title: Chromosomal abnormalities resembling Joubert syndrome: two cases illustrating the diagnostic pitfalls.
abstract: We describe two patients with severe developmental delay, hypotonia and breathing abnormalities initially diagnosed with the autosomal recessive Joubert syndrome (JBS) who at a later stage appeared to carry chromosomal abnormalities. One case was due to a 4.8 Mb terminal 1q44 deletion, and the other due to a 15.5 Mb duplication of Xq27.2-qter containing the MECP2 gene. Critical evaluation of the clinical data showed that, retrospectively, the cases did not fulfil the diagnostic criteria for JBS, and that the diagnosis of JBS was incorrectly made. We discuss the diagnostic pitfalls and recommend adhering strictly to the JBS diagnostic criteria in the case of a negative molecular diagnosis. Critical assessment of the MRI findings by a specialized neuroradiologist is imperative. As chromosomal abnormalities may give rise to symptoms resembling JBS, we recommend array-based screening for segmental aneuploidies as an initial genetic test in all cases with a JBS-like phenotype.
authors.affiliation: Departments of Medical Genetics Pediatric Radiology Child Neurology, University Medical Center, Utrecht Departments of Human Genetics Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Hester Y
authors.initials: HY
authors.lastname: Kroes
authors.forename: Ron
authors.initials: R
authors.lastname: Hochstenbach
authors.forename: Rutger A J
authors.initials: RAJ
authors.lastname: Nievelstein
authors.forename: Anneke I
authors.initials: AI
authors.lastname: Den Hollander
authors.forename: Dorien T
authors.initials: DT
authors.lastname: Lugtenberg
authors.forename: Onno
authors.initials: O
authors.lastname: Van Nieuwenhuizen
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Martin
authors.initials: M
authors.lastname: Poot
mesh_terms: D000015:Abnormalities, Multiple; D002526:Cerebellar Diseases / Q000175:diagnosis* / Q000235:genetics*; D002531:Cerebellum / Q000002:abnormalities; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D003951:Diagnostic Errors; D005124:Eye Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007621:Karyotyping; D052177:Kidney Diseases, Cystic / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012160:Retina / Q000002:abnormalities
chemical_list: D051783:Methyl-CpG-Binding Protein 2