MedGen

With the current widespread use of multigene panels and comprehensive genomic testing, it has become apparent that the phenotypic spectrum of EPG5-related disorder represents a continuum. At the most severe end of the spectrum is classic Vici syndrome (defined as a neurodevelopmental disorder with multisystem involvement characterized by the combination of agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive); at the milder end of the spectrum are attenuated neurodevelopmental phenotypes with variable multisystem involvement. Median survival in classic Vici syndrome appears to be 24 months, with only 10% of children surviving longer than age five years; the most common causes of death are respiratory infections as a result of primary immunodeficiency and/or cardiac insufficiency resulting from progressive cardiac failure. No data are available on life span in individuals at the milder end of the spectrum. [from GeneReviews]

JAK3-deficient severe combined immunodeficiency (SCID) is an inherited disorder of the immune system. Individuals with JAK3-deficient SCID lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with JAK3-deficient SCID are described as opportunistic because they ordinarily do not cause illness in healthy people. Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush, pneumonia, and skin rashes. Persistent illness also causes affected individuals to grow more slowly than other children. Without treatment, people with JAK3-deficient SCID usually live only into early childhood. [from MedlinePlus Genetics]

Chronic mucocutaneous candidiasis (CMC) includes a group of rare disorders with altered immune responses, selective against Candida, characterized by persistent and/or recurrent infections of the skin, nails, and mucous membranes, caused by organisms of the genus Candida, mainly Candida albicans (Zuccarello et al., 2002). Isolated familial chronic mucocutaneous candidiasis is distinct from candidiasis with endocrinopathy (240300). In myeloperoxidase deficiency (254600), susceptibility to candidiasis may be increased. Genetic Heterogeneity of Candidiasis Familial candidiasis-1 (CANDF1) maps to chromosome 2p. CANDF2 (212050) is caused by mutation in the CARD9 gene (607212) on chromosome 9q34.3. CANDF3 (607644), a form restricted to nails of the hands and feet, maps to chromosome 11. CANDF4 (613108) is caused by mutation in the CLEC7A gene (606264) on chromosome 12p13. CANDF6 (613956) is caused by mutation in the IL17F gene (606496) on chromosome 6p12. CANDF7 (614162) is caused by mutation in the STAT1 gene (600555) on chromosome 2q32. CANDF8 (615527) is caused by mutation in the TRAF3IP2 gene (607043) on chromosome 6q21. CANDF9 (616445) is caused by mutation in the IL17RC gene (610925) on chromosome 3p25. A form of familial candidiasis, previously thought to be isolated and designated CANDF5, has been found to be part of a primary immune deficiency (IMD51; 613953) that includes Staphylococcal skin infections and increased susceptibility to chronic bacterial respiratory infections. [from OMIM]

Bare lymphocyte syndrome type II (BLS II) is an inherited disorder of the immune system categorized as a form of combined immunodeficiency (CID). People with BLS II lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system.

BLS II is typically diagnosed in the first year of life. Most affected infants have persistent infections in the respiratory, gastrointestinal, and urinary tracts. Because of the infections, affected infants have difficulty absorbing nutrients (malabsorption), and they grow more slowly than their peers. Eventually, the persistent infections lead to organ failure. Without treatment, individuals with BLS II usually do not survive past early childhood.

In people with BLS II, infection-fighting white blood cells (lymphocytes) are missing specialized proteins on their surface called major histocompatibility complex (MHC) class II proteins, which is where the condition got its name. Because BLS II is the most common and best studied form of a group of related conditions, it is often referred to as simply bare lymphocyte syndrome (BLS). [from MedlinePlus Genetics]

Inability to react to a delayed hypersensitivity skin test. [from HPO]