From Retinitis Pigmentosa to Joubert Syndrome: The Impact of Genomic Testing in Retinal Dystrophy Diagnosis

 

Introduction

Inherited retinal dystrophies (IRDs) are a heterogeneous group of progressive disorders with variable onset and systemic associations¹. Retinitis pigmentosa (RP) is the most common phenotype², but syndromic ciliopathies such as Joubert syndrome (JS) may present with similar retinal findings^3,4. JS is characterised by cerebellar and brainstem malformations, developmental delay, hypotonia, and oculomotor abnormalities^3,4. Variants in AHI1 are strongly associated with JS type 3 and retinal degeneration^5–7.

History

A patient presented with progressive visual field constriction and long-standing visual impairment, initially suspected as RP. Congenital oculomotor apraxia raised suspicion of a syndromic ciliopathy ^3,4.

Examination

Reduced visual acuity, concentric peripheral field loss, bone-spicule pigmentation, vascular attenuation, optic disc pallor, and relative macular preservation.

Investigations

OCT demonstrated preserved macular structure, while electrodiagnostic testing confirmed advanced rod–cone dysfunction in keeping with ISCEV standards⁸ . Genomic testing (gene panel and whole-genome sequencing) identified biallelic pathogenic AHI1 variants, confirming JS type 3 ^5–7 . Further investigations included brain MRI for the “molar tooth sign” and renal assessment for nephronophthisis risk . Multidisciplinary management and family cascade testing were initiated.

Discussion

This case highlights the overlap between RP and syndromic ciliopathies. Although retinal findings were typical of RP² , oculomotor apraxia and macular preservation suggested an alternative diagnosis ^3,4 . AHI1-associated disease demonstrates marked phenotypic variability, limiting clinical differentiation alone^6,7 . Genetic diagnosis is critical for systemic surveillance, prognostication, and family counselling ^3,6, and facilitates access to emerging therapies and registries⁹.

Conclusion

Genomic testing is essential in atypical retinal dystrophy. In this case, it enabled reclassification from RP to AHI1-associated JS, significantly altering multi-system clinical management and follow-up.