Maternal uniparental disomy 7 and Silver–Russell syndrome – Clinical update and comparison with other subgroups

Maternal uniparental disomy (UPD) 7 is found in approximately 5% of patients with Silver–Russell syndrome. By a descriptive and comparative clinical analysis of all published cases (more than 60 to date) their phenotype is updated and compared with the clinical findings in patients with Sliver–Russell syndrome (SRS) of either unexplained etiology or epimutations of the imprinting center region 1 (ICR1) on 11p15. The higher frequency of relative macrocephaly and high forehead/frontal bossing makes the face of patients with epimutations of the ICR1 on 11p15 more distinctive than the face of cases with SRS of unexplained etiology or maternal UPD 7. Because of the distinct micrognathia in the latter, their triangular facial gestalt is more pronounced than in the other groups. However, solely by clinical findings patients with maternal UPD 7 cannot be discriminated unambiguously from patients with epimutations of the ICR1 on 11p15 or SRS of unexplained etiology. Therefore, both loss of methylation of the ICR1 on 11p15 and maternal UPD 7 should be investigated for if SRS is suspected.