Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype.
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.
de Vries
B B
BB
Department of Clinical Genetics, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Fryns
J P
JP
Butler
M G
MG
Canziani
F
F
Wesby-van Swaay
E
E
van Hemel
J O
JO
Oostra
B A
BA
Halley
D J
DJ
Niermeijer
M F
MF
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
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human