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

Authors


  • How to Cite this Article: Ghanim M, Rossignol S, Delobel B, Irving M, Miller O, Devisme L, Plennevaux J-L, Lucidarme-Rossi S, Manouvrier S, Salah A, Chivu O, Netchine I, Vincent-Delorme C. 2013. Possible association between complex congenital heart defects and 11p15 hypomethylation in three patients with severe Silver–Russell syndrome. Am J Med Genet Part A 161A: 572–577.

Abstract

Silver–Russell 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 50–60% and in 5–10% 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. © 2013 Wiley Periodicals, Inc.

Ancillary