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Joubert syndrome

Monday 22 September 2003

Joubert syndrome (JS) is an autosomal recessive developmental brain condition characterized by hypoplasia/dysplasia of the cerebellar vermis and by ataxia, hypotonia, oculomotor apraxia, and neonatal breathing dysregulation.

The association of retinal dystrophy and renal anomalies defines JS type B. JS is a genetically heterogeneous condition with mutations in several genes: AHI1 at 6q23 (MIM.608894), CEP290 at 12q21 (MIM.610412) and TMEM67 at 8q21 (MKS3) (MIM.609884).

Synopsis

- craniofacial anomalies

- ocular anomalies

- respiratory anomalies

  • neonatal breathing dysregulation
  • hyperpnea, episodic
  • tachypnea, episodic
  • central apnea

- +/- ductal plate malformation with hepatic fibrosis (congenital hepatic fibrosis) (7538263)

- Hirschsprung disease (17516083)

- +/- renal anomalies (JS type B)

- limb anomalies

  • postaxial polydactyly (less common) (17160906)
  • mussing digital phalanges (less common)
    - 

- neurological anomalies

Variants

- Joubert syndrome type B: association of JS with retinal dysplasia and nephronophthisis (cerebello-oculo-renal syndrome or CORS)

  • germline mutations in RPGRIP1L

- JBTS3: JS with cortical polymicrogyria (AHI1 mutations)

Etiology

The association of retinal dystrophy and renal anomalies defines JS type B. JS is a genetically heterogeneous condition with mutations in several genes: AHI1 at 6q23 (MIM.608894), CEP290 at 12q21 (MIM.610412) and TMEM67 at 8q21 (MKS3) (MIM.609884).

- Joubert syndrome type 1 (JBTS1 or CORS1 at 9q34.3) (MIM.213300)

  • gene unknown

- Joubert syndrome type 2 (JBTS2 or CORS2 at 11p12-q13.3) (MIM.608091)(12908130)

  • gene unknown

- Joubert syndrome type 3 (JBTS3 or CORS3)

  • Joubert syndrome with cortical polymicrogyria (JBTS3 or CORS3 at 6q23.3)
  • recessive mutations in the gene AHI1 (Abelson helper integration site 1) (MIM.608894)
  • the gene product, jouberin, contains a coiled-coil, an SH3 (src-homology domain 3) and six WD40 domains

- Joubert syndrome type 4 (JBTS4 or CORS4 at 17p11.2) (MIM.609583)

- Joubert syndrome type 5 (JBTS5 or CORS5 at 12q21.32) (MIM.610188)

  • germline mutation in the CEP290 gene
  • allelic to NPHP6 (MIM.610142) on 12q21.32

- Joubert syndrome type 6 (JBTS6 or CORS6 at 8q21-q22) (MIM.610188)

- Joubert syndrome type B (cerebello-oculo-renal syndrome or CORS syndrome at 16q12.2)

  • germline mutations of RPGRIP1L

- NPHP1 Gene Deletion at 2q13 (15138899)

Associations

- occipital encephalocele (17160906)
- polydactyly (17160906)
- Hirschsprung disease (17516083)

See also

- Joubert-related cerebello-oculo-renal syndromes

References

- Brancati F, Barrano G, Silhavy JL, Marsh SE, Travaglini L, Bielas SL, Amorini M, Zablocka D, Kayserili H, Al-Gazali L, Bertini E, Boltshauser E, D’Hooghe M, Fazzi E, Fenerci EY, Hennekam RC, Kiss A, Lees MM, Marco E, Phadke SR, Rigoli L, Romano S, Salpietro CD, Sherr EH, Signorini S, Stromme P, Stuart B, Sztriha L, Viskochil DH, Yuksel A, Dallapiccola B; International JSRD Study Group, Valente EM, Gleeson JG. CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. Am J Hum Genet. 2007 Jul;81(1):104-13. PMID: 17564967

- Tory K, Lacoste T, Burglen L, Moriniere V, Boddaert N, Macher MA, Llanas B, Nivet H, Bensman A, Niaudet P, Antignac C, Salomon R, Saunier S. High NPHP1 and NPHP6 Mutation Rate in Patients with Joubert Syndrome and Nephronophthisis: Potential Epistatic Effect of NPHP6 and AHI1 Mutations in Patients with NPHP1 Mutations. J Am Soc Nephrol. 2007 May;18(5):1566-1575. PMID: 17409309

- Baala L, Romano S, Khaddour R, Saunier S, Smith UM, Audollent S, Ozilou C, Faivre L, Laurent N, Foliguet B, Munnich A, Lyonnet S, Salomon R, Encha-Razavi F, Gubler MC, Boddaert N, de Lonlay P, Johnson CA, Vekemans M, Antignac C, Attie-Bitach T. The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. Am J Hum Genet. 2007 Jan;80(1):186-94. PMID: 17160906

- Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet. 2005 Dec;6(12):928-40. PMID: 16341073

- Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB. Clinical nosologic and genetic aspects of Joubert and related syndromes. J Child Neurol. 1999 Oct;14(10):660-6; discussion 669-72. PMID: 10511339

- Witzleben CL, Sharp AR. "Nephronophthisis-congenital hepatic fibrosis": an additional hepatorenal disorder. Hum Pathol. 1982 Aug;13(8):728-33. PMID: 7106736

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