL Spine \- Spine stiffness \- Scoliosis (rare) Limbs \- Limited forearm rotation \- Absent anterior cruciate ligament bilaterally (in some patients) Hands \- Congenital finger contractures \- Long fingers \- Absent phalangeal creases \- Poorly formed palmar creases \- Limited wrist extension \- Camptodactyly \- Clinodactyly \- Hypermobile first metacarpophalangeal joint (in some patients) Feet \- Bilateral club feet SKIN, NAILS, & HAIR Skin \- Absent phalangeal creases \- Poorly formed palmar creases \- Dimples over large joints MUSCLE, SOFT TISSUES \- Decreased muscle mass (especially in lower limbs) \- Firm muscles NEUROLOGIC Central Nervous System \- Normal intelligence \- Weak or absent tendon reflexes of knees and ankles (in some patients) MOLECULAR BASIS \- Caused by mutation in the PIEZO-type mechanosensitive ion channel component 2 gene (PIEZO2, 613629.0001 ) ▲ 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	ARTHROGRYPOSIS, DISTAL, TYPE 5	c1834523	27,356	omim	https://www.omim.org/entry/108145	2019-09-22T16:44:45	{"doid": ["0050646"], "mesh": ["C538400"], "omim": ["108145"], "orphanet": ["1154"], "synonyms": ["Alternative titles", "ARTHROGRYPOSIS WITH OCULOMOTOR LIMITATION AND ELECTRORETINAL ABNORMALITIES", "OCULOMELIC AMYOPLASIA", "ARTHROGRYPOSIS, DISTAL, TYPE IIB"]}
Stickler syndrome is a group of hereditary connective tissue disorders characterized by distinctive facial features, eye abnormalities, hearing loss, and joint problems. The symptoms of Stickler syndrome may vary but include near-sightedness (myopia), retinal detachment, underdevelopment of the middle of the face, and the development of arthritis at a young age. Stickler syndrome is caused by genetic changes (mutations or pathogenic variants) in one of six genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3. The syndrome can be inherited in an autosomal dominant or autosomal recessive manner. Stickler syndrome can be diagnosed when a doctor observes many symptoms consistent with the syndrome. Genetic testing can be used to confirm the diagnosis. Treatment for Stickler syndrome may include surgeries, medications to reduce joint pain, and hearing aids. [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	Stickler syndrome	c0265253	27,357	gard	https://rarediseases.info.nih.gov/diseases/10782/stickler-syndrome	2021-01-18T17:57:30	{"omim": ["108300"], "orphanet": ["828"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-18 (EIEE18) is caused by homozygous or compound heterozygous mutation in the SZT2 gene (615463) on chromosome 1p34. Description Early infantile epileptic encephalopathy-18 is a severe autosomal recessive neurologic disorder characterized by lack of psychomotor development apparent from birth, dysmorphic facial features, early onset of refractory seizures, and thick corpus callosum and persistent cavum septum pellucidum on brain imaging (summary by Basel-Vanagaite et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features Basel-Vanagaite et al. (2013) reported 2 unrelated children with early-onset epileptic encephalopathy. Both showed severely delayed psychomotor development with hypotonia since infancy, lack of speech, and inability to sit or stand unsupported. A 10-year-old girl, born of unrelated Iraqi Jewish parents, first developed intractable seizures at age 4 years. Seizures were characterized by loss of consciousness, drooling, and perioral cyanosis, and sometimes followed by tonic-clonic generalized seizures. One of her brothers likely had the same condition; he had profound developmental delay and intractable seizures, and died at age 3 years from respiratory infection. The second child, a 9-year-old Spanish boy, developed intractable tonic and absence seizures at age 2 months. EEG in both patients showed abnormal background trace and prominent epileptiform abnormalities, but no suppression burst pattern. Both probands had common facial dysmorphic features, including high forehead, downslanting palpebral fissures, ptosis, and arched, laterally extended eyebrows. Brain MRI in both patients and in the deceased sib of the first patient showed short and thick corpus callosum and persistent cavum septum pellucidum. Inheritance The transmission pattern of EIEE18 in the families reported by Basel-Vanagaite et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 unrelated patients with early infantile epileptic encephalopathy-18, Basel-Vanagaite et al. (2013) identified biallelic truncating mutations in the SZT2 gene (615463.0001-615463.0003). The mutations were found by whole-exome sequencing and segregated with the disorder in the families. The presence of severe developmental delay before the onset of epilepsy in 1 patient suggested that SZT2 mutations also impair brain maturation independently of seizures. Animal Model Frankel et al. (2009) found that mutation in the Szt2 gene in mice increased seizure threshold and epileptogenesis. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- High forehead Eyes \- Downslanting palpebral fissures \- Ptosis \- Arched eyebrows \- Laterally placed eyebrows NEUROLOGIC Central Nervous System \- Lack of psychomotor development \- Intractable seizures \- Focal seizures \- Absence seizures \- Generalized seizures \- Hypotonia \- EEG abnormalities \- Abnormal spike waves \- Slowed background activity \- MRI shows short, thick corpus callosum \- Persistent cavus septum pellucidum Peripheral Nervous System \- Hyporeflexia MISCELLANEOUS \- Delayed psychomotor development apparent in infancy \- Seizure onset in first months or years of life \- Two unrelated patients have been reported (last curated October 2013) MOLECULAR BASIS \- Caused by mutation in the SZT2 subunit of KICSTOR complex gene (SZT2, 615463.0001 ) ▲ 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	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 18	c3809624	27,358	omim	https://www.omim.org/entry/615476	2019-09-22T15:51:59	{"doid": ["0080413"], "omim": ["615476"], "orphanet": ["442835"], "synonyms": ["Undetermined EOEE"]}
Fulminant viral hepatitis is a rapid and severe impairment of liver functions (acute liver failure) with hepatic encephalopathy developing less than 8 weeks after the onset of jaundice, secondary to viral hepatitis mainly due to HBV, but also to HAV. [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	Fulminant viral hepatitis	None	27,359	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35063	2021-01-23T17:55:39	{"icd-10": ["K72"]}
Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach(gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones. Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones. In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent. Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50. ## Frequency Gastric cancer is the fourth most common form of cancer worldwide, affecting 900,000 people per year. HDGC probably accounts for less than 1 percent of these cases. ## Causes It is likely that 20 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. Women who are born with one mutated copy of the CDH1 gene have a 56 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes; men have a 70 percent chance of acquiring a second mutation and developing gastric cancer. When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues. These CDH1 gene mutations also lead to a 40 to 50 percent chance of lobular breast cancer in women, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues. About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. In some individuals, mutations in other cancer-inducing genes cause HDGC, but in some cases, the mechanism is unknown. ### Learn more about the gene associated with Hereditary diffuse gastric cancer * CDH1 Additional Information from NCBI Gene: * CTNNA1 ## Inheritance Pattern HDGC is inherited in an autosomal dominant pattern, which means one copy of the altered CDH1 gene in each cell is sufficient to increase the risk of developing cancer. In most cases, an affected person has one parent with the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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 diffuse gastric cancer	c1708349	27,360	medlineplus	https://medlineplus.gov/genetics/condition/hereditary-diffuse-gastric-cancer/	2021-01-27T08:25:54	{"gard": ["10900"], "mesh": ["D013274"], "omim": ["137215"], "synonyms": []}
Microbrachycephaly-ptosis-cleft lip syndrome is characterised by the association of intellectual deficit, microbrachycephaly, hypotelorism, palpebral ptosis, a thin/long face, cleft lip, and anomalies of the lumbar vertebra, sacrum and pelvis. It has been described in two Brazilian sisters. Transmission appears to be autosomal recessive. [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	Microbrachycephaly-ptosis-cleft lip syndrome	c0796142	27,361	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2511	2021-01-23T17:33:14	{"gard": ["3596"], "mesh": ["C563119"], "omim": ["268850"], "icd-10": ["Q87.8"], "synonyms": ["Richieri Costa-Guion Almeida-Ramos syndrome"]}
HIV-associated pruritus SpecialtyDermatology HIV-associated pruritus is a cutaneous condition, an itchiness of the skin, that occurs in up to 30% of HIV infected people, occurs when the T-cell count drops below 400 per cubic mm.[1]:417 ## See also[edit] * Skin lesion ## 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. * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by region * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji This infection-related 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	HIV-associated pruritus	None	27,362	wikipedia	https://en.wikipedia.org/wiki/HIV-associated_pruritus	2021-01-18T18:45:31	{"wikidata": ["Q5629812"]}
Cleidocranial dysostosis Other namesCleidocranial dysplasia,[1] Marie-Sainton syndrome,[1] mutational dysostosis[2] Facial and forehead changes along with increased mobility of the shoulder girdles SpecialtyMedical genetics SymptomsMissing collarbone, prominent forehead, flat nose, shorter[1] Usual onsetPresent at birth[3] CausesGenetic (RUNX2 gene)[1] Diagnostic methodBased on symptoms and X-rays, confirmed by genetic testing[4] Differential diagnosisMandibuloacral dysplasia, pyknodysostosis, osteogenesis imperfecta, Hajdu-Cheney syndrome[5] TreatmentSupportive care[5] PrognosisNormal life expectancy[3] FrequencyOne per million people[1] Cleidocranial dysostosis (CCD), also called cleidocranial dysplasia, is a birth defect that mostly affects the bones and teeth.[1] The collarbones are typically either poorly developed or absent, which allows the shoulders to be brought close together.[1] The front of the skull often does not close until later, and those affected are often shorter than average.[1] Other symptoms may include a prominent forehead, wide set eyes, abnormal teeth, and a flat nose.[1] Symptoms vary among people; however, intelligence is typically unaffected.[1] The condition is either inherited from a person's parents or occurs as a new mutation.[1] It is inherited in an autosomal dominant manner.[1] It is due to a defect in the RUNX2 gene which is involved in bone formation.[1] Diagnosis is suspected based on symptoms and X-rays with confirmation by genetic testing.[4] Other conditions that can produce similar symptoms include mandibuloacral dysplasia, pyknodysostosis, osteogenesis imperfecta, and Hajdu-Cheney syndrome.[5] Treatment includes supportive measures such as a device to protect the skull and dental care.[5] Surgery may be performed to fix certain bone abnormalities.[4] Life expectancy is generally normal.[3] It affects about one per million people.[1] Males and females are equally commonly affected.[5] Modern descriptions of the condition date to at least 1896.[6] The term is from cleido meaning collarbone, cranial from the Greek κρανιὀς meaning skull, and dysostosis meaning formation of abnormal bone.[7] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 Notable cases * 8 References * 9 External links ## Signs and symptoms[edit] Mouth showing many over-retained deciduous teeth and some missing teeth. Cleidocranial dysostosis is a general skeletal condition[8] so named from the collarbone (cleido-) and cranium deformities which people with it often have. People with the condition usually present with a painless swelling in the area of the clavicles at 2–3 years of age.[9] Common features are: * Clavicles (collarbones) can be partly missing leaving only the medial part of the bone. In 10% of cases, they are completely missing.[10] If the collarbones are completely missing or reduced to small vestiges, this allows hypermobility of the shoulders including ability to touch the shoulders together in front of the chest.[11] The defect is bilateral 80% of the time.[12] Partial collarbones may cause nerve damage symptoms and therefore have to be removed by surgery. * The mandible is prognathic due to hypoplasia of maxilla (micrognathism) and other facial bones.[11] * A soft spot or larger soft area in the top of the head where the fontanelle failed to close, or the fontanelle closes late. * Bones and joints are underdeveloped. People are shorter and their frames are smaller than their siblings who do not have the condition. * The permanent teeth include supernumerary teeth. Unless these supernumeraries are removed they will crowd the adult teeth in what already may be an underdeveloped jaw. If so, the supernumeraries will probably need to be removed to make space for the adult teeth. Up to 13 supernumerary teeth have been observed. Teeth may also be displaced. Cementum formation may be deficient.[13] * Failure of eruption of permanent teeth. * Bossing (bulging) of the forehead. * Open skull sutures, large fontanelles. * Hypertelorism. * Delayed ossification of bones forming symphysis pubis, producing a widened symphysis. * Coxa vara can occur, limiting abduction and causing Trendelenburg gait. * Short middle fifth phalanges,[14] sometimes causing short and wide fingers.[15] * Vertebral abnormalities.[14] * On rare occasions, brachial plexus irritation can occur.[10] * Scoliosis, spina bifida and syringomyelia have also been described.[10] Other features are: parietal bossing, basilar invagination (atlantoaxial impaction), persistent metopic suture, abnormal ear structures with hearing loss, supernumerary ribs, hemivertebrae with spondylosis, small and high scapulae, hypoplasia of illiac bones, absence of the pubic bone, short / absent fibular bones, short / absent radial bones, hypoplastic terminal phalanges.[16] ## Genetics[edit] It is usually autosomal dominant, but in some cases the cause is not known.[17] It occurs due to haploinsufficiency caused by mutations in the CBFA1 gene (also called Runx2), located on the short arm of chromosome 6, which encodes transcription factor required for osteoblast differentiation.[10] It results in delayed ossification of midline structures of the body, particularly membranous bone.[citation needed] A new article reports that the CCD cause is thought to be due to a CBFA1 (core binding factor activity 1) gene defect on the short arm of chromosome 6p21 . CBFA1 is vital for differentiation of stem cells into osteoblasts, so any defect in this gene will cause defects in membranous and endochondral bone formation.[18] ## Diagnosis[edit] Different features of the dysostosis are significant. Radiological imaging helps confirm the diagnosis. During gestation (pregnancy), clavicular size can be calculated using available nomograms. Wormian bones can sometimes be observed in the skull.[19] Diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or by the identification of a heterozygous pathogenic variant in RUNX2 (CBFA1).[20] * Lateral skull radiograph showing open skull sutures, large fontanelles, multiple wormian bones and underdeveloped paranasal sinuses. * Panoramic view of the jaws showing multiple unerupted supernumerary teeth mimicking premolar, missing gonial angles and underdeveloped maxillary sinuses in cleidocranial dysplasia. * Poor development of the clavicles and a bell-shaped rib cage in a person with CCD ## Treatment[edit] Around 5 years of age, surgical correction may be necessary to prevent any worsening of the deformity.[9] If the mother has dysplasia, caesarian delivery may be necessary. Craniofacial surgery may be necessary to correct skull defects.[19] Coxa vara is treated by corrective femoral osteotomies. If there is brachial plexus irritation with pain and numbness, excision of the clavicular fragments can be performed to decompress it.[10] In case of open fontanelle, appropriate headgear may be advised by the orthopedist for protection from injury.[citation needed] ## Prognosis[edit] Several studies have reported that life expectancy appears to be normal for people with CCD.[3][21][22] ## Epidemiology[edit] Cleidocranial dysostosis affects about one per million people.[1] ## Notable cases[edit] In 1987, a young girl named Jessica McClure fell down a narrow well pipe in her family's Texas property. Ron Short, a roofing contractor who was born without collarbones because of cleidocranial dysostosis and thus could collapse his shoulders to work in cramped corners, arrived at the site and offered to go down the shaft. The rescuers did not end up using him,[23][24] though McClure was successfully recovered from the well. Actor Gaten Matarazzo was born with cleidocranial dysplasia, which is incorporated into his character Dustin Henderson's storyline on Stranger Things.[25] Sibling actress-singers Abigail and Milly Shapiro were born with cleidocranial dysplasia, a trait they share with their mother.[26][27] ## References[edit] 1. ^ a b c d e f g h i j k l m n o "cleidocranial dysplasia". GHR. January 2008. Archived from the original on 3 October 2016. Retrieved 2 October 2016. 2. ^ Rare Genetic Disorders That Affect the Skeleton. AuthorHouse. 2013. p. 43. ISBN 9781491815045. Archived from the original on 2017-11-05. 3. ^ a b c d Young, Ian D. (2002). Genetics for Orthopedic Surgeons: The Molecular Genetic Basis of Orthopedic Disorders. Remedica. p. 92. ISBN 9781901346428. Archived from the original on 2016-11-03. 4. ^ a b c "Cleidocranial dysplasia". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2016. Archived from the original on 28 January 2017. Retrieved 29 October 2017. 5. ^ a b c d e "Cleidocranial Dysplasia". NORD. 2004. Archived from the original on 3 October 2016. Retrieved 2 October 2016. 6. ^ Epstein, Charles J.; Erickson, Robert P.; Wynshaw-Boris, Anthony Joseph (2004). Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. Oxford University Press. p. 333. ISBN 9780195145021. Archived from the original on 2016-10-03. 7. ^ "Cleidocranial Dysostosis". UCSF Benioff Children's Hospital. Archived from the original on 29 October 2016. Retrieved 2 October 2016. 8. ^ Garg RK, Agrawal P (2008). "Clinical spectrum of cleidocranial dysplasia: a case report". Cases J. 1 (1): 377. doi:10.1186/1757-1626-1-377. PMC 2614945. PMID 19063717. 9. ^ a b Hefti, Fritz (2007). Pediatric Orthopedics in Practice. Springer. p. 478. ISBN 9783540699644. 10. ^ a b c d e Turek's Orthopaedics: Principles And Their Application. Lippincott Williams & Wilkins. 2005. pp. 251–252. ISBN 9780781742986. 11. ^ a b Juhl, John (1998). Paul and Juhl's essentials of radiologic imaging (7th ed.). Lippincott-Raven. ISBN 9780397584215. 12. ^ Greene, Walter (2006). Netter's Orthopaedics (1st ed.). Masson. ISBN 9781929007028. 13. ^ Textbook of Radiology and Imaging: Volume 2, 7e. Elsevier Science Health Science Division. 2003. p. 1539. ISBN 9780443071096. 14. ^ a b Vanderwerf, Sally (1998). Elsevier's medical terminology for the practicing nurse. Elsevier. p. 65. ISBN 9780444824707. 15. ^ Menkes, John (2006). Child Neurology, 7e. Lippincott Williams & Wilkins. p. 307. ISBN 9780781751049. 16. ^ "Archived copy". Archived from the original on 2015-06-26. Retrieved 2015-06-26.CS1 maint: archived copy as title (link) 17. ^ Tanaka JL, Ono E, Filho EM, Castilho JC, Moraes LC, Moraes ME (September 2006). "Cleidocranial dysplasia: importance of radiographic images in diagnosis of the condition". J Oral Sci. 48 (3): 161–6. doi:10.2334/josnusd.48.161. PMID 17023750.[permanent dead link] 18. ^ Saraswathivilasam S. Suresh, A Family With Cleidocranial Dysplasia And Crossed Ectopic Kidney In One Child, Acta Orthop. Belg. 2009, N° 4 (Vol. 75/4) p.521-527. "Archived copy". Archived from the original on 2015-06-26. Retrieved 2015-06-26.CS1 maint: archived copy as title (link) 19. ^ a b Lovell, Wood (2006). Lovell & Winter's Pediatric Orthopaedics, 6e. Lippincott Williams & Wilkins. p. 240. ISBN 9780781753586. 20. ^ Machol, Keren; et al. (November 16, 2017). "Cleidocranial Dysplasia Spectrum Disorder". GeneReviews. PMID 20301686. 21. ^ Dore; et al. (January 1987). "Cleidocranial Dysostosis and Syringomyelia Review of the Literature and Case Report". Clinical Orthopaedics & Related Research. January 1987 (214): 229–34. PMID 3791747. Archived from the original on 2016-11-03. 22. ^ Nebgen, Denise; Wood, Robert S.; Shapiro, Robert D. (1991). "Management of a mandibular fracture in a patient with cleidocranial dysplasia: Report of a case and review of the literature". Journal of Oral and Maxillofacial Surgery. 49 (4): 405–409. doi:10.1016/0278-2391(91)90380-5. PMID 2005496. 23. ^ Kennedy, J. Michael (1987-10-17). "Jessica Makes It to Safety—After 58 1/2 Hours". Los Angeles Times. Archived from the original on 2010-06-19. 24. ^ Scott, Ronald W. (November 1988). "Cleidocranial Dysplasia - An Enigma Among Anomalies". Journal of Orthopaedic & Sports Physical Therapy. 10 (5): 184–188. doi:10.2519/jospt.1988.10.5.184. PMID 18796963. 25. ^ Oyla, Gabrielle (2016-09-12). "Stranger Things' Gaten Matarazzo Discusses Living with Cleidocranial Dysplasia". People.com. Archived from the original on 2016-09-16. 26. ^ "Milly Shapiro on Instagram: "It was such an honor to attend the CCD Smiles event this past weekend. It was really powerful to..."". Instagram. 7 March 2019. Retrieved 15 June 2020. 27. ^ Starr, Michael (11 June 2020). "Meet new 'Doom Patrol' co-star Abigail Shapiro". New York Post. Retrieved 15 June 2020. ## External links[edit] * Cleidocranial dysostosis at Curlie Classification D * ICD-10: Q74.0 * ICD-9-CM: 755.59 * OMIM: 119600 * MeSH: D002973 * DiseasesDB: 30594 External resources * MedlinePlus: 001589 * GeneReviews: Cleidocranial Dysplasia * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [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	Cleidocranial dysostosis	c0008928	27,363	wikipedia	https://en.wikipedia.org/wiki/Cleidocranial_dysostosis	2021-01-18T18:53:03	{"gard": ["6118"], "mesh": ["D002973"], "umls": ["C0008928"], "orphanet": ["1452"], "wikidata": ["Q781618"]}
Anetoderma Other names(Anetoderma maculosa,[1] Anetoderma maculosa cutis,[1] Atrophia maculosa cutis,[1] and Macular atrophy[2]) SpecialtyDermatology Anetoderma is a localized laxity of the skin with herniation or outpouching resulting from abnormal dermal elastic tissue.[2] Anetoderma comes in three types: * Primary anetoderma * Jadassohn–Pellizzari anetoderma is a benign condition with focal loss of dermal elastic tissue.[3] Jadassohn-Pellizzari is one of two major classifications of primary anetoderma, the other being Schweninger–Buzzi anetoderma. The difference between the two is that Jadassohn–Pellizzari anetoderma is preceded by inflammatory lesions.[1] * Schweninger–Buzzi anetoderma is a cutaneous condition characterized by loss of dermal elastic tissue.[1] * Secondary anetoderma * Familial anetoderma ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ a b c d e Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). Page 1027. McGraw-Hill. ISBN 0-07-138076-0. 3. ^ Laumann, Anne; Minocha, Julia Sanger; Ho, Stephen C (2009-06-22). "Anetoderma". eMedicine. Web MD. Retrieved 17 December 2009. ## External links[edit] Classification D * ICD-10: L90.9 (ILDS L90.910) * MeSH: D057088 * DiseasesDB: 29805 External resources * eMedicine: article/1073850 * 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 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	Anetoderma	c0406550	27,364	wikipedia	https://en.wikipedia.org/wiki/Anetoderma	2021-01-18T18:33:13	{"mesh": ["D057088"], "umls": ["C0406550"], "icd-10": ["L90.9"], "orphanet": ["228272"], "wikidata": ["Q3616643"]}
Fatal familial insomnia (FFI) affects the thalamus, the part of the brain that controls the sleep-wake cycle. Symptoms typically begin between the ages of 40-60 years. The most common symptoms are sleep disturbance, psychiatric problems, weight loss, and balance problems. Other symptoms include high blood pressure, excess sweating, and difficulty controlling body temperature. These symptoms tend to get worse over time. FFI is usually fatal in 6-36 months. Almost all cases of FFI occur due to a specific variant in the PRNP gene and are inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, sleep study, and imaging studies. The results of genetic testing can help confirm the diagnosis. Treatment for FFI is focused on managing the symptoms. [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	Fatal familial insomnia	c0206042	27,365	gard	https://rarediseases.info.nih.gov/diseases/6429/fatal-familial-insomnia	2021-01-18T18:00:31	{"mesh": ["D034062"], "omim": ["600072"], "umls": ["C0206042"], "orphanet": ["466"], "synonyms": ["Familial fatal insomnia", "Insomnia familial fatal"]}
Acute cutaneous lupus erythematosus SpecialtyDermatology Acute cutaneous lupus erythematosus is a cutaneous condition characterized by a bilateral malar rash (also known as a "butterfly rash") and lesions that tend to be transient, and that follow sun exposure.[1] The acute form is distinct from chronic and subacute cutaneous lupus erythematosus, which may have different types of skin lesions.[2] Cutaneous lupus erythematosus is associated with both lupus erythematosus-specific lesions and cutaneous manifestations that are not specific to lupus erythematosus, such as oral ulcers and urticaria.[3] Because of the diagnostic criteria used to diagnose systemic lupus erythematosus, a patient with only cutaneous manifestations may be diagnosed with the systemic form of the disease.[2] ## Contents * 1 Forms * 1.1 Localized form * 1.2 Generalized form * 2 See also * 3 References ## Forms[edit] Acute cutaneous lupus erythematosus can be either localized or generalized.[4] ### Localized form[edit] The localized form of the disease is most commonly associated with the malar rash and normally develops in a patient's twenties. The localized form occurs only above the patient's neck and is not associated with rashes in other parts of the body.[4] ### Generalized form[edit] Generalized acute cutaneous lupus erythematosus includes skin below the patient's neck and is described as a macropapular rash or photosenstive lupus dermatitis.[4] Symptoms include similar erythematic lesions as seen in the localized form, but forms a symmetrical rash and can be mistaken for a drug rash.[4] ## See also[edit] * Lupus erythematosus * List of cutaneous conditions ## References[edit] 1. ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b Werth VP (June 2005). "Clinical manifestations of cutaneous lupus erythematosus". Autoimmunity Reviews. 4 (5): 296–302. doi:10.1016/j.autrev.2005.01.003. PMID 15990077. 3. ^ McCauliffe DP (March 2001). "Cutaneous lupus erythematosus". Seminars in Cutaneous Medicine and Surgery. 20 (1): 14–26. doi:10.1053/sder.2001.23091. PMID 11308132. 4. ^ a b c d Okon LG, Werth VP (June 2013). "Cutaneous lupus erythematosus: diagnosis and treatment". Best Practice & Research. Clinical Rheumatology. Systemic Lupus Erythematosus. 27 (3): 391–404. doi:10.1016/j.berh.2013.07.008. PMC 3927537. PMID 24238695. This dermatology 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	Acute cutaneous lupus erythematosus	c1142226	27,366	wikipedia	https://en.wikipedia.org/wiki/Acute_cutaneous_lupus_erythematosus	2021-01-18T18:43:03	{"umls": ["C1142226"], "wikidata": ["Q4677919"]}
