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TRISOMY 22 MOSAICISM
Under construction
Trisomy 22 is the second most common autosomal trisomy found among spontaneous abortions, accounting for 3-5% of all spontaneous abortions. Full (non-mosaic) trisomy 22 may in very rare cases survive to term. Some common clinical findings in full trisomy 22 include intrauterine growth restriction, microcephaly, hypertelorism, epicanthal folds, hypoplastic or low set ears, midface hypoplasia, hypoplastic distal phalanges, genitalia anomalies in males (Bacino et al.1995). Other findings seen may include Cleft palate, cardiac and/or renal anomalies and anal atresis/stenosis.
Mosiac trisomy 22 diagnosed through prenatal diagnosis can be either confined to the placental tissues or present in the fetus as well. When confined to the placenta, the outcome can be normal, although there is a risk of low birth weight. When present in the fetus, the outcome is variable.
Trisomy 22 detected on CVS
It is difficult at this point to say how often trisomy 22 present at CVS will be confirmed at amniocenetesis. However there are at least multiple cases where 100% trisomy was observed in a CVS culture, no evidence of the trisomy was found in amniotic fluid and the baby appeared normally grown and developed at birth. The behaviour of trisomy 22 confined to the placenta appears similar to that involving trisomy 16: The origin of the trisomy has been maternal meiotic in all 7(?) cases studied to date; the outcome can be normal, but there is a risk of poor intrauterine growth which is generally attributed to the trisomic placenta; and it is possible for trisomy to persist in selected fetal tissues even if absent from most other tissues.
We are aware of 7 cases of trisomy 22 detected on CVS which showed low or absent levels of trisomy in follow-up amniocentesis (Robinson et al. 1997, de Pater et al. 1997, Phillips et al. 1996, Balmer et al. 1999). Of these, 5 showed no trisomy on AF: 3 had a normal outcome and 2 exhibited IUGR. One case which showed 8.5% trisomic cells detected in AF was IUGR at birth and was positive for the trisomy in blood . Another with 20% trisomic cells in AF showed IUGR plus some anomalies (VSD etc) and followup showed the trisomic cells in skin but not in blood cultures.
Maternal uniparental disomy for chromosome 22 has been found in normal individuals and not believed to have a phenotype. A prenatal effect on growth has not been formally excluded, however, and all 5 cases of maternal UPD22 associated with trisomy detected prenatally or at birth did have a low birthweight.
Trisomy 22 detected on amniocentesis
Of 6 cases of trisomy 22 mosaicism present in AF (Schinzel 1981, Robinson et al. 1997, de Pater 1997; Berghella 1998, Hsu et al. 1997, Stoui et al. 1989) blood cultures were negative for the trisomy in all but two cases. Unfortunately little follow-up data is available in these cases. While IUGR was common, 4 of these 6 were not noted to have any obvious anomalies at birth.
Trisomy 22 detected postnatally
Crowe (1997) reviews 10 cases with generalized trisomy 22 mosaicism. Some features found included failure to thrive, mental delay, ptosis, dental anomaly, hearing loss, low posterior hair line, ovarian failure, syndactyly, hemiatrophy, streaked pigmentation. Most of these were however detected in blood or fibroblasts from children ascertained through abnormalitites. They thus likely over-estimate poor outcomes.
Uniparental Disomy (UPD 22)
UPD22 is not known to have a phenotype associated with imprinting. Prenatal testing for UPD is not currently indicated
Link to What is UPD?
Link to Maternal UPD 22 page
Link to Paternal UPD 22 page
Internet Links
- HUGO Chromosome 22 - Chromosome 22 specific sites
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Human Chromosome 22 - 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
Bacino CA, Schreck R, Fischel-Ghodsian N, Pepkowitz S, Prezant TR, Graham JM (1995) Clinical and molecular studies in full trisomy 22: furhter delineation of the phenotype and review of the literature. Am J Med Genet 56:359-365
Balmer D, Bumer A, Rothlisberger B, Schinzel A. (1999) Severe intra-uterine growth retardation in a patient with maternal uniparental disomy 22 and a 22-trisomic placenta. Prenatal Diagnosis. 19:1061-1064 PubMed
Berghella V, Wapner RJ, Yang-Feng T, Mahoney MJ. (1998) Prenatal confirmation of true fetal trisomy 22 mosaicism by fetal skin biopsy following normal fetal blood sampling. Prenatal Diagnosis. 18(4):384-9. PubMed
Crowe CA, Schwartz S, Black CJ, Jaswaney V. (1997) Mosaic trisomy 22: a case presentation and literature review of trisomy 22 phenotypes. American Journal of Medical Genetics. 71(4):406-13 PubMed
de Pater JM, Schuring-Blom GH, van den Bogaard R, van der Sijs-Bos CJ, Christiaens GC, Stoutenbeek P, Leschot NJ. (1997) Maternal uniparental disomy for chromosome 22 in a child with generalized mosaicism for trisomy 22. Prenatal Diagnosis. 17(1):81-6. 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
Kukolich MK, Kulharya A, Jalal SM, Drummond-Borg M. (1989) Trisomy 22: no longer an enigma. American Journal of Medical Genetics. 34:541-544 PubMed
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
Lund HT, Tranebjaerg L. (1990) Case Report: trisomy 22 mosaicism limited to skin fibroblasts in a mentally retarded, dysmorphic girl. Acta Paediatr Scand 79:714-718 PubMed
Schinzel AA, Basaran S, Bernasconi F, Karaman B, Yuksel-Apak M, Robinson WP. (1994) Maternal uniparental disomy 22 has no impact on the phenotype. American Journal of Human Genetics. 54:21-24 PubMed
Stioui S, De Silvestris M, Molinari A, Stripparo L, Ghisoni L, Simoni G. (1989) Trisomic 22 placenta in a case of severe intrauterine growth retardation. Prenatal Diagnosis. 9:673-676 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 |