MedGen

MHC class II deficiency (MHC2D), also known as bare lymphocyte syndrome type II (BLS type II), is a rare autosomal recessive primary immunodeficiency showing genetic heterogeneity. The disorder is characterized by the loss of expression of MHC class II antigens (HLA-DR, HLA-DQ, and HLA-DP) on antigen-presenting cells (APCs) resulting from mutations in regulatory genes required for proper transcription of the MHC class II genes. Affected individuals present in early infancy with severe recurrent infections (bacteria, viruses, fungi, and protozoa), usually affecting the gastrointestinal and respiratory tracts. Protracted diarrhea and failure to thrive is often present. About 20% of patients develop autoimmune features, mainly cytopenias. Laboratory studies show reduced CD4+ T cell counts with an inverted CD4:CD8 ratio, hypogammaglobulinemia, and abnormal lymphocyte proliferation to foreign antigens. Death in infancy or early childhood often occurs, although some patients may have longer survival. MHC type II deficiency may not detected by newborn screening for T-cell receptor excision circles (TRECs). Bone marrow transplantation may be curative, although complications are common (summary by Hanna and Etzioni, 2014; El Hawary et al., 2019). In HLA class II deficiency, the abnormal expression of HLA molecules has been shown to be secondary to defective synthesis (Lisowska-Grospierre et al., 1985), due in turn to an abnormal transacting regulatory gene located outside the major histocompatibility complex (MHC) (Marcadet et al., 1985; de Preval et al., 1985). The transacting regulatory factor, known as RFX, binds to class II promoters and is defective in hereditary HLA deficiency type II, otherwise known as the 'bare lymphocyte syndrome.' The failure of HLA expression leads to immunodeficiency affecting both cellular and humoral responses to antigens. DeSandro et al. (1999) reviewed the molecular bases of the several forms of MHC deficiency. Genetic Heterogeneity of MHC Class II Deficiency MHC2D2 (620815) is caused by mutation in the RFXANK gene (603200); MHC2D3 (620816) and MHC2D5 (620818) are caused by mutation in the RFX5 gene (601863); and MHC2D4 (620817) is caused by mutation in the RFXAP gene (601861). See also MHC class I deficiency (MHC1D1; 604571). [from OMIM]

Long QT syndrome (LQTS) is a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the EKG that are associated with tachyarrhythmias, typically the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing a syncopal event, the most common symptom in individuals with LQTS. Such cardiac events typically occur during exercise and emotional stress, less frequently during sleep, and usually without warning. In some instances, TdP degenerates to ventricular fibrillation and causes aborted cardiac arrest (if the individual is defibrillated) or sudden death. Approximately 50% of untreated individuals with a pathogenic variant in one of the genes associated with LQTS have symptoms, usually one to a few syncopal events. While cardiac events may occur from infancy through middle age, they are most common from the preteen years through the 20s. Some types of LQTS are associated with a phenotype extending beyond cardiac arrhythmia. In addition to the prolonged QT interval, associations include muscle weakness and facial dysmorphism in Andersen-Tawil syndrome (LQTS type 7); hand/foot, facial, and neurodevelopmental features in Timothy syndrome (LQTS type 8); and profound sensorineural hearing loss in Jervell and Lange-Nielson syndrome. [from GeneReviews]

Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18 (summary by de Saint Basile et al., 2004). [from OMIM]

Mycosis fungoides is a malignant T-cell lymphoma of the skin, first reported (and named) by Alibert (1835). Sezary syndrome is a leukemic variant of mycosis fungoides defined by erythroderma with greater than 80% of the skin showing redness, adenopathy and greater than 1,000 circulating Sezary cells/microliter with a CD4+CD26- or CD4+CD7- phenotype. Sezary cells have a type 2 helper T cell cytokine profile. Sezary syndrome has a median overall survival time of only 2.4 years in patients with Sezary cells at a density of greater than 10,000 cells/microliter or 5.4 years in patients with 1,000-10,000 Sezary cells/microliter. Mycosis fungoides and Sezary syndrome are the most common cutaneous T-cell lymphomas. Sezary syndrome can arise de novo or can appear following years of chronic mycosis fungoides. Both are thought to arise from clonal expansion of CD4+ helper T cells responding to chronic antigen stimulation (summary by Wang et al., 2015). [from OMIM]

A type of ventricular tachycardia characterized by polymorphioc QRS complexes that change in amplitue and cycle length, and thus have the appearance of oscillating around the baseline in the EKG. [from HPO]

A distinct form of acute myeloid leukaemia in which this chromosomal anomaly is found de novo or in therapy-related cases. The disease is characterised by frequent extramedullary involvement (mainly hepatomegaly, splenomegaly, lymphadenopathies, cutaneous infiltration, but also gum, bone, central nervous system, testicles involvement), severe coagulation disorder (disseminated intravascular coagulopathy or primary fibrinolysis) and poor prognosis. Morphologically, a blast population with a myelomonocytic stage of differentiation is observed. [from SNOMEDCT_US]