A number sign (#) is used with this entry because this disorder, which comprises seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), is caused by homozygous or compound heterozygous mutation in the KCNJ10 gene (602208) on chromosome 1q23. Clinical Features Scholl et al. (2009) reported 5 patients from 4 families with a complex disorder characterized by onset of generalized seizures in infancy, delayed psychomotor development, ataxia, and sensorineural hearing loss. One patient was reported in detail. She developed seizures at age 3 months and was unable to walk or speak at age 5 years and 7 months. She had markedly reduced muscle strength in the lower limbs, severe ataxia, and progressive axonal neuropathy with hypomyelination confirmed by sural nerve biopsy. Sensorineural hearing loss became apparent at age 18. She had 2 presumably affected sibs: 1 had seizures, was never able to walk, and died at age from a diarrheal illness, and the other presented with seizures and vomiting at age 5 months, was unable to walk until 16 months, and died at 18 months from an infection. The other 4 patients had a similar disorder, with intention tremor and cerebellar atrophy in some of them. Laboratory studies in all patients showed persistent hypokalemia, metabolic alkalosis, and hypomagnesemia. Plasma renin and aldosterone were increased in the absence of hypertension. Urinary studies showed potassium, magnesium, and sodium wasting. Salt craving, enuresis, and polydipsia/polyuria were reported, consistent with renal salt wasting. Scholl et al. (2009) termed this disorder 'SeSAME syndrome.' Bockenhauer et al. (2009) reported a consanguineous family of Pakistani origin in which 4 children presented in infancy with generalized tonic-clonic seizures. Another child from an unrelated consanguineous Arabic family had a similar disorder. All 5 patients had speech and motor delay as well as pronounced gait ataxia, intention tremor, and dysdiadochokinesis, consistent with cerebellar dysfunction. Two patients were unable to walk at age 9 and 3 years, respectively. Brain MRI, electromyographic studies, and nerve conduction velocities were all normal in those patients studied. Four patients developed sensorineural hearing impairment; the fifth patient was not tested. Laboratory studies showed hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. There was no proteinuria or glycosuria, and kidney ultrasound was normal. Blood pressure was at the low end of the normal range. All patients were receiving potassium and magnesium supplements. Bockenhauer et al. (2009) referred to the disorder as 'EAST syndrome' for epilepsy, ataxia, sensorineural deafness, and tubulopathy. Freudenthal et al. (2011) reported 6 patients with genetically confirmed EAST syndrome characterized by epilepsy from infancy, debilitating ataxia from an early age with difficulties in walking, sensorineural deafness, and hypokalemic metabolic acidosis with variable hypomagnesemia. One patient was born of consanguineous Algerian parents, 2 sibs were born of consanguineous Indian parents, 2 sibs were born of unrelated Afro-Caribbean parents, and 1 boy was born of unrelated Iranian parents. Pathogenesis Bockenhauer et al. (2009) noted that the KCNJ10 inwardly rectifying potassium channel is on the basolateral side of distal renal tubule cells and functions to recycle potassium, which is necessary for the function of the primary sodium/potassium ATPase and establishment of a cell-negative transmembrane potential. Alterations in membrane voltage resulting from loss of KCNJ10 secondarily affects other transport processes, such as those for chloride and magnesium. KCNJ10 activity thus provides a mechanism for indirectly regulating reabsorption of renal tubular sodium, which modulates volume homeostasis and maintains blood pressure (145500). Loss of KCNJ10 function results in a compensated state of salt loss, resulting in stimulation of the renin/angiotensin/aldosterone system. A concomitant proximal tubular increase in bicarbonate causes metabolic alkalosis and calcium absorption. In addition, KCNJ10 is expressed in glial cells in the brain, and it is believed to establish the resting membrane potential of the neuron through a process called potassium 'spatial buffering.' Accumulation of potassium extracellularly in the brain decreases the membrane potential and lowers the seizure threshold. Mapping By linkage analysis of 3 informative kindreds, Scholl et al. (2009) mapped the SESAME disease locus to a 2.5-Mb region on chromosome 1q23.2-q23.3 (lod score of 3.0). By linkage analysis of a consanguineous Pakistani family with seizures, ataxia, hearing loss, and electrolyte abnormalities, Bockenhauer et al. (2009) identified a 1.9-cM region on chromosome 1 between rs726640 and rs1268524 (lod score of 4.98). Haplotype analysis indicated that the affected patients were homozygous by descent for the alleles in the critical region. Molecular Genetics In 5 patients from 4 families with a complex syndrome comprising seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance, Scholl et al. (2009) identified 6 different homozygous or compound heterozygous mutations in the KCNJ10 gene (602208.0001-602208.0006). In affected members of a Pakistani family with EAST syndrome, Bockenhauer et al. (2009) identified a homozygous mutation in the KCNJ10 gene (602208.0001). In 6 patients from 4 families with EAST syndrome, Freudenthal et al. (2011) identified 4 different homozygous mutations in the KCNJ10 gene (602208.0006, 602208.0010-602208.0012). In vitro physiologic studies in Xenopus oocytes showed that the mutant proteins caused significantly reduced inwardly rectifying potassium conductance compared to control. Animal Model Studies of Kcnj10-null mice showed motor disability with ataxia (Neusch et al., 2001), profound deafness (Rozengurt et al., 2003), and renal tubular dysfunction (Bockenhauer et al., 2009), similar to the features identified in patients with mutations in the KCNJ10 gene. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (in some patients) HEAD & NECK Ears \- Hearing loss, sensorineural CARDIOVASCULAR Vascular \- No hypertension ABDOMEN Gastrointestinal \- Salt craving \- Polydipsia GENITOURINARY Kidneys \- Renal potassium wasting \- Renal sodium wasting Bladder \- Enuresis \- Polyuria NEUROLOGIC Central Nervous System \- Seizures \- Psychomotor delay \- Mental retardation \- Ataxia \- Some patients do not achieve ability to walk \- Poor speech development \- Hypotonia \- Intention tremor \- Dysdiadochokinesis \- Cerebellar atrophy Peripheral Nervous System \- Axonal neuropathy (rare) \- Hypomyelination of sural nerve (rare) METABOLIC FEATURES \- Metabolic alkalosis LABORATORY ABNORMALITIES \- Hypokalemia \- Hypomagnesemia \- Hypocalciuria \- Increased plasma renin \- Increased plasma aldosterone MISCELLANEOUS \- Onset of seizures in first months of life MOLECULAR BASIS \- Caused by mutation in the potassium channel, inwardly rectifying, subfamily J, member 10 gene (KCNJ10, 602208.0001 ) ▲ 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	SEIZURES, SENSORINEURAL DEAFNESS, ATAXIA, MENTAL RETARDATION, AND ELECTROLYTE IMBALANCE	c2748572	27,367	omim	https://www.omim.org/entry/612780	2019-09-22T16:01:00	{"doid": ["0060484"], "mesh": ["C557674"], "omim": ["612780"], "orphanet": ["199343"], "synonyms": ["Alternative titles", "SESAME SYNDROME", "EPILEPSY, ATAXIA, SENSORINEURAL DEAFNESS, AND TUBULOPATHY", "EAST SYNDROME"]}
Inability of the liver to perform its normal functions Liver failure Other namesHepatic insufficiency A person with massive ascites and caput medusae due to cirrhotic liver failure SpecialtyGastroenterology Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis).[1] Recently, a third form of liver failure known as acute-on-chronic liver failure (ACLF) is increasingly being recognized.[2] ## Contents * 1 Acute * 2 Chronic * 3 Acute on chronic * 4 References * 5 External links ## Acute[edit] Main article: Acute liver failure Acute liver failure is defined as "the rapid development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy) in a patient without known prior liver disease".[3]:1557[4] The disease process is associated with the development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention.[5] The diagnosis of acute liver failure is based on physical exam, laboratory findings, patient history, and past medical history to establish mental status changes, coagulopathy, rapidity of onset, and absence of known prior liver disease respectively.[3]:1557 The exact definition of "rapid" is somewhat questionable, and different sub-divisions exist which are based on the time from onset of first hepatic symptoms to onset of encephalopathy. One scheme defines "acute hepatic failure" as the development of encephalopathy within 26 weeks of the onset of any hepatic symptoms. This is sub-divided into "fulminant hepatic failure", which requires onset of encephalopathy within 8 weeks, and "subfulminant", which describes onset of encephalopathy after 8 weeks but before 26 weeks.[6] Another scheme defines "hyperacute" as onset within 7 days, "acute" as onset between 7 and 28 days, and "subacute" as onset between 28 days and 24 weeks.[3]:1557 ## Chronic[edit] Main article: Chronic liver failure Chronic liver failure usually occurs in the context of cirrhosis, itself potentially the result of many possible causes, such as excessive alcohol intake, hepatitis B or C, autoimmune, hereditary and metabolic causes (such as iron or copper overload, steatohepatitis or non-alcoholic fatty liver disease). ## Acute on chronic[edit] "Acute on chronic liver failure" is said to exist when someone with chronic liver disease develops features of liver failure. A number of underlying causes may precipitate this, such as alcohol misuse or infection. People with ACLF can be critically ill and require intensive care treatment, and occasionally a liver transplant. Mortality with treatment is 50%.[7] ## References[edit] 1. ^ O'Grady JG, Schalm SW, Williams R (1993). "Acute liver failure: redefining the syndromes". Lancet. 342 (8866): 273–5. doi:10.1016/0140-6736(93)91818-7. PMID 8101303. 2. ^ Arroyo, Vicente; Kamath, Patrick; Moreau, Richard; Jalan, Rajiv (2016). "Acute-on-Chronic Liver Failure: A Distinct Clinical Condition". Seminars in Liver Disease. 36 (2): 107–108. doi:10.1055/s-0036-1583287. PMID 27172350. 3. ^ a b c Sleisenger, edited by Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt; consulting editor, Marvin H. (2009). Sleisenger & Fordtran's gastrointestinal and liver disease pathophysiology, diagnosis, management (PDF) (9th ed.). St. Louis, Mo.: MD Consult. ISBN 978-1-4160-6189-2.CS1 maint: extra text: authors list (link) 4. ^ Munoz, SJ; Stravitz, RT; Gabriel, DA (2009). "Coagulopathy of acute liver failure". Clinics in Liver Disease. 13 (1): 95–107. doi:10.1016/j.cld.2008.10.001. ISSN 1089-3261. PMID 19150314. 5. ^ "EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure" (PDF). Journal of Hepatology. Retrieved 30 May 2017. 6. ^ Sood, Gagan K. "Acute Liver Failure". Mescape. Retrieved 14 December 2011. 7. ^ Sarin, Shiv Kumar; Choudhury, Ashok (17 October 2016). "Acute-on-chronic Liver Failure". Current Gastroenterology Reports. 18 (12): 61. doi:10.1007/s11894-016-0535-8. PMID 27747458. ## External links[edit] Classification D * ICD-10: K72.9 * ICD-9-CM: 573.8 * MeSH: D017093 * DiseasesDB: 5728 * SNOMED CT: 59927004 External resources * eMedicine: med/990 * Patient UK: Liver failure * 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 * t * e Organ failure General * Heart failure * Respiratory failure * Liver failure * Acute * Chronic * Renal failure * Acute * Chronic * Encephalopathy Multiple * Multiple organ dysfunction syndrome Authority control * NDL: 01144472 [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	Liver failure	c0085605	27,368	wikipedia	https://en.wikipedia.org/wiki/Liver_failure	2021-01-18T18:48:37	{"mesh": ["D017093"], "umls": ["C0085605"], "icd-9": ["573.8"], "icd-10": ["K72.9"], "wikidata": ["Q970208"]}
Ataxia neuropathy spectrum is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Ataxia neuropathy spectrum now includes the conditions previously called mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). As the name implies, people with ataxia neuropathy spectrum typically have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The neuropathy can be classified as sensory, motor, or a combination of the two (mixed). Sensory neuropathy causes numbness, tingling, or pain in the arms and legs, and motor neuropathy refers to disturbance in the nerves used for muscle movement. Most people with ataxia neuropathy spectrum also have severe brain dysfunction (encephalopathy) and seizures. Some affected individuals have weakness of the external muscles of the eye (ophthalmoplegia), which leads to drooping eyelids (ptosis). Other signs and symptoms can include involuntary muscle twitches (myoclonus), liver disease, depression, migraine headaches, or blindness. ## Frequency The prevalence of ataxia neuropathy spectrum is unknown. ## Causes Ataxia neuropathy spectrum is caused by mutations in the POLG gene or, rarely, the TWNK gene. The POLG gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol γ). The TWNK gene provides instructions for making a protein called Twinkle. Pol γ and Twinkle function in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol γ and Twinkle are both integral to the process of DNA replication by which new copies of mtDNA are produced. Mutated pol γ or mutated Twinkle reduce mtDNA replication. Although the mechanisms are unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), and mutations in the TWNK gene often result in deletions of large regions of mtDNA (mtDNA deletion). MtDNA depletion or deletion occurs most commonly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of ataxia neuropathy spectrum. It is unclear what role mtDNA deletions play in the signs and symptoms of the condition. ### Learn more about the genes associated with Ataxia neuropathy spectrum * POLG * TWNK ## Inheritance Pattern Ataxia neuropathy spectrum can have different inheritance patterns depending on the associated gene. Mutations in the POLG gene cause a form of the condition that is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Mutations in the TWNK gene cause a form of the condition that is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the 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	Ataxia neuropathy spectrum	c1843852	27,369	medlineplus	https://medlineplus.gov/genetics/condition/ataxia-neuropathy-spectrum/	2021-01-27T08:24:38	{"gard": ["9998"], "mesh": ["C564395"], "omim": ["607459"], "synonyms": []}
In epidemiology, force of infection (denoted λ {\displaystyle \lambda } ) is the rate at which susceptible individuals acquire an infectious disease.[1] Because it takes account of susceptibility it can be used to compare the rate of transmission between different groups of the population for the same infectious disease, or even between different infectious diseases. That is to say, λ {\displaystyle \lambda } is directly proportional to β {\displaystyle \beta } ; the effective transmission rate. λ = number of new infections number of susceptible persons exposed × average duration of exposure {\displaystyle \lambda ={\frac {\mbox{number of new infections}}{{\mbox{number of susceptible persons exposed}}\times {\mbox{average duration of exposure}}}}} Such a calculation is difficult because not all new infections are reported, and it is often difficult to know how many susceptibles were exposed. However, λ {\displaystyle \lambda } can be calculated for an infectious disease in an endemic state if homogeneous mixing of the population and a rectangular population distribution (such as that generally found in developed countries) is assumed. In this case, λ {\displaystyle \lambda } is given by: λ = 1 A {\displaystyle \lambda ={\frac {1}{A}}} where A {\displaystyle A} is the average age of infection. In other words, A {\displaystyle A} is the average time spent in the susceptible group before becoming infected. The rate of becoming infected ( λ {\displaystyle \lambda } ) is therefore 1 / A {\displaystyle 1/A} (since rate is 1/time). The advantage of this method of calculating λ {\displaystyle \lambda } is that data on the average age of infection is very easily obtainable, even if not all cases of the disease are reported. ## See also[edit] * Basic reproduction number * Compartmental models in epidemiology * Epidemic * Mathematical modelling of infectious disease ## References[edit] 1. ^ Hens, N.; Aerts, M.; Faes, C.; Shkedy, Z.; Lejeune, O.; Van Damme, P.; Beutels, P. (2010). "Seventy-five years of estimating the force of infection from current status data". Epidemiology and Infection. 138 (6): 802–12. doi:10.1017/S0950268809990781. hdl:10067/791410151162165141. PMID 19765352. ## Further reading[edit] * Muench, H. (1934) Derivation of rates from summation data by the catalytic curve. Journal of the American Statistical Association, 29: 25–38. [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	Force of infection	None	27,370	wikipedia	https://en.wikipedia.org/wiki/Force_of_infection	2021-01-18T18:50:17	{"wikidata": ["Q5467485"]}
Melnick-Needles syndrome is a rare disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which typically involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits). Melnick-Needles syndrome is usually the most severe of the otopalatodigital spectrum disorders and males with this condition generally have more severe signs and symptoms than females. In almost all instances, males with Melnick-Needles syndrome die before or soon after birth. The signs and symptoms of this condition may include: short stature, various skeletal abnormalities, characteristic facial features, and abnormalities of the heart and/or kidneys. This condition is caused by mutations in the FLNA gene, and it is inherited in an X-linked dominant manner. Although there is no specific treatment or cure for Melnick-Needles syndrome, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options for each person. [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	Melnick-Needles syndrome	c0025237	27,371	gard	https://rarediseases.info.nih.gov/diseases/7011/melnick-needles-syndrome	2021-01-18T17:59:10	{"mesh": ["D010009"], "omim": ["309350"], "umls": ["C0025237"], "orphanet": ["2484"], "synonyms": ["Melnick-Needles osteodysplasty", "MNS", "Osteodysplasty of Melnick and Needles"]}
Congenital disorder of glycosylation type IIc Other namesRambam-Hasharon syndrome, CDG-IIc, CDG2C This condition ia inherited via autosomal recessive manner Congenital disorder of glycosylation type IIc or Leukocyte adhesion deficiency-2 (LAD2) is a type of leukocyte adhesion deficiency attributable to the absence of neutrophil sialyl-LewisX, a ligand of P\- and E-selectin on vascular endothelium.[1] It is associated with SLC35C1.[2] This disorder was discovered in two unrelated Israeli boys 3 and 5 years of age, each the offspring of consanguineous parents. Both had severe mental retardation, short stature, a distinctive facial appearance, and the Bombay (hh) blood phenotype, and both were secretor- and Lewis-negative. They both had had recurrent severe bacterial infections similar to those seen in patients with LAD1, including pneumonia, peridontitis, otitis media, and localized cellulitis. Similar to that in patients with LAD1, their infections were accompanied by pronounced leukocytosis (30,000 to 150,000/mm3) but an absence of pus formation at sites of recurrent cellulitis. In vitro studies revealed a pronounced defect in neutrophil motility. Because the genes for the red blood cell H antigen and for the secretor status encode for distinct α1,2-fucosyltransferases and the synthesis of Sialyl-LewisX requires an α1,3-fucosyltransferase, it was postulated that a general defect in fucose metabolism is the basis for this disorder. It was subsequently found that GDP-L-fucose transport into Golgi vesicles was specifically impaired,[3] and then missense mutations in the GDP-fucose transporter cDNA of three patients with LAD2 were discovered. Thus, GDP-fucose transporter deficiency is a cause of LAD2.[4] ## See also[edit] * Congenital disorder of glycosylation * Leukocyte adhesion deficiency ## References[edit] 1. ^ Etzioni A, Harlan JM (2007). "Cell adhesion and leukocyte adhesion defects". In Ochs HD, Smith CI, Puck JM (eds.). Primary immunodeficiency diseases: a molecular and genetic approach. Oxford University Press. pp. 550–564. 2. ^ Yakubenia S, Frommhold D, Schölch D, et al. (August 2008). "Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc". Blood. 112 (4): 1472–81. doi:10.1182/blood-2008-01-132035. PMID 18541720. 3. ^ Sturla L, Puglielli L, Tonetti M, et al. (April 2001). "Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients". Pediatr. Res. 49 (4): 537–42. doi:10.1203/00006450-200104000-00016. PMID 11264438. 4. ^ Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C (May 2001). "Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency". Nat. Genet. 28 (1): 73–6. doi:10.1038/88299. PMID 11326280. ## External links[edit] Classification D * ICD-10: D84.8 * OMIM: 266265 External resources * Orphanet: 99843 * v * t * e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis: * Monocytosis * Histiocytosis * Chronic granulomatous disease ↓ -penia: * Monocytopenia Granulocytes ↑ -cytosis: * granulocytosis * Neutrophilia * Eosinophilia/Hypereosinophilic syndrome * Basophilia * Bandemia ↓ -penia: * Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia * Eosinopenia * Basopenia) Disorder of phagocytosis Chemotaxis and degranulation * Leukocyte adhesion deficiency * LAD1 * LAD2 * Chédiak–Higashi syndrome * Neutrophil-specific granule deficiency Respiratory burst * Chronic granulomatous disease * Neutrophil immunodeficiency syndrome * Myeloperoxidase deficiency * v * t * e Genetic disorder, membrane: Solute carrier disorders 1-10 * SLC1A3 * Episodic ataxia 6 * SLC2A1 * De Vivo disease * SLC2A5 * Fructose malabsorption * SLC2A10 * Arterial tortuosity syndrome * SLC3A1 * Cystinuria * SLC4A1 * Hereditary spherocytosis 4/Hereditary elliptocytosis 4 * SLC4A11 * Congenital endothelial dystrophy type 2 * Fuchs' dystrophy 4 * SLC5A1 * Glucose-galactose malabsorption * SLC5A2 * Renal glycosuria * SLC5A5 * Thyroid dyshormonogenesis type 1 * SLC6A19 * Hartnup disease * SLC7A7 * Lysinuric protein intolerance * SLC7A9 * Cystinuria 11-20 * SLC11A1 * Crohn's disease * SLC12A3 * Gitelman syndrome * SLC16A1 * HHF7 * SLC16A2 * Allan–Herndon–Dudley syndrome * SLC17A5 * Salla disease * SLC17A8 * DFNA25 21-40 * SLC26A2 * Multiple epiphyseal dysplasia 4 * Achondrogenesis type 1B * Recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia * SLC26A4 * Pendred syndrome * SLC35C1 * CDOG 2C * SLC39A4 * Acrodermatitis enteropathica * SLC40A1 * African iron overload see also solute carrier family This genetic disorder 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	Congenital disorder of glycosylation type IIc	c0398739	27,372	wikipedia	https://en.wikipedia.org/wiki/Congenital_disorder_of_glycosylation_type_IIc	2021-01-18T18:33:57	{"gard": ["4634"], "mesh": ["C535755"], "umls": ["C0398739"], "orphanet": ["99843"], "wikidata": ["Q5160418"]}
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: "Alveolar lung disease" – news · newspapers · books · scholar · JSTOR (February 2017) (Learn how and when to remove this template message) Alveolar lung disease Alveolus SpecialtyPulmonology Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.[1] ## Contents * 1 Causes * 2 Diagnosis * 2.1 Initial evaluation and Testing * 2.2 Imaging * 3 Management * 3.1 Supportive Care * 3.2 Treating underlying causes * 4 References ## Causes[edit] Alveoli are the functional units of the lungs. Alveolar lung diseases are classified as processes that affect these units that ultimately lead to issues with ventilation. There are a number of different causes of insult to the alveoli including build up of fluid, hemorrhage, infection, malignancy and build up of protein and mineral deposits. Conditions classified under alveolar lung disease include pulmonary edema (cardiogenic or non-cardiogenic), pneumonia (bacterial or viral), bronchoalveolar carcinoma, pulmonary hemorrhage, alveolar proteinosis and amyloidosis, and alveolar microlithiasis. Alveolar lung disease may be divided into acute or chronic. Causes of acute alveolar lung disease include pulmonary edema (cardiogenic or neurogenic), pneumonia (bacterial or viral), systemic lupus erythematosus, bleeding in the lungs (e.g., Goodpasture syndrome), idiopathic pulmonary hemosiderosis, and granulomatosis with polyangiitis. Chronic alveolar lung disease can be caused by pulmonary alveolar proteinosis, alveolar cell carcinoma, mineral oil pneumonia, sarcoidosis (alveolar form), lymphoma, tuberculosis, metastases, or desquamative interstitial pneumonia. ## Diagnosis[edit] ### Initial evaluation and Testing[edit] Patients with alveolar lung disease may have difficulty breathing and/or a cough which may be productive of sputum or blood. A physician will listen to the patient’s lungs to help determine if there is likely a lower lung disease. Depending on the type of alveolar lung disease, the listener may hear “crackles” that indicate an excess of fluid in the lungs or an absence of lung sounds in certain regions which may indicate poor ventilation due to consolidation of pus or fibrosis.[2] A pulse oximeter is a device that measures the amount of oxygen available in the blood. This is an important measurement in evaluation of a patient with difficulty breathing with suspected alveolar lung disease. ### Imaging[edit] Chest x-ray is the initial imaging modality of choice for evaluation of potential alveolar lung disease. Bedside ultrasound may also be utilized. The absence of radiographic evidence early on in the course of disease does not exclude alveolar disease. Alveolar disease is visible on chest radiography as small, ill-defined nodules of homogeneous density centered on the acini or bronchioles. The nodules coalesce early in the course of disease, such that the nodules may only be seen as soft fluffy edges in the periphery.[1] When the nodules are centered on the hilar regions, the chest x-ray may develop what is called the "butterfly," or "batwing" appearance. The nodules may also have a segmental or lobar distribution. Air alveolograms and air bronchograms can also be seen which indicate fluid in the alveoli with air in the terminal bronchioles indicating disease is alveolar.[1] These findings appear soon after the onset of symptoms and change rapidly thereafter. A segmental or lobar pattern may be apparent after aspiration pneumonia, atelectasis, lung contusion, localized pulmonary edema, obstructive pneumonia, pneumonia, pulmonary embolism with infarction, or tuberculosis. ## Management[edit] The two focuses of management for alveolar disease is supportive care to maintain oxygenation and ventilation to ensure that adequate oxygen is being delivered to blood, and to treat the underlying insult to the alveoli. ### Supportive Care[edit] Maintaining oxygenation and ventilation in alveolar lung disease is achieved through a number of methods. The mechanism of these treatments is primarily to provide oxygen and keep the alveoli open so that they can take up oxygen from and deliver it to the bloodstream. Ventilatory support is recognized as an essential component to treat pulmonary edema and acute respiratory distress syndrome.[3] Non-invasive ventilation is the first step for patient's who require ventilatory support. This can take the form of oxygen delivered via nasal cannula or non-rebreather mask. Patients who require additional support may be given a high-flow nasal cannula which has an added function of providing positive pressure on the alveoli, can warm and humidify air and decrease required inspiratory effort of the patient.[4] BiPAP and CPAP can also be used as next level treatment. Finally, intubation with ventilator support can be used with positive pressure to improve ventilation and oxygenation.[5] In cases where methods to support the lungs to provide oxygen to the blood fail, extracorporeal membrane oxygenation, or ECMO can be considered. ### Treating underlying causes[edit] Treating underlying causes of damage to alveoli is also essential in most alveolar lung disease. Some more commonly seen instances of alveolar lung disease include pulmonary edema and pneumonia. For pulmonary edema, medical treatment in addition to measures to maintain ventilation include diuretics to remove excess fluid from the lungs. Presumed bacterial pneumonia is typically treated with antibiotics. ## References[edit] 1. ^ a b c Al-Tubaikh, JA (2010). "Chapter 3.2 Alveolar lung diseases". Internal Medicine. Springer. p. 113. ISBN 978-3642037085. 2. ^ Reyes, Felix M.; Le, Jacqueline K. (2020), "Lung Exam", StatPearls, StatPearls Publishing, PMID 29083650, retrieved 2020-04-19 3. ^ Fan, Eddy; Brodie, Daniel; Slutsky, Arthur S. (2018-02-20). "Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment". JAMA. 319 (7): 698–710. doi:10.1001/jama.2017.21907. ISSN 0098-7484. PMID 29466596. S2CID 3451752. 4. ^ Lodeserto, Frank J.; Lettich, Thomas M.; Rezaie, Salim R. (2018-11-26). "High-flow Nasal Cannula: Mechanisms of Action and Adult and Pediatric Indications". Cureus. 10 (11): e3639. doi:10.7759/cureus.3639. ISSN 2168-8184. PMC 6358040. PMID 30740281. 5. ^ Bello, Giuseppe; De Santis, Paolo; Antonelli, Massimo (September 2018). "Non-invasive ventilation in cardiogenic pulmonary edema". Annals of Translational Medicine. 6 (18): 355. doi:10.21037/atm.2018.04.39. ISSN 2305-5839. PMC 6186545. PMID 30370282. [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	Alveolar lung disease	c3544166	27,373	wikipedia	https://en.wikipedia.org/wiki/Alveolar_lung_disease	2021-01-18T19:07:38	{"umls": ["C3544166"], "wikidata": ["Q4737951"]}
STT3A-CDG is a form of congenital disorders of N-linked glycosylation characterized by developmental delay, intellectual disability, failure to thrive, hypotonia and seizures. STT3A-CDG is caused by mutations in the gene STT3A (11q23.3). [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	STT3A-CDG	c3810062	27,374	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=370921	2021-01-23T18:37:05	{"omim": ["615596"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type Iw", "CDG-Iw", "CDG1W", "Congenital disorder of glycosylation type 1w", "Congenital disorder of glycosylation type Iw"]}
