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Genetik und Epigenetik des Silver-Russell-Syndroms

Genetics and epigenetics of the Silver-Russell syndrome

Zusammenfassung

Das Silver-Russell-Syndrom (SRS) ist eine angeborene Imprintingerkrankung, die in erster Linie durch eine schwere intrauterine und postnatale Wachstumsretardierung, eine relative Makrozephalie, eine dreieckige Gesichtsform und/oder Asymmetrien des Körpers gekennzeichnet ist. Ein Nachweis (epi)genetischer Veränderungen ist mittlerweile bei etwa 50% der SRS-Patienten möglich: Bei 7–10% liegt eine maternale uniparentale Disomie des Chromosoms 7 (upd(7)mat) vor, bei weiteren etwa 40% der Patienten sind (epi)genetische Veränderungen in der chromosomalen Region 11p15 nachweisbar. In Ergänzung zu konventionell-zytogenetisch erhobenen Befunden erlaubt die molekulare Karyotypisierung zunehmend den Nachweis von submikroskopischen Chromosomenstörungen bei SRS-Patienten. Da es keine klare (Epi)genotyp-Phänotyp-Korrelation gibt und die variable Ausprägung der Symptome eine sichere Diagnosestellung erschwert, sollte auch bei Patienten, die nur eine Teilsymptomatik aufweisen, eine genetische Testung in Erwägung gezogen werden.

Abstract

Silver-Russell syndrome (SRS) is a congenital imprinting disorder mainly characterized by severe intrauterine and postnatal growth retardation, relative macrocephaly, a triangular face and asymmetry of the body. The detection of (epi)genetic aberrations is now possible in about 50% of SRS patients where 7–10% carry a maternal uniparental disomy of chromosome 7 (upd(7)mat) and 40% of the patients show (epi)genetic disturbances in the chromosomal region 11p15. In addition to conventional cytogenetic findings submicroscopic chromosomal imbalances can be detected by molecular karyotyping of the patients. Because there is no unambiguous (epi)genotype-phenotype correlation and clinical diagnosis is complicated due to the variable occurrence of symptoms, genetic testing should be considered in patients showing only some of the typical disease features.

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Correspondence to T. Eggermann.

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Spengler, S., Begemann, M., Binder, G. et al. Genetik und Epigenetik des Silver-Russell-Syndroms. medgen 22, 405–410 (2010). https://doi.org/10.1007/s11825-010-0247-7

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Schlüsselwörter

  • Silver-Russell-Syndrom
  • Genomische Prägung
  • Molekulardiagnostische Techniken
  • Karyotypisierung
  • Genetische Testung

Keywords

  • Silver-Russell syndrome
  • Genomic imprinting
  • Molecular diagnostic techniques
  • Karyotyping
  • Genetic testing