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, Irne
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, Julin
AU - Moore, Gudrun E.
AU - Mackay, Deborah J.G.
AU - Temple, Karen
AU - Gillessen-Kaesbach, Gabriele
AU - Ogata, Tsutomu
AU - Weksberg, Rosanna
AU - Algar, Elizabeth
AU - Lapunzina, Pablo
PY - 2016/6/1
Y1 - 2016/6/1
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84945538788&partnerID=8YFLogxK
UR - https://www.nature.com/articles/ejhg2015224
U2 - 10.1038/ejhg.2015.224
DO - 10.1038/ejhg.2015.224
M3 - Review article
C2 - 26508573
AN - SCOPUS:84945538788
SN - 1018-4813
VL - 24
SP - 784
EP - 793
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -