Joubert Syndrome and related disorders

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.

ISSN: 1750-1172