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome. The deletion region of chromosome 17q11.2 includes the NF1 gene (613113), which is mutant in neurofibromatosis type I (162200). Description Approximately 5 to 20% of all patients with neurofibromatosis type I (162200) carry a heterozygous deletion of approximately 1.4 Mb involving the NF1 gene and contiguous genes lying in its flanking regions (Riva et al., 2000; Jenne et al., 2001), which is caused by nonallelic homologous recombination of NF1 repeats A and C (Dorschner et al., 2000). The 'NF1 microdeletion syndrome' is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, mental retardation, developmental delay, an excessive number of early-onset neurofibromas (Venturin et al., 2004), and an increased risk for malignant peripheral nerve sheath tumors (De Raedt et al., 2003). Clinical Features Kayes et al. (1994) reported 5 NF1 patients with deletions of chromosome 17q11.2 including the NF1 gene. All had mild facial dysmorphism, mental retardation, and/or learning disabilities. Five patients were remarkable for the large number of neurofibromas for their age, suggesting that deletion of an unknown gene in the NF1 region may affect tumor initiation or development. All had plexiform neurofibromas. Four had hypertelorism, 4 had ptosis, and all had micrognathia. Using FISH with intragenic probes, Wu et al. (1995) looked for deletions in 13 unrelated individuals with NF1. Among 6 with severe manifestations, 4 were found to have deletions of the entire NF1 gene. All 4 had severe developmental delay, minor and major anomalies (including 1 with bilateral iris colobomas), and multiple cutaneous neurofibromas or plexiform neurofibromas which were present before age 5 years. Riva et al. (1996) characterized a 12-year-old male patient with sporadic NF1, dysmorphism, mental retardation, and skeletal anomalies associated with a cytogenetically visible deletion at 17q11.2. Analysis of microsatellite markers demonstrated that the patient was hemizygous, due to loss of the paternal allele, at several sites within the NF1 gene and at an extragenic marker distal to the 3-prime end of NF1. The 9-cM deletion in the interval between D17S841 and D17S250 was in agreement with that originally detected cytogenetically. The karyotypes of the parents were normal. The patient had no neurofibromas; the authors attributed this fact to his genetic background, i.e., to the influence of modifying genes. Upadhyaya et al. (1996) claimed to have provided the first physical cytogenetic deletion involving the NF1 gene in a patient with sporadic neurofibromatosis, dysmorphic features, and marked developmental delay. Combined evidence of molecular and cytogenetic techniques predicted that the deletion was approximately 7 Mb. Wu et al. (1997) described a father and son with NF1 due to deletion of the entire NF1 gene detected by FISH. Both had severe NF1, including a large number of cutaneous neurofibromas, facial anomalies, large hands, feet, and head, and developmental impairment. Only the 15-year-old son had seizures and plexiform neurofibromas. Cnossen et al. (1997) studied DNA from 84 unrelated patients with NF1, unselected for clinical features or severity, screening for deletion with intragenic polymorphic repeat markers and Southern analysis with cDNA probes. Deletion of the entire gene was detected in 5 patients from 4 unrelated families. Their phenotype resembled that of 5 previously reported patients with deletions, including intellectual impairment and dysmorphic features, but they could not confirm the existence of an excessive number of dermal neurofibromas. The authors commented on features of postnatal overgrowth suggesting Weaver syndrome (277590) and manifestations somewhat like Noonan syndrome (NS1; 163950). Slight micrognathia and extreme overbite of the maxilla were noted in individual cases. Using a novel multitrack screening strategy, Upadhyaya et al. (1998) studied 67 NF1 families (54 2-generation, 13 3-generation) with a de novo mutation in the germline of the first generation; 2 extragenic and 11 intragenic markers were employed. The pathologic lesion was identified in 31 cases. Loss of heterozygosity in the affected individual revealed a gross gene deletion in 15 of the 2-generation families; in 12 (80%) of them, the deletion was maternally derived. Eleven patients with a gross deletion exhibited developmental delay, 10 had dysmorphic features, and 6 manifested a learning disability. No gross deletion was apparent in any of the 13 3-generation families, suggesting that such lesions are subject to more intense selection. In these 13 families, the new mutation was of paternal origin in 11 and the underlying mutation event could be characterized in 3 of them. Rasmussen et al. (1998) studied 67 patients with NF1 and their parents. Five patients showed loss of heterozygosity, suggesting NF1 gene deletion. These patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features. All 5 deletions were de novo and occurred on the maternal chromosome. Two patients showed partial loss of heterozygosity, consistent with somatic mosaicism for NF1 deletion. Streubel et al. (1999) described what they considered to be the third case of NF1 due to mosaicism for a gross deletion in 17q11.2 covering the entire NF1 gene. The deletion was suspected in Giemsa banded chromosomes and was confirmed by fluorescence in situ hybridization using probes spanning the entire 350-kb genomic DNA of the NF1 gene. The deletion was present in 33% of peripheral blood lymphocytes and 58% of fibroblasts. The clinical manifestations in their 6-year-old male patient were especially severe and extended beyond the typical features of NF1. The patient also displayed facial anomalies, severe and early-onset psychomotor retardation, seizures, spasticity, and microcephaly. These features differed from other large-deletion NF1 patients, even nonmosaic cases. Streubel et al. (1999) suggested that the complex phenotype could be explained by the involvement of coding sequences flanking the NF1 gene, thus supporting the existence of a contiguous gene syndrome in 17q11.2. The other cases of somatic mosaicism for a deletion of the entire NF1 gene as identified by FISH were reported by Tonsgard et al. (1997) and Wu et al. (1997). By combining clinical and genetic evidence from 92 patients with the NF1 microdeletion, Venturin et al. (2004) reviewed specific clinical signs of the NF1 microdeletion syndrome. They found that the most common extra-NF1 clinical signs in patients with the microdeletion were learning disability, cardiovascular malformations, and dysmorphism. They pictured 3 patients with NF1 microdeletion syndrome in whom hypertelorism was a conspicuous feature of the facial dysmorphism. From the gene content of the deleted region, Venturin et al. (2004) proposed that haploinsufficiency of the OMG (164345) and/or CDK5R1 (603460) genes may be implicated in learning disability. In relation to cardiovascular malformations, only JJAZ1 (SUZ12; 606245) and CENTA2 (ADAP2; 608635) were considered plausible candidate genes, by reason of being significantly expressed in the heart. Mautner et al. (2010) reported 29 patients, including a mother and daughter, with the 17q11.2 deletion syndrome whose deletions were accurately characterized using FISH, PCR, and microsatellite analysis. All of the deletions were consistent with 1.4-Mb type 1 deletions encompassing 14 genes. Clinical features included facial dysmorphism (90%), tall stature (46%), large hands and feet (46%), scoliosis (43%), joint hyperflexibility (72%), delayed cognitive development and/or learning disabilities (93%), and mental retardation (38%). These features were more common than observed in the general NF1 population. Compared to the NF1 population, deletion patients also had significantly increased frequencies of plexiform neurofibromas (76%), subcutaneous neurofibromas (76%), spinal neurofibromas (64%) and malignant peripheral nerve sheath tumors (21%). Of the adults, 50% had a very high burden of cutaneous neurofibromas (greater than 1,000). Novel clinical features associated with type 1 NF1 deletions included pes cavus (17%), bone cysts (50%), attention deficits (73%), muscular hypotonia (45%), and speech difficulties (48%). Mautner et al. (2010) concluded that the phenotype associated with NF1 deletions is more severe than that observed in patients with typical neurofibromatosis type 1. ### NF1 Microduplication Syndrome Grisart et al. (2008) reported a large family segregating a microduplication of the NF1 microdeletion syndrome region. Two adult brothers had developmental delay and mild mental retardation associated with early onset of baldness around 14 to 15 years of age, mild facial dysmorphism with sparse eyelashes and eyebrows, long midface, malar hypoplasia, nasal deviation, bifid nose tip, flared nares, thin upper lip, dental enamel hypoplasia, and large testes. Family history included a similarly affected father with 3 mentally retarded half sisters and a mentally retarded half brother. The deceased grandmother was also reportedly affected. Microarray CGH, FISH analysis, and multiple ligation-dependent probe amplification (MLPA) detected a 1.5- to 1.6-Mb duplication on chromosome 17q11 corresponding perfectly to the NF1 microdeletion syndrome region. This duplication was found in all affected individuals studied, as well as in 2 unaffected family members, indicating reduced penetrance. Grisart et al. (2008) noted that the same mechanism, nonallelic homologous recombination, underlies both microdeletion and microduplication. Molecular Genetics About 5% of all patients with neurofibromatosis type I (NF1) have large deletions in 17q11.2 that include both the NF1 gene and its flanking regions. There are 3 main types of chromosome 17q11.2 deletions. The most common deletion is type 1, a 1.4-Mb deletion generated by nonallelic homologous recombination (NAHR) between segmental duplications (NF1-REP A and NF1-REP C) leading to the loss of 14 functional genes. These breakpoint regions are also known as the paralogous recombination sites 1 and 2 (PRS1 and PRS2, respectively). Type 1 is the most common deletion, accounting for 60 to 70% of large NF1 deletions. The less common type 2 deletion spans 1.2 Mb and is also generated by NAHR with breakpoints located within the SUZ12 gene (606245) and its pseudogene SUZ12P, resulting in the loss of 13 genes. Type 2 deletions account for 10 to 20% of large deletions in this region and are frequently associated with somatic mosaicism. The third type of deletions are atypical deletions of variable size, with nonrecurrent breakpoints (summary by Mautner et al., 2010). Kayes et al. (1994) reported 5 patients with a heterozygous deletion of more than 700 kb on chromosome 17. Minimally, each of the deletions involved the entire 350-kb NF1 gene, the 3 genes (EVI2A, 158380; EVI2B, 158381; and OMG, 164345) contained within an NF1 intron, and considerable flanking DNA. In 4 of the patients, the deletion mapped to the same interval; the deletion in the fifth patient was larger, extending farther in both directions. The remaining NF1 allele appeared to be producing functional neurofibromin. The data provided compelling evidence that NF1 results from haploid insufficiency of neurofibromin. Of the 3 documented de novo deletion cases, 2 involved the paternal NF1 allele and 1 the maternal allele. The findings suggested that clinical variability in NF1 may be influenced by genes either contiguous to or contained within the NF1 gene. Dorschner et al. (2000) constructed a 3.5-Mb BAC/PAC/YAC contig at 17q11.2. Analysis of somatic cell hybrids from microdeletion patients showed that 14 of 17 cases had deletions of 1.5 Mb. Deletions encompassed the entire 350 kb NF1 gene, 3 additional genes, 1 pseudogene, and 16 ESTs. In these cases, both proximal and distal breakpoints mapped at chromosomal regions of high identity, which the authors termed NF1-REPs. These REPs, or clusters of paralogous loci, are 15 to 100 kb and harbor at least 4 ESTs and an SH3GL pseudogene. The remaining 3 patients had at least 1 breakpoint outside an NF1-REP element; 1 had a smaller deletion, thereby narrowing the critical region harboring the putative locus that exacerbates neurofibroma development to 1 Mb. These data showed that the likely mechanism of NF1 microdeletion is homologous recombination between NF1-REPs on sister chromatids. NF1 microdeletion is the first REP-mediated rearrangement identified that results in loss of a tumor suppressor gene. Therefore, in addition to the germline rearrangements that Dorschner et al. (2000) identified, NF1-REP-mediated somatic recombination may be an important mechanism for the loss of heterozygosity at the NF1 locus in tumors of NF1 patients. Lopez Correa et al. (2000) analyzed a set of polymorphic dinucleotide-repeat markers flanking the microdeletion on chromosome 17 in a group of 7 unrelated families with a de novo NF1 microdeletion. Six of 7 microdeletions were of maternal origin. The breakpoints of the microdeletions of maternal origin were localized in NF1-REPs. The single deletion of paternal origin was shorter, and no crossover occurred on the paternal chromosome 17 during transmission. Five of the 6 cases of maternal origin were informative, and all 5 showed a crossover (between the flanking markers) after maternal transmission. The observed crossovers flanking the NF1 region suggested to the authors that these NF1 microdeletions resulted from an unequal crossover in maternal meiosis I, mediated by a misalignment of the flanking NF1-REPs. Shen et al. (2000) found that the SLC6A4 (182138) and CPD (603102) genes were deleted in 1 of 17 NF1 patients carrying submicroscopic NF1 contiguous gene deletions. Lopez-Correa et al. (2001) mapped and sequenced the microdeletion breakpoints in 54 NF1 patients. In 25 such patients, recombination events occurred in a discrete 2-kb recombination hotspot within each of the flanking NF1-REPs. Two recombination events were accompanied by apparent gene conversion. A search for recombination-prone motifs revealed a chi-like sequence. Jenne et al. (2001) used molecular techniques to characterize the breakpoints and deleted genes in 8 patients with NF1 and 17q11.2 microdeletion syndrome. The interstitial 17q11.2 microdeletion arose from unequal crossover between 2 highly homologous 60-kb duplicons separated by approximately 1.5 Mb. The authors stated that 13 genes had been located in the deleted region. Kehrer-Sawatzki et al. (2004) identified a high frequency of mosaicism among patients with NF1 caused by microdeletions resulting from somatic recombination of the JJAZ1 gene (SUZ12; 606245). Two types of deletions were observed. The classic 1.4-Mb deletion (type 1) was found in some patients. These type 1 deletions encompass 14 genes and have breakpoints in the NF1 low-copy repeats (LCRs). The 1.2-Mb NF1 deletion (type 2) affected 13 genes and was mediated by recombination between the JJAZ1 gene and its pseudogene. The JJAZ1 gene, which was completely deleted in patients with type 1 NF1 microdeletions and disrupted in type 2 deletions, is highly expressed in brain structures associated with learning and memory. Thus, its haploinsufficiency might contribute to mental impairment in patients with constitutional NF1 microdeletions. Conspicuously, 7 of the 8 mosaic deletions were of type 2, whereas only 1 was a classic type 1 deletion. Therefore, the JJAZ1 gene is a preferred target of strand exchange during mitotic nonallelic homologous recombination. Although type 1 NF1 microdeletions occur by interchromosomal recombination during meiosis, the findings of Kehrer-Sawatzki et al. (2004) implied that type 2 deletions are mediated by intrachromosomal recombination during mitosis. Gervasini et al. (2005) reported an NF1 patient with a 1.5-Mb deletion involving the NF1 gene. High-resolution FISH showed that the centromeric breakpoint was within the SSH2 gene (606779), and the telomeric breakpoint was within IVS23A of the NF1 gene; both breakpoints occurred in Alu sequences. Gervasini et al. (2005) noted that most Alu-mediated deletions are much smaller (up to 200 kb). The patient had a relatively mild phenotype with borderline cognitive deficits and seizures, but no dysmorphism or cardiac anomalies, suggesting that genes mapping downstream from NF1 may account for those manifestations. The breakpoints of the common 1.4-Mb (type 1) 17q11.2 deletion are located within low-copy repeats (NF1-REPs) and cluster within a 3.4-kb hotspot of nonallelic homologous recombination (NAHR). Steinmann et al. (2007) presented a comprehensive breakpoint analysis of the 1.2-Mb type 2 deletions, characterized by breakpoints located within the SUZ12 gene (606245) and its pseudogene. Breakpoint analysis of 13 independent type 2 deletions revealed no obvious hotspots of NAHR. However, an overrepresentation of polypyrimidine/polypurine tracts and triplex-forming sequences was noted in the breakpoint regions that could have facilitated NAHR. All 13 type 2 deletions identified were characterized by somatic mosaicism, which indicates a positional preference for mitotic NAHR with the NF1 gene region. Whereas interchromosomal meiotic NAHR occurs between the NF1-REPs giving rise to type 1 deletions, NAHR during mitosis appears to occur intrachromosomally between the SUZ12 gene and its pseudogene, thereby generating type 2 deletions. Additionally, 12 of the 13 mosaic type 2 deletions were found in females. The marked female preponderance among mosaic type 2 deletions contrasts with the equal sex distribution noted for type 1 and/or atypical NF1 deletions. Although an influence of chromatin structure was strongly suspected, no sex-specific differences in the methylation pattern exhibited by the SUZ12 gene were apparent that could explain the higher rate of mitotic recombination in females. Type 2 NF1 deletions are believed to have an early postzygotic mitotic origin. Using microsatellite analysis, Roehl et al. (2010) analyzed 14 additional type 2 NF1 deletions and found that most type 2 NF1 deletions originated via intrachromosomal NAHR between SUZ12 and its highly homologous pseudogene. Combined with the findings of Steinmann et al. (2007), the results indicated that 16 of 18 type 2 NF1 deletions occurred postzygotically via the same method. Two unrelated patients, 1 with a severe phenotype, apparently had germline type 2 NF1 deletions. ### Associations Pending Confirmation By mutation screening of 12 of the 14 genes deleted in the type 1 chromosome 17q11 microdeletion, Douglas et al. (2007) identified heterozygous mutations in the RNF135 gene (611358.0001-611358.0004) in 4 of 245 unrelated individuals with an overgrowth syndrome characterized by increased postnatal height and weight, macrocephaly, variable learning disability, and dysmorphic facial features. One additional individual had a microdeletion of RNF135 and 4 other genes, but not NF1. Although none had clinical features of NF1, the facial features were similar to the NF1 deletion syndrome, including broad forehead, downslanting palpebral fissures, broad nasal tip, long philtrum, and thin upper lip. Variable features in 1 or 2 patients included deafness, optic nerve hypoplasia, advanced bone age, ataxia, autistic features, and pulmonary stenosis. Douglas et al. (2007) concluded that haploinsufficiency of RNF135 contributes to the overgrowth and facial dysmorphism that is often present in individuals with NF1 microdeletions, as well as learning disabilities and other congenital anomalies. Functional studies were not performed. Wright et al. (2019) used data from 379,768 UK Biobank participants of European ancestry to access the pathogenicity and penetrance of putatively clinically important rare variants. Two variants in the RNF135 gene, Q243X (611358.0001) and a 1-bp insertion, had no statistically significant association with years of education, fluid intelligence, BMI, or height. The Q243X variant was found at a minor allele frequency (MAF) of 0.00215, and the 1-bp insertion at a MAF of 0.05265. Wright et al. (2019) argued that, based on the lack of association with any clinically relevant traits, the probability of 0 of the gene's being loss-of-function (LOF)-intolerant (based on the presence in ExAC of LOF variants in the gene; Lek et al., 2016), the age of the report of Douglas et al. (2007), and the lack of enrichment of de novo mutations in the Deciphering Developmental Disorders Study (2017), RNF135 haploinsufficiency is not a cause of impaired intellectual development. Animal Model Venturin et al. (2014) found that morpholino-mediated knockdown of adap2 in zebrafish embryos resulted in variable circulatory defects at 2 days postfertilization, including total loss of circulation, accumulation of blood cells in the trunk and/or tail, and blood stases in the head. Circulatory defects in adap2 morphants appeared to be caused by abnormal heart development and function, including lack of leftward cardiac jogging, abnormal heart looping (including presence of a completely linear heart tube), reduced ventricle size, and abnormal atrioventricular valve formation. Venturin et al. (2014) hypothesized that occurrence of cardiovascular malformations in NF1 microdeletion patients is due to ADAP2 haploinsufficiency. INHERITANCE \- Autosomal dominant GROWTH Height \- Tall stature (46%) Other \- Generalized overgrowth HEAD & NECK Head \- Macrocephaly (39%) Face \- Facial dysmorphism (in up to 90%) \- Facial asymmetry \- Coarse facies Eyes \- Lisch nodules (iris hamartomas) (93%) \- Hypertelorism CARDIOVASCULAR Heart \- Congenital heart defects (21%) CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum (31%) SKELETAL \- Bone cysts (50%) \- Increased joint laxity (72%) Spine \- Scoliosis (43%) Hands \- Large hands (46%) \- Accelerated carpal bone age Feet \- Large feet (46%) \- Pes cavus (17%) SKIN, NAILS, & HAIR Skin \- Neurofibromas, subcutaneous (76%) \- Neurofibromas, cutaneous (86%) \- Plexiform neurofibroma (76%) \- Cafe-au-lait spots (93%) \- Axillary freckling \- Inguinal freckling MUSCLE, SOFT TISSUES \- Hypotonia (45%) \- Soft fleshy palms (50%) NEUROLOGIC Central Nervous System \- Delayed cognitive development/learning disabilities (93%) \- Mental retardation (38%) \- Speech difficulties (48%) \- Spinal neurofibromas (64%) \- Brain MRI shows T2-weighted hyperintensities (17%) Behavioral Psychiatric Manifestations \- Attention-deficit hyperactivity disorder (33%) \- Attention difficulties (73%) NEOPLASIA \- Optic glioma (19%) \- Malignant peripheral nerve sheath tumors (21%) MISCELLANEOUS \- Contiguous gene deletion syndrome \- Patients have increased numbers and earlier onset of neurofibromas compared to patients with neurofibromatosis-1 due to point mutations MOLECULAR BASIS \- A contiguous gene deletion syndrome involving deletion of 1.4Mb on chromosome 17q11.2 ▲ 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	CHROMOSOME 17q11.2 DELETION SYNDROME, 1.4-MB	c3150928	27,375	omim	https://www.omim.org/entry/613675	2019-09-22T15:57:54	{"doid": ["0060403"], "mesh": ["C563524"], "omim": ["613675"], "orphanet": ["97685", "636", "139474", "137634"], "synonyms": ["Alternative titles", "NEUROFIBROMATOSIS 1 MICRODELETION SYNDROME", "NF1 MICRODELETION SYNDROME", "VAN ASPEREN SYNDROME"]}
Dunnigan and Pelosi (1993) reported an experience with 18 children from 13 unrelated kindreds with idiopathic edema commencing between the neonatal period and age 12 years. A triad of swelling, affective disturbance and functional autonomic symptoms was observed. Sixteen of the children (89%), including all 15 girls, had a family history of idiopathic edema, and 12 children (67%) had a family history of diabetes mellitus. Adherence to a restricted carbohydrate diet and the avoidance of refined carbohydrate appeared to be beneficial. Dunnigan and Pelosi (1993) presented the pedigree of a kindred in which the grandmother, all 4 daughters, and all 5 grandchildren (1 male, 4 females) showed idiopathic edema. Some of the children had severe vomiting, often projectile, beginning at an early age, frequent micturition with poor bladder control; frequent 'accidents' were noted. Irritability, lability of mood, lassitude and fatigue accompanied swelling in some of the children. Intermittent swelling of the face and abdomen was noted as early as the first year of life. Children with later onset often had swelling beginning after a period of weight gain. GU \- Frequent micturition \- Poor bladder control Neuro \- Affective disturbance \- Irritability \- Lability of mood \- Lassitude \- Functional autonomic symptoms Inheritance \- Autosomal dominant Endocrine \- Diabetes mellitus Misc \- Onset neonatal to age 12 years Skin \- Idiopathic edema GI \- Vomiting, often projectile ▲ 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	EDEMA, FAMILIAL IDIOPATHIC, PREPUBERTAL	c1851847	27,376	omim	https://www.omim.org/entry/129840	2019-09-22T16:41:50	{"mesh": ["C565063"], "omim": ["129840"]}
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare and poorly understood lung condition that is characterized by the abnormal overgrowth of certain cells in the lung (called pulmonary neuroendocrine cells) that receive signals from nerve cells (neurons) and produce hormones. People with this diagnosis may have no obvious symptoms or may exhibit features of airway disease such as a chronic, nonproductive cough, shortness of breath with exertion, and wheezing. It is considered to be a precancerous condition as studies suggest it is a precursor for pulmonary carcinoid tumors. The cause of DIPNECH is currently unknown. Because so few cases have been reported in the medical literature, there is limited information on the prognosis and management of 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	Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia	c1333291	27,377	gard	https://rarediseases.info.nih.gov/diseases/10780/diffuse-idiopathic-pulmonary-neuroendocrine-cell-hyperplasia	2021-01-18T18:00:52	{"synonyms": ["DIPNECH"]}
A number sign (#) is used with this entry because hereditary sensory neuropathy type IE (HSN1E) is caused by heterozygous mutation in the DNMT1 gene (126375) on chromosome 19p13. Description Hereditary sensory neuropathy type IE is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia (summary by Klein et al., 2011). For a discussion of genetic heterogeneity of HSN, see HSAN1A (162400). Clinical Features Wright and Dyck (1995) reported a 7-generation kindred with autosomal dominant inheritance of sensory neuropathy with sensorineural hearing loss and early-onset dementia. The neurologic deficits began between the second and fourth decades and were progressive, with death occurring in the fifth and sixth decades. The proband was a 42-year-old man with onset of distal sensory impairment primarily affecting the lower limbs in his early thirties followed by progressive memory and hearing impairment in his late thirties. There were no autonomic or motor symptoms. Physical studies showed severe peripheral sensorineural neuropathy with absent sensory nerve action potentials and moderate to severe hearing loss; brain imaging showed mild diffuse cerebral atrophy. Sural nerve biopsy showed almost complete absence of myelinated fibers of all sizes, without onion bulb formation or regenerating clusters. There were reduced numbers of unmyelinated fibers. Wright and Dyck (1995) classified the disorder as a subtype of HSAN type I. Hojo et al. (1999) reported 3 Japanese sibs with onset of peripheral sensory neuropathy affecting all modalities in young adulthood, followed by hearing loss and progressive frontal dementia in the later thirties and forties. The neuropathy resulted in ulceration of the feet necessitating amputation of the toes in all patients. Two patients reported lancinating pains. Sural nerve biopsy showed almost complete loss of myelinated fibers with moderate loss of unmyelinated fibers. The dementia was characterized by memory loss, irritability, apathy, impulsivity, delusions, somnolence, and decreased speech output. Functional imaging of 2 patients showed frontal and thalamic hypometabolism, and brain imaging of 1 showed frontal atrophy. Their affected mother had died in the fifth decade with painless foot ulcers and dementia. Cerebellar and autonomic dysfunction were not present. Klein et al. (2011) reported 2 additional families with HSN1E. Affected individuals were healthy in their youth, but developed worsening sensorineural deafness and sensory neuropathy by the age of 20 to 35 years. Progressive cognitive and behavioral declines developed by the fourth decade. Brain imaging of the affected persons showed global atrophy, and there was reduced weight of the autopsied brains. Quantitative sensory testing, nerve conductions, and nerve biopsy were indicative of length-dependent progressive sensory axonal loss. Neuropathologic examination of 1 patient who died at age 48 years showed ascending spinal sensory tract degeneration with myelin and axonal loss involving the gracile fasciculus in the posterior columns at all spinal levels. There was also generalized cerebral atrophy, chronic cerebellar Purkinje cell swelling and axonal loss, and severe neuronal loss and gliosis of the inferior olivary nucleus. Klein et al. (2013) reported 2 unrelated families of Norwegian and Scottish descent, respectively, with HSN1E. Affected individuals had onset of hearing loss in their forties, followed by sensory neuropathy, sensory ataxia, behavioral abnormalities, and dementia. One patient had seizures, consistent with neurodegeneration. Neuropathologic examination of 1 patient showed frontal lobe atrophy without distinct histopathology; in particular, no plaques, neurofibrillary tangles, or Lewy bodies were identified, and immunostaining for MAPT (157140), SNCA (163890), and TDP43 (605078) was negative. None of the patients had narcolepsy or cataplexy. Inheritance The transmission pattern of HSN1E in the families reported by Wright and Dyck (1995) and Klein et al. (2011) was consistent with autosomal dominant inheritance. Molecular Genetics By linkage analysis followed by exome sequencing, Klein et al. (2011) identified 2 different heterozygous mutations in the DNMT1 gene (126375.0001 and 126375.0002) in 4 unrelated families with autosomal dominant inheritance of hereditary sensory neuropathy type IE. Two of the families had been reported by Wright and Dyck (1995) and Hojo et al. (1999). In vitro functional expression studies in E. coli and HeLa cells showed that the mutations affected proper folding of DNMT1 and resulted in premature degradation, reduced methyltransferase activity, and impaired heterochromatin binding during the G2 cell cycle phase, leading to global hypomethylation and site-specific hypermethylation. These changes indicated epigenetic dysregulation. The results provided a direct link between DNMT1 defects and a neurodegenerative disorder affecting both the central and peripheral nervous systems, and suggested that DNMT1 participates in a precise mechanism of dynamic regulation of neuronal survival. Klein et al. (2013) identified heterozygous mutations affecting the same codon in exon 20 of the DNMT1 gene (Y495C, 126375.0001 and Y495H, 126375.0006) in affected members of 2 unrelated families with HSN1E. DNMT1 mutations were specific to the phenotype of peripheral neuropathy associated with hearing loss and dementia, as mutations were not found in 48 patients with sensory neuropathy without hearing loss or dementia or in 5 kindreds with familial frontotemporal dementia. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural SKELETAL Feet \- Ulceration of the toes \- Osteomyelitis \- Amputation NEUROLOGIC Central Nervous System \- Memory impairment, progressive \- Dementia, frontal lobe \- Decreased speech \- Cerebral atrophy \- Frontal lobe atrophy \- Hypometabolism of the frontal lobe and thalamic regions Peripheral Nervous System \- Sensory neuropathy affecting all modalities primarily affecting the lower limbs with some mild upper limb involvement \- Hyporeflexia \- Lancinating pains (2 patients) \- Almost complete loss of myelinated fibers seen on sural nerve biopsy \- Loss of unmyelinated fibers Behavioral Psychiatric Manifestations \- Apathy \- Somnolence \- Impulsivity \- Irritability \- Distractibility \- Delirium MISCELLANEOUS \- Onset of peripheral neuropathy or hearing loss in young adulthood (range 16 to 35 years) \- Onset of dementia in the thirties or forties \- Progressive disorder \- Death in the fifth or sixth decade MOLECULAR BASIS \- Caused by mutation in the DNA methyltransferase 1 gene (DNMT1, 126375.0001 ) ▲ 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	NEUROPATHY, HEREDITARY SENSORY, TYPE IE	c3279885	27,378	omim	https://www.omim.org/entry/614116	2019-09-22T15:56:25	{"doid": ["0070158"], "mesh": ["C580162"], "omim": ["614116"], "orphanet": ["456318"], "synonyms": ["NEUROPATHY, HEREDITARY SENSORY, WITH HEARING LOSS AND DEMENTIA", "Hereditary sensory neuropathy-sensorineural hearing loss-dementia syndrome", "HSN IE", "HSN1E", "Alternative titles", "HSAN1E"], "genereviews": ["NBK1358", "NBK84112"]}
