Balkan Journal of Medical Genetics

DOUBLE ISOCHROMOSOME X, A RARE CYTOGENETIC VARIANT OF TURNER SYNDROME: A CASE REPORT AND A REVIEW OF THE LITERATURE
Zerrouki K.1,2, Babakhouya A.1,3, Tajir M.1,2
*Corresponding Author: Khawla Zerrouki; Address: Medical Genetics Laboratory, Mohammed VI University Hospital, BP 4806 Oujda University, 60049 Oujda, Morocco. Phone number: +212642540172; E-mail: khawlazerroukii@gmail.com
page: 4

DISCUSSION AND CONCLUSION

Isochromosome X is a structural chromosomal abnormality of the X chromosome that consists of two copies of either the p arm or the q arm, derived by centromere division (5). This results in an abnormal X chromosome whose two arms are genetically identical and causes TS. The most common isochromosome observed in the literature is the isochromosome for the long arm of the X chromosome (6). With or without mosaicism, its frequency was reported to be 15-18% in TS cases (7). To our knowledge, the double i(X) is a very rare entity, described less than 10 times in the literature. The percentage of double i(X) ranges from 5% in Howell et al. to 36% in Melaragno et al. (8,9). The percentage of double i(X) is 26 % in our case (Table 1). The absence of a normal population 46,XX indicates that the formation of i(X) occurred during meiosis by an isochromatid break and fusion of the daughter chromatids above the centromere or, by transverse division instead of longitudinal division of the centromere during cell division (10). We noticed that in all previously reported cases of TS with double i(X), the isochromosomes were dicentrics. This suggests that mosaicism is a consequence of the instability of the dicentric chromosomes (9). We could pretend, in our case, that the i(X) is dicentric resulting in fusion of daughter chromatids. The segregation of the chromosome during cell division is normal due to one of the two centromeres of the dicentric isochromosome usually becoming non-functional (5) . However, in this case, there is a failure of homologous chromosomes or sister chromatids to separate properly during cell division. There are three forms of nondisjunction: failure of sister chromatids to separate during mitosis (10,11). This latter mechanism is responsible for the presence of these three cell populations in our patient (Figure 2). Failure of a pair of homologous chromosomes to separate in meiosis I and failure of sister chromatids to separate during meiosis II. The structural or numerical abnormality of X chromosome causes TS (4). The phenotypes of TS are very heterogeneous depending on the type of abnormality (12). The most common feature is short stature, which is found in 95% of patients, especially in patients with 46,X,i(Xq). This can be explained by the haplo-insufficiency of the short stature homeobox gene (SHOX), that is in the pseudoautosomal region (PAR1) (refractory to X inactivation) in the short arm of X chromosome (13–16). Ovarian dysgenesis, congenital lymphedema, pterygium colli, and some facial features are also described in TS (17). Some physical appearances of patients are generally related to bone abnormalities such as a short neck, cubitus valgus, and Madelung deformity. In our case, the proband has a short stature, some facial features, and delayed development of secondary sex characteristics, yet she has no heart disease, no bone abnormalities, thyroid function tests are normal and she does not complain from digestive symptoms. In general, the 46,X,i(Xq) and 45,XO karyotype show the same clinical manifestations of Turner’s Syndrome (18). The other patients described with the 3 cells lines with double i(X) have also a phenotype suggesting TS. Most often, Turner Syndrome is a sporadic event, and the risk of recurrence is not increased in subsequent pregnancies (4). As we explained above, the formation of the iso X in our patient took place during meiosis, therefore a karyotype of the parents is not necessary. The parents benefited from a genetic counseling consultation and the patient has regular medical follow-ups with the pediatricians to screen for other possible clinical manifestations and to establish hormonal treatment. Consent for publication Written informed consent for publication was obtained from the parents of the proband List of abbreviations: TS: Turner Syndrome i(X): isochromosome X SD: Standard deviation Competing interests The authors declare no conflict of interest.

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