Joubert Syndrome 4

A number sign (#) is used with this entry because of evidence that Joubert syndrome-4 (JBTS4) is caused by homozygous deletion in the NPHP1 gene (607100) on chromosome 2q13.

Nephronophthisis-1 (NPHP1; 256100) and Senior-Loken syndrome-1 (SLSN1; 256100) are also caused by deletion in the NPHP1 gene.

For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.

Clinical Features

Parisi et al. (2004) reported 2 sibs with a relatively mild form of Joubert syndrome. One sib had mild gross motor delay, mild cognitive impairment, hypotonia, congenital head tilt, abnormal eye movements consistent with oculomotor apraxia, and nephronophthisis diagnosed at age 10 years. MRI scan showed hypoplasia of the cerebellar vermis and the 'molar tooth sign.' Her sister had similar findings, but had normal cognitive function and was without renal involvement at age 8 years. Neither sib had retinal dystrophy or abnormal breathing patterns in infancy.

Molecular Genetics

In 2 sibs with Joubert syndrome, Parisi et al. (2004) demonstrated homozygous deletion of the NPHP1 gene (607100.0005) identical to that which causes juvenile nephronophthisis (256100). The authors concluded that mutations in the NPHP1 gene are a rare cause of Joubert syndrome.

In 4 patients with Joubert syndrome from 3 nonconsanguineous families, Parisi et al. (2006) identified homozygosity for deletion of the NPHP1 gene. The molar tooth sign in these patients had a distinctive appearance, with elongated but not thickened superior cerebellar peduncles.