title: Chromosomal rearrangements in patients with clinical features of Silver-Russell syndrome.
abstract: Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth retardation, relative macrocephaly, asymmetry, and a triangular facial gestalt. In 5-10% of the patients the phenotype is caused by maternal UPD 7, and 38-64% of the patients present with hypomethylation at the imprinting center region 1 (ICR1) on 11p15.5. The etiology of the remaining cases is so far not known and various (sub-)microscopic chromosome aberrations with a phenotype resembling SRS have been published, especially duplication 11p15 (n = 15), deletion 12q14 (n = 19), ring chromosome 15, deletion 15qter, and various other mostly unique chromosomal aberrations (n = 30). In this study the phenotypes of these chromosomal aberrations were revisited and compared with the phenotypes of maternal UPD 7 and hypomethylation at ICR1 on 11p15.5. In some patients with a unique chromosomal aberration even the hallmarks of SRS were missing. Patients with duplication 11p15 show a more variable occipitofrontal head circumference at birth, a higher frequency of intellectual disability, and additional anomalies not reported in SRS. Deletion 12q14 is characterized by less severe pre- and postnatal growth retardation and less impressive relative macrocephaly. Patients with ring chromosome 15 and deletion 15qter have no relative macrocephaly (mostly even microcephaly) and more severe intellectual disability. Finally, deletion 15qter lacks the triangular facial gestalt. In summary, as SRS seems not an adequate diagnosis in many of these patients, diagnosis should focus on the chromosomal aberration than on SRS.
authors.affiliation: Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Siv
authors.initials: S
authors.lastname: Fokstuen
authors.forename: Dieter
authors.initials: D
authors.lastname: Kotzot
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D019175:DNA Methylation; D019066:Facies; D005260:Female; D020440:Gene Duplication; D015321:Gene Rearrangement / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly / Q000235:genetics*; D010641:Phenotype; D056730:Silver-Russell Syndrome / Q000235:genetics*
keywords: Silver-Russell syndrome; chromosomal rearrangement; deletion; duplication