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

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.

• Authors: Mustafa Ghanim, Sylvie Rossignol, Bruno Delobel, Melita Irving, Owen Miller, Louise Devisme, Jean-Louis Plennevaux, Sophie Lucidarme-Rossi, Sylvie Manouvrier, Azzi Salah, Olimpia Chivu, Irène Netchine, Catherine Vincent-Delorme
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 161A Issue 3 Pg. 572-7 (Mar 2013) ISSN: 1552-4833 [Electronic] United States
• PMID: 23401077 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc.

Topics

• Abnormalities, Multiple (diagnosis, genetics)
• Child, Preschool
• Chromosomes, Human, Pair 11 (genetics)
• DNA Methylation
• Fatal Outcome
• Female
• Genetic Association Studies
• Heart Defects, Congenital (diagnosis, genetics)
• Humans
• Infant, Newborn
• Male
• Silver-Russell Syndrome (diagnosis, genetics)