title: Clinical-etiologic correlation in children with Prader-Willi syndrome (PWS): an interdisciplinary study.
abstract: Prader-Willi syndrome (PWS) is a multisystemic disorder caused by the loss of expression of paternally transcribed genes within chromosome 15q11-q13. Most cases are due to paternal deletion of this region; the remaining cases result from maternal uniparental disomy (UPD) and imprinting defects. To better understand the phenotypic variability of PWS, a genotype-phenotype correlation study was performed in 91 children with PWS. Patients were diagnosed by Southern Blot Methylation assay and genetic subtypes were established using FISH and microsatellite analyses. Fifty-nine subjects with deletion (31/28 males/females; mean age 3.86 years), 30 with UPD (14/16 males/females; mean age 3.89 years) and 2 girls with a presumed imprinting defect (mean age 0.43 yrs) were identified. For correlation purposes patients were grouped as "deleted" and "non-deleted." An increased maternal age was found in the UPD group. Four of Holm's criteria were more frequently present in the deleted group: need for special feeding techniques, sleep disturbance, hypopigmentation, and speech articulation defects. Concerning cognitive assessments, only 9.52% of subjects with deletion had Full-Scale IQ (FSIQ) > or =70, while 61.53% of subjects without deletion had FSIQ > or =70. Similar results were found in behavioral measures. Sleep disorders and carbohydrate metabolism were systematically assessed. Polysomnoghaphic studies revealed a higher frequency of central events with desaturations > or =10% in the deleted group (P = 0.020). In summary, the phenotype was significantly different between both groups in certain parameters related to the CNS. These results might be related to the differences in brain gene expression of the genetic subtypes.
authors.affiliation: Hospital de Pediatría Prof. Dr. Juan P. Garrahan - Genética, Buenos Aires, Argentina. mtorrado@fibertel.com.ar
authors.forename: Maria
authors.initials: M
authors.lastname: Torrado
authors.forename: Veronica
authors.initials: V
authors.lastname: Araoz
authors.forename: Edgardo
authors.initials: E
authors.lastname: Baialardo
authors.forename: Karina
authors.initials: K
authors.lastname: Abraldes
authors.forename: Carmen
authors.initials: C
authors.lastname: Mazza
authors.forename: Gabriela
authors.initials: G
authors.lastname: Krochik
authors.forename: Blanca
authors.initials: B
authors.lastname: Ozuna
authors.forename: Vivian
authors.initials: V
authors.lastname: Leske
authors.forename: Silvia
authors.initials: S
authors.lastname: Caino
authors.forename: Virginia
authors.initials: V
authors.lastname: Fano
authors.forename: Lilien
authors.initials: L
authors.lastname: Chertkoff
mesh_terms: D000293:Adolescent; D001837:Body Weights and Measures; D050260:Carbohydrate Metabolism; D002648:Child; D002652:Child Behavior; D002675:Child, Preschool; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007333:Insulin Resistance; D008297:Male; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012106:Research; D012893:Sleep Wake Disorders / Q000209:etiology