Immunodeficiency, and Epileptic encephalopathy

High match MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY; MCSZ

Microcephaly, seizures, and developmental delay is an autosomal recessive neurodevelopmental disorder with onset in infancy. There is a range of phenotypic severity: some patients have a disease course consistent with early infantile epileptic encephalopathy (EIEE), whereas others have more well-controlled seizures and a protracted course associated with cerebellar atrophy and peripheral neuropathy (Shen et al., 2010 and Poulton et al., 2013).For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).

MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY; MCSZ Is also known as epileptic encephalopathy, early infantile, 10|eiee10

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

SOURCES: OMIM MENDELIAN

Low match HERPES SIMPLEX VIRUS ENCEPHALITIS

Herpes simplex virus encephalitis (HSVE) is caused by the infection of the central nervous system by Herpes simplex virus (HSV) that could have a devastating clinical course and a potentially fatal outcome particularly with delay or lack of treatment. HSVE often involves the frontal and temporal lobes, usually asymmetrically, resulting in personality changes, cognitive impairment, aphasia, seizures, and focal weakness.

HERPES SIMPLEX VIRUS ENCEPHALITIS Is also known as herpetic encephalitis|herpes simplex meningo-encephalitis|hsv encephalitis|herpes simplex encephalitis, susceptibility to, 1|hsve|herpes simplex neuroinvasion|hse

• Immunodeficiency
• Encephalopathy
• Encephalitis
• Herpes simplex encephalitis
• Susceptibility to herpesvirus

SOURCES: OMIM ORPHANET MENDELIAN

Low match IMMUNODEFICIENCY 44; IMD44

Immunodeficiency-44 is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to viral infections and adverse multisystemic reaction to vaccination in some patients. Affected individuals appear to have defects in mitochondrial fission and fusion (summary by Shahni et al., 2015).

• Seizures
• Spasticity
• Visual impairment
• Fever
• Immunodeficiency

SOURCES: OMIM MENDELIAN

Low match KAPOSI SARCOMA

Kaposi sarcoma (KS) is a rare human herpes virus 8 (HHV-8)-induced endothelial inflammatory neoplasm that develops is various clinically distinct settings, manifesting mostly as cutaneous lesions, or mucosal or visceral involvement.

KAPOSI SARCOMA Is also known as multiple idiopathic pigmented hemangiosarcoma, susceptibility to

• Neoplasm
• Hypertension
• Fever
• Fatigue
• Edema

SOURCES: OMIM ORPHANET MENDELIAN

Low match X-LINKED LYMPHOPROLIFERATIVE DISEASE

X-linked lymphoproliferative disease is a hereditary immunodeficiency characterized, in the majority of cases, by an inadequate immune response to infection with the Epstein-Barr virus (EBV).

X-LINKED LYMPHOPROLIFERATIVE DISEASE Is also known as xlpd|duncan disease|xlp|immunodeficiency 5|infectious mononucleosis, severe, susceptibility to|purtilo syndrome|imd5|ebvs|lymphoproliferative disease, x-linked|epstein-barr virus infection, familial fatal|lyp|ebv infection, severe, susceptibility to|immun

• Seizures
• Neoplasm
• Anemia
• Hepatomegaly
• Fever

SOURCES: ORPHANET OMIM MENDELIAN

Low match COMBINED IMMUNODEFICIENCY DUE TO ORAI1 DEFICIENCY

Combined immunodeficiency (CID) due to ORAI1 deficiency is a form of CID due to Calcium release activated Ca2+ (CRAC) channel dysfunction (see this term) characterized by recurrent infections, congenital myopathy, ectodermal dysplasia and anhydrosis.

