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.

Gender influences monoallelic expression of ATP10A in human brain

“…Genotype-phenotype analyses of PWS and AS patients have revealed that many genes throughout 15q11-13 contribute to the clinical manifestations of patients (Lossie et al 2001; Torrado et al 2007). Additionally, as maternally derived 15q11-13 duplications often lead to autism-spectrum disorder, the two maternally expressed imprinted genes ATP10A and UBE3A are prime candidate genes for the 15q11-13 associated autism phenotype.…”

Quality of life assessment in a sample of patients affected by Prader–Willi syndrome

“…15,16 In our overall sample 73% of the patients had deletion of chromosome 15 and 27% of the patients had uniparental disomy. The genetic picture was not related to the QoL.…”

Prader-Willi syndrome

“…125 In most studies, those with UPD have a somewhat higher verbal IQ and milder behavior problems. 19,126,127 However, psychosis 128 and autism spectrum disorders 129,130 occur with significantly greater frequency among those with UPD. Individuals with the slightly larger, type 1 deletions (BP1-BP3) have been reported…”