A number sign (#) is used with this entry because of evidence that myopathy with extrapyramidal signs (MPXPS) is caused by homozygous mutation in the MICU1 gene (605084) on chromosome 10q22. Description Myopathy with extrapyramidal signs is an autosomal recessive disorder characterized by early childhood onset of proximal muscle weakness and learning disabilities. While the muscle weakness is static, most patients develop progressive extrapyramidal signs that may become disabling (summary by Logan et al., 2014). Clinical Features Logan et al. (2014) reported 15 patients from 7 families with delayed motor development associated with proximal muscle weakness between 11 months and 8 years of age. All patients over 2 years of age showed learning difficulties. Ten of 15 individuals developed subtle extrapyramidal motor signs that progressed over several years to a debilitating disorder of involuntary movement with variable features, including chorea, tremor, dystonic posturing, and orofacial dyskinesia. Additional variable features found in only a few patients included ataxia, microcephaly, ophthalmoplegia, ptosis, optic atrophy, and axonal peripheral neuropathy. Laboratory studies showed increased serum creatine kinase, and muscle biopsy showed a myopathic process with diffuse variation in fiber size, increased frequency of internal and central nuclei, and clusters of regenerating fibers. Necrotic fibers were rare. Muscle biopsies from some older patients showed frequent focal areas devoid of mitochondria, reminiscent of minicores. Mitochondrial respiratory chain enzymes were normal in muscle biopsies. Inheritance The transmission pattern of MPXPS in the families reported by Logan et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In 15 children from 7 families with myopathy with extrapyramidal signs, Logan et al. (2014) identified 2 different homozygous truncating mutations in the MICU1 gene (605084.0001 and 605084.0002). The mutations were found by whole-exome sequencing. Fibroblasts from 2 patients showed increased velocity of histamine-induced mitochondrial calcium uptake compared to controls, as well as decreased peak cytosolic calcium concentration compared to controls. Confocal imaging of patient cells showed highly fragmented mitochondrial networks. These defects were rescued by expression of wildtype MICU1. Mitochondrial membrane potential and respiratory metabolism were not different in patient fibroblasts compared to controls. Logan et al. (2014) suggested that altered cytoplasmic calcium concentrations may result in reduced calcium signaling, which would affect muscle contraction and synaptic transmission. In addition, chronic elevation of mitochondrial calcium may lead to mitochondrial stress. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (in some patients) Eyes \- Optic atrophy (in some patients) \- Ophthalmoplegia (in some patients) \- Ptosis (in some patients) MUSCLE, SOFT TISSUES \- Muscle weakness, proximal \- Difficulty running \- Difficulty walking \- Increased fiber size variation seen on biopsy \- Increased internal and central nuclei \- Regenerating fibers \- Necrotic fibers \- Fibers devoid of mitochondria NEUROLOGIC Central Nervous System \- Delayed motor development \- Learning difficulties \- Extrapyramidal movements (later onset) \- Dystonia \- Chorea \- Involuntary movements \- Tremor \- Orofacial dyskinesia \- Ataxia (in some patients) Peripheral Nervous System \- Axonal neuropathy (in some patients) LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset in early childhood (11 months to 8 years) \- Slowly progressive or static disease course MOLECULAR BASIS \- Caused by mutation in the mitochondrial calcium uptake protein 1 gene (MICU1, 605084.0001 ) ▲ 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	MYOPATHY WITH EXTRAPYRAMIDAL SIGNS	c3810285	27,379	omim	https://www.omim.org/entry/615673	2019-09-22T15:51:18	{"doid": ["0111335"], "omim": ["615673"], "orphanet": ["401768"], "synonyms": []}
For a general discussion of hereditary prostate cancer, see 176807. Mapping Rokman et al. (2005) performed linkage analysis using 17 fine-mapping markers in 16 multiplex Finnish families with hereditary prostate cancer and found evidence for linkage at 3p26, with a multipoint heterogeneity adjusted lod of 3.39. The highest lod scores were around markers D3S1270 and D3S4559 (alpha = 0.89), narrowing the peak region to approximately 2 cM. Rokman et al. (2005) concluded that 3p26 is likely to contain a predisposing gene for Finnish hereditary prostate cancer, although no disease-segregating variants were found in 2 candidate genes in the region. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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	PROSTATE CANCER, HEREDITARY, 5	c2931456	27,380	omim	https://www.omim.org/entry/609299	2019-09-22T16:06:18	{"doid": ["10283"], "mesh": ["C537243"], "omim": ["609299"], "orphanet": ["1331"]}
A number sign (#) is used with this entry because SIDDT is caused by mutation in the testis-specific protein-like-1 gene (TSPYL1; 604714). Clinical Features Puffenberger et al. (2004) identified a previously unrecognized syndrome, termed sudden infant death with dysgenesis of the testes (SIDDT), in 21 individuals from 9 sibships among the Belleville Old Order Amish community. The condition was not seen among the Lancaster County Old Order Amish population. Affected infants appeared normal at birth, but developed signs of visceroautonomic dysfunction early in life followed by death before age 12 months of abrupt cardiorespiratory distress. Features included bradycardia, hypothermia, severe gastroesophageal reflux, laryngospasm, bronchospasm, and abnormal cardiorespiratory patterns during sleep. Postmortem examination of 2 infants showed no neuropathologic abnormalities; specifically, the brainstem and anterior horn cells were normal. Genotypic males with SIDDT had fetal testicular dysgenesis and ambiguous genitalia, with findings such as intraabdominal testes, dysplastic testes, deficient fetal testosterone production, fusion and rugation of the gonadal sac, and partial development of the penile shaft. Female sexual development was normal. Affected infants had an unusual staccato cry, similar to the cry of a goat. Mapping Using a high-density SNP genome scan, Puffenberger et al. (2004) localized the SIDDT disease locus to a 3.6-Mb interval on chromosome 6q22.1-q22.31 (maximum 2-point lod score of 2.41). Molecular Genetics In 21 affected patients with SIDDT, Puffenberger et al. (2004) identified a homozygous mutation in the TSPYL1 gene (604714.0001). All parents of affected infants were heterozygous for the mutation, and no unaffected sibs were homozygous for the mutation. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth HEAD & NECK Face \- Facial nerve weakness Eyes \- Ocular muscle palsies Mouth \- Tongue fasciculations CARDIOVASCULAR Heart \- Bradycardia \- Variable heart rate (range 52-250 beats per minute) RESPIRATORY \- Abnormal respiratory patterns \- Apnea (central and obstructive) \- Stridor Larynx \- Laryngospasm Airways \- Bronchospasm ABDOMEN Gastrointestinal \- Feeding difficulties \- Gastroesophageal reflux, severe GENITOURINARY \- Variable maturation of genitalia in males External Genitalia (Male) \- Ambiguous genitalia \- Partial development of the penile shaft Internal Genitalia (Male) \- Testicular dysgenesis \- Cryptorchidism \- Dysplastic testes \- Tortuous vascularity in the testes \- Arrested cell development in the testes \- Decreased number of Leydig cells \- Decreased number of Sertoli cells NEUROLOGIC Central Nervous System \- Visceroautonomic dysfunction \- Decreased upper extremity reflexes \- Hyperactive startle reflex \- Tongue fasciculations \- Ocular palsies \- Facial nerve weakness \- Absence of neuropathologic findings in the brainstem and anterior horn cells VOICE \- Staccato cry ('goat-like') LABORATORY ABNORMALITIES \- Abnormal response to human chorionic gonadotropin indicates decreased testosterone MISCELLANEOUS \- Affected infants appear normal at birth \- Symptoms develop immediately after birth \- Death occurs before 12 months of age due to cardiorespiratory arrest MOLECULAR BASIS \- Caused by mutation in the testis-specific protein-like 1 gene (TSPYL1, 604714.0001 ) ▲ 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	SUDDEN INFANT DEATH WITH DYSGENESIS OF THE TESTES SYNDROME	c1837371	27,381	omim	https://www.omim.org/entry/608800	2019-09-22T16:07:09	{"mesh": ["C563856"], "omim": ["608800"], "orphanet": ["168593"]}
A rare pediatric rheumatological disease characterized by the variable occurrence of chronic arthritis, intermittently high spiking fever, maculopapular rash during fever episodes, hepatomegaly and/or splenomegaly, lymphadenopathy, and serositis. ## Epidemiology Juvenile idiopathic arthritis (JIA) is one of the most common pediatric chronic diseases, with a yearly incidence between 1.6 and 23 new cases per 100,000 children. Systemic-onset JIA accounts for roughly 10-20% of all JIA patients, but the percentage is higher in some countries than others; in parts of Asia, for example, it may account for up to 30-40% of all JIA cases. ## Clinical description Onset usually occurs between 3 and 5 years of age. The clinical signs include fever with oscillating temperatures over a 24-hour period and peaks of over 39°C or more. The fever peaks are associated with the transient occurrence of an evanescent macular rash. Any joint, small or large, may be affected at disease onset, and involvement is nearly symmetrical and may be oligo- or polyarticular. Arthritis tends to increase in severity over time, and thus may not appear until later in the disease course. The course of the disease varies between individuals, ranging from a monocyclic disease course, to recurrent predominantly systemic disease course, to a progressive polyarthritis that could lead to severe and destructive joint disease. ## Etiology Whilst the underlying mechanisms and triggering factors are not fully understood, IL-1 and IL-6 play a major role in the pathogenesis of the disease. ## Diagnostic methods Diagnosis is based on clinical and biological findings in a child under the age of 16 presenting with fever for at least 3 consecutive days and 2 major criteria (arthritis and evanescent rash) or 1 major and 2 minor criteria ((1)generalized lymph node enlargement and or hepatomegaly or splenomegaly (2) serositis (3) arthralgias lasting 2 weeks or longer (4)leukocytosis > 15.000/mm3 with neutrophilia) A confirmed diagnosis requires exclusion of other causes of the symptoms. ## Differential diagnosis The differential diagnoses is extensive and includes bacterial infections (including occult bacterial infection, brucellosis, Lyme disease, cat scratch disease, tuberculosis, and infectious mononucleosis), malaria, malignancies (such as leukemia, lymphoma, and neuroblastoma), viral infections, hereditary recurrent fever syndromes, other inflammatory diseases (such as systemic lupus erythematosus, systemic vasculitis, Kawasaki disease, Behçet disease, inflammatory bowel disease, Sweet syndrome, PFAPA, Takayasu syndrome, Castleman syndrome, rheumatic fever, and polyarteritis nodosa), connective tissue diseases, and periodic fever syndromes. ## Management and treatment Management by a specialized multidisciplinary team is required. Treatment is typically first with non-steroidal anti-inflammatory drugs (NSAIDs) and, if the inflammation is not controlled, followed by high dose corticosteroids. Treatment with cytokine inhibitors (anakinra, canakinumab, and tocilizumab) has shown to be highly effective. Furthermore, these drugs can help mitigate damage caused by the inflammatory process. Generally, complications such as macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation continue to be a major issue in patients' care, but have decreased since the use of biological treatment. ## Prognosis The disease course is long with major impact on quality of life. The risk of complications due to the illness or medication has been significantly reduced by the early use of biological treatment. Currently, osteopenia and osteoporosis, growth impairment, erosive arthritis, and secondary or reactive amyloidosis have almost disappeared. Macrophage activation syndrome is little influenced by recent therapeutic strategies and requires rapid care in the intensive care unit. [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-onset juvenile idiopathic arthritis	c0087031	27,382	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85414	2021-01-23T16:56:24	{"gard": ["10966"], "mesh": ["D001171"], "omim": ["604302", "618795"], "umls": ["C0087031", "C1384600"], "icd-10": ["M08.2"], "synonyms": ["Still disease", "Systemic-onset JIA"]}
A rare ciliopathy characterized by congenital cataract with secondary glaucoma, developmental delay, short stature, multiple skeletal abnormalities (spinal deformities, limb anomalies, delayed bone age), dental anomalies (oligodontia, enamel defects), dysmorphic facial features (including coarse facies, low hairline, epicanthal folds, flat and broad nasal bridges, and retrognathia), and stroke. Other recurrent manifestations are hearing loss and nephrocalcinosis. [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	Oculocerebrodental syndrome	None	27,383	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=557003	2021-01-23T18:22:18	{"omim": ["618440"], "synonyms": ["Oculo-cerebro-dental syndrome"]}
Primary cutaneous marginal zone lymphoma SpecialtyDermatology/oncology Primary cutaneous marginal zone lymphomas represent a heterogeneous group of diseases characterized by solitary or multiple dermal or subcutaneous nodules.[1]:741 Lymphomas included in this group are:[1]:741[2] * Primary cutaneous immunocytoma * Marginal zone B-cell lymphoma * Mucosa-associated lymphoid tissue lymphoma ## See also[edit] * Cutaneous B-cell lymphoma * Skin lesion ## References[edit] 1. ^ a b 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. ^ Salama S (November 2000). "Primary cutaneous B-cell lymphoma and lymphoproliferative disorders of skin: current status of pathology and classification". Am. J. Clin. Pathol. 114 Suppl: S104–28. PMID 11996165. 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	Primary cutaneous marginal zone lymphoma	None	27,384	wikipedia	https://en.wikipedia.org/wiki/Primary_cutaneous_marginal_zone_lymphoma	2021-01-18T18:53:02	{"wikidata": ["Q7243121"]}
Childhood-onset spasticity with hyperglycinemia is a rare neurometabolic disease characterized by a childhood onset of progressive spastic ataxia associated with gait disturbances, hyperreflexia, extensor plantar responses and non-ketotic hyperglycinemia typically revealed by biochemical analysis. Additional signs of upper extremity spasticity, dysarthria, learning difficulties, poor concentration, nystagmus, optic atrophy and reduced visual acuity may also be associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-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-onset spasticity with hyperglycinemia	c4225178	27,385	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401866	2021-01-23T18:01:17	{"omim": ["616859"], "icd-10": ["E88.8"], "synonyms": ["Childhood-onset spasticity with variant non-ketotic hyperglycinemia", "Spasticity-ataxia-gait anomalies syndrome"]}
A number sign (#) is used with this entry because the McLeod phenotype is caused by mutation in the XK gene (314850), encoding an antigen of the Kell blood group system (see 110900). Description Hematologically, McLeod syndrome is characterized by the absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease (143100). Onset of neurologic symptoms ranges between 25 and 60 years (mean onset 30-40 years), and penetrance appears to be high. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy (summary by Jung et al., 2007). The cooccurrence of McLeod syndrome and chronic granulomatous disease (CGD; 306400) results from a contiguous gene deletion (Francke et al., 1985). Clinical Features The McLeod phenotype was described by Allen et al. (1961) in a man of that surname. His red cells showed unaccountably weak reactivity to Kell antisera. In 1970, his red cells were noted to be acanthocytic in the absence of abetalipoproteinemia. The precursor missing in McLeod's red cells is called Kx. The X-linked locus determining this substance is called Xk. McLeod had a compensated hemolytic state (Wimer et al., 1976). He did not have CGD. Evidence for X-linkage of Xk was provided by mosaicism in females for both acanthocytosis and red cell Kx. The observations showed that some blood group antigenic substances are important to both structure and function of cell membranes. Jung et al. (2007) stated that Hugh McLeod, the original propositus, died at the age of 69 after developing all major McLeod syndrome manifestations. Symmans et al. (1979) described the second example of the McLeod phenotype in the absence of CGD and the first example of a rare blood group being recognized because of a morphologic abnormality of red cells. Heterozygous females showed mosaicism with a normal and an acanthocytic red cell population. Thus, lyonization of this locus occurs even though nonlyonization holds for the Xg (314700) and ichthyosis (steroid sulfatase) loci (308100) which are in the same small segment of Xp. All cases of X-linked CGD that had been studied had Kx-negative leukocytes (Marsh, 1979). At least two Xg:XK recombinants are known (Tippett, 1981). Danek et al. (2001) remarked that, like other erythrocyte phenotypes, the peculiar pattern of weakly expressed Kell antigens received its name from the propositus. Acanthocytosis was noted much later (Wimer et al., 1977). The diagnosis of the McLeod phenotype in a boy with chronic anemia from a large New Zealand family led to the recognition of features such as hemolysis, hepatomegaly, and splenomegaly (Symmans et al., 1979) and proved the previous assumption of X-linked inheritance. It was Marsh et al. (1981) who recognized muscle involvement and proposed the designation 'McLeod syndrome.' Schwartz et al. (1982) reported areflexia and chorea in the New Zealand family. Faillace et al. (1982) noted the presence of McLeod red cells in a patient with amyotrophic chorea and acanthocytosis. Densen et al. (1981) reported a highly informative family in which 4 of 8 brothers had CGD by clinical history and tests of neutrophil function. All 4 had Kx-negative neutrophils. The remaining 4 were in good health and had normal nitroblue tetrazolium reduction tests. However, 1 of these latter 4 had Kx-negative neutrophils that functioned normally. The findings were interpreted as indicating that closely linked but distinct genes code for CGD and Kx. In addition, close linkage of the XK and Xg loci was demonstrated; no recombinant was found in this sibship. Swash et al. (1983) studied 2 healthy males with the McLeod syndrome. Both had raised creatine kinase levels, with myopathic EMG changes and 'active myopathy' changes on muscle biopsy. Malandrini et al. (1994) described 2 brothers and their maternal uncle with 'atypical' McLeod syndrome presenting with a late-onset choreic syndrome mimicking Huntington disease. The proband also suffered from severe dilated cardiomyopathy and showed slight neuromuscular involvement. Acanthocytosis and weak antigenicity of the Kell blood antigen system were present in combination with prominent neurologic involvement. Danek et al. (2001) analyzed the mutations and clinical findings of 22 men, aged 27 to 72 years, with McLeod neuroacanthocytosis. All of the patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as indicated by the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features developed with age, mainly after the fourth decade. The resemblance of McLeod syndrome to Huntington disease and to autosomal recessive chorea-acanthocytosis (200150) suggested that the corresponding proteins--XK, huntingtin (613004), and chorein (605978)--may belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia. Jung et al. (2007) remarked that patients with McLeod syndrome usually show a slow progression of disease, with a mean onset between 30 and 40 years of age. A review of the literature found that disease duration ranged from 7 to 51 years, and mean age at death was 53 years, ranging from 31 to 69 years. Cardiovascular events, epileptic seizures, and aspiration pneumonia might be the major causes of death in older McLeod patients. Mapping In a patient with CGD and McLeod syndrome, Frey et al. (1988) demonstrated a deletion of the entire CGD gene. They concluded that the CGD and XK loci are physically close in the Xp21 region and are proximal to DMD (300377). Bertelson et al. (1988) studied patients with the McLeod phenotype with or without CGD or DMD. Comparison of the cloned segments absent from 2 cousins with only the McLeod phenotype with the cloned segments absent from 2 DMD boys and a CGD/McLeod patient led to submapping of various cloned DNA segments within the Xp21 region. The results placed the locus for the McLeod phenotype within a 500-kb interval distal from the CGD locus and toward the DMD locus. Molecular Genetics Using nucleotide sequence analysis of the XK gene in 2 unrelated patients with McLeod syndrome, Ho et al. (1994) demonstrated point mutations at invariant residues of 5-prime and 3-prime donor sites (e.g., 314850.0001). Danek et al. (2001) demonstrated that the original propositus carried a 13-bp deletion in the XK gene (314850.0006). INHERITANCE \- X-linked CARDIOVASCULAR Heart \- Dilated cardiomyopathy (in 60% of patients) \- Atrial fibrillation ABDOMEN Liver \- Hepatosplenomegaly (in some patients) Spleen \- Hepatosplenomegaly (in some patients) MUSCLE, SOFT TISSUES \- Muscle weakness or atrophy (in 50% of patients) \- Myopathy, slowly progressive \- Rhabdomyolysis (rare) NEUROLOGIC Central Nervous System \- Choreatic movement disorder (in 30% of patients) \- Facial dyskinesia \- Dysarthria \- Seizures (in 20-40% of patients) \- Subcortical cognitive impairment (seen in 50% of patients with neuromuscular manifestations) Peripheral Nervous System \- Absent deep tendon reflexes \- Sensory-motor axonal neuropathy Behavioral Psychiatric Manifestations \- Psychiatric abnormalities (in 20% of patients) \- Personality disorder \- Anxiety \- Depression \- Obsessive-compulsive disorder HEMATOLOGY \- Absence of Kx red blood cell antigen \- Weak expression of Kell antigen \- Acanthocytosis \- Hemolysis, compensated IMMUNOLOGY \- Granuloma formation (in some patients) \- Recurrent bacterial and fungal infections (in some patients) LABORATORY ABNORMALITIES \- Elevated serum creatine levels MISCELLANEOUS \- Inter- and intrafamilial variability \- Mean age of onset between 30-40 years \- Disease duration ranged from 7-51 years \- Female carriers manifesting the McLeod phenotype have been reported MOLECULAR BASIS \- Caused by mutation in the Kell blood group protein gene (XK, 314850.0001 ) ▲ 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	MCLEOD SYNDROME	c0398568	27,386	omim	https://www.omim.org/entry/300842	2019-09-22T16:19:32	{"mesh": ["C564038"], "omim": ["300842"], "orphanet": ["59306"], "synonyms": ["Alternative titles", "MCLEOD PHENOTYPE", "NEUROACANTHOCYTOSIS, MCLEOD TYPE"], "genereviews": ["NBK1354"]}
A number sign (#) is used with this entry because of evidence that Hennekam lymphangiectasia-lymphedema syndrome-3 (HKLLS3) is caused by homozygous or compound heterozygous mutation in the ADAMTS3 gene (605011) on chromosome 4q13. Description Hennekam lymphangiectasia-lymphedema syndrome-3 (HKKLLS3) is characterized by widespread congenital edema that is more severe in more dependent areas of the body. Associated features include facial dysmorphism and protein-losing enteropathy of variable severity (Brouillard et al., 2017). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510). Clinical Features Brouillard et al. (2017) reported a sister and brother of western European origin born with congenital lymphedema of the lower extremities. Both pregnancies were complicated by polyhydramnios, and the boy also had hydroceles at birth. The lymphedema was widespread, but was more severe in more dependent areas of the body, and was worse in the left leg than the right in both children. Facial edema was minimal; dysmorphic features included flat face, synophrys, hypertelorism, strabismus, upslanting palpebral fissures, and anteverted peaked nostrils. Both had protein-losing enteropathy, for which the girl required gastrostomy tube feedings; she also had growth hormone (139250) deficiency, which responded well to replacement therapy. An unusual feature of the disorder was the nearly complete resolution of lymphedema during febrile illnesses. Neither patient exhibited developmental delay, hepatosplenomegaly, or major skeletal defects. Scheuerle et al. (2018) reported a male born at 32 weeks' gestation following prenatal identification of hydrops fetalis. The parents denied consanguinity, but were from the same area of Mexico. A previous pregnancy had resulted in a stillbirth due to fetal hydrops. At birth, the infant was large for gestational age and hydropic, with dysmorphic facial features, a small omphalocele, and pitting edema. The infant had wide-set eyes with short palpebral fissures and epicanthal folds, low-set ears, a small nose, long philtrum, prominent upper lip, micrognathia, widely spaced nipples, and tetramelic brachydactyly. Umbilical hernia was also present. An echocardiogram showed a small secundum atrial septal defect, a patent ductus arteriosus, and a patent foramen ovale. At age 17 weeks, the infant had respiratory decompensation and died after removal of support. Autopsy showed diffuse lymphatic malformation with tortuous thick-walled lymphatic channels in the bowel mesentery as well as dilated hilar lymphatics of the kidney. Molecular Genetics By whole-exome sequencing in a nonconsanguineous family of western European origin in which 2 sibs had congenital lymphedema, Brouillard et al. (2017) identified compound heterozygosity for missense mutations in the ADAMTS3 gene (L168P, 605011.0001; I291T, 605011.0002). Their parents were each heterozygous for one of the mutations, neither of which was found in an internal cohort of 645 sequenced samples. The I291T variant was not present in public variant databases, whereas the L168P variant was found once in the gnomAD database. In a male infant with Hennekam lymphangiectasia-lymphedema syndrome-3, Scheuerle et al. (2018) identified a homozygous nonsense mutation in the ADAMTS3 gene (R94X; 605011.0003). The mutation, which was found by whole-exome sequencing, was present in heterozygosity in his parents. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial edema, mild \- Flat face Eyes \- Hypertelorism \- Upslanting palpebral fissures \- Strabismus or pseudostrabismus Nose \- Anteverted nares \- Peaked nares ABDOMEN External Features \- Edema \- Stellate-shaped umbilicus (in 1 patient) Gastrointestinal \- Protein-losing enteropathy GENITOURINARY External Genitalia (Male) \- Hydrocele External Genitalia (Female) \- Edema MUSCLE, SOFT TISSUES \- Lymphedema, predominantly of lower extremities PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Based on report of a brother and sister western European origin (last curated October 2018) \- Lymphedema of lower extremities present at birth \- Marked improvement of lymphedema with fever MOLECULAR BASIS \- Caused by mutation in the a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, 3 gene (ADAMTS3, 605011.0001 ) ▲ 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	HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3	c0340834	27,387	omim	https://www.omim.org/entry/618154	2019-09-22T15:43:21	{"mesh": ["C537255"], "omim": ["618154"], "orphanet": ["2136"]}
