Kleine–Levin syndrome, a rare disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Narcolepsy, including excessive daytime sleepiness (EDS), often culminating in falling asleep spontaneously but unwillingly at inappropriate times. ... Hales (eds.). Essentials of neuropsychiatry and clinical neurosciences (4 ed.). ... Discovering psychology (5th ed.). New York, NY: Worth Publishers. p. 157. ... Finkelstein, David (ed.). "Impaired Glucose Tolerance in Sleep Disorders".
A number sign (#) is used with this entry because of evidence that succinic semialdehyde dehydrogenase deficiency (SSADHD) is caused by homozygous or compound heterozygous mutation in the ALDH5A1 gene (610045) on chromosome 6p22. Description Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurologic disorder in which an enzyme defect in the GABA degradation pathway causes a consecutive elevation of gamma-hydroxybutyric acid (GHB) and GABA. The clinical features include developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances (summary by Reis et al., 2012). Clinical Features Jakobs et al. (1981) reported a patient with neurologic abnormalities and urinary excretion of gamma-hydroxybutyric acid. Gibson et al. (1983) demonstrated deficiency of the succinic semialdehyde dehydrogenase enzyme in lymphocyte lysates from 2 patients with gamma-hydroxybutyric aciduria.
Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging.
Summary Clinical characteristics. Succinic semialdehyde dehydrogenase (SSADH) deficiency is characterized by infantile-onset hypotonia, developmental delay, cognitive impairment, expressive language deficit, and mild ataxia. Epilepsy is present in about half of affected individuals and is more common in adults. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all affected individuals, more commonly in those who are older. Basal ganglia signs including choreoathetosis, dystonia, and myoclonus have been reported in a few individuals with earlier-onset, more severe disease. Involvement beyond the central nervous system has not been described.
Succinic semialdehyde dehydrogenase (SSADH) deficiency is a disorder that can cause a variety of neurological and neuromuscular problems. The signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. Some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. SSADH deficiency is caused by mutations in the ALDH5A1 gene and is inherited in an autosomal recessive manner. Management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues.
A rare neurometabolic disorder of gamma-aminobutyric acid (GABA) metabolism with a nonspecific clinical presentation (ranging from mild to severe) with the most frequent symptoms being cognitive impairment with prominent deficit in expressive language, hypotonia, ataxia, epilepsy, and behavioral dysregulation. Epidemiology Approximately 450 cases have been reported in the literature to date. Clinical description The mean age of onset is 11 months. Contrary to what is seen in many metabolic encephalopathies, patients do not present with hypoglycemia, hyper-ammonemia, or intermittent lethargy. Infants usually present with a slowly progressive or static encephalopathy manifesting with hypotonia, hyporeflexia, ataxia and delayed acquisition of motor and language developmental milestones in the first two years of life. Seizures occur in more than half of all affected individuals and are usually generalized tonic-clonic or atypical absence.
Porphyria cutanea tarda (PCT) is a form of porphyria that primarily affects the skin. People affected by this condition generally experience "photosensitivity," which causes painful, blistering lesions to develop on sun-exposed areas of the skin (i.e. the hands and face). Skin in these areas may also be particularly fragile with blistering and/or peeling after minor trauma. In some cases, increased hair growth as well as darkening and thickening of the affected skin may occur. Liver abnormalities may develop in some people with the condition and PCT, in general, is associated with an increased risk of liver cirrhosis and liver cancer.
Description De Verneuil et al. (1978) classified porphyria cutanea tarda (PCT), the most common type of porphyria, into 2 types: type I, or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD; 613521) in liver (Elder et al., 1978; Felsher et al., 1982), and type II, or 'familial' type (176100), characterized by 50% deficient activity of the same enzyme in many tissues (Kushner et al., 1976; Elder et al., 1980). Type I is the most common form of PCT, comprising 70 to 80% of cases. The causes of the deficiency are often unclear and are probably multifactorial (review by Lambrecht et al., 2007). Clinical Features Among 10 families containing 17 patients with PCT, Roberts et al. (1988) found that 4 were of type I. Each of these 4 families contained at least 2 subjects with overt PCT; all members of these families, including 7 patients with overt PCT, had normal red cell uroporphyrinogen decarboxylase immunoreactive concentrations and enzyme activities.
