Analysis of genotype-phenotype correlation in Walker-Warburg syndrome with a novel mutation in different clinical manifestations.

Purpose: Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder characterized by congenital muscular dystrophy and severe brain and eye malformations. This study aims to analyze genotype-phenotype correlations in WWS with a novel cytidine diphosphate-l-ribitol pyrophosphorylase A () mutation in different clinical manifestations.

Case Description: We report a girl with a presentation of multiple brain and ocular anomalies. Her ophthalmological evaluation showed a shallow anterior chamber, cortical cataract, iris hypoplasia, persistent hyperplastic primary vitreous in the right eye, punctate cataract, iris hypoplasia, primary congenital glaucoma, and a widespread loss of fundus pigmentation in the left eye. She was hypotonic, and her deep tendon reflexes were absent. Laboratory investigations showed high serum levels of serum creatine kinase. Brain magnetic resonance imaging demonstrated hydrocephalus, agenesis of the corpus callosum, retrocerebellar cyst, cerebellar dysplasia and hypoplasia, cobblestone lissencephaly, and hypoplastic brainstem. Whole exome sequencing revealed a novel homozygous nonsense mutation in the first exon of the gene (NM_001101426.4, c.217G>T, p.Glu73Ter).

Conclusions: The study findings expand the phenotypic variability of the ocular manifestations in the gene-related WWS. Iris hypoplasia can be a part of clinical manifestations of the gene-related WWS. The uncovering of the genes associated with ocular features can provide preventative methods, early diagnosis, and improved therapeutic strategies.