Main clinical features
MDGA2(MAM domain-containing glycosylphosphatidylinositol anchor 2; MIM #616276) encodes a GPI-anchored cell-surface protein that functions as a critical negative regulator of excitatory synapse development. Biallelic loss-of-function variants in MDGA2cause autosomal recessive developmental and epileptic encephalopathy (DEE). The disorder presents in the first year of life with intractable seizures, profound global neurodevelopmental delay, and infantile hypotonia. Progressive brain atrophy and recognizable dysmorphic features are additional hallmarks. Early mortality has been reported across multiple families.
Inheritance
Autosomal recessive. Both parents are obligate carriers of one pathogenic MDGA2variant and are clinically unaffected. The recurrence risk in future pregnancies is 25%.
Prevalence
The MDGA2-related disorder is ultra-rare. The precise population prevalence remains unknown. To date, nine affected individuals from seven unrelated consanguineous families have been reported.
MDGA2