Novel homozygous mutation in the human RAX homeobox gene in a patient with bilateral anophthalmia and severe endocrine dysfunction - a case report and literature review.

Objectives: Childhood visual impairment due to congenital malformation leads to severe handicaps and lifelong consequences for the affected child. Congenital anophthalmia remains a rare condition marked by a child born with an empty eye socket. The embryonic plant of the eye occurs approximately on day 22 of intrauterine development and ends within the first trimester of pregnancy. Mutations in the RAX gene located on chromosome 18 (# 601881) cause a spectrum of head malformations, ranging from isolated microphthalmia/anophthalmia with cleft lip and palate to complex brain malformations.

Case presentation: Here, we present a child's case diagnosed with bilateral anophthalmia at 33 weeks of gestation. The newborn was delivered vaginally with a RAX-gene-linked syndrome. Besides craniofacial malformations (bilateral anophthalmia, craniofacial hypoplasia, bilateral cleft lip), the female child had severe endocrine dysfunction (congenital hypopituitarism and diabetes insipidus) postnatal that required specialised monitoring and clinical management. Our case study reports a novel homozygous autosomal recessive non-sense mutation (c.106G>T; p.Glu36Ter) of the RAX gene. This is the first description of this pathogenic gene variant in the literature.

Conclusions: Early and precise sonography is crucial in detecting these conditions on time to prepare postpartum care and avoid delays in optimal clinical treatment for the affected child. This case report aims to raise the scientific community's awareness about this rare genetic syndrome, showing an individualised two-year follow-up program that could help guide physicians and future parents of affected children.