title: Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype.
abstract: A special subphenotype of the fragile X syndrome is reported which is characterised by extreme obesity with a full, round face, small, broad hands/feet, and regional skin hyperpigmentation. It resembles the Prader-Willi syndrome (PWS) and might therefore be named 'Prader-Willi-like'. Unlike the PWS, these PW-like fragile X patients lack the neonatal hypotonia with feeding problems during infancy followed by hyperphagia from toddlerhood. We describe five new fragile X patients and present a clinical update of three previously described patients with the PW-like phenotype. In one family, segregation of either the classical Martin-Bell or the PW-like phenotype was observed and in another family there was repeated transmission of the PW-like phenotype. Previously, one of the patients had been misdiagnosed as having classical PWS, based on clinical findings. Molecular studies of the FMR-1 gene showed the typical full mutations as seen in fragile X syndrome males. Molecular analysis of the 15q11-13 region, which is deleted in the majority of classical PWS patients, did not show any detectable abnormalities. In a group of 26 patients with suspected Prader-Willi syndrome but without detectable molecular abnormalities of chromosome 15, one fragile X patient was found. These clinical and molecular findings illustrate the necessity to perform DNA analysis of the FMR-1 gene in mentally retarded patients presenting with a PW phenotype but without the PWS specific cytogenetic/molecular abnormalities of chromosome 15.
authors.affiliation: Department of Clinical Genetics, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
authors.forename: B B
authors.initials: BB
authors.lastname: de Vries
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
authors.forename: M G
authors.initials: MG
authors.lastname: Butler
authors.forename: F
authors.initials: F
authors.lastname: Canziani
authors.forename: E
authors.initials: E
authors.lastname: Wesby-van Swaay
authors.forename: J O
authors.initials: JO
authors.lastname: van Hemel
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: D J
authors.initials: DJ
authors.lastname: Halley
authors.forename: M F
authors.initials: MF
authors.lastname: Niermeijer
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D003937:Diagnosis, Differential; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000175:diagnosis*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D010375:Pedigree; D011218:Prader-Willi Syndrome / Q000175:diagnosis*; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human