title: Meckel syndrome in the Hutterite population is actually a Joubert-related cerebello-oculo-renal syndrome.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Alberta Children's Hospital and University of Calgary, Calgary, Alberta, Canada. kboycott@cheo.on.ca
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.forename: James N
authors.initials: JN
authors.lastname: Scott
authors.forename: D Ross
authors.initials: DR
authors.lastname: McLeod
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Greenberg
authors.forename: T Mary
authors.initials: TM
authors.lastname: Fujiwara
authors.forename: Jean K
authors.initials: JK
authors.lastname: Mah
authors.forename: Julian
authors.initials: J
authors.lastname: Midgley
authors.forename: Andrew
authors.initials: A
authors.lastname: Wade
authors.forename: Francois P
authors.initials: FP
authors.lastname: Bernier
authors.forename: Bernard N
authors.initials: BN
authors.lastname: Chodirker
authors.forename: Martin
authors.initials: M
authors.lastname: Bunge
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D003937:Diagnosis, Differential; D005006:Ethnicity / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008350:Manitoba; D008467:Meckel Diverticulum / Q000145:classification / Q000453:epidemiology* / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D013577:Syndrome