Normal Mother with a Deleted No. 5 Chromosome

Transcription

1 98 Proc. Japan Acad., 47 (1971) [Vol. 47, 24. A Cri du Chat Syndrome Case from the Phenotypically Normal Mother with a Deleted No. 5 Chromosome By Tetsu j i KADOTANI, *) Hiroyuki TAKAHARA, *) Isao NAGAI, * Kouichi KAWAMOTO, **) Hiraku KOBATAKE, ** Takako ISHII,* * a and Saj iro MAKINO* * (Comm. by Yoshimaro TANAKA, M. J. A., Jan. 12, 1971) The characteristic and only visible chromosome abnormality, Bp-, of cri du chat syndrome reported by Lej eune et al. in 1963 have attracted particular attention of human cytogeneticists and considerable information is now available which describes many allied and variant chromosome abnormalities. From some familial cytogenetic surveys of this syndrome evidence have been provided to indicate that there are some cases in which a no. 5 short arm deletion characteristic of this syndrome has occurred as a result of translocation in the parents (review by De Capoa et al. 1967). Further report pointed to two further cases born to mothers with a deleted no. 5, one clinically normal and the other a presumably balanced translocation carrier (De Capoa et al. 1967). We wish to describe in this paper an additional case of this syndrome whose mother is recognized as a balanced translocation carrier for no. 5 chromosome, since familial cytogenetic information is essential as basic criteria for the etiological analysis of the chromosome abnormality in congenital disorders. Case report. The propositus was a 28-day-old developmentally retarded female infant born to a 27-year-old mother and a 42-year-old father as an only child. There was no history of abortion or stillbirth and exposure for atomic bomb in this couple. Clinical examinations revealed that her parents were phenotypically normal having no evidence for mental deficiency. The birth weight of the propositus was 2600 g at 43 weeks of gestation. On clinical examination, a marked degree of developmental retardation, and phenotypical symptoms for cri du chat syndrome were noted in this child (see Table I). Other abnormalities involving *) Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima. **) Department of Pediatrics, Hiroshima University School of Medicine, Hiroshima. ***) Chromosome Research Unit, Faculty of Science, Hokkaido University Sapporo.,

2 No. 1] A Cri du Chat Syndrome Case from a Bp-mother 99 Fig. of 1. cri `1'he du proband, 28-day-old, showing typical chat syndrome. features Table I. Results of age of measurements of the proband at in comparison with standard values 28 days Table II. Dermatoglyphic pictures of the proband microcephaly, protruding occiput, hypertelorism, epicanthic folds, narrow and antimongoloid slant, broad face, low-set and malformed ears, short and left-stiff neck, excess skin at back of the neck, micrognathia, high-arched palate, congenital dislocation of the left hip joint, long toes, and syndactylia cutanea (2nd and 3rd toe) were also demonstrated (Fig. 1). Characteristic dermatoglyphic features of cri du chat syndrome were detected in this patient at a standard level (Table II).

3 100 T. KABOTANI et al. [Vol. 47, Cytological findings. Chromosome slides were made through the routine flame-drying and Giemsa-staining techniques with shortterm leucocyte cultures of the propositus and her parents. Chromosome counts were made on 35 well-delineated metaphases from the above specimens. Karyotype analyses were made on the bases of 20 cells each for the propositus and her mother, and 6 cells for her father. Cytogenetic data derived from the propositus and her parents are given summarizingly in Table III. It was shown that the propositus was characterized by a short arm deletion of one member of the B group chromosomes, very probably of no. 5, because of the fact that the long arm of this chromosome is shorter than the long arm of no. 4 chromosomes (Fig. 2). Of interest is the finding that Table III. Cytogenetic findings in the family here considered Fig. 2. by an Karyotype arrow. of the proband. A deleted no. 5 chromosome is shown

4 No. 1] A Cri du Chat Syndrome Case from a Bp-mother 101 Fig. 3. Karyotype of the no. 5 chromosome. proband's mother showing a deleted a similar abnormality, no. 5 short arm deletion, was found to occur in her mother (Fig. 3). The mother having a deleted no. 5 chromosome is presumed to be a balanced translocation carrier, since she showed clinically no partciular phenotypic abnormality and mental deficiency. Microscopically, evidence for translocation of the deleted segment on any chromosome was not demonstrated with certainty. Her father was chromosomally normal with no slight evidence for abnormality. Remarks and conclusion. The female infant with clinical symptoms of cri du chat syndrome was found to be associated with a short arm deletion of one of the no. 5 chromosome characteristic of this syndrome. Worthmentioning is the fact that her mother was characterized by the same chromosomal abnormality, a deleted no. 5, while she was clinically normal. Considered from her physically and mentally normal conditions, the mother is presumed as a balanced translocation carrier, involving a no. 5 short arm deletion, though the microscopic picture for translocation of the deleted segment was difficult to detect with certainty. Her father was clinically and karyotypically normal. The literature refers to the same cases : De Capoa et al. (1967)

5 102 T. KADOTANI et al. [Vol. 47, reported two families under a similar situation. According to their reports, one mother was clinically normal while the other a balanced translocation carrier. A good deal of information is available to date indicating that many individuals with balanced translocations seem to be phenotypically normal (Kadotani et al. 1970). In gametogenesis of these carriers excluding nondisj unction, the production of four types of gametes is theoretically possible : (1) normal, (2) balanced, (3) unbalanced with excess genetic material, and (4) unbalanced with a deficient amount of genetic material. The no. 5 short arm deletion occurring in the present propositus is most probably transmitted from her mother through the process of category 4. Referring to the data collected by De Capoa et al. (1967), it appears that translocation is rather common as a cause of the cri du chat syndrome. In many cases of this syndrome where both parents were studied, the deletion of a B-chromosome was a characteristic and visible cytogenetic abnormality in the probands. The review by De Capoa et al. (1967) indicated that, in three of those cases (or 1.5%), one parent carried a deleted B-chromosome and was presumably a balanced translocation carrier, and that the estimated frequency of translocation was 13%. This value is somewhat higher than the proportion of Down's syndrome described by Pergament (1970) showing approximately 10%. Evidence presented suggests the importance of unbalanced gamete formation in translocation heterozygotes as a possible cause of the cri du chat syndrome. It is thus evident that the familial cytogenetic survey, particularly in the parents, is significant in order to provide any basic criteria essential for the etiological analysis of the cause of congenital disorders. Summary. A cytogenetic study is carried out with leucocyte cultures in a 28-day-old female infant with the clinical symptoms of cri du chat syndrome and in her parent. The propositus showed the short arm deletion of no. 5 chromosome, characteristic of this syndrome. A similar abnormality is observed in her mother. Because of her normal phenotype, she is presumed as a balanced translocation carrier, though it is impossible to demonstrate the evidence of translocation. Her father shows a normal karyotype, 46, XY, Acknowledgement. We are grateful to Professor Akira Tabuchi, Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, and Professor Tomof usa Usui, Department of Pediatrics, Hiroshima University School of Medicine, for their clinical consideration.

6 No. 1] A Cri du Chat Syndrome Case from a Bp-mother 103 References Capoa, A. De, Warburton, D., Berg, W. R., Miller, D. A., and Miller, 0. J. (1967) : Amer. J. Hum. Genet., 19, Kadotani, T., Ohama, K., Sofuni, T., and Hamilton, H. B. (1970) : Nature, 225, Lejeune, J., Lafourcade, J., Berger, R., Vialette, J., Boeswillwald, M., Seringe, P., and Turpin, R. (1963) : C. R. Acad. Sc. Paris, 257, Pergament, E. (1970) : Lancet, i, 93.