Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Abnormalities of human sex chromosomes

VI. Monozygotic twins with the complement 48,XXXY

  • 21 Accesses


The cytogenetic study of a pair of identical, mentally-retarded twins with the chromosome complement 48,XXXY is reported, along with extensive clinical and endocrinological studies of one twin.

The genetic and clinical features of 30 reported 48,XXXY individuals were summarized and compared to those of 47,XXY and 49,XXXXY individuals. For 47,XXY the mean maternal age clearly is increased; for 48,XXXY it appears definitely but only slightly increased; and for 49,XXXXY it may not be increased at all. Developmental defects, similar in type, appear to be progressively more marked when an additional 1, 2, or 3 X chromosomes are added to the normal male chromosome complement. 47,XXY individuals may be either normal in intelligence or mentally retarded, whereas severe mental retardation has been present in all those with the complements 48,XXXY and 49,XXXXY.

The interesting suggestion of increased twining associated with poly-X male complements is noted.


Die cytogenetische Untersuchung eines Paares eineiiger, geistig zurückgebliebener Zwillinge mit dem Chromosomenstatus 48,XXXY wird dargestellt; bei dem einen Paarling konnten außerdem ausgedehnte klinische und endokrinologische Studien durchgeführt werden.

Außerdem wurden die genetischen und klinischen Merkmale der 30 bekannten Fälle mit 48,XXXY dargestellt und mit denen von Patienten mit 47,XXY und mit 49,XXXXY verglichen. Bei Fällen mit 47,XXY ist das mütterliche Alter deutlich erhöht; bei 48,XXXY ist es eindeutig, aber nur leicht erhöht; es sieht so aus, als ob es für 49,XXXXY überhaupt nicht erhöht wäre. Defekte der Entwicklung, die dem Typ nach ähnlich sind, scheinen dem Ausmaß nach desto mehr ausgeprägt zu sein, je mehr X-Chromosomen zusätzlich bei dem normalen männlichen Chromosomensatz vorhanden sind. 47,XXY Individuen können entweder schwachsinnig sein oder eine normale Intelligenz haben; dagegen zeigten alle Fälle mit 48,XXXY und 49,XXXXY einen schweren Schwachsinn.

Es wird die interessante Frage aufgeworfen, ob die Zwillingshäufigkeit bei Poly X-Männern erhöht ist.

This is a preview of subscription content, log in to check access.


  1. Bamatter, F., Klein, D., Tabibian, Y., Tajmirmova, O., Boreaux, G.: Constitution 48,XXXY chez un enfant de 7 mois dont le pére présente des cassures chromosomiques. Arch. Klaus-Stift. Vererb.-Forsch. 43, 64–68 (1971)

  2. Barr, M. L., Sergovich, R. F., Carr, D. H., Shaver, E. L.: The triplo-X female: An appraisal based on a study of 12 cases and a review of the literature. Canad. med. Ass. J. 101, 247–258 (1969)

  3. Barr, M. L., Shaver, E. L., Carr, D. H., Plunkett, E. R.: An unusual sex chromatin pattern in three mentally deficient subjects. J. ment. Defic. Res. 3, 78–87 (1959)

  4. Bishun, N. P.: Phenotype-karyotype correlations in a series of males with sex abnormalities. Acta genet. (Basel) 18, 316–324 (1968)

  5. Breakey, W. R.: Sex chromatin analysis in a mentally defective population. J. Anat. (Lond.) 95, 618 (1961)

  6. Carr, D. H., Barr, M. L., Plunkett, E. R., Grumbach, M. M., Morishima, A., Chu, E. H. Y.: An XXXY sex chromosome complex in Klinefelter subjects with duplicated sex chromatin. J. clin. Endocr. 21, 491–505 (1961)

  7. Christensen, M. F., Therkelsen, A. J.: A case of the XXXXY chromosomal anomaly with four maternal X chromosomes and diabetic glucose tolerance. Acta paediat. scand. 59, 706–710 (1970)

  8. Court Brown, W. M., Harnden, D. G., Jacobs, P. A., Maclean, N., Mantle, D. J.: Abnormalities of the sex chromosome complements in man. London: Her Majesty's Stationery Office 1964

  9. Essman, V., Nielsen, J., Peterson, G. B.: Klinefelter's syndrome with 48,XXXY and diabetes mellitus. Acta med. scand. 186, 27–33 (1968)

  10. Ferguson-Smith, M. A.: Klinefelter's syndrome and mental deficiency. In: Sex chromatin, Moore, K. L., Ed., pp. 277–315. Philadelphia: Saunders 1966

  11. Ferguson-Smith, M. A., Johnston, A. W., Handmaker, S. D.: Primary amentia and microorchidism associated with an XXXY chromosome constitution. Lancet 1960 II, 184–187

  12. Frøland, A.: Klinefelter's syndrome. Clinical, endocrinological and cytogenetical studies. Copenhagen: Costers Bogtrykkeri 1969

