Possible association between complex congenital heart defects and 11p15 hypomethylation in three patients with severe Silver-Russell syndrome

TY - JOUR

T1 - Possible association between complex congenital heart defects and 11p15 hypomethylation in three patients with severe Silver-Russell syndrome

AU - Ghanim, Mustafa

AU - Rossignol, Sylvie

AU - Delobel, Bruno

AU - Irving, Melita

AU - Miller, Owen

AU - Devisme, Louise

AU - Plennevaux, Jean-Louis

AU - Lucidarme-Rossi, Sophie

AU - Manouvrier, Sylvie

AU - Salah, Azzi

AU - Chivu, Olimpia

AU - Netchine, Irene

AU - Vincent-Delorme, Catherine

PY - 2013/3

Y1 - 2013/3

N2 - SilverRussell syndrome (SRS) is characterized by pre- and post-natal growth restriction that spares head growth, feeding difficulties, and variable dysmorphic facial features without major malformations. Hypomethylation of the paternal 11p15 imprinting control region 1 (ICR1) and maternal uniparental disomy of chromosome 7 are found in 5060% and in 510% of SRS patients, respectively. We report on the pre- and post-natal features of three unrelated SRS patients with unusual congenital heart defects (CHDs). Two patients born prematurely had total anomalous pulmonary venous return and died shortly after birth, and a third patient, now 4 years old, had cor triatriatum sinistrum, which was surgically corrected. In all three patients, the underlying molecular defect was 11p15 ICR1 hypomethylation. Based on a large cohort with molecularly proven SRS, the prevalence of CHD in SRS is estimated at 5.5%. We suggest that the occurrence of CHD in SRS with 11p15 ICR1 hypomethylation is not coincidental, but specific to this genotype.

AB - SilverRussell syndrome (SRS) is characterized by pre- and post-natal growth restriction that spares head growth, feeding difficulties, and variable dysmorphic facial features without major malformations. Hypomethylation of the paternal 11p15 imprinting control region 1 (ICR1) and maternal uniparental disomy of chromosome 7 are found in 5060% and in 510% of SRS patients, respectively. We report on the pre- and post-natal features of three unrelated SRS patients with unusual congenital heart defects (CHDs). Two patients born prematurely had total anomalous pulmonary venous return and died shortly after birth, and a third patient, now 4 years old, had cor triatriatum sinistrum, which was surgically corrected. In all three patients, the underlying molecular defect was 11p15 ICR1 hypomethylation. Based on a large cohort with molecularly proven SRS, the prevalence of CHD in SRS is estimated at 5.5%. We suggest that the occurrence of CHD in SRS with 11p15 ICR1 hypomethylation is not coincidental, but specific to this genotype.

KW - congenital heart defect

KW - SilverRussell syndrome

KW - 11p15 ICR1 hypomethylation

KW - total anomalous pulmonary venous return

KW - cor triatriatum

KW - MATERNAL UNIPARENTAL HETERODISOMY-7

KW - IMPRINTING CENTER REGION

KW - CHROMOSOME 11P15

KW - SYNDROME SRS

KW - H19

KW - METHYLATION

KW - DISEASE

KW - GENE

KW - MOSAICISM

KW - SUBGROUPS

U2 - 10.1002/ajmg.a.35691

DO - 10.1002/ajmg.a.35691

M3 - Article

SN - 1552-4825

VL - 161

SP - 572

EP - 577

JO - American Journal of Medical Genetics. Part A

JF - American Journal of Medical Genetics. Part A

IS - 3

ER -