Frequency of Prader-Willi syndrome in births conceived via assisted reproductive technology.
OBJECTIVE
Prader-Willi syndrome is an imprinting disorder characterized by typical facial, physical, and cognitive/behavioral features, resulting from lack of paternally expressed genes on chromosome 15q11.2-q13. Studies have suggested an increased risk of other imprinting disorders in children conceived by assisted reproductive techniques. This study was designed to determine the association between assisted reproductive technology and Prader-Willi syndrome.


METHODS
Data on individuals with Prader-Willi syndrome were collected from three distinct sources and the proportion of assisted reproductive technology births analyzed.


RESULTS
The proportions of assisted reproductive technology births in the Prader-Willi Syndrome Association (USA), Rare Diseases Clinical Research Network, and University of California, Irvine Medical Center populations were 1.0% (18/1,736), 1.0% (1/98), and 2.0% (1/50), respectively (overall 1.1%; population frequency for the United States was 1.0%). Of note, 2.4% (45/1,898) of participants were co-twins (11 born after assisted reproductive technology procedures); US twin frequency is 1.6% (P = 0.007). The proportion of individuals with maternal disomy 15/imprinting defects born after assisted reproductive technology was higher than that in the total sample, 55.6% (10/18) and 34.5% (431/1,250), respectively.


CONCLUSIONS
This study found no association between assisted reproductive technology and Prader-Willi syndrome. There was an increased frequency of twinning. The number of individuals with maternal disomy 15/imprinting defect was nearly double in the assisted reproductive technology group as compared with the total Prader-Willi syndrome participants.
1] Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA [2] Present address: Division of Medical Genetics and Metabolism, Department Pediatrics, Loma Linda University Medical Center, Loma Linda, California, USA (J.-A.G.); Fetal Diagnostic Center, Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, USA (C.R.); Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA (S.D.).
June-Anne
JA
Gold
1] Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA [2] Present address: Division of Medical Genetics and Metabolism, Department Pediatrics, Loma Linda University Medical Center, Loma Linda, California, USA (J.-A.G.); Fetal Diagnostic Center, Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, USA (C.R.); Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA (S.D.).
Chelsey
C
Ruth
Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA.
Kathryn
K
Osann
Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA.
Pamela
P
Flodman
Prader-Willi Association (USA), Sarasota, Florida, USA.
Barbara
B
McManus
Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida, USA.
Hye-Seung
HS
Lee
1] Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA [2] Present address: Division of Medical Genetics and Metabolism, Department Pediatrics, Loma Linda University Medical Center, Loma Linda, California, USA (J.-A.G.); Fetal Diagnostic Center, Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, USA (C.R.); Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA (S.D.).
Sandra
S
Donkervoort
Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA.
Manaswitha
M
Khare
Vanderbilt Kennedy Center, Vanderbilt University, Nashville, Tennessee, USA.
Elizabeth
E
Roof
Vanderbilt Kennedy Center, Vanderbilt University, Nashville, Tennessee, USA.
Elizabeth
E
Dykens
Jennifer L
JL
Miller
Department of Pediatrics, University of Florida, Gainesville, Florida, USA.
Daniel J
DJ
Driscoll
1] Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA [2] Department of Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA.
Merlin G
MG
Butler
Prader-Willi Association (USA), Sarasota, Florida, USA.
Janalee
J
Heinemann
Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
Suzanne
S
Cassidy
Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, Irvine, California, USA.
Virginia E
VE
Kimonis
D002884:Chromosomes, Human, Pair 15; D018392:Genomic Imprinting; D006306:Health Surveys; D006801:Humans; D011218:Prader-Willi Syndrome / Q000453:epidemiology* / Q000235:genetics; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D014427:Twins; D024182:Uniparental Disomy