Joubert syndrome (JS) is an autosomal recessive disorder presenting with congenital hypotonia evolving into ataxia, developmental delay, and either oculomotor apraxia or abnormalities of respiratory pattern or both. JS is characterised, using magnetic resonance imaging (MRI), by cerebellar vermian hypoplasia and a complex brain stem malformation called the “molar tooth sign” (MTS), consisting of thickened, elongated, and reoriented superior cerebellar peduncles and a deep interpeduncular fossa.¹ JS has been classified into two groups, A and B, the latter being characterised by the occurrence of retinal and/or renal involvement.²

Key associated features of JS are retinal dystrophy and nephronophthisis, but other manifestations include ocular colobomas, liver fibrosis, and polydactyly. The variable involvement of other organs identifies a large spectrum of syndromes sharing the MTS (such as Arima, COACH, and Senior-Löken syndromes) which, together with JS, are termed Joubert syndrome related disorders (JSRD) or MTS related syndromes.^3–5

To date, three genetic loci associated with JSRD have been mapped to chromosome 9q34.3 (JBTS1), 11p11.2–q12.3 (JBTS2), and 6q23 (JBTS3).^6–9 Recently, mutations in the AHI1 gene have been identified in three JBTS3 linked families presenting with a pure cerebellar phenotype.¹⁰

Isolated nephronophthisis (NPH) is an autosomal recessive tubulointerstitial medullary kidney disease and is one of the most frequent monogenic causes of chronic renal failure in childhood. Four genes causing infantile or juvenile NPH have been cloned so far (NPHP1 to 4).^11–14 Of these, NPHP1 is the most commonly mutated gene, being responsible for at least 50% of cases with juvenile NPH.^15,16 A large homozygous deletion of the NPHP1 gene is found in more than 80% of patients, while less than 5% are compound heterozygote for the gene deletion and a point mutation on the other allele.¹⁶ Most patients with the NPHP1 deletion demonstrate …