## Clinical Features Sarralde et al. (1998) described 4 brothers and a sister from a sibship of 9 who had a seemingly distinctive syndrome with prenatal growth retardation, pelvic hypoplasia, and arthrogrypotic changes in the lower limbs. The propositus was approximately 150 cm tall at the age of 16 years. The parents were not known to be related; however, they and the 4 grandparents were born in the same small village of western Mexico. The authors suggested that the disorder most closely resembled that reported by Ray et al. (1986). Inheritance Sarralde et al. (1998) suggested that the inheritance pattern of the disorder in this Mexcian family was autosomal recessive. [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	PELVIC HYPOPLASIA WITH LOWER-LIMB ARTHROGRYPOSIS	c1865294	27,388	omim	https://www.omim.org/entry/602484	2019-09-22T16:13:39	{"mesh": ["C535548"], "omim": ["602484"], "orphanet": ["2840"]}
Rare generic disorder Weill–Marchesani syndrome Other namesSpherophakia-brachymorphia syndrome, congenital mesodermal dystrophy, GEMSS syndrome A six-year-old female with Weill-Marchesani syndrome, which has caused a dislocated lens. SpecialtyOphthalmology, rheumatology, medical genetics Weill–Marchesani syndrome is a rare genetic disorder characterized by short stature; an unusually short, broad head (brachycephaly) and other facial abnormalities; hand defects, including unusually short fingers (brachydactyly); and distinctive eye (ocular) abnormalities. It was named after ophthalmologists Georges Weill (1866–1952) and Oswald Marchesani (1900–1952) who first described it in 1932 and 1939, respectively. The eye manifestations typically include unusually small, round lenses of the eyes (spherophakia), which may be prone to dislocating (ectopia lentis), as well as other ocular defects. Due to such abnormalities, affected individuals may have varying degrees of visual impairment, ranging from nearsightedness myopia to blindness. Researchers suggest that Weill–Marchesani syndrome may have autosomal recessive or autosomal dominant inheritance.[1] ## Contents * 1 Diagnosis * 2 Treatment * 3 Prognosis * 4 See also * 5 References * 6 External links ## Diagnosis[edit] A lens dislocation caused by Weill-Marchesani syndrome Diagnosis is made when several characteristic clinical signs are observed. There is no single test to confirm the presence of Weill–Marchesani syndrome. Exploring family history or examining other family members may prove helpful in confirming this diagnosis.[citation needed] ## Treatment[edit] Eye surgery has been documented to help those with ocular diseases, such as some forms of glaucoma.[2] ## Prognosis[edit] However, long term medical management of glaucoma has not proven to be successful for patients with Weill–Marchesani syndrome. Physical therapy and orthopedic treatments are generally prescribed for problems stemming from mobility from this connective tissue disorder. However, this disorder has no cure, and generally, treatments are given to improve quality of life.[3] ## See also[edit] * ADAMTS10 * ADAMTS17 * FBN1 * LTBP2 ## References[edit] 1. ^ "Weill Marchesani Syndrome". WebMD, LLC. Retrieved 24 December 2012. 2. ^ Harasymowycz, P; Wilson, R (2005). "Surgical treatment of advanced chronic angle closure glaucoma in Weill-Marchesani syndrome". J Pediatr Ophthalmol Strabismus. 41 (5): 295–9. PMID 15478742. 15478742.. 3. ^ Anderson, Charles; Anderson, N (2002). NORD Guide to Rare Disorders. USA: Lippincott Williams & Wilkins. pp. 266–267. ISBN 0-7817-3063-5. ## External links[edit] Classification D * ICD-9-CM: 759.89 * OMIM: 608328 277600 * MeSH: D056846 * DiseasesDB: 29897 External resources * Orphanet: 3449 * GeneReviews/NCBI/NIH/UW entry on Weill-Marchesani Syndrome * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins [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	Weill–Marchesani syndrome	c1869114	27,389	wikipedia	https://en.wikipedia.org/wiki/Weill%E2%80%93Marchesani_syndrome	2021-01-18T19:03:13	{"gard": ["4936"], "mesh": ["D056846"], "umls": ["C1869114"], "orphanet": ["3449"], "wikidata": ["Q3961695"]}
X-linked recessive ocular albinism (XLOA) is a rare disorder characterized by ocular hypopigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity in males. ## Epidemiology The estimated birth prevalence is from 1/60,000 to 1/150,000 live male births. ## Clinical description Nystagmus, sometimes associated with head nodding, usually develops in affected males within the first 3 months of life. It can diminish with time but rarely completely disappears. Best-corrected visual acuity is usually between 20/40 and 20/200, and often improves during childhood. Most patients have photodysphoria, strabismus and absent or reduced stereoacuity. Ocular findings include iris translucency, foveal hypoplasia, hypopigmentation of the fundus and excessive crossing of the nerves from the eye to the brain. Some males have irregular hypopigmented spots on the extremities, but they escape clinical notice. Carrier women, in the vast majority of cases, are asymptomatic. XLOA is less severe in those with dark constitutive skin pigmentation than those who are more lightly pigmented. ## Etiology XLOA is caused by a mutation in the G-protein coupled receptor 143 GPR143 gene located at Xp22.3 that encodes for a membrane glycoprotein found in melanosomes. The few cases where females displayed the same phenotypes as males are thought to have been due to either a homozygous mutation in GPR143, partial monosomy of the X chromosome or X-chromosome inactivation. ## Diagnostic methods Diagnosis is based on the presence of characteristic ocular findings and molecular genetic testing. A family history consistent with X-linked inheritance provides further evidence of XLOA. A GPR143 mutation is found in 90% of affected males. Melanin macroglobules (macromelanosomes) are usually found on skin biopsy but are not pathognomonic. Female obligate carriers are identified by finding patchy mottling or streaking of pigment in the midperipheral retina (pigmentary mosaicism), representing random X inactivation. ## Differential diagnosis Differential diagnoses include various types of oculocutaneous albinism (OCA), blue cone monochromatism, congenital stationary night blindness, ocular albinism with sensorineural deafness, cone dystrophy with supernormal rod response, Leber congenital amaurosis, complete and incomplete achromatopsia, X-linked congenital nystagmus (see these terms), and autosomal dominant infantile nystagmus syndrome. ## Antenatal diagnosis Prenatal testing can be performed when women are known carriers of the GPR143 mutation, using chorionic villus sampling or amniocentesis. Preimplantation genetic diagnosis may be available. ## Genetic counseling XLOA is inherited in an X-linked recessive manner so genetic counseling is possible. Affected males do not transmit the disease causing mutation to their sons but all of their daughters become carriers. Female carriers have a 50% risk of transmitting the mutation to their offspring, whether male or female; however, only sons with the mutation will display the disease. Carrier testing can be offered to at-risk individuals. ## Management and treatment Annual ophthalmologic examinations are recommended for patients under the age of 16, and after that every 2-3 years. Treatment consists of visual correction with eyeglasses or contact lenses. Sunglasses, photochromic lenses or special filter glasses can help to relieve photodysphoria. Extraocular muscle surgery can be performed to restore alignment and/or improve a head posture that is compensatory for nystagmus. Visual aids, changing electronic font size, and special education for the visually impaired may be needed. Patients should wear hats/caps, clothing, and sunscreen on sun-exposed skin to prevent burning and skin cancer. ## Prognosis XLOA is not life threatening. The reduced visual acuity and the social consequences of albinism can however have an impact on a patient's daily life. [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 recessive ocular albinism	c0342684	27,390	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=54	2021-01-23T18:33:32	{"gard": ["8471"], "mesh": ["C537863"], "omim": ["300500"], "umls": ["C0342684"], "icd-10": ["E70.3"], "synonyms": ["OA1", "Ocular albinism type 1", "Ocular albinism, Nettleship-Falls type", "XLOA"]}
Cornea plana 2 SpecialtyMedical genetics Cornea plana 2 (CNA2) is an extremely rare congenital hereditary deformity of the eye surface, leading to severe decrease in corneal curvature. There is evidence that cornea plana 2 is caused by mutations in KERA gene encoding keratocan.[1] ## See also[edit] * Cornea plana 1 ## References[edit] 1. ^ Pellegata NS, Dieguez-Lucena JL, Joensuu T, Lau S, Montgomery KT, Krahe R, Kivelä T, Kucherlapati R, Forsius H, de la Chapelle A (May 2000). "Mutations in KERA, encoding keratocan, cause cornea plana". Nat. Genet. 25 (1): 91–5. doi:10.1038/75664. PMID 10802664. ## External links[edit] Classification D * ICD-10: Q13.4 * OMIM: 217300 External resources * Orphanet: 53691 * Congenital Clouding of the Cornea \- eMedicine; by Noah S Scheinfeld, MD, JD, FAAD and Benjamin D Freilich, MD, FACS * 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 Congenital malformations and deformations of eyes Adnexa Eyelid * Ptosis * Ectropion * Entropion * Distichia * Blepharophimosis * Ablepharon * Marcus Gunn phenomenon Lacrimal apparatus * Congenital lacrimal duct obstruction Globe Entire eye * Anophthalmia (Cystic eyeball, Cryptophthalmos) * Microphthalmia Lens * Ectopia lentis * Aphakia Iris * Aniridia Anterior segment * Axenfeld–Rieger syndrome Cornea * Keratoglobus * Megalocornea Other * Buphthalmos * Coloboma (Coloboma of optic nerve) * Hydrophthalmos * Norrie 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	Cornea plana 2	c1857574	27,391	wikipedia	https://en.wikipedia.org/wiki/Cornea_plana_2	2021-01-18T18:50:10	{"mesh": ["C565677"], "icd-10": ["Q13.4"], "orphanet": ["53691"], "synonyms": [], "wikidata": ["Q4365211"]}
Juvenile nephronophthisis Juvenile nephronophthisis is inherited via an autosomal recessive manner Juvenile nephronophthisis is the juvenile form of nephronophthisis that causes end stage kidney disease around the age of 13; infantile nephronophthisis and adolescent nephronophthisis cause ESKD around the ages of 1 and 19, respectively. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 5 Epidemiology * 6 References * 7 External links ## Signs and symptoms[edit] Typically, the signs and symptoms of juvenile nephronophthisis are limited to the kidneys. They include polyuria, polydipsia, weakness, and fatigue.[1] Anemia, growth retardation, no hypertension. Proteinuria and hematuria are usually absent. Polyuria is resistant to vasopressin. When other organ systems are affected, symptoms can include situs inversus, heart abnormalities, and liver fibrosis. Juvenile nephronophthisis can also be associated with other rare disorders, including Senior–Løken syndrome and Joubert syndrome.[1] ## Pathophysiology[edit] Juvenile nephronophthisis causes fibrosis and scarring of the kidneys, which accounts for the symptoms observed. The kidneys also often have corticomedullary cysts.[1] * Inability to conserve sodium because of defect of tubules leading to polyuria and polydipsia. * Anemia is attributed to a deficiency of erythropoietin production by failing kidneys. * Growth retardation, malaise and pallor are secondary to anemia. * No hypertension as nephronophthisis is a salt-losing enteropathy. ## Diagnosis[edit] Ultrasonography shows bilateral small kidneys with loss of corticomedullary junction and multiple cysts only in the medulla. Cysts may only be seen if they are large enough, they are rarely visible early in disease.[citation needed] ### Differential diagnosis[edit] Patients with medullary cystic disease present with similar features as juvenile nephronophthisis but they can be differentiated by: 1. Absence of growth retardation. 2. Age of presentation is third or fourth decade. 3. Hypertension may occur (in JN, hypertension is not seen). In polycystic kidney disease, there is bilateral enlargement of kidneys (small kidneys in JN). ## Treatment[edit] This section is empty. You can help by adding to it. (July 2015) ## Epidemiology[edit] It is the most common genetic cause of end stage kidney disease (kidney failure) in childhood and adolescence.[citation needed] ## References[edit] 1. ^ a b c "Nephronophthisis". Genetics Home Reference. Retrieved 2015-07-25. ## External links[edit] Classification D * ICD-10: Q61.5 * OMIM: 615382 External resources * Orphanet: 93592 [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	Juvenile nephronophthisis	c1855681	27,392	wikipedia	https://en.wikipedia.org/wiki/Juvenile_nephronophthisis	2021-01-18T19:10:30	{"orphanet": ["93592"], "wikidata": ["Q24975508"]}
A rare, aggressive, primary cutaneous B-cell lymphoma characterized by rapidly progressive, red to bluish, often ulcerating, nodular tumors predominantly involving the lower legs. Histology shows sheets of centroblasts and immunoblasts that spare the epidermis, but infiltrate the dermis and subcutaneous tissues, and often disseminate extracutaneously. The neoplastic cells typically express CD20, CD79a, Bcl-2, MUM-1, and FOXP1, but are negative for CD10. [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	Primary cutaneous diffuse large B-cell lymphoma, leg type	c1709656	27,393	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178544	2021-01-23T17:20:14	{"icd-10": ["C83.3"], "synonyms": ["PCDLBCL,LT"]}
Form of diabetes mellitus Type 1 diabetes Other namesDiabetes mellitus type 1, insulin-dependent diabetes,[1] juvenile diabetes[2] A blue circle, the symbol for diabetes.[3] Pronunciation * /daɪəbiːtəs/ SpecialtyEndocrinology SymptomsFrequent urination, increased thirst, increased hunger, weight loss[4] ComplicationsDiabetic ketoacidosis, nonketotic hyperosmolar coma, poor healing, cardiovascular disease, damage to the eyes[2][4][5] Usual onsetRelatively short period of time[1] DurationLong term[4] CausesBody does not produce enough insulin[4] Risk factorsFamily history, celiac disease[5][6] Diagnostic methodBlood sugar, A1C[5][7] PreventionUnknown[4] TreatmentInsulin, diabetic diet, exercise[1][2] Frequency~7.5% of diabetes cases[8] Type 1 diabetes (T1D), previously known as juvenile diabetes, is a form of diabetes in which very little or no insulin is produced by the islets of Langerhans in the pancreas.[4] Insulin is a hormone required for the body to use blood sugar.[2] Before treatment this results in high blood sugar levels in the body.[1] The classic symptoms are frequent urination, increased thirst, increased hunger, and weight loss.[4][9] Additional symptoms may include blurry vision, tiredness, and poor wound healing.[2] Symptoms typically develop over a short period of time, often a matter of weeks.[1] The cause of type 1 diabetes is unknown,[4] but it is believed to involve a combination of genetic and environmental factors.[1] Risk factors include having a family member with the condition.[5] The underlying mechanism involves an autoimmune destruction of the insulin producing beta cells in the pancreas.[2] Diabetes is diagnosed by testing the level of sugar or glycated hemoglobin (HbA1C) in the blood.[5][7] Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies.[5] There is no known way to prevent type 1 diabetes.[4] Treatment with insulin is required for survival.[1] Insulin therapy is usually given by injection just under the skin but can also be delivered by an insulin pump.[10] A diabetic diet and exercise are important parts of management.[2] If left untreated, diabetes can cause many complications.[4] Complications of relatively rapid onset include diabetic ketoacidosis and nonketotic hyperosmolar coma.[5] Long-term complications include heart disease, stroke, kidney failure, foot ulcers and damage to the eyes.[4] Furthermore, complications may arise from low blood sugar caused by excessive dosing of insulin.[5] Type 1 diabetes makes up an estimated 5–10% of all diabetes cases.[8] The number of people affected globally is unknown, although it is estimated that about 80,000 children develop the disease each year.[5] Within the United States the number of people affected is estimated at one to three million.[5][11] Rates of disease vary widely, with approximately 1 new case per 100,000 per year in East Asia and Latin America and around 30 new cases per 100,000 per year in Scandinavia and Kuwait.[12][13] It typically begins in children and young adults.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Genetics * 2.2 Environmental * 2.2.1 Chemicals and drugs * 3 Pathophysiology * 3.1 Alpha cell dysfunction * 3.1.1 Hyperglucagonemia * 3.1.2 Hypoglycemic glucagon impairment * 4 Diagnosis * 4.1 Autoantibodies * 5 Prevention * 5.1 Immunosuppressive drugs * 5.2 Diet * 6 Management * 6.1 Lifestyle * 6.2 Insulin * 6.3 Pancreas transplantation * 6.4 Islet cell transplantation * 7 Complications * 7.1 Urinary tract infection * 7.2 Sexual dysfunction * 7.2.1 Males * 7.2.2 Females * 8 Epidemiology * 9 History * 10 Society and culture * 11 Research * 11.1 Diet * 11.1.1 Virus * 11.2 Gene therapy * 11.3 Stem cells * 11.4 Vaccine * 12 References * 13 External links ## Signs and symptoms[edit] Overview of the most significant symptoms of diabetes A posterior subcapsular cataract is an uncommon symptom in those with type 1 DM[14] The classic symptoms of type 1 diabetes include: polyuria (increased urination), polydipsia (increased thirst), dry mouth, polyphagia (increased hunger), fatigue, and weight loss.[4] Type 1 diabetes is often diagnosed when diabetic ketoacidosis occurs. The signs and symptoms of diabetic ketoacidosis include dry skin, rapid deep breathing, drowsiness, increased thirst, frequent urination, abdominal pain, and vomiting.[15] Some people with type 1 diabetes experience dramatic and recurrent swings in glucose levels, often occurring for no apparent reason; this is called "unstable diabetes", "labile diabetes" or "brittle diabetes".[16] The results of such swings can be irregular and unpredictable hyperglycemias, sometimes involving ketoacidosis, and sometimes serious hypoglycemias. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics.[16] Type 1 diabetes is associated with alopecia areata (AA).[17]:39–54 Type 1 diabetes is also more common in the family members of people with AA.[17]:103–133 ## Cause[edit] The cause of type 1 diabetes is not yet known.[4] A number of explanatory theories have been put forward, and the cause may be one or more of the following: genetic susceptibility, a diabetogenic trigger, and exposure to an antigen.[18] ### Genetics[edit] Main article: Genetic causes of type 1 diabetes Type 1 diabetes is a disease that involves many genes. The risk of a child developing type 1 diabetes is about 5% if the father has it, about 8% if a sibling has it, and about 3% if the mother has it.[19] If one identical twin is affected there is about a 40% to 50% chance the other will be too.[20][21][22] Some studies of heritability have estimated it at 80 to 86%.[23][24] More than 50 genes are associated with type 1 diabetes. Depending on locus or combination of loci, they can be dominant, recessive, or somewhere in between. The strongest gene, IDDM1, is located in the MHC Class II region on chromosome 6, at staining region 6p21. Certain variants of this gene increase the risk for decreased histocompatibility characteristic of type 1. Such variants include DRB1 0401, DRB1 0402, DRB1 0405, DQA 0301, DQB1 0302 and DQB1 0201, which are common in North Americans of European ancestry and in Europeans.[25] Some variants also appear to be protective.[25] ### Environmental[edit] There is on the order of a 10-fold difference in occurrence among Caucasians living in different areas of Europe.[18] Environmental triggers and protective factors under research include dietary agents such as proteins in gluten,[26] time of weaning, gut microbiota,[27] viral infections,[28][29] and bacterial infections like paratuberculosis.[30] #### Chemicals and drugs[edit] Some chemicals and drugs selectively destroy pancreatic cells. Pyrinuron (Vacor), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1 diabetes after accidental poisoning.[31] Pyrinuron was withdrawn from the U.S. market in 1979 and it is not approved by the Environmental Protection Agency for use in the U.S.[32] Streptozotocin (Zanosar), an antineoplastic agent, is selectively toxic to the beta cells of the pancreatic islets. It is used in research for inducing type 1 diabetes on rodents[33] and for treating metastatic cancer of the pancreatic islet cells in patients whose cancer cannot be removed by surgery.[34] Other pancreatic problems, including trauma, pancreatitis, or tumors (either malignant or benign) can also lead to loss of insulin production. Monoclonal antibodies used for the treatment of cancer (checkpoint inhibitors inhibiting PD-1 and PD-L1), especially nivolumab and pembrolizumab have been reported to occasionally induce autoimmune diabetes.[35] ## Pathophysiology[edit] The pathophysiology in diabetes type 1 is a destruction of beta cells in the pancreas, regardless of which risk factors or causative entities have been present. Individual risk factors can have separate pathophysiological processes to, in turn, cause this beta cell destruction. Still, a process that appears to be common to most risk factors is a type IV hypersensitivity autoimmune response towards beta cells, involving an expansion of autoreactive CD4+ T helper cells and CD8+ T cells, autoantibody-producing B cells and activation of the innate immune system.[25][36] After starting treatment with insulin a person's own insulin levels may temporarily improve.[37] This is believed to be due to altered immunity and is known as the "honeymoon phase".[37] ### Alpha cell dysfunction[edit] Onset of autoimmune diabetes is accompanied by impaired ability to regulate the hormone glucagon,[38] which acts in antagonism with insulin to regulate blood sugar and metabolism. While the causes and mechanisms are still being studied and hypotheses abound, what is clear and agreed upon is that progressive beta cell destruction leads to dysfunction in the neighboring alpha cells which secrete glucagon, exacerbating excursions away from euglycemia in both directions; overproduction of glucagon after meals causes sharper hyperglycemia, and failure to stimulate glucagon upon incipient hypoglycemia prevents a glucagon-mediated rescue of glucose levels.[39] #### Hyperglucagonemia[edit] Onset of type 1 diabetes is followed by an increase in glucagon secretion after meals. Increases have been measured up to 37% during the first year of diagnosis, while c-peptide levels (indicative of islet-derived insulin), decline by up to 45%.[40] Insulin production will continue to fall as the immune system follows its course of progressive beta cell destruction, and islet-derived insulin will continue to be replaced by therapeutic exogenous insulin. Simultaneously, there is measurable alpha cell hypertrophy and hyperplasia in the early overt stage of the disease, leading to expanded alpha cell mass. This, together with failing beta cell insulin secretion, begins to account for rising glucagon levels that contribute to hyperglycemia.[39] Some researchers believe glucagon dysregulation to be the primary cause of early stage hyperglycemia.[41] Leading hypotheses for the cause of postprandial hyperglucagonemia suggest that exogenous insulin therapy is inadequate to replace the lost intraislet signalling to alpha cells previously mediated by beta cell-derived pulsatile insulin secretion.[42][43] Under this working hypothesis intensive insulin therapy has attempted to mimic natural insulin secretion profiles in exogenous insulin infusion therapies.[44] #### Hypoglycemic glucagon impairment[edit] Hypoglycemia in type 1 diabetics is often a result of over-administered insulin therapy, though being in a fasting state, exercising without proper adjustment of insulin, sleep, and alcohol can also contribute.[45] The normal counter regulatory responses to hypoglycemia are impaired in type 1 diabetics. Glucagon secretion is normally increased upon falling glucose levels, but normal glucagon response to hypoglycemia is blunted when measured in type 1 diabetics and compared to healthy individuals experiencing an equal insulin-induced hypoglycemic trigger.[46][47] Beta cell glucose sensing and subsequent suppression of administered insulin secretion is absent, leading to islet hyperinsulinemia which inhibits glucagon release.[46][48] Autonomic inputs to alpha cells are much more important for glucagon stimulation in the moderate to severe ranges of hypoglycemia, yet the autonomic response is blunted in a number of ways. Recurrent hypoglycemia leads to metabolic adjustments in the glucose sensing areas of the brain, shifting the threshold for counter regulatory activation of the sympathetic nervous system to lower glucose concentration.[48] This is known as hypoglycemic unawareness. Subsequent hypoglycemia is met with impairment in sending of counter regulatory signals to the islets and adrenal cortex. This accounts for the lack of glucagon stimulation and epinephrine release that would normally stimulate and enhance glucose release and production from the liver, rescuing the diabetic from severe hypoglycemia, coma, and death. Numerous hypotheses have been produced in the search for a cellular mechanism of hypoglycemic unawareness, and a consensus has yet to be reached.[49] The major hypotheses are summarized in the following table: [50][48][49] Mechanisms of hypoglycemic unawareness Glycogen supercompensation Increased glycogen stores in astrocytes might contribute supplementary glycosyl units for metabolism, counteracting the central nervous system perception of hypoglycemia. Enhanced glucose metabolism Altered glucose transport and enhanced metabolic efficiency upon recurring hypoglycemia relieves oxidative stress that would activate sympathetic response. Alternative fuel hypothesis Decreased reliance on glucose, supplementation of lactate from astrocytes, or ketones meet metabolic demands and reduce stress to brain. Brain neuronal communication Hypothalamic inhibitory GABA normally decreases during hypoglycemia, disinhibiting signals for sympathetic tone. Recurrent episodes of hypoglycemia result in increased basal GABA which fails to decrease normally during subsequent hypoglycemia. Inhibitory tone remains and sympathetic tone is not increased. In addition, autoimmune diabetes is characterized by a loss of islet specific sympathetic innervation.[51] This loss constitutes an 80-90% reduction of islet sympathetic nerve endings, happens early in the progression of the disease, and is persistent though the life of the patient.[52] It is linked to the autoimmune aspect of type 1 diabetics and fails to occur in type 2 diabetics. Early in the autoimmune event, the axon pruning is activated in islet sympathetic nerves. Increased BDNF and ROS that result from insulitis and beta cell death stimulate the p75 neurotrophin receptor (p75NTR), which acts to prune off axons. Axons are normally protected from pruning by activation of tropomyosin receptor kinase A (Trk A) receptors by NGF, which in islets is primarily produced by beta cells. Progressive autoimmune beta cell destruction therefore causes both the activation of pruning factors and the loss of protective factors to the islet sympathetic nerves. This unique form of neuropathy is a hallmark of type 1 diabetes, and plays a part in the loss of glucagon rescue of severe hypoglycemia.[51] ## Diagnosis[edit] See also: Glycated hemoglobin and Glucose tolerance test WHO diabetes diagnostic criteria[53][54] edit Condition 2-hour glucose Fasting glucose HbA1c Unit mmol/L mg/dL mmol/L mg/dL mmol/mol DCCT % Normal < 7.8 < 140 < 6.1 < 110 < 42 < 6.0 Impaired fasting glycaemia < 7.8 < 140 6.1–7.0 110–125 42–46 6.0–6.4 Impaired glucose tolerance ≥ 7.8 ≥ 140 < 7.0 < 126 42–46 6.0–6.4 Diabetes mellitus ≥ 11.1 ≥ 200 ≥ 7.0 ≥ 126 ≥ 48 ≥ 6.5 Diabetes is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:[55] * Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dL). * Plasma glucose at or above 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test. * Symptoms of hyperglycemia and casual plasma glucose at or above 11.1 mmol/L (200 mg/dL). * Glycated hemoglobin (hemoglobin A1C) at or above 48 mmol/mol (≥ 6.5 DCCT %). (This criterion was recommended by the American Diabetes Association in 2010, although it has yet to be adopted by the WHO.)[56] About a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis (a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids) by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening, detection of hyperglycemia during other medical investigations, and secondary symptoms such as vision changes or unexplained fatigue. Diabetes is often detected when a person suffers a problem that may be caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia (low blood sugar).[citation needed] A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test.[57] According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes.[citation needed] In type 1, pancreatic beta cells in the islets of Langerhans are destroyed, decreasing endogenous insulin production. This distinguishes type 1's origin from type 2. Type 2 diabetes is characterized by insulin resistance, while type 1 diabetes is characterized by insulin deficiency, generally without insulin resistance. Another hallmark of type 1 diabetes is islet autoreactivity, which is generally measured by the presence of autoantibodies directed towards the beta cells.[citation needed] ### Autoantibodies[edit] The appearance of diabetes-related autoantibodies has been shown to be able to predict the appearance of diabetes type 1 before any hyperglycemia arises, the main ones being islet cell autoantibodies, insulin autoantibodies, autoantibodies targeting the 65-kDa isoform of glutamic acid decarboxylase (GAD), autoantibodies targeting the phosphatase-related IA-2 molecule, and zinc transporter autoantibodies (ZnT8).[18] By definition, the diagnosis of diabetes type 1 can be made first at the appearance of clinical symptoms and/or signs, but the emergence of autoantibodies may itself be termed "latent autoimmune diabetes". Not everyone with autoantibodies progresses to diabetes type 1, but the risk increases with the number of antibody types, with three to four antibody types giving a risk of progressing to diabetes type 1 of 60–100%.[18] The time interval from emergence of autoantibodies to clinically diagnosable diabetes can be a few months in infants and young children, but in some people it may take years – in some cases more than 10 years.[18] Islet cell autoantibodies are detected by conventional immunofluorescence, while the rest are measured with specific radiobinding assays.[18] ## Prevention[edit] Type 1 diabetes is not currently preventable.[58] Some researchers believe it might be prevented at the latent autoimmune stage, before it starts destroying beta cells.[25] ### Immunosuppressive drugs[edit] Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta cells (on the basis of reduced insulin usage), but its kidney toxicity and other side effects make it highly inappropriate for long-term use.[25] Anti-CD3 antibodies, including teplizumab and otelixizumab, had suggested evidence of preserving insulin production (as evidenced by sustained C-peptide production) in newly diagnosed type 1 diabetes patients.[25] A probable mechanism of this effect was believed to be preservation of regulatory T cells that suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens.