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Meckel syndrome in the Hutterite population is actually a Joubert‐related cerebello‐oculo‐renal syndrome
Author(s) -
Boycott Kym M.,
Parboosingh Jillian S.,
Scott James N.,
McLeod D. Ross,
Greenberg Cheryl R.,
Fujiwara T. Mary,
Mah Jean K.,
Midgley Julian,
Wade Andrew,
Bernier Francois P.,
Chodirker Bernard N.,
Bunge Martin,
Innes A. Micheil
Publication year - 2007
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31832
Subject(s) - joubert syndrome , polydactyly , hypotonia , hypertelorism , anatomy , medicine , ataxia , encephalocele , ciliopathy , hydrocephalus , ptosis , pediatrics , biology , surgery , cilium , biochemistry , psychiatry , gene , phenotype , microbiology and biotechnology
Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)‐related disorders (JSRDs) or cerebello‐oculo‐renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy–Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep‐set eyes, down‐slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down‐turned corners, and posteriorly rotated low‐set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity‐by‐descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD. © 2007 Wiley‐Liss, Inc.