Trisomy 7 Mosaicism
Posted October 30, 2008on:
TRISOMY 7 MOSAICISM
Complete trisomy 7 has never been reported in a liveborn child. Trisomy 7 is one of the most common aneuploidies detected on chorionic villus sampling. In general, prenatal detection of trisomy 7 is associated with a good outcome. However maternal UPD 7 is strongly associated with severe growth restriction (Ledbetter & Engel, 1995; Kalousek et al, 1996). Trisomy 7 which is confined to the placenta (CPM) appears to be primarily of mitotic origin, resulting from somatic duplication of chromosome 7. This explains the generally good outcome in the majority of cases. Given the mitotic origin the risk of fetal UPD 7 is low. Kalousek et al (1996) showed that CPM for trisomy 7 with biparental inheritance has no adverse effect on fetal growth.
Thus, CVS alone is a poor predictor of pregnancy outcome for trisomy 7. When CVS is combined with DNA studies to reveal the origin of CPM (mitotic or meiotic) and parental origin of the chromosome 7s, a more reliable prediction for pregnancy outcome can be discussed (Kalousek et al, 1996).
Trisomy 7 detected on CVS 29 cases of confined placental mosaicism for trisomy 7 were reported in a large study of chromosomal mosaicism detected on CVS. The findings were not confirmed in any of the fetuses (Hahnemann & Vejerslev, 1997).
Sachs et al (1990) reported on 5 cases of trisomy 7 mosaicism. In these cases the percentage of abnormal cells measured onCVS direct studies ranged from 5%-68%. In all 5 cases the pregnancies resulted in a normal outcome.
Kalousek et al (1996) described 14 pregnancies which were diagnosed as mosaic trisomy 7 on CVS. Follow-up amniocenteses showed a normal diploid karyotype in all 14 cases. Fetal UPD 7 was present only in one case; in eight other cases biparental inheritance was demonstrated.
Trisomy 7 detected on amniocentesis
Hsu (1997) reviewed six postnatal diagnoses of trisomy 7 mosaicism. Three of the cases were found to have kidney abnormalities.
Uniparental Disomy (UPD 7) An imprinting effect is known for maternal UPD 7. Maternal UPD 7 is well established to be associated with severe growth restriction and is found in approximately 10% of cases with Russell-Silver syndrome phenotype (Robinson et al, 1997). In 1988, Spence et al reported the first example of UPD in a 16-year-old female with short stature and cystic fibrosis. Cystic fibrosis (CF) is an autosomal recessive condition. She inherited two copies of the maternal chromosome 7 with a CF mutation from her mother who was a carrier for CF. Several reports have confirmed that postnatal growth restriction leading to short stature is the main finding of maternal UPD 7 (Ledbetter & Engel, 1995; Kalousek et al, 1996).
Langlois et al. 1995 reported a case of prenatally (CVS) detected trisomy mosaicism with maternal UPD7 in the diploid lineage. Both pre- and post-natal growth restriction were present. High levels of trisomy in the placenta may be associated with IUGR. It is also possible that the UPD 7 cells in placenta as well as fetus have an effect on growth and cases of UPD 7 arising from a somatic event may not show as severe prenatal effects.
An imprinting effect has been firmly established for maternal UPD7. Molecular evaluation of UPD 7 should be considered in patients with unexplained growth retardation or features similar to Russell-Silver syndrome. DNA studies should be considered when prenatal diagnosis indicates trisomy 7 mosaicism.