Samenvatting
Doel.
Een beschrijving geven van de klinische verschijningsvorm van het Silver-Russell-syndroom (SRS) bij kinderen in Nederland. Dit cohort SRS-kinderen maakt deel uit van een gepubliceerde internationale studie, waarbij de klinische verschillen tussen diverse genetische oorzaken van SRS zijn onderzocht.
Methode.
Voor deze studie werden er 38 kinderen met genetisch bewezen SRS in Nederland geïdentificeerd. Hiervan zijn 23 kinderen voor deze studie geïncludeerd en systematisch beoordeeld. De mate van hypomethylatie (de methylatie-index, MI) van H19 werd geanalyseerd en vergeleken met de ernst van (specifieke kenmerken) van het SRS.
Resultaten.
Van de 23 geïncludeerdekinderen met SRS vertoonden 20 een hypomethylatie van de H19-regio en drie kinderen een mUPD7. In dit Nederlandse cohort bleken geen significante verschillen te bestaan tussen de verschijningsvorm van de twee genetische oorzaken, in de grotere internationale studie werd dit echter wel gevonden. Als groep vertonen de kinderen met SRS een klinisch herkenbaar beeld met intra-uteriene en postnatale groeiachterstand, asymmetrie van het lichaam en gelaat, en een aantal typische faciale kenmerken (triangulair gelaat, micrognathie en relatieve macrocefalie). Er bleek geen correlatie te bestaan tussen de MI en de ernst van het syndroom. Drie van de 20 kinderen met een hypomethylatie van H19 werden geboren na gebruik vanassisted reproductive technologies (ART), twee na IVF en één na ICSI.
Conclusie.
Het klinische beeld van SRS is goed te herkennen. Dit artikel illustreert de kliniek van kinderen met SRS in Nederland. Het relatief grote aantal kinderen geboren na IVF/ICSI is opvallend en wijst op een associatie tussen ART en het vóórkomen van een methylatiestoornis zoals het Silver-Russell-syndroom.
Summary
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-H19 was compared with the severity of (specific features) of SRS.
Results.
Of the 23 included children, 20 have a hypomethylation of the H19-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-H19 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.
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afdeling Kindergeneeskunde
DNA Diagnostisch Laboratorium
Correspondentieadres: Dr. J.M. Cobben, klinisch geneticus, afdeling Kindergeneeskunde en Klinische Genetica, Emma Kinderziekenhuis AMC, Meibergdreef 9, 1105 AZ Amsterdam
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Lammers, T., van Haelst, M., Alders, M. et al. Het Silver-Russell-syndroom in Nederland. TIJDSCHR. KINDERGENEESKUNDE 80, 86–91 (2012). https://doi.org/10.1007/s12456-012-0025-3
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DOI: https://doi.org/10.1007/s12456-012-0025-3