Common trisomy mosaicism diagnosed in amniocytes involving chromosomes 13, 18, 20 and 21: karyotype-phenotype correlations

Abstract

Karyotype-phenotype correlations of common trisomy mosaicism prenatally diagnosed via amniocentesis was reviewed in 305 new cases from a collaboration of North American cytogenetic laboratories. Abnormal outcome was noted in 10/25 (40%) cases of 47,+13/46, 17/31 (54%) cases of 47,+18/46, 10/152 (6.5%) cases of 47,+20/46, and in 49/97 (50%) cases of 47,+21/46 mosaicism. Risk of abnormal outcome in pregnancies with less than 50% trisomic cells and greater than 50% trisomic cells were: 26% (4/15) versus 60% (6/10) for 47,+13/46, 52% (11/21) versus 75% (6/8) for 47,+18/46, 4.5% (6/132) versus 20% (4/20) 47,+20/46, and 45% (27/60) versus 59% (22/37) for 47,+21/46. Phenotypically normal liveborns were observed with mean trisomic cell lines of 9.3% for 47,+13/46, 8.6% for 47,+18/46, 27% for 47, +20/46, and 17% for 47,+21/46. Cytogenetic confirmation rates were 46% (6/13 cases) for 47,+13/46 mosaicism, 66% (8/12 cases) for 47, +18/46, 10% (10/97 cases) for 47,+20/46, and 44% (24/54 cases) for 47,+21/46. There were higher confirmation rates in pregnancies with abnormal versus normal outcome: 50% versus 44% for 47,+13/46 mosaicism, 100% versus 33% for 47,+18/46, 66% versus 7% for 47, +20/46, and 55% versus 40% for 47,+21/46. Repeat amniocentesis is not helpful in predicting clinical outcome. It may be considered when there is insufficient number of cells or cultures to establish a diagnosis. Fetal blood sampling may have a role in mosaic trisomy 13, 18, and 21 as the risk for abnormal outcome increases with positive confirmation: 1/5 (20%) normal cases versus 5/8 (62%) abnormal cases. High resolution ultrasound examination(s) is recommended for clinical correlation and to facilitate genetic counselling.

Constitutional and Acquired Autosomal Aneuploidy

“…Chromosome-specific differences in the frequency of prenatally diagnosed autosomal mosaicism have been identified, with trisomies involving chromosomes 13, 18, 20, and 21 being seen most frequently in amniocytes [ 24,25 ].…”

“…As a result of this phenotypic overlap, the term “general chromosomal mosaic syndrome” has been coined [ 35 ]. However, for a subset of these conditions, specific syndromic patterns have emerged (summarized in Table 2 [ 4,16,21,23-25,33-75 ]), thereby facilitating the recognition of the chromosomal basis for these individual's health/developmental problems. The provision of genetic counseling following a prenatal diagnosis of autosomal mosaicism can be especially challenging.…”

The virtual diagnostic laboratory: A new way of teaching undergraduate medical students about genetic testing

“…For the prenatal 14 allowing them to predict with greater confidence the potential outcome for the virtual patient. We discussed two cases in each 2-hour session.…”

Follow-up of a girl with cleft lip and palate and multiple malformations: Trisomy 20 mosaicism

“…This karyotype is rarely detected in peripheral lymphocytes. A study comprising 152 cases of patients with trisomy 20 mosaicism found, through amniocentesis, an abnormal outcome in six live-born patients: one with facial dysmorphism and developmental delay, one with structural brain abnormalities and seizures, and four with intrauterine growth retardation [7]. In a study of 103 cases from 102 pregnancies diagnosed as trisomy 20 mosaicism through amniocentesis, 75 pregnancies (one carried twins) were continued, 26 terminated, and one spontaneously aborted.…”