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Case Report Down syndrome child with 48,XXY,+21 karyotype

Cyrus Cyril, Chandra N, Jegatheesan T*, Chandralekha K*, Ramesh A, Gopinath P. M.**, Marimuthu K. M.*** Department of Genetics, Dr. ALM. PG. Institute of Basic Medical Sciences, University of Madras, Taramani, *Institute of Obstetrics and Gynecology, Madras Medical College, Government Hospital for Women and Children, Egmore, **KMC Life Sciences Center, Manipal Academy of Higher Education, Manipal - 576104, ***26, II Main Road, Indira Nagar, Adyar, Chennai, India

Cytogenetic analysis in 60 clinically suspected cases of Down syndrome and their parents was carried out using conventional Giemsa­trypsin-banding technique. Fifty-five individuals (91%) exhibited a free trisomy 21. Robertsonian translocations were seen in three cases and two cases exhibited a normal karyotype. A four-month-old child, the second-born of non-consanguineous parents, possessed an extra X chromosome in addition to trisomy 21. The proband's parents and his brother showed a normal karyotype. The phenotypic characteristics of this child have been discussed in the light of the published reports on double aneuploidies of XXY and trisomy 21. Key Words: Down syndrome, Klinefelter syndrome, double trisomy

men with Down syndrome suggest that there might be an increased selection against these individuals after birth.[4] Several cases of double aneuploidy of XXY and trisomy 21 have been published since the first report by Ford et al.[5] This abnormality has also been recently described in a pair of monozygotic twins.[6] Further, both the sibs of the proband showing 48,XXY,+21 were found to exhibit trisomy 21 in yet another study.[7] The clinical features of a 4-month-old boy who exhibited the karyotype 48,XXY,+21 have been presented in this paper. Case History


The existence of two chromosomal abnormalities in the same individual is relatively a rare phenomenon. Double aneuploidy leading to trisomy and / or monosomy of two different chromosomes arises because of two meiotic non-disjunctional events. Both these aneuploidies could have the same or different parental origin.[1] The coincidence rate of both Down and Klinefelter syndromes in the same individual is estimated to lie in the range 0.27 to 0.7 × 10-5.[2] However, neonatal survey data has revealed that the incidence of XXY and trisomy 21 double trisomy at birth is higher than expected from the incidence of either alone.[3] On the other hand, lower values of XXY pattern recorded in older boys and

A 4-month-old male infant was referred for chromosomal analysis because of dysmorphic features suggestive of Down syndrome. He was the second child of an unrelated couple. The mother was 22 years of age and the father was 33 years old at the time of the child's birth. The couple also has a healthy 1.5-year-old son. The proband showed open fontanelle, microcephaly, flat occiput, slanting palpebral fissures, hypertelorism, low set and malformed ears, thick furrowed protruding tongue, open mouth, hypotonia, short broad hand, clinodactyly, gap between 1st and 2nd toes and plantar furrow. The child was born following a normal gestation and delivery.


Chromosomal analysis was carried out in proband,

Address for correspondence: Dr. N. Chandra, Department of Genetics, Dr. Almpgibms, University of Madras, Taramani, Chennai - 600 113, India. E-mail: [email protected] Indian Journal of Human Genetics January-April 2005 Volume 11 Issue 1


48,XXY,+21 ­ A case report

parents and normal sib. Chromosomal preparations obtained from PHA ­ stimulated peripheral blood cultures, were subjected to GTG banding and karyotyping was done according to ISCN 1995. Chromosomal analysis of proband revealed 48, XXY, +21 [Figure 1] with no evidence of mosaicism. Parental and normal sib's karyotypes were found to be normal. Discussion

an error in paternal meiosis I and the remaining in maternal meiosis I or II. On the other hand, trisomy 21 can originate in either of the divisions in both parents. The present case and most of the published cases of 48,XXY,+21 have showed features typical of Down syndrome alone. This is only expected, as features characteristic of Klinefelter syndrome are not apparent until the post-pubertal stage.[10] On the other hand, abnormalities of external genitalia characteristic of Klinefelter syndrome only were observed in a 13-month-old boy probably due to the occurrence of a mosaic pattern of 47,XXY [80.6%] / 48,XXY,+21 [19.4%].[2] This report of double aneuploidy of XXY and trisomy 21 highlighting the clinical characteristics will aid in a better understanding of the phenotype-genotype relationship. References

1. Lorda-Sanchez I, Petersen MB, Binkert F, Maechler M, Schmid W, Adelsberger PA, et al. A 48,XXY,+21 Down syndrome patient with additional paternal X and maternal 21. Hum Genet 1991;87:54-6. 2. Yamaguchi T, Hamasuna R, Hasui Y, Kitada S, Osada Y. 47,XXY/ 48,XXY,+21 chromosomal mosaicism presenting as hypospadias with scrotal transposition. J Urol 1989;142:797-8. 3. Taylor AI, Moores EC. A sex chromatin survey of newborn children in two London hospitals. J Med Genet 1967;4:258. 4. Hecht F, Nievaard JE, Duncanson N, Miller JR, Higgins JV, Kimberling WJ, et al. Double aneuploidy: The frequency of XXY in males with Down syndrome. Am J Hum Genet 1969;21:352-9. 5. Ford CE, Jones KW, Miller OJ, Mittwoch U, Penrose LS, Ridler M, et al. The chromosomes in a patient showing both mongolism and the Klinefelter syndrome. Lancet 1959;1:709-10. 6. Iliopoulos D, Poultsides G, Peristeri V, Kouri G, Andreou A, Voyiatzis N. A Double trisomy (48,XXY,+21) in monozygotic twins: Case report and review of the literature. Ann de Genet 2004;47:95-8. 7. Al Awadi SA, Naguib KK, Bastaki L, Gouda S, Mohammed F M, Abulhasan SJ, et al. Down syndrome in Kuwait: Recurrent familial trisomy 21 in siblings. Downs Syndr Res Pract 1998;5:131-7. 8. Mikkelsen M, Fisher G, Stene J, Stene E, Petersen E. Incidence study of Down syndrome in Copenhagen, 1960 -1971: With chromosome investigation. Ann Hum Genet 1976;40:177-82. 9. Stene J, Stene E, Mikkelsen M. Risk of chromosome abnormality at amniocentesis following a child with a non-inherited chromosome aberration. Prenat Diag 1984;4:81-95. 10. Rajangam S, Verghese M, Tilak P, Thomas IM. A 48,XXY,+21 ­ Down / Klinefelter Syndrome. J Clin Genet Tribal Res 1996;2:126-9.

The proband is a 4-month-old boy who exhibited features typical of Down syndrome and has the karyotype 48,XXY,+21. It is of great interest to note that this case of double aneuploidy is the first case of its kind in more than 1500 cases of Down syndrome referred to our department during the past 25 years. Studies on the incidence of an XXY chromosome pattern among Down individuals have revealed that this double aneuploidy might be more frequent than predicted by multiplying the frequencies of the individual aneuploidies.[8] This observation together with the well-documented increased risk for aneuploidies after the birth of a trisomic child has been attributed to a possibly inherited predisposition to non-disjunction.[9] However, an elucidation of the different factors predisposing to non-disjunction would require determination of the parental origin of the supernumerary chromosomes.[1] This was not feasible in the present study, as the patient was lost for followup. Theoretically, 50% of XXY cases could arise from

Figure 1: GTG-banded karyotype of the proband showing double aneuploidy - 48,XXY,+21



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