For a phenotypic description and a discussion of genetic heterogeneity of vitiligo susceptibility, see VAMAS1 (606579). Mapping Arcos-Burgos et al. (2002) collected pedigree data on vitiligo from a set of 56 multigeneration families belonging to the Paisa community in Antioquia, Colombia, with the goal of applying the unified model of complex segregation and linkage disequilibrium analyses to test the hypotheses of the existence of a major gene predisposing to vitiligo and that allelic or haplotype polymorphisms of microsatellite loci at 6p21.4-p21.3 spanning HLA are associated with this predisposition. Among the 15 models of complex segregation used, the one that best fit the data was that of a major dominant gene and the existence of strong environmental effects acting on the recessive genotype. The penetrance and risk estimations discriminated 2 sets of vitiligo patients: those with early onset of vitiligo cosegregating with a dominant mode of inheritance without environmental effects, and those with late onset of vitiligo cosegregating with the recessive genotype and being influenced by environmental effects. After establishing the normal distribution of allelic frequencies and performing correction for multiple comparisons, the linkage disequilibrium analysis suggested that a major genetic factor could be located at 6p21.3, because significant case-control differences for allele 122 at marker D6S265 and significant linkage disequilibrium between D6S276 and D6S273 were detected in cases but not in controls.
These include the following: Prader-Willi syndrome ; Norrie disease ; Niemann–Pick disease, type C ; and myotonic dystrophy . ... Hypersomnia can also develop within months after viral infections such as Whipple's disease , mononucleosis , HIV , and Guillain–Barré syndrome . [9] Behaviorally induced insufficient sleep syndrome must also be considered in the differential diagnosis of secondary hypersomnia. ... "Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation". ... M., File, J., Farber, N., & Mignot, E. (2005). Kleine–Levin syndrome: A systematic review of 186 cases in the literature. ... Familial Recurrent Hypersomnia: Two Siblings with Kleine-Levin Syndrome and Menstrual-Related Hypersomnia.
Clinical Features Smith and Strang (1958) described a disorder, which they called oasthouse urine disease. The infant had white hair, hyperpnea, convulsions, and mental retardation. The urine had a characteristic and unique odor like that of an oasthouse (building for drying hops). Although phenylpyruvic acid was found in the urine, the odor was different from that of phenylketonuria. The defect was thought to concern the utilization of the alpha-keto acids of all essential amino acids as a result of which alpha-keto acids, their amino acid precursors or hydroxy acid derivatives accumulated in the blood and overflowed in the urine.
It is an accepted medical sign of a midbrain lesion, first described in 1927 by J Collier. [3] With the eyes in the primary position, the sclera can be seen above the cornea , and further upgaze increases the distance between the eyelids and irises. [4] Causes include upper dorsal midbrain supranuclear lesions such as Parinaud's syndrome , 'top of the basilar syndrome', [2] midbrain infarction, neurodegeneration or tumour, multiple sclerosis , encephalitis , and Miller-Fisher syndrome . [5] The cause is thought to be damage to the posterior commissure levator inhibitory fibres [2] which originate in the M-group of neurons . [4] References [ edit ] ^ "Colliers sign" . biology-online.org. 2019-10-07. ^ a b c Larner, Andrew J. (2010).
Clinical Features Haack et al. (2012) reported 2 patients with mitochondrial complex I deficiency manifesting as Leigh syndrome (see 256000). One patient had developmental delay, hypotonia, and ataxia. ... Molecular Genetics In 2 unrelated patients with mitochondrial complex I deficiency nuclear type 27 manifesting as Leigh syndrome, Haack et al. (2012) identified homozygosity or compound heterozygosity for mutations in the MTFMT gene (611766.0001 and 611766.0004). INHERITANCE - Autosomal recessive HEAD & NECK Eyes - Gaze palsy - Optic atrophy GENITOURINARY Bladder - Neurogenic bladder dysfunction MUSCLE, SOFT TISSUES - Hypotonia NEUROLOGIC Central Nervous System - Developmental delay - Impaired intellectual development - Spasticity - White matter abnormalities consistent with Leigh syndrome LABORATORY ABNORMALITIES - Mitochondrial complex I deficiency in various tissues MISCELLANEOUS - Onset in infancy - Two unrelated patients have been reported (last curated January 2019) MOLECULAR BASIS - Caused by mutation in the mitochondrial methionyl-tRNA formyltransferase gene (MTFMT, 611766.0001 ) ▲ Close
Some diseases, including epilepsy , schizophrenia , and migraine headaches were once considered functional disorders, but are no longer generally classified that way. [1] Examples [ edit ] Irritable bowel syndrome Fibromyalgia Chronic fatigue syndrome Chronic pelvic pain Cyclic vomiting syndrome Interstitial cystitis Temporomandibular joint pain, functional neurological symptom disorder See also [ edit ] Idiopathic disease Functional gastrointestinal disorder Functional symptom Inborn errors of metabolism References [ edit ] ^ Natelson, Benjamin H. (1998).
