MedGen

Idiopathic generalized epilepsy is a broad term that encompasses several common seizure phenotypes, classically including childhood absence epilepsy (CAE, ECA; see 600131), juvenile absence epilepsy (JAE, EJA; see 607631), juvenile myoclonic epilepsy (JME, EJM; see 254770), and epilepsy with grand mal seizures on awakening (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). These recurrent seizures occur in the absence of detectable brain lesions and/or metabolic abnormalities. Seizures are initially generalized with a bilateral, synchronous, generalized, symmetrical EEG discharge (Zara et al., 1995; Lu and Wang, 2009). See also childhood absence epilepsy (ECA1; 600131), which has also been mapped to 8q24. Of note, benign neonatal epilepsy 2 (EBN2; 121201) is caused by mutation in the KCNQ3 gene (602232) on 8q24. Genetic Heterogeneity of Idiopathic Generalized Epilepsy EIG1 has been mapped to chromosome 8q24. Other loci or genes associated with EIG include EIG2 (606972) on 14q23; EIG3 (608762) on 9q32; EIG4 (609750) on 10q25; EIG5 (611934) on 10p11; EIG6 (611942), caused by mutation in the CACNA1H gene (607904) on 16p; EIG7 (604827) on 15q14; EIG8 (612899), caused by mutation in the CASR gene (601199) on 3q13.3-q21; EIG9 (607682), caused by mutation in the CACNB4 gene (601949) on 2q23; EIG10 (613060), caused by mutation in the GABRD gene (137163) on 1p36; EIG11 (607628), caused by variation in the CLCN2 gene (600570) on 3q36; EIG12 (614847), caused by mutation in the SLC2A1 gene (138140) on 1p34; EIG13 (611136), caused by mutation in the GABRA1 gene (137160) on 5q34; EIG14 (616685), caused by mutation in the SLC12A5 gene (606726) on 20q12; EIG15 (618357), caused by mutation in the RORB gene (601972) on 9q22; EIG16 (618596), caused by mutation in the KCNMA1 gene (600150) on chromosome 10q22; EIG17 (602477), caused by mutation in the HCN2 gene (602781) on chromosome 19p13.3; and EIG18 (619521) caused by mutation in the HCN4 gene (605206) on chromosome 15q24. [from OMIM]

A red eruption of the skin. [from HPO]

SOFT syndrome is characterized by severely short long bones, peculiar facies associated with paucity of hair, and nail anomalies. Growth retardation is evident on prenatal ultrasound as early as the second trimester of pregnancy, and affected individuals reach a final stature consistent with a height age of 6 years to 8 years. Relative macrocephaly is present during early childhood but head circumference is markedly low by adulthood. Psychomotor development is normal. Facial dysmorphism includes a long, triangular face with prominent nose and small ears, and affected individuals have an unusual high-pitched voice. Clinodactyly, brachydactyly, and hypoplastic distal phalanges and fingernails are present in association with postpubertal sparse and short hair. Typical skeletal findings include short and thick long bones with mild irregular metaphyseal changes, short femoral necks, and hypoplastic pelvis and sacrum. All long bones of the hand are short, with major delay of carpal ossification and cone-shaped epiphyses. Vertebral body ossification is also delayed (summary by Sarig et al., 2012). [from OMIM]

Immunodeficiency disease that arises independent of another pathologic process, disease, or injury. [from NCI]

Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA. [from GeneReviews]

An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. [from HPO]

Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). [from HPO]

A condition that is characterized by elevated serum IgE, dermatitis, and respiratory infections. [from NCI]

Disorders in which phagocytic cells cannot kill ingested bacteria; characterized by frequent recurring infection with formulation of granulomas. [from MONDO]

A disease involving leukocytes. [from MONDO]

STAT3 hyper IgE syndrome (STAT3-HIES) is a primary immune deficiency syndrome characterized by elevated serum IgE, eczema, and recurrent skin and respiratory tract infections, together with several nonimmune features. This disorder typically manifests in the newborn period with a rash (often diagnosed as eosinophilic pustulosis) that subsequently evolves into an eczematoid dermatitis. Recurrent staphylococcal skin boils and bacterial pneumonias usually manifest in the first years of life. Pneumatoceles and bronchiectasis often result from aberrant healing of pneumonias. Mucocutaneous candidiasis is common. Nonimmune features may include retained primary teeth, scoliosis, bone fractures following minimal trauma, joint hyperextensibility, and characteristic facial appearance, which typically emerges in adolescence. Vascular abnormalities have been described and include middle-sized artery tortuosity and aneurysms, with infrequent clinical sequelae of myocardial infarction and subarachnoid hemorrhage. Gastrointestinal (GI) manifestations include gastroesophageal reflux disease, esophageal dysmotility, and spontaneous intestinal perforations (some of which are associated with diverticuli). Fungal infections of the GI tract (typically histoplasmosis, Cryptococcus, and Coccidioides) also occur infrequently. Survival is typically into adulthood, with most individuals now living into or past the sixth decade. Most deaths are associated with gram-negative (Pseudomonas) or filamentous fungal pneumonias resulting in hemoptysis. Lymphomas occur at an increased frequency. [from GeneReviews]

An abnormally increased overall level of immunoglobulin E in blood. [from HPO]

A condition of decreased or absent presence or activity of dedicator of cytokinesis protein 8. Deficiency of this protein is associated with autosomal recessive hyper-IgE recurrent infection syndrome. [from NCI]

Hyper-IgE syndrome-2 with recurrent infections (HIES2) is an autosomal recessive immunologic disorder characterized by recurrent staphylococcal infections of the skin and respiratory tract, eczema, elevated serum immunoglobulin E, and hypereosinophilia. It is distinguished from autosomal dominant HIES1 (147060) by the lack of connective tissue and skeletal involvement (Renner et al., 2004). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see 147060. See also TYK2 deficiency (611521), a clinically distinct disease entity that includes characteristic features of both autosomal recessive HIES2 and mendelian susceptibility to mycobacterial disease (MSMD; 209950) (Minegishi et al., 2006). [from OMIM]

An abnormality of the premaxilla (the embryonic structure that forms the anterior part of the maxilla) causing it to appear relatively small in size compared to the other parts of the maxilla or other facial structures. [from HPO]