Mixoploidy in humans: Two surviving cases of diploid‐tetraploid mixoploidy and comparison with diploid‐triploid mixoploidy

Abstract

We report on 2 cases of diploid/tetraploid (2n/4n) mixoploidy in surviving females, 11 and 21 years old. Both individuals manifested severe mental retardation, reduced peripheral limb muscle bulk, asymmetric growth deficiency, seizure disorder, and skin pigmentary dysplasia. Previous lymphocyte karyotypes had been normal on 2 occasions, but when skin fibroblast karyotypes were done, 33% of the cells were tetraploid on the younger woman, and over 60% were tetraploid in the older woman (on 2 separate occasions). In both individuals, the distal limbs and digits were long and thin, with reduced small muscle bulk. The similarity in distal limb findings prompted reexamination of the younger woman's chromosomal constitution in skin fibroblasts. We concluded that the clinical findings in these cases are unique and similar, and we caution clinicians about uniformly dismissing tetraploidy as artifactual in amniocytes from normal patients, especially since this phenotype would be very difficult to detect, even with directed prenatal ultrasonography. We compare the 2n/4n phenotype with that in diploid/triploid (2n/3n) mixoploidy and note subtle differences which might be detected postnatally. These findings should be useful in guiding clinicians on when to request skin fibroblast karyotypes in mentally-deficient individuals with asymmetric growth deficiency and pigmentary skin variation.

Diploid/tetraploid/t(1;6) mosaicism in a 17‐year‐old female with hypomelanosis of Ito, multiple congenital anomalies, and body asymmetry

“…The phenotype of diploid-tetraploid mosaicism consists of mental retardation, reduced peripheral limb muscle bulk, asymmetric growth deficiency, seizures, and skin pigmentary dysplasia, not necessarily that of hypomelanosis of Ito [Edwards et al, 1994]. Our patient had a very similar appearance, but had the characteristic streaks of hypomelanosis of Ito and no seizure disorder.…”

“…In terms of long-term survivors, there have only been five such individuals over the age of 6 years described [Atnip and Summitt, 1971;Wittwer and Wittwer, 1985;Vormittag et al, 1992; [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.] Edwards et al, 1994]. Most had multiple anomalies and developmental delay.…”

Rare finding of 2n/4n mixoploidy in mother and fetus with severe immune hydrops

“…Tetraploidy mosaics occur with a wide variation of congenital anomalies and varying degrees of mental and growth retardation. Reduced peripheral limb muscle bulk, asymmetric growth deficiency, seizures, skin pigmentary dysplasia, genito-urinary and craniofacial abnormalities are the most common manifestations but there is no correlation between the percentage of tetraploid cells and the severity of the malformations (Wullich et al, 1991;Edwards et al, 1994;Leonard and Tomkins, 2002). In the present case, the mother also showed tetraploidy mosaicism and was thoroughly evaluated for the presence of abnormalities.…”

“…In 2n/4n mixoploidy, the abnormal cell line has 92 chromosomes. Mixoploidy or mosaic tetraploidy (diploid/tetraploid mixoploidy) is a rare condition with decreased survival (Edwards et al, 1994). Tetraploidy occurs frequently in amniotic cells (Klinger and Schwarzacher, 1960) and diploidy-tetraploidy mosaicism is generally considered a culture artifact wherein the fetus is chromosomally normal and the tetraploid cells are thought to arise from the amniocytes and not from the fetus (Montanari et al, 2000).…”

Omphalocele with absent radial ray (ORR): A case with diploid-triploid mixoploidy

“…However, Calzolari et al [1993] found triploidy in only 1 of 45 cases of omphalocele combined with other malformations, indicating that triploidy is not a major cause [Nicolaides et al, 1992;St.-Vil et al, 1996]. Similarly, radial ray malformations have not been reported in triploidy or diploid-triploid mixoploidy [Harris et al, 1981;Graham et al, 1981;Edwards et al, 1994].…”