A CHROMOSOME ABNORMALITY IN HYPOSPADIAS PATIENTS

By GRAZIELLA LUPO, MASSIMO LUPO, CESARINA MAGNANY and MARIO BERGAMASCHI

Section of Plastic Surgery, S. Anna Hospital, Como, Italy, and Tumour Centre and Research Centre, Donegani, Novara, Italy

SINCE 1969 we have studied the karyotypes of 134 patients with degrees of hypospadias varying from glandular to scrotal. In every case we examined I 50 cultured lymphoctyes

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Karyotype of paternal grandfather of a hypospadiac. 109 of 134 hypospadiacs showed delection of genetic material from one of the chromosomes in pair 20 as indicated. 17 01 23 paternal grandfathers of hypospadiacs, but themselves without the deformity, showed similar changes in pair 20, but the genetic material had been added (translocated) to:one

of pair 16.

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236 BRITISH JOURNAL OF PLASTIC SURGERY

in metaphase in order to determine the modal number. Ten photographs were taken to establish the karyotype.

In 109 cases (81 per cent) we have detected in the aploid 46 chromosome karyotypes a loss or “delection” of one or more genes, indicated by the disappearance of a segment of one of the chromosomes in pair 20 (Fig. I).

We next extended our research to the parents, grandparents, siblings, aunts and uncles of our patients. The only positive finding was in paternal grandfathers; I 7 of the 23 studied had an abnormal karyotype (Fig. I). There were 2 morphological changes; the loss of the upper part of one of the chromosomes of pair 20 similar to that of the hypospadiacs, and the addition of the genetic material to one of the chromosomes of pair 16. This is a translocation of genes rather than a loss and none of the cases with these abnormalities had hypospadias.

All other relatives studied had normal karyotypes and included mothers (108), fathers (94), maternal grandfathers (21) and 191 assorted grandmothers, siblings, aunts and uncles.

It may be premature to claim that the alterations we have found connected with hypospadias are a characteristic feature of this malformation; our data, however, suggest that the alteration appearing in the karyotype of the paternal grandfather, although with normal genetic constitution as indicated by lack of any phenotypic abnormality, can be transmitted through his son acting as a healthy bearer to the hypospadiac grandson. During this transmission the genetic material translocated in the grandfather is lost and is missing in the grandson.

Other authors have studied smaller numbers of cases of hypospadias: some have found morphological changes in other chromosome pairs (Leao et al., 1967; Aarskog, 1969); others have found none (Juberg et al., 1969). Such discrepancies suggest that it is still too early to assume that hypospadias has hereditary characteristics and further studies are required to clarify the role of chromosomal abnormalities in this condition.

REFERENCES

AARSKOG, D. (1969). A familial 3/18 reciprocal translocation resulting in chromosome duplication-deficiency (3 ? + -18q-). Acta Pediatrica Scandinavica, 58, 397-406.

AARSKOG, D. (1970). Clinical and cytogenetic studies in hypospadias. Acta Pediatrica Scandinavica. Sunnlement 201. 1-62.

CAMPBELL, M. g. (i9b9). Anomalies of the genital tract. 1v Campbell, M. F. (ed.) “Urology”, Vol. 2, p. 1713. Philadelphia: W. B. Saunders Co.

JUBERG, R. C., JEWSON, D. V., TAYLOR, M. B. and MOORE, V. L. (1969). Chromosome studies in natients with hvnosnadias. Pediatrics, 42, $78-582. , .__ _I

LEAO, J. C., BERGMAN, G. J.; -NE;, R. L., KAJII, T. and GARDNER, L. E. (1967). New syndrome associated with partial delection of short arms of chromosome no. 4. Journal of the American Medical Association, 202, 434-437.

LEJEUNE, J. (1965). Techniques d’etude des chromosomes humains. In Turpin, R. and Lejeune, J. (eds.), “Les chromosomes humains”, p. 43. Paris: Gauthier-Villars.

LUPO, G., MAGNANI, C. and BERGAMASCHI, M. (1970). Modifications caryotypiques des petites lymphocytes hCmatiques chez des subjets atteints d’hypospadias. Mc!dicine er HygiLne, Feb. 1970.

MOORHEAD, P. S., NOWELL, P. C., MELLMAN, W. S., BATTIPS, D. M. and HUNGERFORD, D. A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Experimental Cell Research, 20, 613-616.

MULDAL, S. and OCKEY, C. H. (1962). Delection of Y chromosome in a family with muscular dystrophy and hypospadias. British Medical Journal? I, 291-294.

SORENSEN, H. R. (1953). The aetiology of hypospadla. In “Opera Domo Biologiae Hereditarie”, p. 31. Hum. Kbl. Copenhagen, Munksgaard.