Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: A challenge for molecular analysis and genetic counseling
Lombardi, Maria Paola
Krajewska, Walasek Malgorzata
Moore, Gudrun E
Mackay, Deborah JG
Prenatal testing in Silver-Russell and Beckwith Wiedemann syndrome
European Journal of Human Genetics
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Eggermann, T., Brioude, F., Russo, S., Lombardi, M. P., Bliek, J., Maher, E., Larizza, L., et al. (2015). Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: A challenge for molecular analysis and genetic counseling. European Journal of Human Genetics, 24 784-793. https://doi.org/10.1038/ejhg.2015.224
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.
Beckwith-Wiedemann syndrome, Silver-Russell syndrome, prenatal diagnosis, molecular genetic testing, imprinting disorders
The authors are members of the COST Action BM1208 and EUCID.net (European congenital imprinting disorders network; www.imprinting-disorders.eu). TE, MB, LS, KE and DP are supported by the Bundesministerium für Bildung und Forschung (Network “Imprinting Diseases”, 01GM1513B/C). KCH and MK-W by National Science Centre projects No. 1149/B/P01/2011/40 (NN407114940) and 2853/B/P01/2010/39 (NN407285339). PL is supported by a Grant of the Ministry of Science (ISCIII, PI 11/02491). FB and IN are funded by INSERM, UPMC Paris 6 funding, and EPIFEGRO2010 (Novonordisk grant). SR and LL are funded by the Ministero della Salute (IT) (08C207_2012).
External DOI: https://doi.org/10.1038/ejhg.2015.224
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252327