Clinical‐etiologic correlation in children with Prader‐Willi syndrome (PWS): An interdisciplinary study
- 12 December 2006
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 143A (5), 460-468
- https://doi.org/10.1002/ajmg.a.31520
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) ≥70, while 61.53% of subjects without deletion had FSIQ ≥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 ≥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.Keywords
This publication has 43 references indexed in Scilit:
- Prevalence of Type 2 Diabetes Mellitus and Impaired Glucose Tolerance in Obese Argentinean Children and AdolescentsJournal of Pediatric Endocrinology and Metabolism, 2005
- Impact of molecular mechanisms, including deletion size, on Prader–Willi syndrome phenotype: study of 75 patientsClinical Genetics, 2004
- Insulin resistance and obesity‐related factors in Prader–Willi syndrome: Comparison with obese subjectsClinical Genetics, 2004
- Prader-Willi syndromeEuropean Child & Adolescent Psychiatry, 2004
- Relationship between clinical and genetic diagnosis of Prader-Willi syndromeJournal of Medical Genetics, 2002
- Imprinting-Mutation Mechanisms in Prader-Willi SyndromeAmerican Journal of Human Genetics, 1999
- Sporadic Imprinting Defects in Prader-Willi Syndrome and Angelman Syndrome: Implications for Imprint-Switch Models, Genetic Counseling, and Prenatal DiagnosisAmerican Journal of Human Genetics, 1998
- PW71 methylation test for Prader-Willi and angelman syndromesAmerican Journal of Medical Genetics, 1996
- The 1993–94 Généthon human genetic linkage mapNature Genetics, 1994
- PRADER‐WILLI SYNDROME IN A SWEDISH RURAL COUNTY: EPIDEMIOLOGICAL ASPECTSDevelopmental Medicine and Child Neurology, 1991