[25] The duration of the effect is still unknown, however.[25] In 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy, potentially due to an insufficient dosing schedule.[59][60] An anti-CD20 antibody, rituximab, inhibits B cells and has been shown to provoke C-peptide responses three months after diagnosis of type 1 diabetes, but long-term effects of this have not been reported.[25] ### Diet[edit] Some research has suggested breastfeeding decreases the risk in later life[61][62] and early introduction of gluten-containing cereals in the diet increases the risk of developing islet cell autoantibodies;[63] various other nutritional risk factors are being studied, but no firm evidence has been found.[64] Giving children 2000 IU of vitamin D daily during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.[65] Children with antibodies to beta cell proteins (i.e. at early stages of an immune reaction to them) but no overt diabetes, and treated with niacinamide (vitamin B3), had less than half the diabetes onset incidence in a seven-year time span than did the general population, and an even lower incidence relative to those with antibodies as above, but who received no niacinamide.[66] People with type 1 diabetes and undiagnosed celiac disease have worse glycaemic control and a higher prevalence of nephropathy and retinopathy. Gluten-free diet, when performed strictly, improves diabetes symptoms and appears to have a protective effect against developing long-term complications. Nevertheless, dietary management of both these diseases is challenging and these patients have poor compliance of the diet.[67] ## Management[edit] Further information: Diabetes management Diabetes is often managed by a number of health care providers including a dietitian, nurse educator, eye doctor, endocrinologist, and podiatrist.[68] ### Lifestyle[edit] There is limited evidence for the usefulness of routine use of low-carbohydrate dieting for people with type 1 diabetes.[69] Although for certain individuals it may be feasible to follow a low-carbohydrate regime combined with carefully managed insulin dosing, this is hard to maintain and there are concerns about possible adverse health effects caused by the diet.[69] In general, people with type 1 diabetes are advised to follow an individualized eating plan rather than a pre-decided one.[69] There are camps for children to teach them how and when to use or monitor their insulin without parental help.[70] As psychological stress may have a negative effect on diabetes, a number of measures have been recommended including: exercising, taking up a new hobby, or joining a charity, among others.[71] ### Insulin[edit] Main article: Insulin therapy Injections of insulin – via subcutaneous injection using either a syringe or using an insulin pump – are necessary for those living with type 1 diabetes because it cannot be treated by diet and exercise alone.[72] Insulin dosage is adjusted taking into account food intake, blood glucose levels and physical activity. Untreated type 1 diabetes can commonly lead to diabetic ketoacidosis which can result in death.[73] Diabetic ketoacidosis can cause cerebral edema (accumulation of liquid in the brain). This is a life-threatening issue and children are at a higher risk for cerebral edema than adults, causing ketoacidosis to be the most common cause of death in pediatric diabetes.[74] Treatment of diabetes focuses on lowering blood sugar or glucose (BG) to the near normal range, approximately 80–140 mg/dL (4.4–7.8 mmol/L).[75] The ultimate goal of normalizing BG is to avoid long-term complications that affect the nervous system (e.g. peripheral neuropathy leading to pain and/or loss of feeling in the extremities), and the cardiovascular system (e.g. heart attacks, vision loss). This level of control over a prolonged period of time can be varied by a target HbA1c level of less than 7.5%.[5] There are four main types of insulin: rapid acting insulin, short-acting insulin, intermediate-acting insulin, and long-acting insulin. The rapid acting insulin is used as a bolus dosage. The action onsets in 15 minutes with peak actions in 30 to 90 minutes. Short acting insulin action onsets within 30 minutes with the peak action around 2 to 4 hours. Intermediate acting insulin action onsets within one to two hours with peak action of four to 10 hours. Long-acting insulin is usually given at the same time once per day.[76] The action onset is roughly 1 to 2 hours with a sustained action of up to 24 hours. Some insulins are biosynthetic products produced using genetic recombination techniques; formerly, cattle or pig insulins were used, and even sometimes insulin from fish.[77] People with type 1 diabetes always need to use insulin, but treatment can lead to low BG (hypoglycemia), i.e. BG less than 70 mg/dL (3.9 mmol/L). Hypoglycemia is a very common occurrence in people with diabetes, usually the result of a mismatch in the balance among insulin, food and physical activity. Symptoms include excess sweating, excessive hunger, fainting, fatigue, lightheadedness and shakiness.[78] Mild cases are self-treated by eating or drinking something high in sugar. Severe cases can lead to unconsciousness and are treated with intravenous glucose or injections with glucagon. Continuous glucose monitors can alert patients to the presence of dangerously high or low blood sugar levels, but continuous glucose monitors still have a margin of error.[79] As of 2016 an artificial pancreas continues to look promising with safety issues still being studied.[80] In 2018 they were deemed to be relatively safe.[81] ### Pancreas transplantation[edit] Main article: Pancreas transplantation In some cases, a pancreas transplant can restore proper glucose regulation. However, the surgery and accompanying immunosuppression required may be more dangerous than continued insulin replacement therapy, so is generally only used with or some time after a kidney transplant. One reason for this is that introducing a new kidney requires taking immunosuppressive drugs such as cyclosporine, which allows the introduction of a new pancreas to a person with diabetes without any additional immunosuppressive therapy. However, pancreas transplants alone may be beneficial in people with extremely labile type 1 diabetes.[82] ### Islet cell transplantation[edit] Main article: Islet cell transplantation Islet cell transplantation may be an option for some people with type 1 diabetes that is not well controlled with insulin.[83] Difficulties include finding donors that are compatible, getting the new islets to survive, and the side effects from the medications used to prevent rejection.[83][84] Success rates, defined as not needing insulin at 3 years following the procedure, occurred in 44% of people on registry from 2010.[83] In the United States, as of 2016, it is considered an experimental treatment.[84] ## Complications[edit] Further information: Complications of diabetes Complications of poorly managed type 1 diabetes may include cardiovascular disease, diabetic neuropathy, and diabetic retinopathy, among others. However, cardiovascular disease[85] as well as neuropathy[86] may have an autoimmune basis, as well. Women with type 1 DM have a 40% higher risk of death as compared to men with type 1 DM.[87] The life expectancy of an individual with type 1 diabetes is 11 years less for men and 13 years less for women.[88] People with type 1 diabetes are higher risk for other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and lupus.[89] About 12 percent of people with type 1 diabetes have clinical depression.[90] About 6 percent of people with type 1 diabetes also have celiac disease, but in most cases there are no digestive symptoms[6][91] or are mistakenly attributed to poor control of diabetes, gastroparesis or diabetic neuropathy.[91] In most cases, celiac disease is diagnosed after onset of type 1 diabetes. The association of celiac disease with type 1 diabetes increases the risk of complications, such as retinopathy and mortality. This association can be explained by shared genetic factors, and inflammation or nutritional deficiencies caused by untreated celiac disease, even if type 1 diabetes is diagnosed first.[6] ### Urinary tract infection[edit] People with diabetes show an increased rate of urinary tract infection.[92] The reason is bladder dysfunction is more common in people with diabetes than people without diabetes due to diabetes nephropathy. When present, nephropathy can cause a decrease in bladder sensation, which in turn, can cause increased residual urine, a risk factor for urinary tract infections.[93] ### Sexual dysfunction[edit] Sexual dysfunction in people with diabetes is often a result of physical factors such as nerve damage and poor circulation, and psychological factors such as stress and/or depression caused by the demands of the disease.[94] #### Males[edit] The most common sexual issues in males with diabetes are problems with erections and ejaculation: "With diabetes, blood vessels supplying the penis’s erectile tissue can get hard and narrow, preventing the adequate blood supply needed for a firm erection. The nerve damage caused by poor blood glucose control can also cause ejaculate to go into the bladder instead of through the penis during ejaculation, called retrograde ejaculation. When this happens, semen leaves the body in the urine." Another cause of erectile dysfunction is reactive oxygen species created as a result of the disease. Antioxidants can be used to help combat this.[95] #### Females[edit] Sexual problems are common in women who have diabetes,[94] including reduced sensation in the genitals, dryness, difficulty/inability to orgasm, pain during sex, and decreased libido. Diabetes sometimes decreases estrogen levels in females, which can affect vaginal lubrication. Less is known about the correlation between diabetes and sexual dysfunction in females than in males.[94] Oral contraceptive pills can cause blood sugar imbalances in women who have diabetes. Dosage changes can help address that, at the risk of side effects and complications.[94] Women with type 1 diabetes show a higher than normal rate of polycystic ovarian syndrome (PCOS).[96] The reason may be that the ovaries are exposed to high insulin concentrations since women with type 1 diabetes can have frequent hyperglycemia.[97] ## Epidemiology[edit] Type 1 diabetes makes up an estimated 5–10% of all diabetes cases[8] or 11–22 million worldwide.[58] In 2006 it affected 440,000 children under 14 years of age and was the primary cause of diabetes in those less than 10 years of age.[98] The incidence of type 1 diabetes has been increasing by about 3% per year.[98] Rates vary widely by country. In Finland, the incidence is a high of 57 per 100,000 per year, in Japan and China a low of 1 to 3 per 100,000 per year, and in Northern Europe and the U.S., an intermediate of 8 to 17 per 100,000 per year.[99][100] In the United States, type 1 and 2 diabetes affected about 208,000 youths under the age of 20 in 2015. Over 18,000 youths are diagnosed with Type 1 diabetes every year. Every year about 234,051 Americans die due to diabetes (type I or II) or diabetes-related complications, with 69,071 having it as the primary cause of death.[101] In Australia, about one million people have been diagnosed with diabetes and of this figure 130,000 people have been diagnosed with type 1 diabetes. Australia ranks 6th-highest in the world with children under 14 years of age. Between 2000 and 2013, 31,895 new cases were established, with 2,323 in 2013, a rate of 10–13 cases per 100,00 people each year. Aboriginals and Torres Strait Islander people are less affected.[102][103] ## History[edit] Further information: History of diabetes Type 1 diabetes was described as an autoimmune disease in the 1970s, based on observations that autoantibodies against islets were discovered in diabetics with other autoimmune deficiencies.[104] It was also shown in the 1980s that immunosuppressive therapies could slow disease progression, further supporting the idea that type 1 diabetes is an autoimmune disorder.[105] The name juvenile diabetes was used earlier as it often first is diagnosed in childhood. ## Society and culture[edit] See also: List of people with type 1 diabetes Type 1 and 2 diabetes was estimated to cause $10.5 billion in annual medical costs ($875 per month per diabetic) and an additional $4.4 billion in indirect costs ($366 per month per person with diabetes) in the U.S.[106] In the United States $245 billion every year is attributed to diabetes. Individuals diagnosed with diabetes have 2.3 times the health care costs as individuals who do not have diabetes. One in ten health care dollars are spent on individuals with type 1 and 2 diabetes.[101] ## Research[edit] Funding for research into type 1 diabetes originates from government, industry (e.g., pharmaceutical companies), and charitable organizations. Government funding in the United States is distributed via the National Institute of Health, and in the UK via the National Institute for Health Research or the Medical Research Council. The Juvenile Diabetes Research Foundation (JDRF), founded by parents of children with type 1 diabetes, is the world's largest provider of charity-based funding for type 1 diabetes research.[citation needed] Other charities include the American Diabetes Association, Diabetes UK, Diabetes Research and Wellness Foundation,[107] Diabetes Australia, the Canadian Diabetes Association. A number of approaches have been explored to understand causes and provide treatments for type 1. ### Diet[edit] Data suggest that gliadin (a protein present in gluten) might play a role in the development of type 1 diabetes, but the mechanism is not fully understood.[26][63] Increased intestinal permeability caused by gluten and the subsequent loss of intestinal barrier function, which allows the passage of pro-inflammatory substances into the blood, may induce the autoimmune response in genetically predisposed individuals to type 1 diabetes.[6][63] There is evidence from experiments conducted in animal models that removal of gluten from the diet may prevent the onset of type 1 diabetes[26][108] but there has been conflicting research in humans.[108] #### Virus[edit] One theory proposes that type 1 diabetes is a virus-triggered autoimmune response in which the immune system attacks virus-infected cells along with the beta cells in the pancreas.[28][109] Several viruses have been implicated, including enteroviruses (especially coxsackievirus B), cytomegalovirus, Epstein–Barr virus, mumps virus, rubella virus and rotavirus, but to date there is no stringent evidence to support this hypothesis in humans.[110] A 2011 systematic review and meta-analysis showed an association between enterovirus infections and type 1 diabetes, but other studies have shown that, rather than triggering an autoimmune process, enterovirus infections, as coxsackievirus B, could protect against onset and development of type 1 diabetes.[111] Some studies have found a decreased risk with oral rotavirus vaccine while others found no effect.[112][113] ### Gene therapy[edit] Gene therapy has also been proposed as a possible cure for type 1 diabetes.[114] ### Stem cells[edit] Pluripotent stem cells can be used to generate beta cells but previously these cells did not function as well as normal beta cells.[115] In 2014 more mature beta cells were produced which released insulin in response to blood sugar when transplanted into mice.[116][117] Before these techniques can be used in humans more evidence of safety and effectiveness is needed.[115] ### Vaccine[edit] Vaccines are being looked at to treat or prevent type 1 diabetes by inducing immune tolerance to insulin or pancreatic beta cells.[118] While Phase II clinical trials of a vaccine containing alum and recombinant GAD65, an autoantigen involved in type 1 diabetes, were promising, as of 2014 Phase III had failed.[118] As of 2014, other approaches, such as a DNA vaccine encoding proinsulin and a peptide fragment of insulin, were in early clinical development.[118] The rotavirus vaccine and BCG vaccine are associated with a lower risk of type 1 diabetes.[119][120][121] Research continues to look at the BCG vaccine in type 1 diabetes as of 2019[update].[121] ## References[edit] 1. ^ a b c d e f g h "Causes of Diabetes". 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[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	Type 1 diabetes	c0011854	27,394	wikipedia	https://en.wikipedia.org/wiki/Type_1_diabetes	2021-01-18T18:45:39	{"gard": ["10268"], "mesh": ["D003922"], "umls": ["C0011854"], "icd-9": ["250.01"], "orphanet": ["181371", "243377"], "wikidata": ["Q124407"]}
## Summary ### Clinical characteristics. Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form (which is usually mild and can manifest from infancy to adulthood). While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females. ### Diagnosis/testing. The diagnosis of CPT II deficiency is established in a proband by the finding of reduced CPT enzyme activity in muscle or the identification of biallelic pathogenic variants in CPT2 on molecular genetic testing. ### Management. Treatment of manifestations: High-carbohydrate (70%) and low-fat (<20%) diet to provide fuel for glycolysis; use of carnitine to convert potentially toxic long-chain acyl-CoAs to acylcarnitines; avoidance of known triggers. Prevention of primary manifestations: Infusions of glucose during intercurrent infections to prevent catabolism; frequent meals; avoiding extended fasting and prolonged exercise. Prevention of secondary complications: Providing adequate hydration during an attack of rhabdomyolysis and myoglobinuria to prevent renal failure. Agents/circumstances to avoid: Valproic acid, general anesthesia, ibuprofen, and diazepam in high doses. Evaluation of relatives at risk: If the pathogenic variants have been identified in an affected family member, molecular genetic testing of at-risk relatives can reduce morbidity and mortality through early diagnosis and treatment; if the pathogenic variants in the family are not known, screening for alterations in acylcarnitines may be of use in identifying other affected family members. ### Genetic counseling. CPT II deficiency 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 a carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are usually asymptomatic; however, manifesting carriers have been reported. Prenatal testing for a pregnancy at increased risk for one of the severe forms of the disease is possible either by molecular genetic testing of CPT2, if the two pathogenic variants in the family are known, or by assay of CPT II enzyme activity. ## Diagnosis ### Suggestive Findings Carnitine palmitoyltransferase II (CPT II) deficiency should be suspected in individuals with the following clinical features (by age) and supportive laboratory findings. Clinical features (by age) * Lethal neonatal form presents within days after birth. Characterized by: * Episodes of liver failure with hypoketotic hypoglycemia * Cardiomyopathy * Cardiac arrhythmias * Seizures and coma after fasting or infection * Facial abnormalities or structural malformations (e.g., cystic renal dysplasia, neuronal migration defects or brain dysgenisis) * Severe infantile hepatocardiomuscular form presents in the first year of life. Characterized by: * Liver failure * Cardiomyopathy * Seizures * Hypoketotic hypoglycemia * Peripheral myopathy * Attacks of abdominal pain and headache * Myopathic form has variable onset (1st to 6th decade). Characterized by: * Recurrent attacks of myalgia accompanied by myoglobinuria precipitated by prolonged exercise (especially after fasting), cold exposure, or stress * Possible weakness during attacks * Usually no signs of myopathy (weakness, myalgia, elevation of serum creatine kinase [CK] concentration) between attacks Supportive laboratory findings * High-performance liquid chromatography tandem mass spectrometry of serum/plasma acylcarnitines (i.e, the acylcarnitine profile) that demonstrates an elevation of C12 to C18 acylcarnitines, notably of C16 and C18:1 (See Differential Diagnosis for other disorders with this acylcarnitine profile.) Note: CPT II deficiency cannot be excluded based on acylcarnitine quantification in dried blood spots alone and investigation of plasma is recommended [de Sain-van der Velden et al 2013]. * Serum CK concentration more than fivefold of normal when heart or brain disease is excluded * Most individuals with the myopathic form of CPT II deficiency have normal serum CK concentration (<80 U/L) between attacks. * Permanent elevation of serum CK concentration (≤313 U/L) is observed in approximately 10% of affected individuals [Wieser et al 2003]. ### Establishing the Diagnosis The diagnosis of CPT II deficiency is established in a proband by the finding of reduced CPT enzyme activity in muscle or by the identification of biallelic pathogenic variants in CPT2 on molecular genetic testing (see Table 1). Molecular genetic testing approaches can include single-gene testing and use of a multigene panel: * Single-gene testing. Sequence analysis of CPT2 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. * A multigene panel that includes CPT2 and other genes of interest (see Differential Diagnosis) may also be considered. 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; thus, clinicians need to determine which multigene panel 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. (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. ### Table 1. Molecular Genetic Testing Used in Carnitine Palmitoyltransferase II Deficiency View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method CPT2Sequence analysis 3>95% 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 allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. The following pathogenic variants are found with the approximate stated frequency in individuals who have the myopathic form: p.Ser113Leu in 60%; p.Lys414ThrfsTer7 in 20%; p.Pro50His, p.Arg503Cys, p.Gly549Asp, p.Lys414ThrfsTer7, and p.Met214Thr in 15% [Taggart et al 1999, Thuillier et al 2003, Wieser et al 2003, Fanin et al 2012]. 5\. The severe infantile hepatocardiomuscular form and the lethal neonatal form are associated with severe pathogenic variants including p.Lys414ThrfsTer7 [Vladutiu et al 2002b, Thuillier et al 2003]. 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\. No deletions or duplications involving CPT2 as causative of CPT II deficiency have been reported. #### CPT II Enzyme Activity Affected individuals. Tests of total CPT enzyme activity (both CPT I and CPT II) rely on the basic reaction: palmitoyl-CoA + carnitine ↔ palmitoylcarnitine + CoA. Activity of CPT II represents only 20%-40% of total CPT activity. Measured enzyme activity is dependent on assay conditions, which have not been standardized, making comparisons of published data from different laboratories difficult: * The "radio isotope exchange assay" described by Norum [1964] is still widely used. * The "isotope forward assay" measures total CPT enzyme activity (CPT I and CPT II) by the incorporation of radio-labeled carnitine into palmitoylcarnitine [Zierz & Engel 1985]. Total CPT enzyme activity is normal in both affected individuals and controls. In this assay, CPT II enzyme activity is measured as the fraction that is not inhibited by malonyl-CoA. * CPT II activity can also be determined spectroscopically [Motlagh et al 2016]. The lethal neonatal form and the severe infantile hepatocardiomuscular form are associated with less than 10% of normal CPT II enzyme activity in lymphoblasts and skeletal muscle. Although the CPT II enzyme defect in the myopathic form can be detected using other tissues (e.g., liver, fibroblasts, leukocytes), preparation of tissue for assay of CPT II enzyme activity is difficult, and comparison of CPT II enzyme activity in different tissues yields inconsistent results. Therefore, only muscle tissue is recommended for assay of enzyme activity for the myopathic form of CPT II deficiency. Rettinger et al [2002] developed a tandem mass spectrometric assay (MS/MS) for the determination of CPT II enzyme activity based on the stoichometric formation of acylcarnitine, which directly correlates with the CPT II enzyme activity. The assay allows unambiguous detection of individuals with the myopathic form of CPT II deficiency [Gempel et al 2002]. ## Clinical Characteristics ### Clinical Description Three carnitine palmitoyltransferase II (CPT II) deficiency phenotypes are recognized: a lethal neonatal form; a severe infantile hepatocardiomuscular form; and a myopathic form, in which onset ranges from infancy to adulthood. #### Lethal Neonatal Form Liver failure, hypoketotic hypoglycemia, cardiomyopathy, respiratory distress, and/or cardiac arrhythmias occur. Affected individuals have liver calcifications and cystic dysplastic kidneys [Vladutiu et al 2002b, Sigauke et al 2003]. Neuronal migration defects including cystic dysplasia of the basal ganglia have been reported [Pierce et al 1999]. Among 19 individuals with the neonatal phenotype a characteristic pattern of malformations was seen. In addition to polycystic kidneys (found in 9 affected individuals), the following was also seen: hydrocephalus (in 8 individuals); cerebellar vermian hypoplasia (5); polymycrogyria, pachygyria and other neuronal migration defects (4); cerebral calcifications (3); cystic dysplasia of the brain (2); and agenesis of the corpus callosus (1) [Boemer et al 2016]. Prognosis is poor. Death occurs within days to months. The lethal neonatal form is characterized by reduced CPT II enzyme activity in multiple organs, reduced serum concentrations of total and free carnitine, and increased serum concentrations of long-chain acylcarnitines and lipids. #### Severe Infantile Hepatocardiomuscular Form This form is characterized by hypoketotic hypoglycemia, liver failure, cardiomyopathy, and peripheral myopathy. Cardiac arrhythmias can result in sudden death during infancy [Vladutiu et al 2002b]. Sudden infant death also occurred in a boy age ten months during an acute illness. Post-mortem analysis revealed hepatomegaly and acylcarnitine profile compatible with CPT II deficiency [Bouchireb et al 2010]. Another instance of sudden infant death occurred in an infant age 13 days who was homozygous for the c.534_558del25insT pathogenic variant. The infant had a Dandy-Walker malformation [Yahyaoui et al 2011]. #### Myopathic Form The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and is the most frequent cause of hereditary myoglobinuria. In vivo investigation of fatty acid oxidation in CPT2-deficient persons by indirect calorimetry and stable isotope methodology shows an impaired oxidation of long chain fatty acids during low-intensity exercise, with normal oxidation at rest [Ørngreen et al 2005]. Clinically almost all individuals with the myopathic form experience myalgia. Approximately 60% have muscle weakness during the attacks. Occasionally, muscle cramps occur, although they are not typical of the disease. Myoglobinuria with brown-colored urine during the attacks occurs in approximately 75% of individuals. Age at onset and age at diagnosis vary widely. Detailed clinical data obtained from 23 of 32 individuals with the myopathic form revealed age of onset ranging from one to 61 years; age at diagnosis ranged from seven to 62 years [Wieser et al 2003, Deschauer et al 2005]. In 70%, the disease started in childhood (age 0-12 years); in 26%, the first attacks occurred in adolescence (age 13-22 years); and in one individual, symptoms began in late adulthood (age 61 years). Exercise is the most common trigger of attacks, followed by infections (~50% of affected individuals) and fasting (~20%). The severity of exercise that triggers symptoms is highly variable. In some individuals, only long-term exercise induces symptoms, and in others, only mild exercise is necessary. Cold, general anesthesia, sleep deprivation, and conditions that are normally associated with an increased dependency of muscle on lipid metabolism are also reported as trigger factors. Most individuals are mildly affected; some are even serious athletes [Deschauer et al 2005]. Affected individuals are generally asymptomatic with no muscle weakness between attacks. Some individuals have only a few severe attacks and are asymptomatic most of their lives, whereas others have frequent myalgia, even after moderate exercise, such that daily activities are impaired and disease may worsen. End-stage renal disease caused by interstitial nephritis with acute tubular necrosis requiring dialysis occasionally occurs [Kaneoka et al 2005]. The preponderance of affected males is notable. In the series of 32 individuals of Wieser et al [2003], the ratio of males to females was nearly two to one (20/12); in a series published by Anichini et al [2011], the ratio of males to females was 7.3:1 (22/3); in earlier reports, ratios as high as five to one were reported. The reason for the preponderance of males is unknown; hormonal factors may play a role but cannot explain the gender disproportion completely [Vladutiu et al 2002a]. Females may be less likely to develop myoglobinuria and therefore remain undetected. ### Genotype-Phenotype Correlations A consistent genotype-phenotype correlation is found between CPT2 missense pathogenic variants (including the common p.Ser113Leu) and the myopathic form; these are referred to as pathogenic variants that cause "mild" form of the disease. CPT2 pathogenic null variants leading either to truncation of the protein or to mRNA degradation are referred to as pathogenic variants associated with the lethal neonatal form. However, several pathogenic variants are associated with both the mild and severe forms of CPT II deficiency, suggesting a role for other unknown modulators (intragenic variants; epigenetic or environmental factors) [Vladutiu et al 2000b, Musumeci et al 2007]. For a list of variants and their predicted phenotype, see Isackson et al [2008], Anichini et al [2011], and Fanin et al [2012]. Lethal neonatal form. Homozygosity for the severe pathogenic variants p.Pro227Leu, p.Lys414ThrfsTer7, and p.Lys642ThrfsTer6 [Isackson et al 2008] is associated with the lethal neonatal form. This subtype of the disease is also described in compound heterozygous states in combination with a pathogenic variant usually associated with mild disease (c.