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PMID: 23870701 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Joubert syndrome: congenital cerebellar ataxia with the molar tooth.

The Lancet. Neurology ·Vol. 12 ·No. 9 ·2013-09-00 ·Pages 894-905

Romani M, Micalizzi A, Valente EM

Abstract

Joubert syndrome is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, the diagnostic hallmark of which is a unique cerebellar and brainstem malformation recognisable on brain imaging-the so-called molar tooth sign. Neurological signs are present from the neonatal period and include hypotonia progressing to ataxia, global developmental delay, ocular motor apraxia, and breathing dysregulation. These signs are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 21 causative genes have been identified so far, all of which encode for proteins of the primary cilium or its apparatus. The primary cilium is a subcellular organelle that has key roles in development and in many cellular functions, making Joubert syndrome part of the expanding family of ciliopathies. Notable clinical and genetic overlap exists between distinct ciliopathies, which can co-occur even within families. Such variability is probably explained by an oligogenic model of inheritance, in which the interplay of mutations, rare variants, and polymorphisms at distinct loci modulate the expressivity of the ciliary phenotype.

MeSH Terms
Abnormalities, Multiple Cerebellar Diseases/congenital,epidemiology,genetics Cerebellum/abnormalities Eye Abnormalities/epidemiology,genetics Humans Kidney Diseases, Cystic/congenital,epidemiology,genetics Retina/abnormalities
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Romani Marta
Neurogenetics Unit, Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Micalizzi Alessia
Neurogenetics Unit, Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Valente Enza Maria
Neurogenetics Unit, Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Department of Medicine and Surgery, University of Salerno, Salerno, Italy. Electronic address: [email protected].
Supplementary Concepts
Agenesis of Cerebellar Vermis (Disease)
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Article Info
Journal
The Lancet. Neurology
Abbr.
Lancet Neurol
ISSN
1474-4465
DOI
10.1016/S1474-4422(13)70136-4
Email
[email protected]
Published
2013-09-00
Epub
2013-00-17
Pages
894-905
Language
English
Region
England
NLM ID
101139309
PMCID
PMC3809058
Subset
IM
Grants
European Research Council · 260888 · International
NINDS NIH HHS · R01NS048453 · United States
NINDS NIH HHS · R01 NS048453 · United States
NINDS NIH HHS · R01 NS052455 · United States
NICHD NIH HHS · P01 HD070494 · United States
External Links
PubMed source DOI: 10.1016/S1474-4422(13)70136-4 PMC Full Text View journal details
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