The ophthalmic phenotype of IFT140-related ciliopathy ranges from isolated to syndromic congenital retinal dystrophy

Background Conorenal syndrome is a systemic skeletal ciliopathy characterised by skeletal and renal findings and caused by biallelic mutations in the gene intraflagellar transport 140 Chlamydomonas homologue (IFT140). Most studies have focused on syndromic features and are by non-ophthalmologists. We highlight the ophthalmic phenotype. Methods Retrospective consecutive case series (2010-2014). Results Twelve subjects with confirmed homozygous mutations were identified (11 consanguineous families; 7 boys; assessed at age 10 months to 20 years, average and median age 6.5 and 4 years). All were homozygous for the same IFT140 mutation (c.1990G>A; p. Glu664Lys) except one who was homozygous for c.1541_1542delinsAA. All had poor vision and nystagmus since birth, with visual acuity after 5 years old of hand motions or light perception. In early childhood, nine were noted to stare at lights, four were noted to have a happy demeanour, high hyperopia was typical, and electroretinography was non-recordable. Fundus appearance was grossly normal before the age of 1 year but thereafter appeared dystrophic. Eight children had developmental delay, two had short stubby fingers, and one had renal disease, but four had no evident extraocular disease, including one aged 18 years who also had two older affected siblings in their twenties who remained non-syndromic and were excelling academically. Conclusions Recessive IFT140 mutations cause a severe congenital retinal dystrophy with high hyperopia and often early photophilia. Developmental delay is common but not universal and not all patients have obvious extraocular findings. The c.1990G>A mutation represents a founder effect or mutational hotspot on the Arabian Peninsula.