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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 on CVS 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) summarized the findings of 8 reported cases of trisomy 7 mosaicism found in amniotic fluid. Only one was found to have facial asymmetry, mild developmental delay and hypomelanosis of Ito at 7 years. The other 7 liveborns were reported to be normal. Mosaicism was confirmed in skin fibroblasts in 2 cases with 4 year follow-up.
Trisomy 7 detected prenatally
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.
Link to What is UPD?
Link to Maternal UPD 7 page
Link to Paternal UPD 7 page
Internet Links
- HUGO Chromosome 7 - Chromosome 7 specific site
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Human Chromosome 7 - Provides links to gene maps, sequences, associated genetic disorders, nonhuman genetic models, identified genes, research efforts and laboratories, and other information as available. Links are very scientific.
References
Bernard LE, Penaherrera MS, Van Allen MI, Wang MS, Yong SL, Gareis F, Langlois S, Robinson WP. (1999 ) Clinical and molecular findings in two patients with Russell-Silver syndrome and UPD7:comparison with non-UPD7 cases. American Journal of Medical Genetics 87:230-6 PubMed
Eggermann T, Wollmann HA, Kuner R, Eggermann K, Enders H, Kaiser P, Ranke MB. (1997) Molecular studies in 37 Silver-Russell syndrome patients: frequency and etiology of uniparental disomy. Human Genetics 100:415-9. PubMed
Hahnemann JM, Vejerslev LO. ( 1997) European collaborative research on mosaicism in CVS (EUCROMIC)--fetal and extrafetal cell lineages in 192 gestations with CVS mosaicism involving single autosomal trisomy. American Journal of Medical Genetics 70(2):179-87. PubMed
Hsu LY, Yu MT, Neu RL, Van Dyke DL, Benn PA, Bradshaw CL, Shaffer LG, Higgins RR, Khodr GS, Morton CC, Wang H, Brothman AR, Chadwick D, Disteche CM, Jenkins LS, Kalousek DK, Pantzar TJ, Wyatt P. (1997) Rare trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: karyotype/phenotype correlations. Prenatal Diagnosis 17(3):201-42. PubMed
Kalousek DK, Langlois S, Robinson WP, Telenius A, Bernard L, Barrett IJ, Howard-Peebles PN, Wilson RD. (1996) Trisomy 7 CVS mosaicism: pregnancy outcome, placental and DNA analysis in 14 cases. American Journal of Medical Genetics 65:348-52. PubMed
Kotzot D, Balmer D, Baumer A, Chrzanowska K, Hamel BC, Ilyina H, Krajewska-Walasek M, Lurie IW, Otten BJ, Schoenle E, Tariverdian G, Schinzel A. (2000) Maternal uniparental disomy 7--review and further delineation of the phenotype. Eur J Pediatr. 159(4):247-56. PubMed
Langlois S, Yong SL, Wilson RD, Kwong LC, Kalousek DK. Prenatal and postnatal growth failure associated with maternal heterodisomy for chromosome 7. J Med Genet. 1995 Nov;32(11):871-5. Review. PMID: 8592330
Ledbetter DH, Engel E. (1995) Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Human Molecular Genetics 4:1757-1764 PubMed
Robinson WP, Barrett IJ, Bernard L, Telenius A, Bernasconi F, Wilson RD, Best RG, Howard-Peebles PN, Langlois S, Kalousek DK. (1997) Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction. American Journal of Human Genetics, 60(4):917-27. PubMed
Sachs ES, Jahoda MG, Los FJ, Pijpers L, Reuss A, Wladimiroff JW. (1990) Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies. American Journal of Medical Genetics 37:268-71. PubMed
Spence JE, Perciaccante RG, Greig GM, Willard HF, Ledbetter DH, Hejtmancik JF, Pollack MS, O'Brien WE, Beaudet AL. (1988) Uniparental disomy as a mechanism for human genetic disease. American Journal of Human Genetics 42:217-226 PubMed
Wolstenholme J. (1996) Confined placental mosaicism for trisomies 2, 3, 7, 8, 9, 16, and 22: their incidence, likely origins, and mechanisms for cell lineage compartmentalization. Prenatal Diagnosis.16(6):511-24. PubMed |