[1737delC];[520G>A]) [Semba et al 2008]. Severe infantile hepatocardiomuscular form. Compound heterozygosity for pathogenic variants associated with mild and severe forms has been reported. A detailed analysis associated the following pathogenic variants with this type of the disease: p.Tyr120Cys, p.Arg151Gln, p.Asp328Gly, p.Arg382Lys, p.Arg503Cys, p.Tyr628Ser, and p.Arg631Cys [Vladutiu et al 2002b, Thuillier et al 2003, Isackson et al 2008, Fanin et al 2012]. Myopathic form. The variant p.Ser113Leu accounts for 60% of pathogenic alleles in the myopathic form of CPT II deficiency. In a series of 32 affected individuals, 14 were homozygous for this common allele [Wieser et al 2003]; 17 were compound heterozygous for this common pathogenic variant and a second pathogenic variant. Testing for the p.Ser113Leu variant alone would suggest the diagnosis in 31 out of 32 individuals. In northern Europeans the pathogenic variants p.Ser113Leu, p.Pro50His, and p.Lys414ThrfsTer7 are most frequently found, whereas in the Japanese the variant p.Phe383Tyr appears to have the highest prevalence [Taggart et al 1999, Isackson et al 2008, Yasuno et al 2008]. Heterozygotes have a biochemically intermediate phenotype (with markedly reduced enzyme activity) but generally do not display symptoms. However, a few symptomatic heterozygotes have been reported [Taggart et al 1999, Olpin et al 2003, Rafay et al 2005, Fanin et al 2012]. Heterozygotes have also been shown to have impaired fat oxidation during exercise as compared to controls [Ørngreen et al 2005]. Histopathologic changes in asymptomatic carriers of CPT II deficiency (heterozygotes) and in affected individuals (homozygotes) are inconsistent. A recent study found histopathologic abnormalities quite frequently (in all but one heterozygote). Lipid accumulation, found in all homozygotes, was mild or absent in heterozygotes. ### Prevalence Some twenty families with the lethal neonatal form [Smeets et al 2003, Thuillier et al 2003, Isackson et al 2008, Semba et al 2008, Boemer et al 2016] have been described. Since pregnancies in which a fetus has severe cerebral malformations are frequently interrupted, CPT II deficiency or other fatty acid oxidation disorders may be missed and the prevalence higher than previously suspected. Approximately 28 families with the severe infantile hepatocardiomuscular form have been described. Since the first description of the myopathic form of CPT II deficiency by DiMauro & DiMauro [1973], findings in more than 300 cases have been published [Thuillier et al 2003, Bonnefont et al 2004, Isackson et al 2006, Fanin et al 2012, Joshi et al 2013]. Symptoms of the myopathic form can be mild and physical impairment may not occur; thus, this form of CPT II deficiency may be under-recognized. ## Differential Diagnosis Elevated acylcarnitines. The differential diagnosis of an elevation of C12 to C18 acylcarnitines, notably of C16 and C18:1, includes glutaricacidemia type II (OMIM 231680) and carnitine-acylcarnitine translocase deficiency (OMIM 212138), which can be excluded by additional screening of urinary metabolites such as glutaric and 3-OH-glutaric acid. ### Neonatal Form Carnitine-acylcarnitine translocase (CACT) deficiency (OMIM 212138). The neonatal phenotype of CACT deficiency, one of the most severe and usually lethal mitochondrial fatty-acid oxidation abnormalities, is characterized by hypoketotic hypoglycemia, hyperammonemia, cardiac abnormalities, and early death. Tandem mass spectrometry shows increased concentration of 16-2 H3 palmitoylcarnitine, suggesting either CPT II deficiency or CACT deficiency. One report shows that heat-denaturing high-performance liquid chromatography (DHPLC) is of use for diagnosing CACT deficiency [Fukushima et al 2013]. CACT deficiency is an autosomal recessive condition caused by compound heterozygous or homozygous pathogenic variants in SLC25A20. Note: The differentiation of CACT deficiency from CPT II deficiency continues to be difficult using current acylcarnitine profiling techniques either from plasma or blood spots, or in the intact cell system (fibroblasts/amniocytes). Specific enzyme assays are required to unequivocally differentiate CACT enzyme activity from CPT II enzyme activity [Roe et al 2006]. Alternatively, molecular genetic testing could be used to distinguish between these two conditions. Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty-acid oxidation in which clinical symptoms usually occur with a concurrent febrile or gastrointestinal illness when energy demands are increased. The recognized phenotypes are: acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in CPT1A that cause CPT1A deficiency; and hepatic encephalopathy, in which individuals (typically children) present with hypoketotic hypoglycemia and sudden onset of liver failure. Individuals with hepatic encephalopathy typically present with hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and total carnitine. The ratio of free-to-total carnitine in serum or plasma on a newborn screen bloodspot may be elevated in CPT1A deficiency. CPT1 enzyme activity on cultured skin fibroblasts is 1%-5% of normal in most affected individuals. In individuals with an enzymatically confirmed diagnosis of CPT1A deficiency, the CPT1A pathogenic variant detection frequency using sequence analysis is greater than 90%. Inheritance is autosomal recessive. ### Myopathic Form The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and is the most frequent cause of hereditary myoglobinuria. If clinical history is suggestive of a metabolic myopathy, routine laboratory tests including measurement of concentrations of lactate, pyruvate, creatine kinase, amino acids, and free acylcarnitine in blood should be performed. Careful family history should be taken. In early reports, elevation of acylcarnitines, notably C16 and C18:1, suggestive of a defect in mitochondrial β-oxidation, was detected by screening for acylcarnitines [Chace 2001]. Differential diagnosis of this finding includes CPT II deficiency, glutaricacidemia II (OMIM 231680), carnitine-acylcarnitine translocase deficiency (OMIM 212138), and TANGO2-related metabolic encephalopathy and arrhythmias (a condition characterized by metabolic encephalomyopathic crises, rhabdomyolysis, cardiac arrhythmias, and neurodegeneration and caused by pathogenic variants in TANGO2). Unlike CPT II deficiency, TANGO2-related metabolic encephalopathy and arrhythmias is frequently accompanied by cardiac arrhythmias, cognitive impairment, epilepsy, spasticity, and brain atrophy. Additional tests are necessary to reach a definite diagnosis [Albers et al 2001]. Rhabdomyolysis and/or myoglobinuria. Rhabdomyolysis is etiologically heterogeneous, most cases being apparently acquired – for example, as a result of mechanical or vascular damage. Recurrent rhabdomyolysis preceded by exercise or infection is more likely to have an underlying metabolic defect, and strategic diagnostic procedures are warranted. History and physical examination are likely to identify the acquired and drug-related forms. However, one has to bear in mind that sometimes myoglobinuria with episodes of dark urine is ignored, and pronounced muscle pain after only light exercise is not considered a sign of disease. Screening for metabolic disorders (carnitine profile, amino acids, tandem mass spectrometry) may point in specific directions. Muscle biopsy for histologic and biochemical analysis should be performed. However, in a significant proportion of individuals, no cause of rhabdomyolysis can be identified. Acquired causes of rhabdomyolysis * Excessive use of muscle force (e.g., sports, seizures, dystonia) * Muscle damage (e.g., crush, cold, ischemia, embolism) * Infections (bacterial/viral/fungal) * Temperature changes * Inflammatory myopathies (polymyositis, vasculitis) Drug-related causes of rhabdomyolysis * Induction of an autoimmune reaction (e.g., cyclosporine, penicillamine) * Hypokalemia (amphotericin, caffeine) * Membrane disruption (cemitidin, colchicine) * Disturbance of Na/K ATPase (antidepressants, arsen, azathioprine, bezafibrates) * Neuroleptic syndrome (all neuroleptics, lithium) * Serotonergic syndrome (amphetamines, MAO-inhibitor, SSRI) Metabolic-toxic causes of rhabdomyolysis * Defects of glucose/glycogen metabolism (e.g., McArdle disease, Tarui disease [OMIM 232800]). Deficiencies of the six enzymes involved in glycogen breakdown (phosphorylase, phosphorylase kinase, phosphofructokinase, phosphoglycerate kinase, phosphoglycerate mutase, lactate dehydrogenase) result in exercise intolerance and recurrent rhabdomyolysis. * Defects of lipid metabolism (carnitine deficiency). Mitochondrial β-oxidation of long-chain fatty acids is a major source of energy production, particularly at times of stress or fasting. Skeletal muscle can use carbohydrates or lipids as fuel, depending on the degree of activity. At rest or during prolonged low-intensity exercise, approximately 70% of the energy requirement is met by the oxidation of long-chain fatty acids. Two defects of lipid metabolism primarily affecting the skeletal muscle are known: carnitine palmitoyltransferase II deficiency and systemic primary carnitine deficiency characterized by progressive proximal weakness and cardiomyopathy. * Defects of oxidative phosphorylation (complex II deficiency, complex III defect, cytochrome c oxidase deficiency) (See Mitochondrial Disorders Overview.) * TANGO2-related encephalopathy and arrhythmias * Malignant hyperthermia (See Malignant Hyperthermia Susceptibility.) * Dystrophinopathies (Duchenne muscular dystrophy, Becker muscular dystrophy) * Myoadenylate deaminase deficiency (MAD) (OMIM 615511) ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with carnitine palmitoyltransferase II (CPT II) deficiency, the following are recommended: * Neurologic examination * Strength testing * Review of dietary association of symptoms * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Current treatment for long-chain fatty-acid oxidation disorders: * Avoid known triggers. * Reduce the amount of long-chain dietary fat while covering the need for essential fatty acids. * Provide carnitine to convert potentially toxic long-chain acyl-CoAs to acylcarnitines. * Provide a large fraction of calories as carbohydrates to reduce body fat utilization and prevent hypoglycemia. * Provide approximately one third of the calories as even-chain medium chain triglycerides (MCT). Metabolism of the eight to ten carbon fatty acids in MCT oil, for example, is independent of CPT I, carnitine/acylcarnitine translocase, CPT II, very-long-chain acyl-CoA dehydrogenase (VLCAD), trifunctional protein, and long-chain hydroxy-acyl-CoA dehydrogenase deficiency (LCHAD) enzyme activities. ### Prevention of Primary Manifestations Appropriate measures include the following: * Infusions of glucose during intercurrent infections to prevent catabolism Note: Oral glucose cannot achieve this effect. * High-carbohydrate (70%) and low-fat (<20%) diet to provide fuel for glycolysis * Frequent meals and avoidance of extended fasting * Avoidance of prolonged exercise and other known triggers ### Prevention of Secondary Complications The most important aim while treating an individual with CPT II deficiency is to prevent renal failure during an episode of rhabdomyolysis and myoglobinuria. Therefore, sufficient hydration and, if necessary, dialysis must be performed immediately when renal failure is imminent. ### Surveillance Annual or more frequent monitoring to regulate medication and diet is indicated. ### Agents/Circumstances to Avoid Extended fasting and prolonged exercise are to be avoided. Reports of medication-induced side effects in individuals with CPT II deficiency are rare. Relying mostly on case reports, the following agents should be avoided: * Valproic acid [Kottlors et al 2001] * General anesthesia * Ibuprofen * Diazepam in high doses [Bonnefont et al 1999] ### Evaluation of Relatives at Risk It is appropriate to evaluate apparently asymptomatic at-risk relatives so that morbidity and mortality can be reduced by early diagnosis and treatment. In addition, predictive testing for at-risk asymptomatic family members may be advisable before general anesthesia. Complications of general anesthesia (including rhabdomyolysis and suxamethonium hypersensitivity in individuals with a variety of neuromuscular diseases and renal post-anesthetic failure in individuals with CPT II deficiency in particular) have been observed [Katsuya et al 1988, Wieser et al 2008]. * Molecular genetic testing is appropriate if the pathogenic variants in the family are known. * If the pathogenic variants in the family are not known, screening for alterations in acylcarnitines may be of use to identify other affected family members. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management While a variety of maternal complications have been observed in association with other fatty acid oxidation disorders (severe preeclampsia; acute fatty liver of pregnancy; maternal liver disease; and hemolysis, elevated liver enzymes, and low platelets), none of these complications has been associated with CPT II deficiency [Preece & Green 2002, Shekhawat et al 2005]. ### Therapies Under Investigation Promising results have been obtained with treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using anaplerotic odd-chain triglycerides [Roe et al 2002]. These results were confirmed in seven individuals with CPT II deficiency, who avoided rhabdomyolysis or hospitalization while on the triheptanoin (anaplerotic) diet. Affected individuals returned to normal physical activity including strenuous sports [Roe et al 2008]. Fibrates are a class of hypolipidemic drugs that increase high-density lipoprotein levels by mRNA upregulation of many lipid-metabolism genes through interaction with the steroid/thyroid transcription factor PPARa. Studies have demonstrated that bezafibrate increases CPT2 mRNA and normalizes enzyme activity in mild forms of CPT II-deficient cultured fibroblasts and myoblasts [Bonnefont et al 2009]. In a trial including six affected individuals treated with bezafibrate, the level of fatty acid oxidation in muscle biopsies was elevated, accompanied by a significant increase in palmitoyl-L-carnitine oxidation, increased CPT2 mRNA, and increased translated protein. A reduction of episodes of rhabdomyolysis could be observed, as well as amelioration of quality of life (measured by SF-36) as shown by an increase in physical activity and a decline in muscular pain [Bonnefont et al 2009, Bonnefont et al 2010]. Another study did not show beneficial effects of bezafibrate on fatty acid oxidation and other disease manifestations; this study, however, was heavily criticized for methodologic shortcomings [Ørngreen et al 2014, Bastin et al 2015] 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. ### Other Carnitine supplementation is essentially a cure for the carnitine membrane transporter defect. While oral carnitine supplementation of 50 mg/kg/d is often prescribed in the treatment of other fat oxidation disorders, controlled trials of its effectiveness in CPT II deficiency are lacking. In addition, carnitine administration is controversial, given the possibility of accumulation of acyl-CoAs and consequent depletion of free CoA in the mitochondria [Yoshino et al 2003]. In acutely ill infants aggressive treatment with IV glucose and cardiac support is critical, and should be complemented with L-carnitine supplementation. [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	Carnitine Palmitoyltransferase II Deficiency	c0342790	27,395	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1253/	2021-01-18T21:36:19	{"mesh": ["C535589"], "synonyms": ["CPT II Deficiency"]}
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: "Leukocyte adhesion deficiency" – news · newspapers · books · scholar · JSTOR (January 2008) (Learn how and when to remove this template message) Leukocyte-adhesion deficiency SpecialtyImmunology Leukocyte adhesion deficiency (LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections.[1] LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.[2][3] ## Contents * 1 Characteristics * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Characteristics[edit] LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The adhesion defects result in poor leukocyte chemotaxis, particularly neutrophil, inability to form pus and neutrophilia.[3] Individuals with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens. These individuals do not form abscesses because granulocytes cannot migrate to the sites of infection. ## Cause[edit] Leukocyte-adhesion deficiency has an autosomal recessive pattern of inheritance. Types of leukocyte adhesion deficiency include LAD1, LAD2, and LAD3. LAD1 is the most common.[citation needed] Type OMIM Gene LAD1 116920 ITGB2 LAD2 or CDG2C 266265 SLC35C1 LAD3 612840 FERMT3 Patients with LAD1 have an inherited molecular defect that causes a deficiency of the β-2 integrin subunit,[4] also called CD18, which is encoded by the ITGB2 gene found on chromosome 21. This subunit is involved in the formation of the β-2 integrins (LFA-1, Integrin alphaXbeta2, and Mac-1/CR3) by dimerization with different CD11 subunits.[citation needed] Mutations in the ITGB2 gene lead to absent, reduced, or aberrant CD18 protein expression, causing a lack of expression in the leukocyte membrane of the β-2 integrins. The main function of these proteins is to allow neutrophils to make their way out of the blood stream and into the infected tissues by adhering to different ligands expressed by the endothelium, e.g. ICAM-1. In LAD-I patients, neutrophils cannot extravasate and fight against bacteria in tissues. The bacteria can then proliferate, leading to symptomatic infection, which can spread unimpeded and cause serious injury to important tissues.[citation needed] ## Diagnosis[edit] Typically, diagnosis involves several preliminary tests of immune function, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels. In the case of LAD-I, specific diagnosis is done by flow cytometry. This technique will reveal absent or reduced CD18 expression in the leukocyte membrane. Recently, prenatal diagnosis systems has been established, allowing an early detection of the disease. LAD-II diagnosis includes the study of different glycosylated forms of the transferrin protein. In LAD-III, as platelet function is also affected, this could be used to differentiate it from the other types.[citation needed] ## Treatment[edit] Although patients can receive intensive antibiotherapy and even granulocyte transfusions from healthy donors, the only current curative therapy is the hematopoietic stem cell transplant.[5] However, progress has been made in gene therapy, an active area of research. Both foamyviral and lentiviral vectors expressing the human ITGB2 gene under the control of different promoters have been developed and have been tested so far in preclinical LAD-I models (such as CD18-deficient mice and canine leukocyte adhesion deficiency-affected dogs).[citation needed] ## Prognosis[edit] A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), the survival rate was 75%.[6] ## Epidemiology[edit] LAD is a rare disease, with an estimated prevalence of one in 100,000 births, with no described racial or ethnic predilection. The most common type is LAD1. ## See also[edit] * Leukocyte adhesion cascade * Congenital disorder of glycosylation ## References[edit] 1. ^ "Leukocyte Adhesion Deficiency: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01. 2. ^ Robert P; Canault M; Farnarier C; Nurden A; Grosdidier C; Barlogis V; … Alessi MC (2011). "A novel leukocyte adhesion deficiency III variant: kindlin-3 deficiency results in integrin- and nonintegrin-related defects in different steps of leukocyte adhesion". Journal of Immunology. 186 (9): 5273–83. doi:10.4049/jimmunol.1003141. PMID 21441448. 3. ^ a b Abbas AK, Lichtman AH, Pillai S (2012). Cellular and molecular immunology (7th ed.). Philadelphia: Elsevier/Saunders. ISBN 978-1-4377-1528-6. 4. ^ Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA (1987). "Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency". Cell. 50 (2): 193–202. doi:10.1016/0092-8674(87)90215-7. PMID 3594570. S2CID 40388710. 5. ^ van Vliet DN, Brandsma AE, Hartwig NG (2004). "Leukocyte-adhesion deficiency - a rare disorder of inflammation". Ned. Tijdschr. Geneeskd. 148 (50): 2496–2500. PMID 15638198. 6. ^ Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E.Graham; Davis, Jeffery; Duval, Michel; Eames, Gretchen; Farinha, Nuno; Filopovich, Alexandra; Fischer, Alain (2016-11-17). "Allogeneic hematopoietic stem cell transplantation for Leukocyte Adhesion Deficiency". Pediatrics. 123 (3): 836–840. doi:10.1542/peds.2008-1191. ISSN 0031-4005. PMC 3380632. PMID 19255011. ## External links[edit] Classification D * ICD-10: D84.8 * OMIM: 116920 * MeSH: D018370 External resources * eMedicine: ped/1302 * Orphanet: 2968 * v * t * e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis: * Monocytosis * Histiocytosis * Chronic granulomatous disease ↓ -penia: * Monocytopenia Granulocytes ↑ -cytosis: * granulocytosis * Neutrophilia * Eosinophilia/Hypereosinophilic syndrome * Basophilia * Bandemia ↓ -penia: * Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia * Eosinopenia * Basopenia) Disorder of phagocytosis Chemotaxis and degranulation * Leukocyte adhesion deficiency * LAD1 * LAD2 * Chédiak–Higashi syndrome * Neutrophil-specific granule deficiency Respiratory burst * Chronic granulomatous disease * Neutrophil immunodeficiency syndrome * Myeloperoxidase deficiency [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	Leukocyte adhesion deficiency	c0242597	27,396	wikipedia	https://en.wikipedia.org/wiki/Leukocyte_adhesion_deficiency	2021-01-18T19:09:14	{"gard": ["9544"], "mesh": ["D018370"], "umls": ["C0242597"], "orphanet": ["2968"], "wikidata": ["Q1154422"]}
Chronic periodontitis is one of the seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system. Chronic periodontitis is a common disease of the oral cavity consisting of chronic inflammation of the periodontal tissues that is caused by the accumulation of profuse amounts of dental plaque. Periodontitis initially begins as gingivitis and can progress onto chronic and subsequent aggressive periodontitis according to the 1999 classification. Diagnosing chronic periodontitis is important in its early stages to prevent severe and irreversable damage to the protective and supportive structures of the tooth. However, due to chronic periodontitis being a painless progressing disease, few patients will seek dental care in the early stages. Mild to moderate chronic periodontitis can be managed by proper mechanical removal of the biofilm and calculus subgingivally. Full and effective oral hygiene and regular 3 monthly periodontal checkups are important for maintaining the stability of the disease. Chronic periodontitis is prevalent in adults and seniors worldwide. In the US around 35% of adults (30–90 years) are affected.[1] The cumulative effects of alveolar bone loss, attachment loss and pocket formation is more apparent with an increase in age. Age is related to the incidence of periodontal destruction: "...in a well-maintained population who practises oral home care and has regular check-ups, the incidence of incipient periodontal destruction increases with age, the highest rate occurs between 50 and 60 years, and gingival recession is the predominant lesion before 40 years, while periodontal pocketing is the principal mode of destruction between 50 and 60 years of age."[2] There are a variety of periodontal risk factors which can affect the prevalence, rate, extent and severity of the disease progression. Major risk factors include smoking, lack of oral hygiene with inadequate plaque biofilm control. There is a slow to moderate rate of disease progression but the patient may have periods of rapid progression ("bursts of destruction"). Chronic periodontitis can be associated with local predisposing factors (e.g. tooth-related or iatrogenic factors). The disease may be modified by and be associated with systemic diseases (e.g. diabetes mellitus, HIV infection) It can also be modified by factors other than systemic disease such as smoking and emotional stress, anxiety and depression. Care should be taken however, when diagnosing a patient who smokes as smoking can alter some of the results of an examination. In smokers, the gingiva are pale and fibrous and tend to bleed less while being probed due to the effect of nicotine on the vasculature by vasoconstricting them. Thus, a lowered response is produced and this explains why incorrect data can be gained. There is also an increase in supragingival calculus alongside visible nicotine staining. The anterior dentition occasionally have recession and maxillary anterior and palatal surfaces are more adversely affected. ## Contents * 1 Pathophysiology * 1.1 Plaque hypothesis * 2 Signs and symptoms * 3 Diagnosis * 3.1 1999 classification * 3.2 2017 classification * 4 Treatment * 4.1 Open flap debridement * 4.2 Guided tissue regeneration * 4.3 Enamel matrix derivative * 4.4 Adjunctive systemic antibiotic treatment * 4.5 Locally delivered adjunctive antimicrobial treatment * 4.6 Modulating the host response * 5 Systemic Factors * 5.1 Diabetes Mellitus * 5.2 Cardiovascular Disease * 6 Costs of treatment * 7 Research * 7.1 Management * 7.2 Tentative links to other conditions * 8 References * 9 External links ## Pathophysiology[edit] Chronic periodontitis is initiated by Gram-negative tooth-associated microbial biofilms that elicit a host response, which results in bone and soft tissue destruction. In response to endotoxin derived from periodontal pathogens, several osteoclast-related mediators target the destruction of alveolar bone and supporting connective tissue such as the periodontal ligament. Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins, and other osteoclast-derived enzymes. ### Plaque hypothesis[edit] At least two mechanisms of the microbiology of periodontitis have been described: the specific plaque hypothesis and the non-specific plaque hypothesis. Consensus is that neither view is entirely correct, but via a middle path, that damage is due to a shift in the relative populations of more and less dangerous bacteria in the plaque. This is called the ecological plaque hypothesis. The disease is associated with a variable microbial pattern.[3] Anaerobic species of bacteria Porphyromonas gingivalis, Bacteroides forsythus, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Eubacterium sp. have all been implicated in chronic periodontitis.[4] Microaerophile bacteria Actinomyces actinomycetemcomitans, Campylobacter rectus, and Eikenella corrodens also may play a role in chronic periodontitis.[4] ## Signs and symptoms[edit] In the early stages, chronic periodontitis has few symptoms and in many individuals the disease has progressed significantly before they seek treatment. Symptoms may include the following: * Redness or bleeding of gums while brushing teeth, using dental floss or biting into hard food (e.g. apples) (though this may occur even in gingivitis, where there is no attachment loss) * Gum swelling that reoccurs * Halitosis, or bad breath, and a persistent metallic taste in the mouth * Gingival recession, resulting in apparent lengthening of teeth. (This may also be caused by heavy-handed brushing or with a stiff tooth brush.) * Deep pockets between the teeth and the gums (pockets are sites where the attachment has been gradually destroyed by collagen-destroying enzymes, known as collagenases) * Loose teeth, in the later stages (though this may occur for other reasons as well) * Drifting of incisors Gingival inflammation and bone destruction are often painless. Patients sometimes assume that painless bleeding after teeth cleaning is insignificant, although this may be a symptom of progressing chronic periodontitis in that patient. Subgingival calculus is a frequent finding as well as supragingival calculus due to the bacteria migrating apically and the combined effect of the host response system of the body. ## Diagnosis[edit] ### 1999 classification[edit] Chronic periodontitis is one of the seven destructive periodontal diseases as listed in the 1999 classification.