Hidradenocarcinoma is a rare tumor caused by the abnormal growth of cells in a sweat gland . It is a type of cancer that usually begins as a single spot ( lesion ) on the skin of the head or neck, but can be been found on other parts of the body. This type of tumor most often develops in people between the ages of 30-60 years old, but has been found in children. Hidradenocarcinoma is usually painless and tends to grow slowly, but may spread into nearby tissues, especially lymph nodes, or to more distant parts of the body (metastasis). The cause of the tumor is unknown. Diagnosis is usually made by careful examination and a series of special skin tests.
Mutation in the PCDH15 gene can also cause Usher syndrome type IF (602083). Clinical Features Ahmed et al. (2003) reported 3 families with isolated deafness. ... Detailed examination of 2 homozygous carriers in middle age showed no evidence of Usher syndrome and no vestibular abnormalities. ... INHERITANCE - Autosomal recessive HEAD & NECK Ears - Deafness, neurosensory - Severe to profound deafness Eyes - Normal vision MISCELLANEOUS - Prelingual onset - Allelic disorder to Usher syndrome type 1F ( 602083 ) MOLECULAR BASIS - Caused by mutation in the protocadherin-15 gene (PCDH15, 605514.0006 ) ▲ Close
Clinical Features Goolamali et al. (1976) observed this syndrome of recurrent inflammatory lesions of the mouth, genitalia, and eyes in 5 persons in 4 generations of a family. ... In the family reported, 2 brothers suffered from an unusual schizoaffective disorder and their mother, who also had Behcet syndrome, had severe alopecia areata, Raynaud phenomenon, and rheumatoid arthritis. ... They also investigated whether disease activity or the duration of Behcet syndrome correlated with leptin concentration. The mean serum leptin concentrations in patients with Behcet syndrome were significantly higher than in healthy control volunteers. Active Behcet syndrome patients had significantly higher leptin concentrations when compared with patients in inactive periods.
"Thalidomide in the treatment of the mucocutaneous lesions of the Behcet syndrome. A randomized, double-blind, placebo-controlled trial". ... "Optimal use of ivig in a patient with Behçet syndrome and common variable immunodeficiency". ... "Gastrointestinal involvement in Behçet's syndrome". Am. J. Gastroenterol . 93 (12): 2633. PMID 9860455 . ^ "Behcet's Syndrome: MedlinePlus" . nih.gov . Archived from the original on 4 July 2016 . ... "Number VII Behçet's disease (Adamantiades syndrome)". Oral Dis . 12 (2): 78–84. doi : 10.1111/j.1601-0825.2005.01144.x .
Behçet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behçet disease result from widespread inflammation of blood vessels (vasculitis). This inflammation most commonly affects small blood vessels in the mouth, genitals, skin, and eyes. Painful mouth sores called aphthous ulcers are usually the first sign of Behçet disease. These sores can occur on the lips, tongue, inside the cheeks, the roof of the mouth, the throat, and the tonsils.
Behçet disease leads to swelling of the blood vessels and affects multiple organs throughout the body. Symptoms generally begin when individuals are in their 20s or 30s, but may occur at any age. Symptoms may include ulcers affecting the mouth and genitals, various skin lesions, and swelling of the membranes affecting the eyes. In some people, symptoms include arthritis (swollen, painful, stiff joints), skin problems, and inflammation of the digestive tract, brain, and spinal cord. Symptoms of Behçet disease may be active and then become inactive, but they never completely go away.
