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Eur J Hum Genet. 2016 Jun;24(6):784-93. doi: 10.1038/ejhg.2015.224. Epub 2015 Oct 28.

Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling.

Author information

1
Institut für Humangenetik, RWTH University Aachen, Aachen, Germany.
2
INSERM, UMR_S 938, Paris, France.
3
Sorbonne Universities, UPMC Univ Paris 06, Paris, France.
4
Armand Trousseau Hospital, Pediatric Endocrinology, Paris, France.
5
Laboratory of Cytogenetics and Molecular Genetics Istituto Auxologico Italiano IRCCS, Milano, Italy.
6
Department of Clinical Genetics, Academic Center, University of Amsterdam, Amsterdam, The Netherlands.
7
Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
8
Center for Pediatrics and Adolescent Medicine, University Medical Center, Mainz, Germany.
9
Department of Medical Genetics, Armand Trousseau Hospital, AP-HP, Paris, France.
10
Sorbonne Universitie, UPMC Univ Paris 06, Paris, France.
11
Clinical Genetic Unit, Kennedy Center, Rigshospitalet, Copenhagen University Hospital, Glostrup, Denmark.
12
Imprinting and Cancer Group, Cancer Epigenetic and Biology Program (PEBC), Institut d'Investigació Biomedica de Bellvitge (IDIBELL), Barcelona, Spain.
13
Department of Medical Genetics, The Children's Memorial Health Insitute, Warsaw, Poland.
14
Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.
15
CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
16
Fetal Growth and Developmental group, Genetics and Genomic Medicine Programme, UCL-ICH, London, UK.
17
Human Genetics and Genomic Medicine, Faculty of Medicine University of Southampto; Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
18
Institut für Humangenetik, Universität zu Lübeck, Lübeck, Germany.
19
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamastu, Japan.
20
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
21
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
22
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
23
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
24
Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
25
Genetics and Molecular Pathology Laboratory, Monash Health and Hudson Institute, Clayton, Victoria, Australia.

Abstract

Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% of the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge concerning the inheritance and recurrence risks for the epigenetic abnormalities, which are hallmarks of these developmental disorders. In this paper, experts in the field of BWS and SRS, including members of the European network of congenital IDs (EUCID.net; www.imprinting-disorders.eu), put together their experience and work in the field of 11p15.5-associated IDs with a focus on prenatal testing. Altogether, prenatal tests of 160 fetuses (122 referred for BWS, 38 for SRS testing) from 5 centers were analyzed and reviewed. We summarize the current knowledge on BWS and SRS with respect to diagnostic testing, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders.

PMID:
26508573
PMCID:
PMC4867462
DOI:
10.1038/ejhg.2015.224
[Indexed for MEDLINE]
Free PMC Article

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