Bilateral Iris and Chorioretinal Colobomas in a Child With Suspected Lamb-Shaffer Syndrome.

Abstract

Lamb-Shaffer syndrome (LSS) is a rare neurodevelopmental disorder caused by haploin-sufficiency of the SRY-related HMB box (SOX5) gene. Most cases result from de novo variants; however, some cases follow autosomal dominant inheritance patterns. Classic features of LSS include global developmental delay, dysmorphic facial features, musculoskeletal abnormalities, and cardiac and genitourinary defects. Ophthalmic manifestations of LSS such as strabismus and optic nerve abnormalities have been described in approximately 55% of patients with LSS. We report a case of a 22-month-old boy with a history of bilateral iris and chorioretinal colobomas, bilateral lens subluxation, and strabismus and a past medical history of developmental delay, syndactyly, and hearing loss. Genetic testing identified a missense variant of uncertain significance in exon 14 of the SOX5 gene, which is linked to LSS. An inherited retinal disorders panel revealed the patient was a carrier of a pathogenic variant of the PHYH gene and a variant of uncertain significance of the COL9A2 gene. Results of the inherited retinal disorders panel did not identify variants implicated with iris and chorioretinal colobomas; therefore, we postulate colobomas as an additional ophthalmic manifestation of LSS. This case serves to broaden characterization of the LSS phenotype, while presenting an additional variant potentially associated with LSS. There is currently no treatment for LSS; however, robust understanding of LSS's heterogenous phenotypic and genetic profile will lead to improved knowledge of the syndrome and diagnostic aptitude. [Ophthalmic Surg Lasers Imaging Retina 2025;56:XX-XX.].