Clinical and molecular findings in two patients with russell-silver syndrome and UPD7: comparison with non-UPD7 cases.

The clinical presentation of prenatal and postnatal growth deficiency, triangular face, relative macrocephaly, and body asymmetry is frequently diagnosed as Russell-Silver syndrome (RSS). Maternal uniparental disomy (UPD) of chromosome 7 was reported previously in a small subset of individuals with RSS phenotype or primordial growth retardation. The primary purpose of this study was to identify RSS patients with UPD7 and determine whether or not they present phenotypic findings that distinguish them from RSS patients without UPD7. UPD7 testing was performed in 40 patients with unexplained growth retardation, including 21 patients with a diagnosis of RSS. In addition, a subset of patients was screened with markers spanning chromosome 7 to detect potential microdeletions or segmental uniparental disomy. Two of the RSS cases were identified to have maternal UPD7; no cases with deletion or partial UPD were detected. Together with previously published studies, UPD7 was identified in 11/120 (9%) of individuals with classical RSS phenotype. Our patients with UPD7 and those previously published had a classical RSS phenotype and were not clinically distinguishable from other children diagnosed with RSS.

Bernard LE ，Peñaherrera MS ，Van Allen MI ，Wang MS ，Yong SL ，Gareis F ，Langlois S ，Robinson WP ... -  《american journal of medical genetics》

[Uniparental disomy 7 in the pathogenesis of Silver-Russell syndrome].

Mergenthaler S ，Dobos M ，Wollmann H ，Eggermann K ，Schwanitz G ，Eggermann T ... -  《ORVOSI HETILAP》

Broad clinical spectrum in Silver-Russell syndrome and consequences for genetic testing in growth retardation.

Eggermann T ，Gonzalez D ，Spengler S ，Arslan-Kirchner M ，Binder G ，Schönherr N ... -  《-》

Clinical outcome and follow-up of the first reported case of Russell-Silver syndrome with the unique combination of maternal uniparental heterodisomy 7 and mosaic trisomy 7.

Russell-Silver syndrome (RSS) has been associated with maternal uniparental disomy (UPD) for chromosome 7 although the etiology of the syndrome is still unknown. Cases of RSS associated with maternal UPD7 have involved isodisomies, heterodisomies, and mixed isodisomy with heterodisomy simultaneously. This publication is a follow-up report of the postnatal clinical outcome of the first prenatally suspected case of combined mosaic trisomy 7 with maternal uniparental disomy of chromosome 7 (UPD7). The diagnosis of RSS in the proband was suspected prenatally because trisomy 7 mosaicism (47,XX,+7[13]/46,XX[19]) and maternal uniparental heterodisomy 7 were both found in amniotic fluid cells. Cord blood karyotype analysis showed only disomic cells (46,XX[50]), whereas postpartum chorionic villus analysis was completely trisomic for chromosome 7 (47,XX,+7[19]). Postnatally, the diagnosis of RSS was confirmed by physical findings, her trisomy 7 mosaicism was confirmed by cytogenetic analysis of her skin biopsy (47,XX,+7[9]/46,XX[20]) and her UPD7 was confirmed on both peripheral blood and skin biopsy using microsatellite markers. During infancy, the proband experienced growth deficiency, persistent hypoglycemia, and psychomotor developmental delay. Trisomic rescue as a life-saving mechanism, with subsequent chromosomal mosaicism in combination with UPD may occur more frequently in RSS than has been reported. Systematic testing of cases suspected prenatally or postnatally would be informative regarding the individual contribution of each factor. Imprinting, loss of heterozygosity for recessive genes, and mosaicism may explain the short stature, asymmetry, and the variable expression of the phenotype. The contribution of these mechanisms to the syndrome should be evaluated in these cases.

Font-Montgomery E ，Stone KM ，Weaver DD ，Vance GH ，Das S ，Thurston VC ... -  《birth defects research part a-clinical and molecular teratology》

Maternal uniparental disomy 7 and Silver-Russell syndrome - clinical update and comparison with other subgroups.

Kotzot D 《-》