  13. Giannelli, F.: The pattern of X-chromosome deoxyribonucleic acid synthesis in two women with abnormal sex-chromosome complements. Lancet 1963 I, 863–865

  14. Gilly, R., Germain, D., Laurent, C., Robert, M.: Syndrome de Klinefelter de jeune enfant. Caryotype à 48 chromosomes XXXY. Pédiatrie 20, 323–338 (1965)

  15. Greenstein, R. M., Harris, D. J., Luzzatti, L., Cann, H. M.: Cytogenetic analysis of a boy with the XXXY syndrome. Origin of the X-chromosomes. Pediatrics 45, 677–686 (1970)

  16. Hambert, G.: Males with positive sex chromatin. Göteborg: Akademiförlaget 1966

  17. Hunter, H.: A controlled study of the psychopathology and physical measurement of Klinefelter's syndrome. Brit. J. Psychiat. 115, 443–448 (1969)

  18. Makino, S., Takagi, N., Hikita, M.: Two phenotypic males with XXXXY and XXXY sex chromosomes. Proc. Jap. Acad. 40, 427–431 (1964)

  19. McGann, B. R., Alexander, M., Fox, F. A.: XXXY chromosome abnormality in a child. Calif. Med. 112, 30–32 (1970)

  20. Money, J., Hirsch, S. R.: Chromosome anomalies, mental deficiency and schizophrenia. Arch. gen. Psychiat. 8, 243–251 (1963)

  21. Nakagome, Y., Matsui, I., Komiya, K., Momma, K., Arima, M.: Sex chromosome abnormalities in mentally defective children. Pediat. Univ. Tok. 11, 41–46 (1965)

  22. Nielsen, J.: Twins in sibships with Klinefelter's syndrome. J. med. Genet. 3, 114–116 (1968a)

  23. Nielsen, J.: Twins and Klinefelter's syndrome. Acta Genet. med. (Roma) 17, 385–388 (1968b)

  24. Nielsen, J.: Klinefelter's syndrome and the XYY syndrome. Acta psychiat. scand. 45. Suppl. 29, 1–353 (1969)

  25. Nielsen, J.: Twins in sibships with Klinefelter's syndrome and the XYY syndrome. Acta Genet. med. (Roma) 19, 399–403 (1970)

  26. Nielsen, J., Fischer, M.: Sex chromatin and sex-chromosome abnormalities in male hypogonadal mental patients. Brit. J. Psychiat. 111, 614–647 (1965)

  27. Scott, C. I., Smith, W. K.: The triple-XY syndrome. Birth Defects: Original Article Series 5(5), 140–141 (1969)

  28. Simpson, J. L., Morillo-Cucci, G., Horwith, M., Stiefel, F. S., Feldman, F.: Monozygotic twins with 48, XXXY Klinefelter's syndrome. (Abstracts, IV Inter. Congress Human Genetics, Paris, France, Sept. 6–11, 1971). Excerpta Medica Inter. Congress Series 233, 166 (1971)

  29. Soltan, H. C.: Genetic characteristics of families of XO and XXY patients, including evidence of source of X chromosomes in 7 aneuploid patients. J. med. Genet. 5, 173–180 (1968)

  30. Takayasu, H., Kinoshita, K., Tsuboi, T., Kurihara, T.: Twins with Klinefelter's syndrome. Lancet 1967 II, 1424

  31. Vague, J., Boyer, J., Nicolino, J., Mattei, A., Luciani, J., Arnaud, A., Pouch, J. Valette, A.: Maladie de Klinefelter chez deux jemeaux monozygotes. Ann. Endocr. (Paris) 29, 709–729 (1968)

  32. Walczak, M., Krawczynski, M., Simm, S., Pawlaczyk, B., Wajciechowski, K., Erikson, E.: Zespol Klinefeltera a 16-letneigo chlopca z kariotypem 48,XXXY. Endokr. pol. 22, 187–192 (1971)

  33. Zaleski, W. A., Houston, C. S., Pozsonyi, J., Ying, K. L.: The XXXXY chromosome anomaly: Report of three new cases and review of 30 cases from the literature. Canad. med. Ass. J. 94, 1143–1154 (1966)

  34. Zollinger, H.: Das XXXY-Syndrom. Zwei neue Beobachtungen im Kleinkindesalter und eine Literaturübersicht. Helv. paediat. Acta 24, 589–599 (1969)

Download references

Author information

Additional information

Research supported by grants HD 04134, HL 09011, RR-47, AM-11105, and TIAM 53950-11 from the National Institutes of Health.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Simpson, J.L., Morillo-Cucci, G., Horwith, M. et al. Abnormalities of human sex chromosomes. Hum Genet 21, 301–308 (1974). https://doi.org/10.1007/BF00273367

Download citation


  • Developmental Defect
  • Chromosome Complement
  • Severe Mental Retardation
  • Male Chromosome
  • Endocrinological Study