A Case Report of Conradi–Hünermann–Happle Syndrome in an Indian Neonate: Clinical, Radiological, and Genetic Insights

Abstract

Conradi–Hünermann–Happle syndrome (CHHS) is a rare X-linked dominant disorder caused by mutations in the emopamil-binding protein ( EBP ) gene, disrupting cholesterol biosynthesis and resulting in skeletal, cutaneous, and multisystem abnormalities. We report a case of a female neonate born to nonconsanguineous parents in India, presenting with classical features of CHHS, including rhizomelic limb shortening, midface hypoplasia, macrocephaly, ichthyosiform skin lesions in a blaschkoid distribution, and patchy alopecia. Radiological evaluation revealed epiphyseal stippling, a hallmark of the condition, and genetic testing identified a variant of uncertain significance in the EBP gene (c.484G>C, p.Asp162His), supporting the clinical diagnosis and mutation in the COL1A1 and ROR2 genes. This report highlights the diagnostic challenges of interpreting multiple variants of uncertain significance in rare disorders and emphasizes the role of multidisciplinary evaluation. Our findings expand the phenotypic spectrum of CHHS and contribute valuable insights into its clinical and genetic heterogeneity.