Carcinoma, and Myoclonus

Ataxia-telangiectasia is the association of severe combined immunodeficiency (affecting mainly the humoral immune response) with progressive cerebellar ataxia. It is characterised by neurological signs, telangiectasias, increased susceptibility to infections and a higher risk of cancer.

ATAXIA-TELANGIECTASIA Is also known as at1|louis-bar syndrome

• Intellectual disability
• Seizures
• Short stature
• Microcephaly
• Scoliosis

SOURCES: ORPHANET OMIM MENDELIAN

Beckwith-Wiedemann syndrome is a pediatric overgrowth disorder involving a predisposition to tumor development. The clinical presentation is highly variable; some cases lack the hallmark features of exomphalos, macroglossia, and gigantism as originally described by Beckwith (1969) and Wiedemann (1969) (summary by Weksberg et al., 2010).Mussa et al. (2016) provided a review of Beckwith-Wiedemann syndrome, including the wide spectrum of phenotypic manifestations, delineation of the frequencies of manifestations according to genotype, and discussion of the molecular and epigenetic defects that underlie the disorder.

BECKWITH-WIEDEMANN SYNDROME; BWS Is also known as emg syndrome|exomphalos-macroglossia-gigantism syndrome|wiedemann-beckwith syndrome|wbs

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Hypertelorism

SOURCES: OMIM MENDELIAN

Gamma-glutamyl transpeptidase deficiency is characterized by increased glutathione concentration in the plasma and urine.

GAMMA-GLUTAMYL TRANSPEPTIDASE DEFICIENCY Is also known as glutathionuria|gtg deficiency|ggt deficiency|gamma-glutamyltransferase deficiency|gamma-glutamyltranspeptidase deficiency

• Intellectual disability
• Seizures
• Hypertelorism
• Strabismus
• Low-set ears

SOURCES: OMIM ORPHANET MESH MENDELIAN

Adult-onset type II citrullinemia is an autosomal recessive metabolic disorder characterized clinically by the sudden onset of various neuropsychologic symptoms such as disorientation, abnormal behavior, convulsions, and coma due to hyperammonemia. In some cases, rapid progression can lead to brain edema and death if liver transplantation is not possible. Some patients may present with nonalcoholic hepatic steatosis or may develop hepatic fibrosis or hepatocellular carcinoma. Patients with this disorder have a natural aversion to carbohydrates and favor protein, which is in contrast to protein aversion usually observed in patients with urea cycle defects (summary by Komatsu et al., 2008).

CITRULLINEMIA, TYPE II, ADULT-ONSET; CTLN2 Is also known as citrin deficiency

• Seizures
• Tremor
• Edema
• Vomiting
• Diarrhea

SOURCES: ORPHANET OMIM MENDELIAN

HIGM is a rare immunodeficiency characterized by normal or elevated serum IgM levels associated with markedly decreased IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections and an increased susceptibility to opportunistic infections. Patients with X-linked HIGM also tend to have neutropenia, as well as a high rate of gastrointestinal and central nervous system infections, often resulting in severe liver disease and/or neurodegeneration (summary by Levy et al., 1997). Genetic Heterogeneity of Immunodeficiency with Hyper-IgMOther forms of HIGM include HIGM2 (OMIM ), which results from mutation in the AICDA gene (OMIM ), HIGM3 (OMIM ), which results from mutation in the CD40 gene (OMIM ), and HIGM5 (OMIM ), which results from mutation in the UNG gene (OMIM ). See also HIGM4 (OMIM ).

IMMUNODEFICIENCY WITH HYPER-IGM, TYPE 1; HIGM1 Is also known as hyper-igm immunodeficiency, x-linked|hyper-igm syndrome 1|ihis|hyper-igm syndrome|xhim|imd3|higm|immunodeficiency 3

• Seizures
• Global developmental delay
• Failure to thrive
• Cognitive impairment
• Anemia

SOURCES: OMIM MENDELIAN

Pheochromocytomas are catecholamine-secreting tumors that usually arise within the adrenal medulla. Approximately 10% arise in extraadrenal sympathetic ganglia, and are referred to as 'paragangliomas.' Approximately 10% are malignant, and approximately 10% are hereditary (Maher and Eng, 2002; Dluhy, 2002).Bolande (1974) introduced the concept and designation of the neurocristopathies, and identified 'simple,' including pheochromocytoma and medullary carcinoma of the thyroid, and 'complex' neurocristopathies and neurocristopathic syndromes, including NF1 and MEN2.Knudson and Strong (1972) applied Knudson's 2-mutation theory to pheochromocytoma (see discussion in {180200}) and concluded that it fits.Maher and Eng (2002) reviewed the clinical entities and genes associated with pheochromocytoma.

