Table 1

Classification of Joubert syndrome and related disorders based on associated clinical features

Clinical subtypes

Mandatory features

Preferentially associated features*

Previously used nosology

Major gene(s)**

Pure Joubert syndrome (JS)

MTS

JS

Mutations in many genes

JS type A

JS with ocular defect (JS-O)

MTS

Retinal dystrophy (including LCA)

JS type B

AHI1

JS with renal defect (JS-R)

MTS

NPHP1

NPH

RPGRIP1L

MTS

Cerebellooculorenal s.

JS with oculorenal defects (JS-OR)

Retinal dystrophy (often LCA)

(CHF reported in few cases)

SLS plus MTS

CEP290

NPH

JS type B

Dekaban-Arima s.

JS with hepatic defect (JS-H)

MTS

Colobomas

COACH s.

TMEM67

CHF

NPH

Gentile s.

JS with orofaciodigital defects (JS-OFD)

MTS

Váradi-Papp s.

Lobulated/bifid tongue (incl. hamartomas)

Cleft lip/palate

Orofaciodigital VI s.

TMEM216 (2 patients only)

Polydactyly

*Features not correlated with a specific clinical subtype include: postaxial polydactyly; encephalocele and other central nervous system malformations; neuronal migration defects (e.g. polymicrogyria); Hirschsprung's disease; congenital heart defects; laterality defects.

**Besides the major genes listed here, other genes have been occasionally associated with clinical subtypes. Mutations in the CC2D2A gene give rise to a wide phenotypic spectrum [13,73,85]. For INPP5E, ARL13B and OFD1 genes, only few mutated patients have been described to date [68-70]. Abbreviations: CHF: congenital hepatic fibrosis; incl.: including; JS: Joubert syndrome; LCA: Leber congenital amaurosis; MTS: molar tooth sign; NPH: nephronophthisis; s.: syndrome; SLS: Senior-Löken syndrome.

Brancati et al. Orphanet Journal of Rare Diseases 2010 5:20   doi:10.1186/1750-1172-5-20