Document Detail

Clinical nosologic and genetic aspects of Joubert and related syndromes.
MedLine Citation:
PMID:  10511339     Owner:  NLM     Status:  MEDLINE    
Joubert syndrome is an autosomal-recessive disorder characterized by cerebellar hypoplasia, hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements. The biochemical and genetic basis of Joubert syndrome is unknown and a specific chromosomal locus for this disorder has not been identified. Review of this disorder and related syndromes suggests that (1) hypoplasia of the cerebellar vermis in Joubert syndrome is frequently associated with a complex brain stem malformation represented as the "molar tooth sign" on magnetic resonance imaging, (2) the "molar tooth sign" could be present in association with the Dandy-Walker malformation and occipital encephalocele, (3) cerebellar hypoplasia is present in conditions related to Joubert syndrome such as Arima syndrome; Senior-Loken syndrome; cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndrome; and juvenile nephronophthisis due to NPH1 mutations, and (4) the brainstem-vermis malformation spectrum is probably caused by at least two and probably several genetic loci. We have ascertained previously a cohort of 50 patients with a putative diagnosis of Joubert syndrome in order to evaluate the presence of associated malformations, and to initiate studies leading to the identification of genes causing Joubert and related syndromes. Among the associated malformations found in patients ascertained as having Joubert syndrome, 8% of patients had polydactyly, 4% had ocular colobomas, 2% had renal cysts, and 2% had soft-tissue tumors of the tongue. The WNT1 gene has been tested as a candidate gene for Joubert syndrome based on its expression in the developing cerebellum and an associated mutation in the swaying mouse. A search for mutations in WNT1 in a series of patients with Joubert syndrome did not detect mutations at this locus. This analysis suggested that mutations in WNT1 might not have a significant role in Joubert syndrome, and other functional candidate genes related to development of the cerebellum need to be examined. A genome-wide linkage analysis carried out in 10 Joubert syndrome pedigrees did not identify a specific chromosomal locus for this disorder. This observation, along with those from clinical studies, provides further evidence that Joubert and related syndromes are genetically heterogeneous.
P F Chance; L Cavalier; D Satran; J E Pellegrino; M Koenig; W B Dobyns
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Journal of child neurology     Volume:  14     ISSN:  0883-0738     ISO Abbreviation:  J. Child Neurol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-19     Completed Date:  1999-11-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8606714     Medline TA:  J Child Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  660-6; discussion 669-72     Citation Subset:  IM    
Department of Pediatrics, University of Washington School of Medicine and Children's Hospital and Regional Medical Center, Seattle 98195, USA.
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MeSH Terms
Brain Stem / abnormalities,  pathology
Cerebellum / abnormalities*,  pathology
Chromosome Aberrations / genetics*
Chromosome Disorders
DNA Mutational Analysis
Developmental Disabilities / diagnosis,  genetics*
Diagnosis, Differential
Genes, Recessive / genetics*
Magnetic Resonance Imaging
Mice, Neurologic Mutants
Spinocerebellar Ataxias / diagnosis,  genetics*
Grant Support
R0130804//PHS HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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