PHEOCHROMOCYTOMA Is also known as pheochromocytoma, susceptibility to

• Neoplasm
• Hypertension
• Tremor
• Fatigue
• Congestive heart failure

SOURCES: ORPHANET OMIM MENDELIAN

Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by extreme sensitivity to ultraviolet (UV)-induced changes in the skin and eyes, and multiple skin cancers. It is subdivided into 8 complementation groups, according to the affected gene: classical XP (XPA to XPG) and XP variant (XPV) (see these terms).

XERODERMA PIGMENTOSUM Is also known as xeroderma pigmentosum i|xp1|xp, group a|xp

• Intellectual disability
• Seizures
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: OMIM ORPHANET MENDELIAN

Cowden syndrome (CS) is a difficult to recognize, under-diagnosed genodermatosis characterized by the presence of multiple hamartomas in various tissues and an increased risk for malignancies of the breast, thyroid, endometrium, kidney and colorectum. When CS is accompanied by germline PTEN mutations, it belongs to the PTEN hamartoma tumor syndrome (PHTS; see this term) group.

COWDEN SYNDROME Is also known as bzs|cowden disease|bbrs|macrocephaly, multiple lipomas, and hemangiomata|pten hamartoma tumor syndrome with granular cell tumor|bannayan-zonana syndrome|macrocephaly, pseudopapilledema, and multiple hemangiomata|cs|cd|mham|pten hamartoma tumor syndrome|ri

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Fabry disease (FD) is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.

FABRY DISEASE Is also known as ceramide trihexosidase deficiency|hereditary dystopic lipidosis|fd|alpha-galactosidase a deficiency|diffuse angiokeratoma|gla deficiency|angiokeratoma corporis diffusum|anderson-fabry disease

• Seizures
• Short stature
• Hearing impairment
• Sensorineural hearing impairment
• Pain

SOURCES: ORPHANET OMIM MESH MENDELIAN

The Heidelberg histologic classification of renal cell tumors subdivides renal cell tumors into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most common documented genetic abnormalities (Kovacs et al., 1997). Malignant tumors are subclassified into common or conventional renal cell carcinoma (clear cell); papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and unclassified renal cell carcinoma. The common or conventional type accounts for about 75% of renal cell neoplasms and is characterized genetically by a highly specific deletion of chromosome 3p. Papillary renal cell carcinoma (see {605074}) accounts for about 10% of renal cell tumors. Chromophobe renal cell carcinoma accounts for approximately 5% of renal cell neoplasms. Genetically, chromophobe RCC is characterized by a combination of loss of heterozygosity of chromosomes 1, 2, 6, 10, 13, 17, and 21 and hypodiploid DNA content. Collecting duct carcinoma accounts for about 1% of renal cell carcinoma.Renal cell carcinoma occurs nearly twice as often in men as in women; incidence in the United States is equivalent among whites and blacks. Cigarette smoking doubles the likelihood of renal cell carcinoma and contributes to as many as one-third of cases. Obesity is also a risk factor, particularly in women. Other risk factors include hypertension, unopposed estrogen therapy, and occupational exposure to petroleum products, heavy metals, or asbestos (summary by Motzer et al., 1996). Genetic Heterogeneity of Renal Cell CarcinomaGermline mutation resulting in nonpapillary renal cell carcinoma of the clear cell and chromophobe type occurs in the HNF1A gene (OMIM ) and the HNF1B gene (OMIM ).Somatic mutations in renal cell carcinomas occur in the VHL gene (OMIM ), the TRC8 gene (OMIM ), the OGG1 gene (OMIM ), the ARMET gene (OMIM ), the FLCN gene (OMIM ), and the BAP1 gene (OMIM ).See also RCCX1 (OMIM ) for a discussion of renal cell carcinoma associated with translocations of chromosome Xp11.2 involving the TFE3 gene (OMIM ).For a discussion of papillary renal cell carcinoma, see RCCP1 (OMIM ). Occurrence of Renal Cell Carcinoma in Other DisordersVon Hippel-Lindau syndrome (OMIM ) is a familial multicancer syndrome in which there is a susceptibility to a variety of neoplasms, including renal cell carcinoma of clear cell histology and renal cysts. A syndrome of predisposition to uterine leiomyomas and papillary renal cell carcinoma has been reported (OMIM ). Medullary carcinoma of the kidney is believed to arise from the collecting ducts of the renal medulla and is associated with sickle cell trait (OMIM ) (Kovacs et al., 1997). Renal cell carcinoma occurs in patients with the Birt-Hogg-Dube syndrome (OMIM ).Bertolotto et al. (2011) identified a missense mutation in the MITF (OMIM ) gene that increases the risk of renal cell carcinoma with or without malignant melanoma (CMM8 ).

RENAL CELL CARCINOMA, NONPAPILLARY; RCC Is also known as hypernephroma|adenocarcinoma of kidney

• Neoplasm
• Hypertension
• Obesity
• Carcinoma
• Falls

SOURCES: OMIM ORPHANET MENDELIAN