A novel mutation in the human RAX gene in patients with microphthalmia and coloboma: A case report and literature review

Rationale: Microphthalmia, anophthalmia, and coloboma (MAC) form a spectrum of severe developmental eye anomalies. Reports of human MAC associated with RAX mutations remain limited, exhibiting substantial phenotypic heterogeneity. Clinically managing these ocular anomalies or investigating their genetic mechanisms continues to present significant challenges. Patient concerns: A 28-year-old female and her 2 sisters L and Q presented with lifelong poor vision, ocular examination revealed similar phenotype among them, including narrow palpebral fissures, bilateral ptosis with epicanthus and esotropia, small cornea, iris coloboma and microspherophakia with uneven lens opacity, in addition to irreversible low vision. Diagnoses: Based on ocular examination, the proband was diagonosised with microphthalmia and coloboma, and her 2 sisters were diagonosised with coloboma. WES detected a novel RAX mutation in the 3 affected siblings. Interventions: Cataract extraction surgeries combined with complicate scleral fixation of intraocular lens were performed bilaterally in the proband and unilaterally in the right eyes of patient L and Q. Outcomes: The proband demonstrated improved bilateral visual acuity postoperatively, reaching 20/125 and 20/100. Patient Q’s right eye achieved 20/200 visual acuity, while Patient L’s right eye showed no change. The corrected intraocular pressure in Patient L’s right eye maintained below 21 mm Hg without requiring antiglaucoma medication. Lessons: The clinical management of MAC remains challenging. Identifying pathogenic genes could enable curative approaches for this condition. In pediatric patients with visual impairment, prompt intervention targeting ocular and systemic complications proves essential for optimizing visual outcomes.