Porphyria cutanea tarda (PCT) is the most common form of chronic hepatic porphyria (see this term). It is characterized by bullous photodermatitis. Epidemiology The prevalence in western Europe is estimated at about 1/25,000 and men are more affected than women. Clinical description The disease manifests in adulthood. PCT is acquired (75% of cases) or familial (25% of cases). Generally manifestations of the disease appear earlier in familial cases. Some risk factors can precipitate symptoms: excessive consumption of alcohol, hepatitis C, estrogen, and mutations of the genes that control iron metabolism, leading to iron overload (hemochromatosis).
A number sign (#) is used with this entry because porphyria cutanea tarda type II, or familial PCT, is caused by heterozygous mutation in the gene encoding uroporphyrinogen decarboxylase (UROD; 613521). Hepatoerythropoietic porphyria (HEP) is caused by homozygous or compound heterozygous mutation in the UROD gene. Description Porphyria cutanea tarda (PCT) is characterized by light-sensitive dermatitis and the excretion of large amounts of uroporphyrin in urine (Elder et al., 1980). De Verneuil et al. (1978) and others classified porphyria cutanea tarda, the most common type of porphyria, into 2 types: type I (176090), or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD) in liver (Elder et al., 1978; Felsher et al., 1982), and type II, or 'familial' type, characterized by 50% deficient activity of the same enzyme in many tissues (Kushner et al., 1976; Elder et al., 1980). PCT type II is an autosomal dominant disorder with low penetrance and constitutes about 20% of cases of PCT.
Robbins Basic Pathology (8th ed.). Philadelphia: Saunders/Elsevier. p. 384. ... First aid for the USMLE step 2 CK (8th ed.). New York: McGraw–Hill Medical. p. 357. ... Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. pp. 270, 400–401.
Interauricular communication is a congenital malformation characterized by a communication between the atrial chambers of the heart. Epidemiology Overall, openings between the atrial chambers account for about 6 to 8% of all congenitally malformed hearts. As a group, such defects are detected in 1:1500 live births, with a female-to-male ratio of 2-4:1. The estimated prevalence in the general population is 1 in 25,000. Clinical description Not all communications between the atrial chambers of the heart represent deficiencies of the atrial septum, and the other forms of interatrial communication should also be recognized. There are four types of defect, named according to their position relative to the atrial septum.
A number sign (#) is used with this entry because of evidence that atrial septal defect-5 (ASD5) is caused by heterozygous mutation in the ACTC1 gene (102540) on chromosome 15q14. For a phenotypic description and discussion of genetic heterogeneity in atrial septal defect, see ASD1 (108800). Mapping Matsson et al. (2008) studied 2 large Swedish families segregating autosomal dominant isolated secundum atrial septal defect (ASD) with variable clinical expression. Genotyping with microsatellite markers in 'family 1' revealed a specific haplotype in all affected individuals spanning a 15.1-cM region of chromosome 15q13-q21; analysis of 'family 2' identified a minimal haplotype with significant linkage to ASD consisting of markers GT44248, GATA12322, and ACTC. All affected individuals genotyped had identical allele sizes for the marker haplotype, suggesting a shared ancestral mutation for the 2 families.
A number sign (#) is used with this entry because atrial septal defect-2 (ASD2) is caused by heterozygous mutation in the GATA4 gene (600576) on chromosome 8p23. For discussion of genetic heterogeneity in atrial septal defect, see ASD1 (108800). Clinical Features Garg et al. (2003) identified a large kindred spanning 5 generations in which 16 individuals had congenital heart defects. Detailed clinical evaluations reviewed for all available family members demonstrated an autosomal dominant pattern of inheritance. All affected family members had atrial septal defects. Eight individuals had additional congenital heart defects, including ventricular septal defects (VSD), atrioventricular septal defects (AVSD), pulmonary valve thickening, or insufficiency of the cardiac valves.
A number sign (#) is used with this entry because of evidence that atrial septal defect-9 (ASD9) is caused by heterozygous mutation in the GATA6 gene (601656) on chromosome 18q11. For discussion of genetic heterogeneity of atrial septal defect (ASD), see ASD1 (108800). Molecular Genetics Lin et al. (2010) analyzed the GATA6 gene in 270 unrelated Chinese patients with congenital heart defects and identified heterozygosity for a missense mutation in the GATA6 gene (S184N; 601656.0005) in 2 Chinese children with atrial septal defect. One of the ASD patients was a 3-year-old girl with an ostium secundum ASD and mild pulmonary arterial hypertension, whereas the other was a 4-year-old boy with an ostium secundum ASD and mild tricuspid valve disease and pulmonary valve replacement. The S184N mutation was detected in the unaffected father of the girl as well as in the clinically unaffected mother of the boy; the latter parent was found to have bicuspid aortic valve on echocardiography.
A number sign (#) is used with this entry because of evidence that atrial septal defect-8 (ASD8) can be caused by heterozygous mutation in the CITED2 gene (602937) on chromosome 6q23.3. For discussion of genetic heterogeneity of atrial septal defect, see ASD1 (108800). Molecular Genetics Sperling et al. (2005) screened a cohort of 392 patients with congenital heart defects and 192 controls for mutations in the CITED2 gene and identified a 27-bp insertion (602937.0002) in a patient with a secundum atrial septal defect, and a 6-bp deletion (602937.0003) in a patient with a sinus venosus atrial septal defect and abnormal pulmonary venous return to the right atria. Functional analysis of the mutations, which were not found in controls, revealed that both significantly reduced the capacity of CITED2 to transrepress HIF1A (603348). INHERITANCE - Autosomal dominant CARDIOVASCULAR Heart - Atrial septal defect, secundum type (in some patients) - Atrial septal defect, sinus venosus type (in some patients) Vascular - Abnormal pulmonary venous return to right atria (in some patients) MOLECULAR BASIS - Caused by mutation in the CBP/p300-interacting transactivator, with glu/asp-rich C-terminal domain, 2 gene (CITED2, 602937.0001 ) ▲ Close
Description Secundum atrial septal defect (ASD) is a common congenital heart malformation that occurs as an isolated anomaly in 10% of individuals with congenital heart disease. Uncorrected ASD can cause pulmonary overcirculation, right heart volume overload, and premature death (summary by Benson et al., 1998). Genetic Heterogeneity of Atrial Septal Defect The ASD1 locus has been mapped to chromosome 5p. Other forms of atrial septal defect that are associated with other congenital heart disease but no conduction defects or noncardiac abnormalities include ASD2 (607941), caused by mutation in the GATA4 gene (600576), and ASD4 (611363), caused by mutation in the TBX20 gene (606061). ASD3 (614089) and ASD5 (612794), in which atrial septal defect is not associated with other cardiac abnormalities, are caused by mutation in the MYH6 (160710) and ACTC1 (102540) genes, respectively.
A number sign (#) is used with this entry because of evidence that atrial septal defect-6 (ASD6) is caused by heterozygous mutation in the TLL1 gene (606742) on chromosome 4q32. For a general phenotypic description and discussion of genetic heterogeneity in atrial septal defect, see ASD1 (108800). Molecular Genetics Based on data from mouse models of incomplete heart septation associated with inactivation of mouse Tll1, Stanczak et al. (2009) analyzed the candidate gene TLL1 in 19 unrelated patients with atrial septal defect and identified heterozygosity for 3 missense mutations in 3 patients (606742.0001-606742.0003, respectively). One of the patients had an isolated ostium primum defect; the other 2 patients, who had ostium secundum defects, displayed additional features including interatrial aneurysm and cardiac arrhythmias. INHERITANCE - Autosomal dominant CARDIOVASCULAR Heart - Atrial septal defect, type I or II - Aneurysm of interatrial septum (in some patients) - Atrial fibrillation (in some patients) - Bradycardia (in some patients) MOLECULAR BASIS - Caused by mutation in the tolloid-like 1 gene (TLL1, 606742.0001 ) ▲ Close
Ferri's differential diagnosis : a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders (2nd ed.). ... Retrieved 23 December 2017. ^ a b Fletcher's Diagnostic Histopathology of Tumors (3rd ed.). pp. 692–4. ^ Mäkinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, Gentile M, Yan J, Enge M, Taipale M, Aavikko M, Katainen R, Virolainen E, Böhling T, Koski TA, Launonen V, Sjöberg J, Taipale J, Vahteristo P, Aaltonen LA (2011). ... Orozco LJ (ed.). "Mifepristone for uterine fibroids". Cochrane Database of Systematic Reviews. 8 (8): CD007687. doi:10.1002/14651858.CD007687.pub2. ... Metwally M (ed.). "Surgical treatment of fibroids for subfertility". Cochrane Database of Systematic Reviews. 11: CD003857. doi:10.1002/14651858.CD003857.pub3.
A number sign (#) is used with this entry because at least one form of uterine leiomyoma (UL) is known to be due to fusion between an isoform of the recombinational repair gene RAD51B (602948) and the high mobility group protein gene HMGIC (HMGA2; 600698). Uterine leiomyomas have been observed with other fusion partners of the HMGIC gene, namely ALDH2 (100650), COX6C (124090), and HEI10 (608249). Uterine leiomyomata also occur in association with skin leiomyomata and renal cell cancer on the basis of mutations in the gene encoding fumarate hydratase (FH; 136850; see 150800). There is evidence also that leiomyoma development involves a myofibroblast phenotype characterized by dysregulation of genes encoding extracellular matrix proteins, particularly reduced expression of dermatopontin (125597), a feature shared with keloids (148100). Cytogenetics In histologically benign uterine leiomyomas from 34 patients, Heim et al. (1988) found an apparently identical reciprocal translocation t(12;14)(q14-15;q23-24) in the tumors of 4 patients.
A number sign (#) is used with this entry because of evidence that Burkitt lymphoma can be caused by somatic mutation in the MYC gene (190080) in addition to translocations involving the MYC gene and immunoglobulin genes (see 147220). Description Burkitt lymphoma is a rare, aggressive B-cell lymphoma that accounts for 30 to 50% of lymphomas in children but only 1 to 2% of lymphomas in adults (Harris and Horning, 2006). It results from chromosomal translocations that involve the MYC gene (190080) and either the lambda or the kappa light chain immunoglobulin genes (147220, 147200). Burkitt lymphoma is causally related to the Epstein-Barr virus (EBV), although the pathogenetic mechanisms are not clear. Clinical Features Anderson et al. (1986) described 2 sisters in an American family who died of Burkitt lymphoma at ages 11 and 22 years.
A number sign (#) is used with this entry because of evidence that susceptibility to acute lymphoblastic leukemia-3 (ALL3) is conferred by heterozygous mutation in the PAX5 gene (167414) on chromosome 9p13. For a general phenotypic description and a discussion of genetic heterogeneity of acute lymphoblastic leukemia, see 613065. Clinical Features Shah et al. (2013) reported 2 unrelated families in which multiple individuals in several generations had childhood onset of B-cell acute lymphoblastic leukemia (B-ALL). Relapse was common. One of the families was of Puerto Rican descent and the other was of African American descent. Gu et al. (2019) characterized 2 subtypes of B-ALL, PAX5alt (PAX5-altered) and PAX5 pro80 to arg (P80R), that are defined by PAX5 alterations (see MOLECULAR GENETICS).
Burkitt lymphoma (BL) is a very fast-growing type of cancer. It is a form of B-cell non-Hodgkin's lymphoma. There are 3 recognized forms of BL: Endemic (African) - the most common form, found mainly in central Africa, where it is associated with the Epstein Barr virus (EBV). It is most common in children. This form often manifests as enlargement of the jaw or facial bones. Sporadic - a rarer form, seen in all parts of the world, that often develops in the abdomen with bone marrow involvement. The kidneys, ovaries, breasts or other organs may also be involved. This form commonly affects children and young adults.
Burkitt lymphoma is a rare form of malignant mature B-cell non-Hodgkin lymphoma. Epidemiology In Europe and north America it represents around half of all malignant non-Hodgkin lymphoma in children and around 2% in adults. Two incidence peaks occur: one in childhood/adolescence and the second after the age of 40 years. In Europe the standardized incidence ratio is 1/530,000 for individuals aged between 0 and 14 years and 1/670,000 for individuals aged between 15 and 19 years. Males are affected more than females. Clinical description Patients with HIV in whom antiviral treatment is ineffective are particularly susceptible to Burkitt lymphoma.
Multiple system atrophy is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure. The most frequent autonomic symptoms associated with multiple system atrophy are a sudden drop in blood pressure upon standing (orthostatic hypotension), urinary difficulties, and erectile dysfunction in men. Researchers have described two major types of multiple system atrophy, which are distinguished by their major signs and symptoms at the time of diagnosis. In one type, known as MSA-P, a group of movement abnormalities called parkinsonism are predominant.
Multiple system atrophy (MSA) causes the progressive loss of nerve cells in the brain (a neurodegenerative disease). MSA affects several areas of the brain, including the cerebellum, which is involved in controlling movement and some emotions, as well as certain types of learning and memory, and the autonomic nervous system, which controls your body’s automatic, or regulating functions, such as blood pressure, digestion and temperature.The initial symptoms of MSA start around age 50, and are very similar to the initial symptoms of Parkinson’s disease. These symptoms may include slowness of movement, tremor, or rigidity (stiffness), clumsiness or coordination problems, difficulties with speech, orthostatic hypotension (a condition in which blood pressure drops when rising from a seated or lying down position), and bladder control problems. Other symptoms of MSA may include muscle contractures, abnormal posture, bending of the neck, involuntary sighing, trouble sleeping and emotional problems. As MSA progresses, breathing problems while sleeping (sleep apnea) and irregular heart rhythms may develop.
Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure (cardiovascular and/or urinary), parkinsonism, cerebellar impairment and corticospinal signs with a median survival of 6-9 years. Epidemiology Prevalence ranges from 1/50,000-1/20,000. MSA-parkinsonian type (MSA-p) predominates in the Western Hemisphere and MSA-cerebellar type (MSA-c) predominates in the Eastern Hemisphere. Genders are equally distributed. Clinical description MSA is an adult-onset disorder (>30 years, mean age 55-60 years). Clinical manifestations include autonomic failure (orthostatic hypotension, syncope, respiratory disturbances (sleep apnea, stridor and inspiratory sighs), constipation, bladder dysfunction (early urinary incontinence), erectile dysfunction in males and Raynaud syndrome). In some cases, pyramidal signs (generalized hyperreflexia and positive Babinski sign) are observed.
A number sign (#) is used with this entry because of evidence that susceptibility to multiple system atrophy-1 (MSA1) can be conferred by heterozygous, homozygous, or compound heterozygous mutation in the COQ2 gene (609825) on chromosome 4q21. Description Multiple system atrophy (MSA) is a distinct clinicopathologic entity that manifests as a progressive adult-onset neurodegenerative disorder causing parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Two main subtypes are recognized: 'subtype C,' characterized predominantly by cerebellar ataxia, and 'subtype P,' characterized predominantly by parkinsonism. MSA is characterized pathologically by the degeneration of striatonigral and olivopontocerebellar structures and glial cytoplasmic inclusions (GCIs) that consist of abnormally phosphorylated alpha-synuclein (SNCA; 163890) or tau (MAPT; 157140) (Gilman et al., 1998; Gilman et al., 2008; Scholz et al., 2009). 'Subtype C' of MSA has been reported to be more prevalent than 'subtype P' in the Japanese population (65-67% vs 33-35%), whereas 'subtype P' has been reported to be more prevalent than 'subtype C' in Europe (63% vs 34%) and North America (60% vs 13%, with 27% of cases unclassified) (summary by The Multiple-System Atrophy Research Collaboration, 2013).
Description Gastroesophageal reflux (GER) is characterized by the retrograde movement of stomach contents into the esophagus. In its most severe form, GER results in extensive tissue damage caused by acid reflux. In adolescents and adults, and even infrequently in children, chronic GER is associated with the risk of developing Barrett metaplasia (614266), a premalignant lesion of the esophageal mucosa (Hu et al., 2000). In turn, Barrett metaplasia is correlated with the development of adenocarcinoma of the esophagus (see 614266), estimated as the fifth most prevalent neoplasia in the Western world (Lagergren et al., 1999). Mapping To identify a genetic locus that cosegregates with a severe pediatric GER phenotype in families with multiple affected members, Hu et al. (2000) performed a genomewide scan using microsatellite markers spaced at an average interval of 8 cM.
Consequently, less intensive (de-intensification) use of radiotherapy or chemotherapy, as well as specific therapy, is under investigation, enrolling HPV+OPC in clinical trials to preserve disease control and minimise morbidity in selected groups based on modified TNM staging and smoking status. HPV+ cancer of the oropharynx are staged as (AJCC 8th ed. 2016): Tumour stage T0 no primary identified T1 2 cm or less in greatest dimension T2 2–4 cm T3 >4 cm, or extension to lingual surface of epiglottis T4 moderately advanced local disease, invading larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond Nodal stage Nx regional lymph nodes cannot be assessed N0 no regional lymph nodes involved N1 one or more ipsilateral nodes involved, less than 6 cm N2 contralateral or bilateral lymph nodes, less than 6 cm N3 lymph node(s) larger than 6 cm Clinical stage Stage I: T0N1, T1–2N0–1 Stage II: T0N2, T1–3N2, T3N0–2 Stage III: T0–3N3, T4N0-3 Stage IV: any metastases (M1) However, the published literature and ongoing clinical trials use the older seventh edition that does not distinguish between HPV+OPC and HPV-OPC - see Oropharyngeal Cancer - Stages. The T stages are essentially similar between AJCC 7 and AJCC 8. with two exceptions.