Prenatal and postnatal growth failure associated with maternal heterodisomy for chromosome 7.

Abstract

The association of maternal uniparental disomy for chromosome 7 and postnatal growth failure has been reported in four cases and suggests the presence ofgenomic imprinting of one or more growth related genes on chromosome 7. However, in the reported cases, the possibility of homozygosity for a recessive mutation could not be excluded as the cause of the growth failure as in all cases isodisomy rather than heterodisomy for chromosome 7 was present. We report a case of prenatal and postnatal growth retardation associated with a prenatal diagnosis ofmosaicism for trisomy 7 confined to the placenta. DNA typing of polymorphic markers on chromosome 7 has established that the zygote originated as a trisomy 7 with two maternal and one paternal chromosomes 7 with subsequent loss of the paternal chromosome resulting in a disomic child with maternal heterodisomy for chromosome 7. The growth failure seen in this child with heterodisomy 7 lends strong support to the hypothesis of imprinted gene(s) on chromosome 7.

Human EGFR, a candidate gene for the Silver-Russell syndrome, is biallelically expressed in a wide range of fetal tissues

“…[1][2][3] More recently, approximately 10% of cases of Silver-Russell syndrome (SRS) have also been found to be associated with mUPD7. 4,5 SRS is characterised by intrauterine and postnatal growth retardation with relative sparing of cranial growth, triangular facies and downturned corners of the mouth.…”

Correlation of Confined Placental Mosaicism with Fetal Intrauterine Growth Retardation

“…Intrauterine fetal growth was not greatly affected by the presence of trisomy 7 cell line in the placenta. However, the adverse effect of CPM with associated maternal UPD 7 is reported in the study of Langlois et al [39]. There are only few reported cases of placental mosaicism and uniparental disomy for chromosome 9.…”

Genetics of Silver-Russell Syndrome

“…In all 5 probands there is a mixture of hetero- and isodisomy which is compatible with the anomaly arising as the result of a maternal meiosis-I non-disjunction with a minimum of 2–5 recombination events in the individual families. Between the 5 probands there are no consistent regions of isodisomy which, as in the case referred to above [23], effectively excludes the possibility of an exposed recessive gene accounting for the phenotype.…”

“…One also had some features of SRS. In addition a more recent report describes a child with severe pre- and post-natal growth retardation and mUPD7 [23]; there were no reported dysmorphic features. In this case the child had inherited one copy of each of the mother’s chromosome 7 (heterodisomy) so that the phenotype could not be explained by the exposure of a recessive gene as in the cystic fibrosis patients.…”