Male Goltz Syndrome due to Postzygotic PORCN Mosaicism: A Case Report

Abstract

Goltz syndrome, also known as focal dermal hypoplasia (FDH), is a rare X‐linked dominant genetic disorder caused by loss‐of‐function mutations in the PORCN gene, which is crucial for Wnt protein secretion and signaling during embryonic development. The syndrome primarily affects females, as hemizygous males with pathogenic variants in the gene typically die in utero, while surviving males are usually mosaic for the variant. Patients typically present with diverse phenotypic features, including dermal hypoplasia, musculoskeletal abnormalities, ocular malformations, and dental defects, often distributed asymmetrically along Blaschko’s lines. Despite the identification of the PORCN gene as the main gene involved in the pathogenesis of the disease, a significant gap remains in understanding the broad spectrum of PORCN mutations and the resulting variability in clinical presentation among Goltz syndrome patients, particularly concerning the factors that contribute to the differences in disease severity and expression. This study reports a 9‐year‐old male patient presenting with non‐healing skin lesions, syndactyly, limb length discrepancy, and scoliosis, consistent with clinical findings of Goltz syndrome. Whole‐exome sequencing identified a hemizygous nonsense variant in the PORCN gene (c.915G > A), resulting in a truncated protein (p.Trp305Ter). This nucleotide‐level variant is distinct from, but affects the same residue as, a previously reported pathogenic variant reported by Lasocki et al., further supporting the clinical relevance of truncating changes at this codon and providing insight into the mosaicism associated with milder male phenotypes.