Het Silver-Russell-syndroom in Nederland

Aim: To describe the clinical characteristics of all Dutch children with Silver-Russell Syndrome (SRS). This cohort is part of a larger collaborative international study, analysing the clinical differences between children with SRS due to a different genetic cause. Methods: Thirty-eight Dutch children were identified with a clinical and molecular proven diagnosis SRS. Twenty-three children with SRS were included and clinically assessed. The grade of methylation (MI) in patients with hypo-Hi9 was compared with the severity of (specific features) of SRS. Results: Of the 23 included children, 20 have a hypomethylation of the Hi9-region and three have mUPD7. No significant correlation was identified between the clinical outcome of the two genetic subgroups of Dutch SRS-children, whereas the international study did find significant but not impressive differences. As a group, SRS is characterised by severe intrauterine and postnatal growth retardation, limb and body asymmetry, a typical facial appearance (triangular face, micrognathia, relative macrocephaly). No correlation is found between the MI and clinical outcome. Interestingly, in the Dutch cohort, pregnancies of three out of 20 SRS-children with hypo-Hia were the result of assisted reproductive technologies (ART), two after IVF and one after ICSI. Conclusion: SRS is a clinically recognizable syndrome. This article illustrates the clinical outcome of Dutch SRS-children. A high proportion of the pregnancies of the SRS-children were the result of ART, which suggests an association between ART and methylation disorders.