Differentiating the Clinical and Variant Spectrum of Hardikar Syndrome From Other MED12-Related Developmental Disorders

Heterozygous MED12 variants (frameshift, splice, nonsense), differentiation of MED12 syndromes (Hardikar vs Opitz-Kaveggia vs Lujan-Fryns)

This study systematizes the differential diagnosis of Hardikar syndrome (HDKR) versus other MED12-related disorders (Opitz-Kaveggia, Lujan-Fryns syndromes). It describes the first case of maternal transmission of HDKR, broadening the previously assumed transmission patterns for this X-linked female-restricted syndrome. The distinctive clinical picture includes orofacial, digestive, genitourinary, and cardiac malformations, with generally preserved cognition — unlike male-expressed MED12 syndromes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Hardikar syndrome is underdiagnosed because MED12 is primarily known for its X-linked forms in males. This clarification of the clinical spectrum and transmission patterns directly improves interpretation of MED12 variants in pediatric genetic panels and guides genetic counseling in affected families.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 7/10