Beckers et al. (2015) reported 18 patients with XLAG syndrome, including 13 previously studied by Trivellin et al. (2014). ... Beckers et al. (2015) stated that a unifying feature of XLAG syndrome is the strikingly early age at onset, given that the children appear clinically normal at birth. ... Daly et al. (2016) concluded that GHRH hypersecretion can accompany the pituitary abnormalities seen in XLAG syndrome, and suggested that the pathology of the disorder may include hypothalamic dysregulation of GHRH secretion, consistent with localization of GPR101 (300393) in the hypothalamus. ... Daly et al. (2016) concluded that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at Xq26.3 in male patients. ... Immunohistochemical analysis confirmed the tumor as a typical XLAG mixed GH- and PRL-secreting adenoma; however, Ki-67 (see 176741) was 3.5% and there were more than 2 mitoses per high-powered field, indicating higher proliferation than in other XLAG syndrome cases. Naves et al. (2016) stated that this case illustrated the aggressive nature of tumor evolution and the challenging clinical management in XLAG syndrome, emphasizing the importance of early intervention.
Differential Diagnosis Pituitary gigantism can be nonsyndromic or can be associated with other manifestations as part of a syndrome (Figure 4) [Caimari & Korbonits 2016]. Figure 4. Syndromic and nonsyndromic genetic causes of pituitary gigantism Approximately 50% of all individuals with pituitary gigantism have a known predisposing genetic variant [Rostomyan et al 2015, Iacovazzo et al 2016]. ... Disorders to Consider in the Differential Diagnosis of Pituitary Gigantism View in own window Disease Name Gene Prevalence of Pituitary Disease by Gender Age of Onset of GH Excess Clinically Evident GH Excess (% of Affected Individuals) Pituitary Findings Extrapituitary Manifestations McCune-Albright syndrome 1 GNAS 2 Equal Variable (~30% diagnosed < age 16 yrs) ~20% 3 GH-secreting pituitary adenoma or mixed GH- & prolactin-secreting pituitary adenoma &/or hyperplasia of GH- & prolactin-secreting pituitary cells Polyostotic fibrous dysplasia, café au lait spots, precocious puberty, other manifestations Multiple endocrine neoplasia type 1 1 MEN1 ↑ Female 4 Typically adult-onset; gigantism is rare 2%-5% GH-secreting pituitary adenoma, mixed GH- & prolactin-secreting pituitary adenoma; pituitary hyperplasia secondary to a GHRH-secreting neuroendocrine tumor; other pituitary adenoma subtypes can occur: prolactinoma, NFPA, corticotropinoma Primary hyperparathyroidism, pancreatic neuroendocrine tumors, other manifestations Carney complex 1 PRKAR1A 5 Equal Typically adult-onset, but gigantism can occur ~10% 6 GH-secreting pituitary adenoma or mixed GH- & prolactin-secreting pituitary adenoma &/or hyperplasia of GH- & prolactin-secreting pituitary cells; corticotropinomas described in 2 persons 7 Skin hyperpigmentation, myxomas, PPNAD, other manifestations AIP -related familial isolated pituitary adenoma 8 AIP ↑ Male Typically 2nd decade of life ~80% GH- or mixed GH- & prolactin-secreting pituitary adenoma; pituitary hyperplasia rare; characteristically, can present w/pituitary apoplexy 9 ; other pituitary adenoma subtypes can occur: prolactinoma, NFPA, corticotropinoma, thyrotropinoma No X-linked acrogigantism 8 GPR101 ↑ Female Early onset (in all cases < age 4 yrs) 100% Mixed GH- & prolactin-secreting pituitary adenoma &/or hyperplasia of GH- & prolactin-secreting pituitary cells; pituitary apoplexy not described No GH = growth hormone; GHRH = growth hormone-releasing hormone; NFPA = nonfunctioning pituitary adenoma; PPNAD = primary pigmented nodular adrenal disease 1. Syndromic 2. McCune-Albright syndrome is caused by early embryonic postzygotic somatic activating mutation of GNAS 3.
Differential diagnosis In early childhood pituitary gigantism due to a growth hormone secreting pituitary adenoma can be associated with other conditions like AIP germline mutations, McCune-Albright syndrome, and rarely MEN1 syndrome, or Carney complex.
X-linked acrogigantism (X-LAG) is a condition that causes abnormally fast growth beginning early in life. Babies with this condition are a normal size at birth but begin to grow rapidly in infancy or early childhood, and affected children are taller than their peers. This rapid growth is caused by an abnormality of the pituitary gland . The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions, including growth. Individuals with X-LAG may have the condition as a result of enlargement (hyperplasia) of the gland or development of a noncancerous tumor in the gland (called a pituitary adenoma).
