Novel OFD1 Mutation Results in Unusually Early-Onset Polycystic Kidney Disease.

Introduction: Mutations of the OFD1 gene cause oral-facial-digital syndrome type 1 (OFD 1) and variations of the related ciliopathies Joubert syndrome and primary ciliary dyskinesia. OFD 1 manifests with skeletal, CNS, and renal abnormalities with prevalence estimated between 1 in 50,000 and 1 in 250,000. Cilia help regulate responses to mechanical forces in the renal tubules, and polycystic kidney disease (PKD) resulting from defective cilia is the primary determinant of morbidity in OFD 1. PKD associated with OFD 1 is rare before adulthood but may increase markedly with age, progressing to end-stage renal disease (ESRD) in 80% of cases.

Case presentation: We report an 18-year-old female with congenital ciliopathy presenting with declining renal function and an increase of serum creatinine to 1.7 mg/dL. A 24-h urine collection yielded 0.8 g of creatinine and 500 mg of total protein. Imaging was conducted and genetic studies were repeated as her early childhood results were not available. MRI revealed numerous bilateral renal cysts consistent with progression of ciliopathy-associated PKD. Genetic testing confirmed the presence of a novel c.1332del frameshift mutation in the OFD1 gene, prematurely truncating the OFD1 protein. Modifications to diet and hydration to preserve renal function and delay progression to ESRD were initiated.

Conclusion: This case of unusually early renal decline highlights the challenge of treating OFD 1. There are no currently approved medications and management consists of supportive measures to delay progression. Further research to better characterize and identify treatments for OFD 1 and related ciliopathies is warranted.