Short stature, hearing loss, retinitis pigmentosa, and distinctive facies: an ophthalmological description of a new case of SHRF syndrome

INTRODUCTION: Short stature, Hearing loss, Retinitis pigmentosa, and distinctive Facies (SHRF) syndrome is an ultra-rare autosomal recessive disorder caused by pathogenic variants in the EXOSC2 gene. We report the fifth known case worldwide, involving an 18-year-old female with the homozygous p.Gly30Val variant and novel ophthalmological findings. METHODS: A retrospective observational study was conducted at the Federal University of Minas Gerais, Brazil. Clinical, audiological, neurological, and ophthalmological data were reviewed. Ophthalmological evaluation included visual acuity testing, slit-lamp biomicroscopy, fundus examination, optical coherence tomography, fundus autofluorescence, and electroretinography. Molecular diagnosis was established by whole exome sequencing and ACMG-based variant classification. RESULTS: The patient presented the classical SHRF phenotype, including short stature, developmental delay, brachydactyly, progressive sensorineural hearing loss, and retinal dystrophy. Additional findings included bilateral corneal calcium deposits progressing to band keratopathy and stable anterior polar cataracts, suggesting accelerated ocular aging. Retinal imaging demonstrated retinal pigment epithelium rarefaction, perifoveal hyperautofluorescent ring, and rapid ellipsoid zone loss, while electroretinography confirmed severe rod-cone dystrophy. Whole exome sequencing identified the pathogenic homozygous EXOSC2 p.Gly30Val variant, alongside variants of uncertain significance in PKHD1 and ELP2. CONCLUSIONS: This case expands the phenotypic spectrum of SHRF syndrome and supports the genotype-phenotype association of the EXOSC2 p.Gly30Val variant. Comprehensive genomic analysis is essential to distinguish syndromic manifestations from coexisting genetic conditions in consanguineous families.