Changes in the glutamate system and GABA system may play an important role at different time points during benzodiazepine withdrawal syndrome . [6] Alcohol [ edit ] See also: Alcohol-related brain damage Binge drinking may induce brain damage due to the repeated cycle of acute intoxication followed by an acute abstinence withdrawal state. [7] Based on animal studies, regular binge drinking in the long-term is thought to be more likely to result in brain damage than chronic (daily) alcoholism. ... Ethanol (alcohol) has a very similar mechanism of tolerance and withdrawal to benzodiazepines, involving the GABA A receptors , NMDA receptors and AMPA receptors , but the majority of research into kindling has primarily focused on alcohol. [6] An intensification of anxiety and other psychological symptoms of alcohol withdrawal also occurs. [10] Treatment [ edit ] Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death. [11] Acamprosate , a drug used to promote abstinence from alcohol, an NMDA antagonist drug, reduces excessive glutamate activity in the central nervous system and thereby may reduce excitotoxicity and withdrawal related brain damage. [12] [13] See also [ edit ] Kindling model References [ edit ] ^ a b Stephens, DN.; Duka, T. ... "Identification and management of alcohol withdrawal syndrome" . Drugs . 75 (4): 353–65. doi : 10.1007/s40265-015-0358-1 . ... PMID 25666543 . v t e Psychoactive substance-related disorder General SID Substance intoxication / Drug overdose Substance-induced psychosis Withdrawal : Craving Neonatal withdrawal Post-acute-withdrawal syndrome (PAWS) SUD Substance abuse / Substance-related disorders Physical dependence / Psychological dependence / Substance dependence Combined substance use SUD Polysubstance dependence SID Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases Alcoholic cardiomyopathy Alcohol flush reaction (AFR) Gastrointestinal diseases Alcoholic liver disease (ALD): Alcoholic hepatitis Auto-brewery syndrome (ABS) Endocrine diseases Alcoholic ketoacidosis (AKA) Nervous system diseases Alcohol-related dementia (ARD) Alcohol intoxication Hangover Neurological disorders Alcoholic hallucinosis Alcoholic polyneuropathy Alcohol-related brain damage Alcohol withdrawal syndrome (AWS): Alcoholic hallucinosis Delirium tremens (DTs) Fetal alcohol spectrum disorder (FASD) Fetal alcohol syndrome (FAS) Korsakoff syndrome Positional alcohol nystagmus (PAN) Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis) Wernicke encephalopathy (WE) Respiratory tract diseases Alcohol-induced respiratory reactions Alcoholic lung disease SUD Alcoholism (alcohol use disorder (AUD)) Binge drinking Caffeine SID Caffeine-induced anxiety disorder Caffeine-induced sleep disorder Caffeinism SUD Caffeine dependence Cannabis SID Cannabis arteritis Cannabinoid hyperemesis syndrome (CHS) SUD Amotivational syndrome Cannabis use disorder (CUD) Synthetic cannabinoid use disorder Cocaine SID Cocaine intoxication Prenatal cocaine exposure (PCE) SUD Cocaine dependence Hallucinogen SID Acute intoxication from hallucinogens (bad trip) Hallucinogen persisting perception disorder (HPPD) Nicotine SID Nicotine poisoning Nicotine withdrawal SUD Nicotine dependence Opioids SID Opioid overdose SUD Opioid use disorder (OUD) Sedative / hypnotic SID Kindling (sedative–hypnotic withdrawal) benzodiazepine : SID Benzodiazepine overdose Benzodiazepine withdrawal SUD Benzodiazepine use disorder (BUD) Benzodiazepine dependence barbiturate : SID Barbiturate overdose SUD Barbiturate dependence Stimulants SID Stimulant psychosis amphetamine : SUD Amphetamine dependence Volatile solvent SID Sudden sniffing death syndrome (SSDS) Toluene toxicity SUD Inhalant abuse
Facial features include a wide nasal bridge, widely-spaced eyes , prominent, low-set ears , a flat nose tip and a small mouth. [2] [3] Less common features include congenital spinal abnormalities , hearing loss or seizures . [2] [4] The syndrome is caused by a mutation in the CDK13 gene , which encodes the protein cyclin-dependent kinase 13. ... CDK13 promotes expression of genes involved in various developmental processes, and these processes are disrupted or not completed when the gene is mutated. [1] [3] [5] The syndrome is diagnosed when genetic testing confirms a mutation in CDK13 . [2] Treatment centres around the symptoms. ... "Heterozygous mutations affecting the protein kinase domain of CDK13 cause a syndromic form of developmental delay and intellectual disability" . ... "De novo variants in CDK13 associated with syndromic ID/DD: Molecular and clinical delineation of 15 individuals and a further review" (PDF) . ... "Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing" .