Phenotypic and genotypic findings in Joubert syndrome: A case series in Saudi Arabia

Abstract: PURPOSE: The purpose of this study was to describe the ophthalmological features and genetic findings in a group of patients with Joubert syndrome (JS) from Saudi Arabia and to explore genotype–phenotype correlations. METHODS: This case series included six patients diagnosed with JS based on clinical features, brain imaging, and genetic testing. All patients underwent comprehensive ophthalmic examinations including visual acuity testing, cycloplegic refraction, fundus examination, optical coherence tomography (OCT), and electroretinography (ERG) when feasible. Systemic evaluation included neurodevelopmental assessment and imaging studies. Genetic analysis was performed using whole exome sequencing or targeted gene sequencing based on family history. RESULTS: The six patients (four males, two females) were aged between 10 months and 30 years at diagnosis. All patients had a positive family history of consanguinity. Mutations were identified in three genes: AHI1 (three patients), INPP5E (two patients), and CC2D2A (one patient). Visual acuity varied from normal to fixation only. Oculomotor apraxia was observed in five patients and nystagmus in two. Retinal pigment epithelium changes and attenuation of retinal vessels were common findings. OCT showed photoreceptor loss in two patients, while ERG revealed rod-cone dystrophy in all patients. One patient with a CC2D2A mutation had a single kidney; the rest had no renal or hepatic abnormalities. All patients exhibited motor and cognitive developmental delays. CONCLUSION: JS presents with diverse ophthalmologic and systemic features, with AHI1 being the most frequently mutated gene in this cohort. Retinal degeneration and oculomotor abnormalities are common. Genetic analysis is essential for confirming diagnosis, understanding phenotypic variability, and guiding multidisciplinary care.