TY - JOUR

T1 - Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes

T2 - a challenge for molecular analysis and genetic counseling

AU - Eggermann, Thomas

AU - Brioude, Frédéric

AU - Russo, Silvia

AU - Lombardi, Maria P

AU - Bliek, Jet

AU - Maher, Eamonn R

AU - Larizza, Lidia

AU - Prawitt, Dirk

AU - Netchine, Irène

AU - Gonzales, Marie

AU - Grønskov, Karen

AU - Tümer, Zeynep

AU - Monk, David

AU - Mannens, Marcel

AU - Chrzanowska, Krystyna

AU - Walasek, Malgorzata K

AU - Begemann, Matthias

AU - Soellner, Lukas

AU - Eggermann, Katja

AU - Tenorio, Jair

AU - Nevado, Julián

AU - Moore, Gudrun E

AU - Mackay, Deborah Jg

AU - Temple, Karen

AU - Gillessen-Kaesbach, Gabriele

AU - Ogata, Tsutomu

AU - Weksberg, Rosanna

AU - Algar, Elizabeth

AU - Lapunzina, Pablo

PY - 2016

Y1 - 2016

N2 - 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.European Journal of Human Genetics advance online publication, 28 October 2015; doi:10.1038/ejhg.2015.224.

AB - 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.European Journal of Human Genetics advance online publication, 28 October 2015; doi:10.1038/ejhg.2015.224.

U2 - 10.1038/ejhg.2015.224

DO - 10.1038/ejhg.2015.224

M3 - Review

C2 - 26508573

VL - 24

SP - 784

EP - 793

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -