title: 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: Centre de Référence Anomalies du Développement et Syndromes Malformatifs Nord de France, CHRU Lille, France. mustafa.ghanim@najah.edu
authors: Mustafa
authors: M
authors: Ghanim
authors: Sylvie
authors: S
authors: Rossignol
authors: Bruno
authors: B
authors: Delobel
authors: Melita
authors: M
authors: Irving
authors: Owen
authors: O
authors: Miller
authors: Louise
authors: L
authors: Devisme
authors: Jean-Louis
authors: JL
authors: Plennevaux
authors: Sophie
authors: S
authors: Lucidarme-Rossi
authors: Sylvie
authors: S
authors: Manouvrier
authors: Azzi
authors: A
authors: Salah
authors: Olimpia
authors: O
authors: Chivu
authors: Irène
authors: I
authors: Netchine
authors: Catherine
authors: C
authors: Vincent-Delorme
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019175:DNA Methylation; D017809:Fatal Outcome; D005260:Female; D056726:Genetic Association Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D056730:Silver-Russell Syndrome / Q000175:diagnosis* / Q000235:genetics