The Principles of Clinical Cytogenetics - Extra Materials - Springer

150 Jin-Chen Wang
microcephaly and an abnormally large and cystic placenta usually classified as partial hydatidiform
moles. The parental origin of the extra haploid set of chromosomes in such cases is determined to be
paternal (diandry) by analysis of cytogenetic heteromorphisms (177,178) or DNA polymorphisms
(179). Diandry results from the fertilization of a normal ovum with either two sperm (dispermy) or a
sperm that has a diploid chromosome complement resulting from a failure of meiotic division. The
other type is characterized by severe intrauterine growth retardation with relative macrocephaly and
a small and noncystic placenta. The extra haploid set of chromosomes in such cases is maternal (digyny)
(177–180). Digyny can result from a failure of the first maternal meiotic division, generating a diploid
egg, or from retention of the second polar body. Although the occurrence of triploidy does not appear
to be associated with maternal age, digyny can play a major role in the generation of triploidy in the
advanced maternal age group (176). Early cytogenetic studies indicated that the majority of triploid
conceptuses were diandric partial moles (178,181). Later studies based on DNA polymorphisms have
suggested that a maternal contribution to triploidy could occur more frequently than was previously
realized (179,182). Yet, in a most recent study of 87 informative cases of triploid spontaneous abortuses
at 5–18 weeks of gestation, Zaragoza et al. (183) showed that approximately two-thirds are
androgenetic in origin and that many, but not all, androgenetic triploids developed a partial molar
phenotype. The sex chromosome complement in triploidy is either XXX or XXY, with XYY occurring
only rarely. For example, the reported numbers of XXX : XXY : XYY cases in two studies
performed on spontaneous abortuses were 82 : 92 : 2 (3) and 26 : 36 : 1 (176), and in one study
performed on amniotic fluid cells, this ratio was 6 : 8 : 0 (184). It has been suggested that 69,XYY
triploid conceptuses are incompatible with significant embryonic development (3).
The observation that the phenotype of triploidy depends on the parental origin of the extra set of
chromosomes is an example of genomic imprinting, or the differential expression of paternally and
maternally derived genetic material (185,186). It correlates well with observations obtained from
mouse embryo studies using nuclear transplantation techniques, which demonstrated that maternal
and paternal genomes function differently and are both required for normal development (187–189)
(see Chapter 19).
More than 50 cases of apparently nonmosaic triploidy, either 69,XXX or XXY, have been reported
in liveborns. Most patients died shortly after birth. Eight patients with survival longer than 2 months
have been reported (reviewed in ref. 190), with the longest being 10 months (191). The origin of the
extra set of chromosomes was determined by cytogenetic polymorphisms or human leukocyte antigen
(HLA) to be maternal in three cases and paternal in one case (192). One study based on DNA
polymorphism in an infant who survived for 46 days indicated a maternal meiosis II failure as the
origin of the triploid (reviewed in ref. 192). These findings suggest that, in general, digynic triploids
survive longer than diandric triploids. The most frequent phenotypic abnormalities include intrauterine
growth retardation, hypotonia, craniofacial anomalies (macro/hydrocephalus, low-set dysplastic
ears, broad nasal bridge), syndactyly, malformation of the extremities, adrenal hypoplasia, cardiac
defects, and brain anomalies.
Mosaic triploidy (diploid/triploid mixoploidy) has been reported in approximately 20 patients. Triploid
cells were found in both lymphocytes and fibroblasts, although in a number of cases, the triploid
cell line was limited to fibroblasts (193). Patients with such mixoploidy are less severely affected than
nonmosaics and survival beyond 10 years has been observed. Usual clinical features include intrauterine
growth retardation, psychomotor retardation, asymmetric growth, broad nasal bridge, syndactyly, genital
anomalies, and irregular skin pigmentation (194). Truncal obesity was seen in some patients (195).
Mitotic nondisjunction cannot readily explain the occurrence of diploid and triploid cell lines in
the same individual. One possible mechanism is double fertilization of an ovum by two sperms; one
sperm nucleus fuses with the ovum nucleus, producing the diploid line, followed by a second sperm
fertilizing one of the early blastomeres producing the triploid line. Cytogenetic evidence for such a
mechanism has been reported in at least one case (196). Another proposed mechanism supported by