[5] Not every case of gingivitis will progress onto chronic periodontitis, but all chronic perodontitis results from gingivitis. Therefore it is important to control the first step; gingival inflammation. A difficulty which arises with diagnosing chronic periodontitis patients is due to the slow and painless progression of the disease. The most effective and timely diagnosis would be during the mild to moderate stage. However, usually when presenting complaints do arise the effects of mobility and alveolar bone loss have become severe. A full mouth examination and recording is required to document and track periodontal disease including: * Pocket Depth (PD) * Clinical Attachment Loss (CAL) * Bleeding On Probing (BOP) * Plaque index/score * Furcation involvement * Suppuration * Mobility * Radiographs Measuring disease progression is carried out by measuring probing pocket depth (PPD) and bleeding indices using a periodontal probe. Pockets greater than 3mm in depth are considered to be unhealthy. True pocket formation of 4 mm or more are specifically related to chronic periodontitis. Bleeding on probing is considered to be a sign of active disease. Discharge of pus, involvement of the root furcation area and deeper pocketing may all indicate reduced prognosis for an individual tooth. Evidence of alveolar bone loss is also required to differentiate between true bone loss and not attributions of gingival oedema. Usually, a horizontal pattern of bone loss would be found however, vertical (infrabony) bone loss may also be present on specific sites. A Basic Periodontal Examination (BPE) or Periodontal Screening and Recording (PSR) should give a score of 3 or 4. A correct diagnosis is vital to allow the formation of a specific treatment plan for the patient and to arrest the disease progression. Chronic periodontitis can be further classified into: 1. Extent (can be either localised affecting < 30% of sites; or generalised if > 30% of sites are affected) 2. Severity (slight = 1–2 mm CAL; moderate = 3–4 mm CAL; severe ≥5 mm CAL) ### 2017 classification[edit] Chronic periodontitis is not included within the newer 2017 World Workshop classification. The 2017 classification of Periodontal Diseases and Conditions includes:[6] Periodontitis: 1. Necrotizing periodontal diseases 2. Periodontitis 3. Periodontitis as a manifestation of systemic disease Therefore, in accordance to the 2017 classification, a diagnosis would be achieved through the patient assessment individually on the basis of: * Type * Distribution: localised (up to 30% of teeth) or generalised (more than 30% of teeth) and the molar/incisor pattern * Stage and grading * Stages: I (early/mild) with <15% or <2mm interproximal bone loss, II (moderate) with coronal third of root bone loss, III (severe) with mid third of root bone loss, IV (very severe) with apical third of root bone loss * Grading: A (slow) with <0.5% bone loss/age, B (moderate) with 0.5-1.0% bone loss/age, C (rapid) with >1.0% bone loss/age * Status: stable, remission or unstable (see Table 1) * Risk factors, which include systemic diseases such as diabetes or extrinsic factors such as smoking. Table 1. Periodontitis status Stable Remission Unstable Bleeding on Probing <10% ≥10% \- Periodontal Pocket Depth ≤4mm ≤4mm ≥5mm Bleeding on Probing at 4mm sites ✗ ✗ ✓ ## Treatment[edit] There is professional agreement among dentists that smoking cessation and good oral hygiene are key to effective treatment and positive outcomes for patients. Similarly, any plaque retentive factors which exist and are modifiable should be corrected, such as overhangs on restorations. Treatment can involve both non-surgical and surgical therapies. The typical initial treatment known to be effective is scaling and root planing (SRP) to mechanically debride the depths of the periodontal pocket and disrupt the biofilm present. This is done using a powered ultrasonic or sonic scaler and/or unpowered hand instruments. "In patients with chronic periodontitis, subgingival debridement (in conjunction with supragingival plaque control) is an effective treatment in reducing probing pocket depth and improving the clinical attachment level. In fact it is more effective than supragingival plaque control alone".[7] It is important for patients to be reviewed within 8–12 weeks to assess the treatment response. Full mouth disinfection protocols are favoured by some clinicians. There is no evidence that full mouth disinfection or full mouth scaling protocols improve the outcome when compared to standard mechanical scaling and root planing.[8] ### Open flap debridement[edit] Open flap debridement is used by some practitioners particularly in deeper pocket areas. The advantages of this approach is better visualization of the root surface to be cleaned. This must be weighed against the risks of surgery. Open flap surgery is more effective than non-surgical periodontal therapy in deep pocketing : "Both scaling and root planing alone and scaling and root planing combined with flap procedure are effective methods for the treatment of chronic periodontitis in terms of attachment level gain and reduction in gingival inflammation. In the treatment of deep pockets open flap debridement results in greater PPD reduction and clinical attachment gain."[9] ### Guided tissue regeneration[edit] Guided tissue regeneration (GTR) using PTFE membranes is favoured by some practitioners, despite its cost and complexity: "GTR has a greater effect on probing measures of periodontal treatment than open flap debridement, including improved attachment gain, reduced pocket depth, less increase in gingival recession and more gain in hard tissue probing at re-entry surgery. However there is marked variability between studies and the clinical relevance of these changes is unknown. As a result, it is difficult to draw general conclusions about the clinical benefit of GTR. Whilst there is evidence that GTR can demonstrate a significant improvement over conventional open flap surgery, the factors affecting outcomes are unclear from the literature and these might include study conduct issues such as bias. Therefore, patients and health professionals need to consider the predictability of the technique compared with other methods of treatment before making final decisions on use."[10] ### Enamel matrix derivative[edit] Enamel matrix derivative (EMD) is favoured by some practitioners despite its high cost: "One year after its application, EMD significantly improved probing attachment levels (1.1 mm) and probing pocket depth reduction (0.9 mm) when compared to a placebo or control, however, the high degree of heterogeneity observed among trials suggests that results have to be interpreted with great caution. In addition, a sensitivity analysis indicated that the overall treatment effect might be overestimated. The actual clinical advantages of using EMD are unknown. With the exception of significantly more postoperative complications in the GTR group, there was no evidence of clinically important differences between GTR and EMD. Bone substitutes may be associated with less gingival recession than EMD." [11] However, studies have shown that regardless of the conventional periodontal treatments, 20-30% of chronic periodontitis patients do not respond favorably to their treatment.[1] There are many factors which account for these including: ineffective removal of calculus, defective restorations, impaired immune response as a result of a systemic condition, poor plaque control, smoking, etc. ### Adjunctive systemic antibiotic treatment[edit] Systemic antibiotics such as amoxicillin or metronidazole are sometimes used in addition to debridement based treatments. "Systemic antimicrobials in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and probing pocket depth (PPD) change, and reduced risk of additional CAL loss. However, differences in study methodology and lack of data precluded an adequate and complete pooling of data for a more comprehensive analyses. It was difficult to establish definitive conclusions, although patients with deep pockets, progressive or 'active' disease, or specific microbiological profile, can benefit more from this adjunctive therapy."[12] ### Locally delivered adjunctive antimicrobial treatment[edit] Chemical antimicrobials may be used by the clinician to help reduce the bacterial load in the diseased pocket. "Among the locally administered adjunctive antimicrobials, the most positive results occurred for tetracycline, minocycline, metronidazole, and chlorhexidine. Adjunctive local therapy generally reduced PD levels....Whether such improvements, even if statistically significant, are clinically meaningful remains a question." [13] Minocycline is typically delivered via slim syringe applicators. Chlorhexidine impregnated chips are also available. Hydrogen peroxide is a naturally occurring antimicrobial that can be delivered directly to the gingival sulcus or periodontal pocket using a custom formed medical device called a Perio Tray. [Title = Custom Tray Application of Peroxide Gel as an Adjunct to Scaling and Root Planing in the Treatment of Periodontitis: A Randomized, Controlled Three-Month Clinical Trial J Clin Dent 2012;23:48–56.] Hydrogen peroxide gel was demonstrated to be effective in controlling the bacteria biofilm [Subgingival Delivery of Oral Debriding Agents: A Proof of Concept J Clin Dent 2011;22:149–158] The research shows that a direct application of hydrogen peroxide gel killed virtually all of the bacterial biofilm, was directly and mathematically delivered up to 9mm into periodontal pockets. ### Modulating the host response[edit] Sub-antimicrobial doses of doxycycline (SDD) have been used to alter host response to the periodontal pathogens. This is believed to disrupt the action of matrix metalloproteinases and thus minimise host mediated tissue destruction. "The adjunctive use of SDD with SRP is statistically more effective than SRP alone in reducing PD and in achieving CAL gain."[14] ## Systemic Factors[edit] Chronic periodontitis is an inflammatory immune response against the presence of bacteria present. Recent research has suggested that epithelial lining ulceration in chronic periodontal pockets are due to systemic bacterial dissemination and widespread bacterial inflammatory markers present in the host. Two of the most widely investigated systemic diseases associated with chronic periodontitis is diabetes mellitus and cardiovascular disease.[15] ### Diabetes Mellitus[edit] Both type 1 and type 2 diabetes have shown a link with the treatment and progression of chronic periodontitis. Chronic periodontitis is more serve in patients that have diabetes than those without, confirming a significant association. With type 2 diabetes patients being shown to have 3.8 times more bone loss and 2.8 times more clinical attachment loss than non-diabetic individuals. With patients with poorly controlled diabetes having a higher risk of alveolar bone loss.[16] Chronic periodontitis can also be a metabolic stressor influencing diabetes control, influencing insulin resistance or becoming a source of inflammatory marker secretion which may strengthen the amount of advanced glycation end product (AGE) mediated cytokine response.[17] Monocytic hyperresponsiveness to bacterial antigen is a biological mechanism that links periodontal disease and diabetes. Increased production of proinflammatory cytokines and mediators cause tissue destruction, attachment loss as well as bone loss causing delayed wound healing.[18] ### Cardiovascular Disease[edit] Chronic periodontitis is a marker for cardiovascular disease (CVD).[19] Mechanisms associated with cardiovascular risk are that chronic periodontitis increases inflammatory mediator levels and this may contribute to the onset of CVD, while treatment of chronic periodontitis reduces systemic levels of inflammatory mediators.[20] Certain bacteria found in the periodontal pockets have also been associated to cause atheromatous plaques.[21] Treatment protocol for chronic periodontitis with CVD does not need to be modified as normal periodontal treatment techniques are seen to be effective in CVD patients with additional supportive therapy.[22] ## Costs of treatment[edit] "Costs for tooth retention via supportive periodontal therapy are relatively low compared with alternatives (e.g. implants or bridgework) even in periodontally impaired teeth.".[23] However, health outcomes of periodontal therapy are not directly comparable with those from implants or bridgework.[24] ## Research[edit] ### Management[edit] Long term randomized clinical trials need to be conducted to determine if regular routine scaling and polishing is clinically effective for reducing the risk of chronic periodontitis in healthy adults.[25] Lasers are increasingly being used in treatments for chronic periodontitis. However, there is some controversy over their use: "No consistent evidence supports the efficacy of laser treatment as an adjunct to non-surgical periodontal treatment in adults with chronic periodontitis."[26] ### Tentative links to other conditions[edit] There is little evidence linking progression of periodontal disease to low birth weight or preterm birth: "In these women with periodontitis and within this study's limitations, disease progression was not associated with an increased risk for delivering a pre-term or a low birthweight infant."[27] There is recently emerged evidence linking chronic periodontitis with head and neck squamous cell carcinoma: "Patients with periodontitis were more likely to have poorly differentiated oral cavity SCC than those without periodontitis (32.8% versus 11.5%; P = 0.038)".[28] There is evidence to suggest that periodontal disease may play a role in the pathogenesis of Alzheimer's Disease.[29] ## References[edit] 1. ^ a b Shaddox, Luciana M; Walker, Clay B (2010-08-11). "Treating chronic periodontitis: current status, challenges, and future directions". Clinical, Cosmetic and Investigational Dentistry. 2: 79–91. doi:10.2147/CCIDE.S7712. ISSN 1179-1357. PMC 3645457. PMID 23662085. 2. ^ Heitz-Mayfield LJ, Schätzle M, Löe H, et al. (October 2003). "Clinical course of chronic periodontitis. II. Incidence, characteristics and time of occurrence of the initial periodontal lesion". J. Clin. Periodontol. 30 (10): 902–8. doi:10.1034/j.1600-051X.2003.00399.x. PMID 14710770. 3. ^ Moore WE, Holdeman LV, Cato EP, Smibert RM, Burmeister JA, Ranney RR (November 1983). "Bacteriology of moderate (chronic) periodontitis in mature adult humans". Infect. Immun. 42 (2): 510–5. doi:10.1128/IAI.42.2.510-515.1983. PMC 264458. PMID 6642641. 4. ^ a b Loesche WJ, Grossman NS (October 2001). "Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment". Clin. Microbiol. Rev. 14 (4): 727–52, table of contents. doi:10.1128/CMR.14.4.727-752.2001. PMC 89001. PMID 11585783. 5. ^ Armitage GC (1999). "Development of a classification system for periodontal diseases and conditions". Ann. Periodontol. 4 (1): 1–6. doi:10.1902/annals.1999.4.1.1. PMID 10863370. 6. ^ Caton, Jack G.; Armitage, Gary; Berglundh, Tord; Chapple, Iain L. C.; Jepsen, Søren; Kornman, Kenneth S.; Mealey, Brian L.; Papapanou, Panos N.; Sanz, Mariano; Tonetti, Maurizio S. (2018). "A new classification scheme for periodontal and peri-implant diseases and conditions – Introduction and key changes from the 1999 classification". Journal of Clinical Periodontology. 45 (S20): S1–S8. doi:10.1111/jcpe.12935. ISSN 1600-051X. PMID 29926489. 7. ^ Van der Weijden GA, Timmerman MF (2002). "A systematic review on the clinical efficacy of subgingival debridement in the treatment of chronic periodontitis". J. Clin. Periodontol. 29 (S3): 55–71. doi:10.1034/j.1600-051X.29.s3.3.x. PMID 12787207. Archived from the original on 2013-01-05. 8. ^ Eberhard, Joerg; Jepsen, Sören; Jervøe-Storm, Pia-Merete; Needleman, Ian; Worthington, Helen V. (2015-04-17). "Full-mouth treatment modalities (within 24 hours) for chronic periodontitis in adults" (PDF). The Cochrane Database of Systematic Reviews (4): CD004622. doi:10.1002/14651858.CD004622.pub3. ISSN 1469-493X. PMID 25884249. 9. ^ Heitz-Mayfield LJ, Trombelli L, Heitz F, Needleman I, Moles D (2002). "A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis". J. Clin. Periodontol. 29 (Suppl 3): 92–102, discussion 160–2. doi:10.1034/j.1600-051X.29.s3.5.x. PMID 12787211. 10. ^ Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ (2006). Needleman I (ed.). "Guided tissue regeneration for periodontal infra-bony defects". Cochrane Database Syst Rev (2): CD001724. doi:10.1002/14651858.CD001724.pub2. PMID 16625546. 11. ^ Esposito M, Grusovin MG, Papanikolaou N, Coulthard P, Worthington HV (2009). Esposito M (ed.). "Enamel matrix derivative (Emdogain(R)) for periodontal tissue regeneration in intrabony defects". Cochrane Database Syst Rev (4): CD003875. doi:10.1002/14651858.CD003875.pub3. PMC 6786880. PMID 19821315. 12. ^ Herrera D, Sanz M, Jepsen S, Needleman I, Roldán S (2002). "A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients". J. Clin. Periodontol. 29 (Suppl 3): 136–59, discussion 160–2. doi:10.1034/j.1600-051X.29.s3.8.x. PMID 12787214. 13. ^ Bonito AJ, Lux L, Lohr KN (August 2005). "Impact of local adjuncts to scaling and root planing in periodontal disease therapy: a systematic review". J. Periodontol. 76 (8): 1227–36. doi:10.1902/jop.2005.76.8.1227. PMID 16101353. 14. ^ Reddy MS, Geurs NC, Gunsolley JC (December 2003). "Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review". Ann. Periodontol. 8 (1): 12–37. doi:10.1902/annals.2003.8.1.12. PMID 14971246. 15. ^ Shaddox, Luciana M; Walker, Clay B (2010-08-11). "Treating chronic periodontitis: current status, challenges, and future directions". Clinical, Cosmetic and Investigational Dentistry. 2: 79–91. doi:10.2147/CCIDE.S7712. ISSN 1179-1357. PMC 3645457. PMID 23662085. 16. ^ Taylor, George W.; Burt, Brian A.; Becker, Mark P.; Genco, Robert J.; Shlossman, Marc; Knowler, William C.; Pettitt, David J. (1998). "Non-Insulin Dependent Diabetes Mellitus and Alveolar Bone Loss Progression Over 2 Years". Journal of Periodontology. 69 (1): 76–83. doi:10.1902/jop.1998.69.1.76. hdl:2027.42/141702. ISSN 1943-3670. PMID 9527565. 17. ^ Löe, Harald (1993-01-01). "Periodontal Disease: The sixth complication of diabetes mellitus". Diabetes Care. 16 (1): 329–334. doi:10.2337/diacare.16.1.329. ISSN 0149-5992. PMID 8422804. S2CID 7257038. 18. ^ Salvi, Giovanni E.; Collins, John G.; Yalda, Behnaz; Arnold, Roland R.; Lang, Niklaus P.; Offenbacher, Steven (1997). "Monocytic TNFα secretion patterns in IDDM patients with periodontal diseases". Journal of Clinical Periodontology. 24 (1): 8–16. doi:10.1111/j.1600-051X.1997.tb01178.x. ISSN 1600-051X. PMID 9049792. 19. ^ Humphrey, Linda L.; Fu, Rongwei; Buckley, David I.; Freeman, Michele; Helfand, Mark (December 2008). "Periodontal Disease and Coronary Heart Disease Incidence: A Systematic Review and Meta-analysis". Journal of General Internal Medicine. 23 (12): 2079–2086. doi:10.1007/s11606-008-0787-6. ISSN 0884-8734. PMC 2596495. PMID 18807098. 20. ^ D'Aiuto, Francesco; Parkar, Mohamed; Nibali, Luigi; Suvan, Jean; Lessem, Jan; Tonetti, Maurizio S. (May 2006). "Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial". American Heart Journal. 151 (5): 977–984. doi:10.1016/j.ahj.2005.06.018. ISSN 1097-6744. PMID 16644317. 21. ^ Peruzzo, Daiane C.; Benatti, Bruno B.; Ambrosano, Glaucia M. B.; Nogueira-Filho, Getúlio R.; Sallum, Enilson A.; Casati, Márcio Z.; Nociti, Francisco H. (August 2007). "A systematic review of stress and psychological factors as possible risk factors for periodontal disease". Journal of Periodontology. 78 (8): 1491–1504. doi:10.1902/jop.2007.060371. ISSN 0022-3492. PMID 17668968. 22. ^ Offenbacher, Steven; Beck, James D.; Moss, Kevin; Mendoza, Luisito; Paquette, David W.; Barrow, David A.; Couper, David J.; Stewart, Dawn D.; Falkner, Karen L.; Graham, Susan P.; Grossi, Sara (February 2009). "Results from the Periodontitis and Vascular Events (PAVE) Study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease". Journal of Periodontology. 80 (2): 190–201. doi:10.1902/jop.2009.080007. ISSN 0022-3492. PMC 2778200. PMID 19186958. 23. ^ Pretzl B, Wiedemann D, Cosgarea R, et al. (August 2009). "Effort and costs of tooth preservation in supportive periodontal treatment in a German population". J. Clin. Periodontol. 36 (8): 669–76. doi:10.1111/j.1600-051X.2009.01409.x. PMID 19566541. 24. ^ Pennington M; Vernazza; Heasman; et al. (August 2009). "Making the leap from cost analysis to cost-effectiveness". J. Clin. Periodontol. 36 (8): 667–668. doi:10.1111/j.1600-051X.2009.01424.x. PMID 19566540. 25. ^ Worthington, Helen V.; Clarkson, Jan E.; Bryan, Gemma; Beirne, Paul V. (2013-11-07). "Routine scale and polish for periodontal health in adults". The Cochrane Database of Systematic Reviews (11): CD004625. doi:10.1002/14651858.CD004625.pub4. ISSN 1469-493X. PMID 24197669. 26. ^ Karlsson MR, Diogo Löfgren CI, Jansson HM (November 2008). "The effect of laser therapy as an adjunct to non-surgical periodontal treatment in subjects with chronic periodontitis: a systematic review". J. Periodontol. 79 (11): 2021–8. doi:10.1902/jop.2008.080197. PMID 18980508. 27. ^ Michalowicz BS, Hodges JS, Novak MJ, et al. (April 2009). "Change in periodontitis during pregnancy and the risk of pre-term birth and low birthweight". J. Clin. Periodontol. 36 (4): 308–14. doi:10.1111/j.1600-051X.2009.01385.x. PMC 2741139. PMID 19426177. 28. ^ Tezal M, Sullivan MA, Hyland A, et al. (September 2009). "Chronic periodontitis and the incidence of head and neck squamous cell carcinoma". Cancer Epidemiol. Biomarkers Prev. 18 (9): 2406–12. doi:10.1158/1055-9965.EPI-09-0334. PMID 19745222. 29. ^ http://www.journaloforalmicrobiology.net/index.php/jom/article/view/29143 ## External links[edit] Classification D ICD-10: K05.3 * ICD-9-CM: 523.4 * MeSH: D055113 * DiseasesDB: 29362 * Medicine portal * British Society for Periodontology * American Society of Periodontology * https://web.archive.org/web/20090720042329/http://www.uic.edu/classes/peri/peri323/syallbus/class/charac1.htm * v * t * e Acquired tooth disease Hard tissues * Caries (tooth decay) * Attrition * Abrasion * Erosion * Hypercementosis * tooth resorption (External resorption, Internal resorption, Root resorption) Pulp/periapical (Endodontal) Pulpal * External resorption * Internal resorption * Irreversible pulpitis * Reversible pulpitis * Pulp necrosis * Pink tooth of Mummery Periapical * Acute apical periodontitis * Chronic apical periodontitis * Combined periodontic-endodontic lesions * Fistula * Periapical abscess * Phoenix abscess * Vertical root fracture Ungrouped * Pulpitis * Radicular cyst * Periapical abscess Gingiva/periodontal (Periodontal) * Gingivitis * Periodontitis (Chronic periodontitis) * Periodontal disease Bone cyst * Dentigerous cyst * Calcifying odontogenic cyst * Glandular odontogenic cyst Other * Cracked tooth syndrome To be grouped from periodontology Diagnoses * Chronic periodontitis * Localized aggressive periodontitis * Generalized aggressive periodontitis * Periodontitis as a manifestation of systemic disease * Necrotizing periodontal diseases * Abscesses of the periodontium * Combined periodontic-endodontic lesions Pathogenesis * A. actinomycetemcomitans * Capnocytophaga sp. * F. nucleatum * P. gingivalis * P. intermedia * T. forsythia * T. denticola Pathologic entities * Calculus * Edentulism * Fremitus * Furcation defect * Gingival enlargement * Gingival pocket * Gingivitis * Horizontal bony defect * Linear gingival erythema * Occlusal trauma * Periodontal pocket * Periodontal disease * Periodontitis * Plaque * Recession * Vertical bony defect * v * t * e Dentistry involving supporting structures of teeth (Periodontology) Anatomy * Periodontium * Alveolar bone * Biologic width * Bundle bone * Cementum * Free gingival margin * Gingiva * Gingival fibers * Gingival sulcus * Junctional epithelium * Mucogingival junction * Periodontal ligament * Sulcular epithelium * Stippling Disease Diagnoses * Chronic periodontitis * Localized aggressive periodontitis * Generalized aggressive periodontitis * Periodontitis as a manifestation of systemic disease * Periodontosis * Necrotizing periodontal diseases * Abscesses of the periodontium * Combined periodontic-endodontic lesions Infection * A. actinomycetemcomitans * Capnocytophaga sp. * F. nucleatum * P. gingivalis * P. intermedia * T. forsythia * T. denticola * Red complex * Entamoeba gingivalis (amoebic) * Trichomonas tenax Other * Calculus * Clinical attachment loss * Edentulism * Fremitus * Furcation defect * Gingival enlargement * Gingival pocket * Gingival recession * Gingivitis * Horizontal bony defect * Linear gingival erythema * Occlusal trauma * Periodontal pocket * Periodontal disease * Periodontitis * Plaque * Vertical bony defect Treatment and prevention * Periodontal examination * Ante's law * Brushing * Bleeding on probing * Chlorhexidine gluconate * Flossing * Hydrogen peroxide * Mouthwash * Oral hygiene * Tetracycline * Triclosan * Host modulatory therapy Treatment Conventional therapy * Debridement * Scaling and root planing * Full mouth disinfection * Full mouth ultrasonic debridement Surgery * Apically positioned flap * Bone graft * Coronally positioned flap * Crown lengthening * Free gingival graft * Gingival grafting * Gingivectomy * Guided bone regeneration * Guided tissue regeneration * Enamel matrix derivative * Implant placement * Lateral pedicle graft * Open flap debridement * Pocket reduction surgery * Socket preservation * Sinus lift * Subepithelial connective tissue graft * Tools * Curette * Membrane * Probe * Scaler Important personalities * Tomas Albrektsson * Frank Beube * Per-Ingvar Brånemark * Robert Gottsegen * Gary Greenstein * Jan Lindhe * Brian Mealey * Preston D. Miller * Willoughby D. Miller * Carl E. Misch * John Mankey Riggs * Jay Seibert * Jørgen Slots * Paul Roscoe Stillman * Dennis P. Tarnow * Hom-Lay Wang * James Leon Williams * W. J. Younger Other specialties * Endodontology * Orthodontology * Prosthodontology * v * t * e Dentistry Specialties * Endodontics * Oral and maxillofacial pathology * Oral and maxillofacial radiology * Oral and maxillofacial surgery * Orthodontics and dentofacial orthopedics * Pediatric dentistry * Periodontics * Prosthodontics * Dental public health * Cosmetic dentistry * Dental implantology * Geriatric dentistry * Restorative dentistry * Forensic odontology * Dental traumatology * Holistic dentistry Dental surgery * Dental extraction * Tooth filling * Root canal therapy * Root end surgery * Scaling and root planing * Teeth cleaning * Dental bonding * Tooth polishing * Tooth bleaching * Socket preservation * Dental implant Organisations * American Association of Orthodontists * British Dental Association * British Dental Health Foundation * British Orthodontic Society * Canadian Association of Orthodontists * Dental Technologists Association * General Dental Council * Indian Dental Association * National Health Service See also * Index of oral health and dental articles * Outline of dentistry and oral health * Dental fear * Dental instruments * Dental material * History of dental treatments * Infant oral mutilation * Mouth assessment * Oral hygiene [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	Chronic periodontitis	c0266929	27,397	wikipedia	https://en.wikipedia.org/wiki/Chronic_periodontitis	2021-01-18T18:59:09	{"mesh": ["D055113"], "umls": ["C0266929"], "icd-9": ["523.4"], "icd-10": ["K05.3"], "wikidata": ["Q5113988"]}
A number sign (#) is used with this entry because of evidence that immunodeficiency-25 (IMD25) is caused by homozygous mutation in the CD247 (CD3Z) gene (186780) on chromosome 1q24. One such patient has been reported. Clinical Features Rieux-Laucat et al. (2006) described a boy, of Caribbean origin and of unknown paternity, with primary T-cell immunodeficiency. He presented at the age of 4 months with erythroderma, protracted diarrhea, and pulmonary abscesses caused by Pseudomonas aeruginosa. During the next 2 years, he had recurrent episodes of herpes simplex virus infection of the mouth and skin, 2 episodes of oral and skin infections with Candida albicans, and 2 pulmonary infections. The patient's T-cell counts were very low, B-cell counts were normal, and there was eosinophilia. A haploidentical bone marrow transplantation, with the mother as the donor, was performed when the patient was 30 months old. The transplant resulted in sustained donor-recipient chimerism and correction of the immunodeficiency. Three years later, the patient was well and living at home. Molecular Genetics In a boy with primary T-cell immunodeficiency, Rieux-Laucat et al. (2006) identified homozygosity for a germline Q70X mutation in the CD247 gene (186780.0001). Some of the patient's T cells had low levels of the T-cell receptor-CD3 complex and carried the Q70X mutation on both alleles of the CD3Z gene, whereas other T cells had normal levels of the complex and bore the Q70X mutation on only 1 allele of CD3Z, plus 1 of 3 heterozygous somatic mutations of CD3Z on the other allele (186780.0002-186780.0004), allowing expression of poorly functional T-cell receptor-CD3 complexes. Thus the patient had both inherited and somatic CD3Z mutations as the basis of the T-cell deficiency. History Alarcon et al. (1988) described 2 brothers who had low expression of antigen receptor on the surface of their T lymphocytes. Functional analyses of their T cells showed impaired immune response to alloantigens, tetanus toxoid, and mitogens. Biochemical studies showed reduced intracellular expression of CD3-zeta chains; all other components of the T-cell receptor-CD3 complex were expressed normally intracellularly. Alarcon et al. (1988) suggested that the impaired association of the CD3-zeta chain with the other chains of the complex was the primary defect leading to the low expression of T-cell receptor-CD3 complex and immunodeficiency in these children. However, further studies of these brothers by Arnaiz-Villena et al. (1991, 1992) indicated a CD3-gamma abnormality, and genetic analysis identified compound heterozygous mutation in the CD3G gene (186740.0001 and 186740.0002), consistent with primary immunodeficiency due to a defect in the gamma subunit of the CD3 complex (IMD17; 615607). INHERITANCE \- Autosomal recessive IMMUNOLOGY \- Recurrent infections \- Viral infections \- Fungal infections \- Bacterial infections \- Low number of T cells \- Decreased expression of the TCR/CD3 complex \- Eosinophilia MISCELLANEOUS \- Onset in infancy \- One patient has been reported (last curated June 2016) MOLECULAR BASIS \- Caused by mutation in the CD247 antigen gene (CD247, 186780.0001 ) ▲ 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	IMMUNODEFICIENCY 25	c1857798	27,398	omim	https://www.omim.org/entry/610163	2019-09-22T16:05:00	{"mesh": ["C565712"], "omim": ["610163"], "orphanet": ["169160"], "synonyms": ["IMMUNODEFICIENCY DUE TO DEFECT IN CD3-ZETA", "T-B+ SCID due to CD3delta/CD3epsilon/CD3zeta", "Alternative titles"]}
Leschke syndrome is a condition characterized by growth retardation and intellectual disability.[1] The syndrome is named after German internist Erich Leschke. Further symptoms may include diabetes mellitus, genital hypoplasia, and hyperthyroidism.[2] ## See also[edit] * Silver–Russell syndrome * 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. 831. ISBN 978-1-4160-2999-1. 2. ^ Schneiderman, Paul; Grossman, Marc (2006). A Clinician's Guide to Dermatologic Differential Diagnosis, Volume 1: The Text. CRC Press. p. 540. ISBN 9780203090527. ## External links[edit] * synd/1418 at Who Named It? This dermatology 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	Leschke syndrome	None	27,399	wikipedia	https://en.wikipedia.org/wiki/Leschke_syndrome	2021-01-18T18:59:57	{"wikidata": ["Q6530306"]}

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