Branchial Cleft Cyst in Simpson-Golabi-Behmel Syndrome: A Case Report Expanding the Phenotypic Spectrum of GPC3-Related Disorders

Background: Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked overgrowth disorder caused by pathogenic variants or copy number changes in the GPC3 gene located at Xq26.2. GPC3 encodes a heparan sulfate proteoglycan involved in the regulation of Wnt, FGF, BMP, and SHH signaling pathways during embryogenesis. Dysfunction of GPC3 disrupts these pathways, leading to abnormal cell proliferation, impaired apoptosis, and tissue overgrowth. Case Presentation: We report a male infant born at 30 weeks of gestation with prenatal findings of polyhydramnios, macrosomia, and hydronephrosis. Postnatal evaluation revealed coarse facial features, macroglossia, hypertelorism, rib anomalies, and bilateral multicystic dysplastic kidneys. Chromosomal microarray analysis identified an 84.5 kb duplication encompassing GPC3 at Xq26.2, confirming the diagnosis of SGBS. During follow-up, a lobulated cystic lesion measuring 15 × 9 × 12 mm was detected in the left carotid sheath, consistent with a third branchial cleft cyst on MRI. Conclusion: To our knowledge, branchial cleft cysts associated with Simpson-Golabi-Behmel syndrome (SGBS) have not previously been reported in the literature. This case expands the phenotypic spectrum of GPC3-related disorders and suggests a possible link between GPC3 dysfunction and abnormal branchial arch development. Additional case reports and further molecular studies are needed to better understand the relationship between these two conditions.