TRISOMY 12 MOSAICISM
Currently, the majority of cases of trisomy 12 detected prenatally have had normal outcomes. However, abnormal outcome was observed in 6 of the 23 cases of trisomy 12 detected in amniotic fluid reviewed by Hsu et al. 1997. As with other rare mosacism, there is likely a bias to excess reporting of the abnormal cases.
Trisomy 12 detected on CVS
Two cases of trisomy 12 were reported in a large study of chromosomal mosaicism detected on CVS. The trisomy 12 findings were confirmed in the fetus in the one case with non-mosaic findings on CVS (Hahneman & Vejerslev, 1997). In another case, 71% of cultured CVS cells showed trisomy 12, which was also found in 6% of AF cells; However, outcome was normal (Robinson et al. 1997). In this later case and two additional unpublished cases we have investigated with trisomy 12 detected on CVS and normal outcome, uniparental disomy was excluded.
Trisomy 12 detected on amniocentesis
Hsu et al. (1997) summarized findings in 23 cases of trisomy 12 mosaicism detected in amniotic fluid--20 of which were female and only three were male. A bias towards females has been noted in other cases of trisomy mosaicism (e.g. trisomy 16) and suggests either preferential survival of female mosaics or a greater tendency to mosaicism in females.
Of the 10 cases which resulted in a livebirth, 7 (5 females and 2 males) were developmentally normal at birth. Of these, three had postnatal follow-up, at 5 months, 9 months and 5 years and all were reportedly normal (trisomy had been confirmed in urine sediment in one of these cases). Three liveborn infants had abnormal findings : one female was born with congenital heart disease (Epstein anomaly) and some digit anomalies but showed normal psychomotor development at 8 months. Another female with multiple congenital heart defects died at 5 weeks of age, while a third female was born prematurely (33 weeks) with multiple congenital anomalies and died shortly after birth.
Two pregnancies ended with fetal demise, one in association with IUGR. The remaining 11 pregnancies were electively terminated. Of this latter group, autopsy reports were normal in 10 of the cases, while in one case facial dysmorphism and multiple anomalies (short colon, liver anomalies, congestive heart failure, large ovaries) were noted.
Presence of the trisomy is rarely observed in blood samples from these cases, but is often confirmed in fetal tissues. However from the limited data currently available, it is unclear whether confirmation in fetal tissues is predictive of abnormal outcome. For example skin was positive for the trisomy in 3 of 7 cases examined all with apparently normal phenotype. while in one pregnancy ending in fetal demise, trisomy was found in placenta but not in kidney, skin, or liver.
Trisomy 12 detected postnatally
Delozier-Blanchet et al. (2000) reported a case of trisomy 12 diagnosed in a newborn and summarized results for 4 other cases of trisomy 12 mosaicism diagnosed postnatally. The phenotype has been variable.
Uniparental Disomy (UPD 12)
There are no reports of imprinted genes on chromosome 12 (Ledbetter & Engel, 1995).
Link to What is UPD?
- HUGO Chromosome 12 - Chromosome 12 specific sites
Human Chromosome 12 - 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.
Bischoff FZ, Zenger-Hain J, Moses D, Van Dyke DL, Shaffer LG. (1995) Mosaicism for trisomy 12: four cases with varying outcomes. Prenatal Diagnosis 15(11):1017-1026. PubMed
Brosens JJ, Overton C, Lavery SA, Thornton S. (1996) Trisomy 12 mosaicism diagnosed by amniocentesis. Acta Obstet Gynecol Scand. 75(1):79-81. PubMed
Delozier-Blanchet CD, Roeder E, Denis-Arrue et al. (2000) Trisomy 12 mosaicism confirmed in multiple organs from a liveborn child. Am J Med Genet 95:444-449. PubMed
English CJ, Goodship JA, Jackson A, Lowry M, Wolstenholme J. (1994) Trisomy 12 mosaicism in a 7 year old girl with dysmorphic features and normal mental development. Journal of Medical Genetics. 31(3):253-254. 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
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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
Sikkema-Raddatz B, Bouman K, Verschuuren-Bemelmans CC, de Jong B. (1999) Trisomy 12 mosaicism in CVS culture confirmed in the fetus. Prenatal Diagnosis 19(12):1176-1177. PubMed