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Indian Journal of Human Genetics, Vol. 8, No. 2, Jul-Dec, 2002 pp. 73-74 Case Report Down syndrome with Fragment X - A case Report Aruna N, Preetha Thilak, Sayee Rajangam Division of Human Genetics, Department of Anatomy, St. Johns' Medical College, Bangalore - 560034. Code Number: hg02015 This article reports a case of four-month-old female infant referred to Division of Human Genetics, St. Johns' Medical College, for karyotyping with suspicion of Down syndrome. On karyotyping all analysed spreads showed trisomy 21 but a few spreads (6.66%) showed fragment X. X was broken at the centromere and both short and long arms were present in the spread. GTG bands of the two fragments correlated with the normal X counter parts. The mechanism behind isochromosome formation is discussed. Thus, this case is free trisomy 21 for Down syndrome and a mosaic for the X structural anomaly. Key words: Isochromosome, trisomy21, fragment X, delX. Introduction Isochromosome, a structural chromosomal anomaly shows loss of one arm of the chromosome with duplication of the other. Isochromosome is formed when the centromere divides transversely rather than longitudinally during anaphase stage of a cell division. The most commonly encountered isochromosome is that of long arms of x, which accounts for approximately 20% of all cases of turner syndrome1. Down syndrome is the commonest autosomal chromosomal anomaly with an incidence of 1in 700 to 1000 live births. This article reports the presence of a fragment x along with trisomy 21 and also the mechanism of isochromosome formation. Case report A four-month-old infant, second birth order, born to non-consanguineous couple aged 25 and 29 years was referred to division of human genetics, department of anatomy, st. John's medical college with clinical suspicion of Down syndrome for karyotyping. The child was phenotypically female and had most of the common dysmorphic features of down syndrome like short palpebral fissures, mongoloid slant, epicanthic folds, hypertelorism, depressed nasal bridge, small mouth, high arched palate and bilateral clinodactyly. Weighed 5.5 kgs and had not attained any developmental milestones. Neonatal history revealed septicemia, right ectopic kidney and anorectal malformation for which sigmoido-colostomy has been performed. First pregnancy ended in a spontaneous abortion with 6 weeks of amenorrhea. Antenatal history was insignificant except for detection of ectopic kidney in the fetus by ultrasonogram during 8th month. Family history was non-significant. Investigations Cytogenetic analysis was done with peripheral blood lymphocyte culture and gtg banding. 30 metaphase spreads were analysed, all spreads showed free trisomy 21, but 2 spreads (6.66%) showed 48 chromosomes. In these spreads in addition to the 44 autosomes, one extra 21, only one normal X and two fragments were observed. Gtg identified these two fragments with centromeres as of X origin. X was broken at the centromere and both short and long arms were present in the spread. Hence the Karyotype: 47, XX+21 / 48,X+21+ del Xp (pter®centromere) + del Xq (centromere®qter). (in view of non-cooperation neither repeat culture nor parental karyotyping could be carried out.) Discussion On review of literature, Down syndrome has been known to be associated with Klinefelter syndrome, Turner syndrome. The mechanism behind the formation of the observed karyotype in the proband has been discussed. Trisomy 21 is due to meiotic non-disjunction of 21 in one of the parental gametogenesis. It could also be due to mitotic non-disjunction during first cleavage of zygote with subsequent loss of the cell line with 45 chromosomes resulting in free trisomy. Zygote being prone for non-disjunction seems to become prone for further mitotic errors in other chromosomes2 especially the X. One of the mitotic errors could be the isochromosome formation of X where the centromere splits transversely resulting in isochromosome of its short i (Xp) or long i (Xq) arms. Analysed spreads have shown trisomy 21 (47 chromosomes) in all spreads. But, in 2 spreads 48 chromosomes were seen. 48 includes all autosomes, one normal X, one extra 21, one short arm of X and one long arm of X. The short arm of X was present from its tip that is telomere to the X centromere. Likewise, the long arm was present from its tip to centromere. Thus the karyotype becomes 47, xx+21 / 48, x+21+ del x (pter®centromere) + del X (centromere®qter) 63.6%/6.6%. Thus, this case is free trisomy 21 for Down syndrome and a mosaic for the X structural anomaly. Gtg bands of the two fragments correlated with the normal X counter parts. These two cell lines with X structural anomaly, in further mitotic divisions, would have resulted in cell lines with either iso x p or iso X q or 45, X. In this study, coincidentally the reproducible metaphases spread have been caught at the correct time showing the steps involved in isochromosome formation. For the first time, such a case is reported. Couple was counselled for the low recurrence risk of <1% keeping in mind their age and insignificant family history inspite of first pregnancy being an abortion, second being proband with trisomy 21 and with mitotic irregularity in the X. Counselling regarding rearing of the child was given and emphasis was laid on prenatal diagnostic options during next pregnancy. Specific request was made for a follow up around the puberty, to repeat the karyotype to observe the mosaicism status of the X and its influence on the secondary sexual features of the proband. References
Copyright 2002 - the Indian Society of Human Genetics |
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