COMBINED IMMUNODEFICIENCY DUE TO ORAI1 DEFICIENCY Is also known as cid due to orai1 deficiency|immune dysfunction with t-cell inactivation due to calcium entry defect 1

• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive
• Muscle weakness

SOURCES: OMIM MESH ORPHANET MENDELIAN

Low match HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 1; FHL1

Zur Stadt et al. (2005) summarized the clinical features of hemophagocytic lymphohistiocytosis (HLH), a rare autosomal recessive disorder characterized by massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently central nervous system involvement. In FHL, the familial form of the disease, first episodes occur mostly during infancy, with a rapidly fatal outcome if untreated. Diagnostic criteria also include low fibrinogen and high triglyceride and ferritin levels. Chemoimmunotherapy based on corticosteroids, epipodophyllotoxins, and cyclosporin succeeds in controlling the disease in the majority of patients, although remission is rarely obtained (Henter et al., 2002). Most patients suffer an early death unless they are treated by hematopoietic stem cell transplantation (Durken et al., 1999). Genetic Heterogeneity of Familial Hemophagocytic LymphohistiocytosisFamilial hemophagocytic lymphohistiocytosis exhibits genetic heterogeneity. In some families, familial hemophagocytic lymphohistiocytosis has been found to be linked to chromosome 9q (HPLH1, FHL1). FHL2 (OMIM ) is caused by mutation in the PRF1 gene (OMIM ) on chromosome 10q22; FHL3 (OMIM ) is caused by mutation in the UNC13D gene (OMIM ) on chromosome 17q25; FHL4 (OMIM ) is caused by mutation in the syntaxin-11 gene (STX11 ) on chromosome 6q24; and FHL5 (OMIM ) is caused by mutation in the syntaxin-binding protein-2 (STXBP2 ), which is an interaction partner of STX11, on chromosome 19p13.Furthermore, before the identification of mutations in the RAG1 (OMIM ) and RAG2 (OMIM ) genes, both of which map to 11p, Omenn syndrome (familial reticuloendotheliosis with eosinophilia; {603554}) was not thought to be clearly distinct from other reported cases of hemophagocytic lymphohistiocytosis.

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 1; FHL1 Is also known as hemophagocytic reticulosis, familial|hlh1|hemophagocytic lymphohistiocytosis, familial|erythrophagocytic lymphohistiocytosis, familial|reticulosis, familial histiocytic|hplh1|fhl|fhlh|hplh|fel

• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia
• Neoplasm

SOURCES: OMIM MENDELIAN

Low match PROPIONIC ACIDEMIA

Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.

PROPIONIC ACIDEMIA Is also known as glycinemia, ketotic|ketotic hyperglycinemia|propionyl-coa carboxylase deficiency|propionic aciduria|pcc deficiency|hyperglycinemia with ketoacidosis and leukopenia

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

SOURCES: ORPHANET OMIM MESH MENDELIAN

Low match X-LINKED CEREBRAL ADRENOLEUKODYSTROPHY

X-linked cerebral adrenoleukodystrophy (X-CALD), a subtype of X-linked adrenoleukodystrophy (X-ALD, see this term), is a peroxisomal disease characterized by severe inflammatory demyelination in the brain, and often associated with adrenal insufficiency.

X-LINKED CEREBRAL ADRENOLEUKODYSTROPHY Is also known as siemerling-creutzfeldt disease|addison disease and cerebral sclerosis|bronze schilder disease|melanodermic leukodystrophy

• Seizures
• Hearing impairment
• Ataxia
• Spasticity
• Cognitive impairment

SOURCES: ORPHANET OMIM MENDELIAN

Low match TIMOTHY SYNDROME

Timothy syndrome is a multi-system disorder characterized by cardiac, hand, facial and neurodevelopmental features that include QT prolongation, webbed fingers and toes, flattened nasal bridge, low-set ears, small upper jaw, thin upper lip, and characteristic features of autism or autistic spectrum disorders.

TIMOTHY SYNDROME Is also known as lqt8|long qt syndrome 8|long qt syndrome with syndactyly|long qt syndrome-syndactyly syndrome|long qt syndrome type 8

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hypertelorism

SOURCES: OMIM ORPHANET MENDELIAN