Intrafamilial phenotypic variation in four Palestinian siblings with CFAP418-related ciliopathy: a familial case series.

Abstract

Background: Biallelic CFAP418 variants cause retinal degeneration with variable extraocular findings. The principal contribution of this familial case series is a comparison of four affected siblings carrying the same previously reported splice-donor variant, with explicit separation of original clinical records from recalled history and historical summaries.

Case presentation: Four Palestinian siblings from a consanguineous family had homozygosity for CFAP418 NM_177965.3:c.155 + 1G > A reported in a 2018 family research letter; a 2019 clinical laboratory report confirmed the variant in the older brother and sister and heterozygosity in both parents. At history collection in March 2026, the male twins reported an age of 27 years, their older brother 30 years and their sister 26 years. The twins, described by the family as monozygotic without independent zygosity confirmation, had congenital postaxial polydactyly; the other siblings did not. Dated records for the twins documented severe visual impairment, posterior subcapsular cataract, pigmentary retinal degeneration, macular outer-retinal abnormalities, markedly constricted Goldmann fields and virtually absent rod and mixed electroretinographic responses with residual cone responses. Acuity differed across visits and testing conditions. Contemporary standardized ophthalmic data were unavailable for the other two siblings. Participants reported photophobia, progressive visual difficulty and substantial effects on mobility, education, daily tasks and family roles. Documented care included ophthalmic and low-vision follow-up, optical-aid recommendations and supportive prescriptions; no measured treatment benefit was established.

Conclusions: The family demonstrates a documented contrast in polydactyly alongside a shared molecular and retinal disease context. Recalled symptoms do not establish an electrophysiological transition between retinal diagnoses. The 2026 genotype-informed Bardet-Biedl diagnostic algorithm supports a syndromic interpretation across the sibship, while incomplete systemic ascertainment limits characterization of organ involvement. Standardized retinal follow-up, low-vision care, genetic counselling and multidisciplinary surveillance are warranted.