Calloso‐adreno‐scrotal agenesis associated with biallelic MAPK‐activating death domain protein (MADD) variant: Further phenotypic delineation of MADD deficiency

Abstract

AbstractMAPK‐activating death domain protein (MADD) deficiency is associated with a broad clinical spectrum ranging from mild developmental impairment to fatal multisystem disorder. We report an additional case of severe form with some overlapping and unreported systemic features in a growth‐restricted full‐term male newborn. The novel findings include corpus callosum agenesis, bilateral adrenal agenesis, scrotal aplasia, and abnormal skin pigmentation. Microscopic changes are only remarkable in thyroid gland that shows decreased, variously sized follicles with absent or non‐vacuolated pale colloid. This unique constellation of birth defects is associated with a novel homozygous in‐frame MADD gene deletion (NM_003682.4: c.4853_4855delGCT:p.Cys1618del). This case report expands the phenotypic and genetic spectrum of MADD deficiency.