Volume 83 Number 3
True hermaphroditism Mth X X / X Y mosaicism." Report of a case I. Shanfield, M.D., Ph.D., R. B. Young, M.D., a n d D a v i d M. Hume, M.D.,t Richmond, Va. T R U E h e r m a p h r o d i t i s m with X X / X Y mosaicism is rare, 1-1~ and its occurrence with n o r m a l male genitals has never been previously described. We would like to r e p o r t such a case presenting as an incidental finding during the r e p a i r of an inguinal hernia.
CASE REPORTS The propositus, a 2-year-01d white boy, was born May 9, 1970; he was born after a full-term pregnancy of a 24-year-old mother. He was the mother's fourth child; the three siblings, ages 7, 6, and 5 years, were all normal. Physical examination of the propositus at birth revealed an empty scrotal sac on the left. At three months of age, a swelling was noted in the left side of t h e scrotum, and a diagnosis of inguinal hernia was made. The patient had normal male external genitals with the urethral meatus at the tip of the glans and a gonad palpable in the right side of the scrotum. Complete physical examination revealed no other obvious asymmetries such as heterochromia or other pigmentary abnormalities.
SURGICAL AND PATHOLOGICAL FINDINGS T h e hernia was repaired when the child was 2 year of age. A sliding hernia was
From the Divisions o[ Pediatric Surgery and Pediatric Endocrinology, Department o[ Surgery, Medical College o] Virginia, Health Sciences Division, Virginia Commonwealth University. Reprint address: 1. Shanfield, Division o[ Pediatric Surgery, Medical College el Virginia, Health Sciences Division, Virginia Commonwealth University, Richmond, Va. 23298. "~Deeeased, Ma~, 19, 1973.
Brie[ clinical and laboratory observations
found and, on o p e n i n g the sac, a normala p p e a r i n g ovary and tube with i n f u n d i b u l u m a n d fimbriae were seen. A biopsy of the ovary was obtained a n d showed typical juvenile ovarian tissue with numerous follicles and ovocytes in the cortex. T h e opposite g o n a d was biopsied; grossly it a p p e a r e d to be a testis. Microscopic study showed an i m m a t u r e testis consisting principally of testicular tubules lined by Sertoli cells. A few isolated spermatogonia were seen. At exploratory l a p a r o t o m y a n o r m a l - a p p e a r i n g left ovary was seen. T h e left tube consisted of the i n f u n d i b u l u m a n d a proximal portion e x t e n d i n g about two thirds of the distance t o w a r d the midline. Thereafter it ended blindly in a fibrous cord extending down to the posterior aspect of the bladder, to which it was attached. T h e ovary, tube, and fibrous r e m n a n t of the uterus were removed in their entirety. T h e distal end of the tube consisted of a small uterus-like structure with a cavity and which microscopically contained smooth a n d skeletal nmscle a n d nerve fibers. T h e tube a n d ovary were n o r m a l microscopically.
CHROMOSOMAL STUDIES A buccal smear was 18 per cent chromatin positive consistent with an X X sex karyotype. Chromosome culture studies were performed according to s t a n d a r d methods. 11 T h e chromosome count was 46 in the 18 cells studied. T w o classes of cells were present; 6 of the 18 cells were XY, and 12 were X X . An a t t e m p t e d culture a n d chromosome analysis of the ovary and skin were unsuccessful. I t was felt at this time that the p a t i e n t was a true h e r m a p h r o d i t e with a complete male external sexual phenotype.
LABORATORY RESULTS An intravenous pyelogram was obtained, which revealed a n o r m a l excretory system. T h e 24 hour u r i n a r y o u t p u t of 17-ketosteroids and pregnanetriol was within normal limits; the values were 0.35 mg. a n d 0.4 rag., respectively.
Brief clinical and laboratory observations
The Journal o[ Pediatrics September 1973
Case Gartler et al. (1962) Overzier (1964) Josso et al. (i965) Brogger and Aegenaes ( 1965 ) Massimo and Vianello ( 1965 ) Segni et al. ( 1965 ) Manuel et al. (1965)
Age when diagnosed (y~.) 2 16 2o
4 2 2 20
Female Female Male
Ambiguous genitals Ambiguous genitals Ambiguous genitals Breast development Monthly urethrorrhagia
Male Female Male
Ambiguous genitals Ambiguous genitals Ambiguous genitals Breast development Ambiguous genitals Ambiguous genitals Skin, pigment mosaicism Ambiguous genitals Breast development Monthly urethrorrhagia
Lejeune et al. (I966) Corey et al. (1967)
Kakati et al. (1971)
DISCUSSION T r u e hermaphroditism is defined as the presence of both ovarian a n d testicular tissue in the same individual. This is usually associated with varying degrees of intersexual differentiation with ambiguous external genitals. Over 200 cases have been described, 2 and in the last 10 years it has been possible to study the sex chromosome complement in some of these cases. These studies have shown that the majority of individuals with true hermaphroditism have the normal female X X sex chromosome complement. I n the review by Brogger a n d Aegenaes 4 in 1965, 28 out of 48 cases were XX, 8 were XY, and 15 had varying degrees of sex chromosome mosaicism, with at least two cell lines, one of them bearing the Y chromosome a n d the other lacking it. Four of these patients had X X / X Y mosaicism. Six additional cases of this particular type of mosaicism have been reported since, not i n c l u d i n g the present report. T h e clinical a n d pathologic data of these cases are described in T a b l e I. T h e X X / X Y mosaicism in some cases was generalized, i.e., found in all tissues examined. However, more frequently the X Y chromosome pattern is very elusive and might easily escape detection. For example, in the case described by Brogger a n d Aege-
naes, 4 the X Y pattern was detected only in the second biopsy of the left gonad. SUMMARY
A 2-year-old phenotypic male was diagnosed as having true hermaphroditism when a left ovary and tube were discovered during routine repair of an i n g u i n a l hernia. Peripheral blood leukocytes showed an X X / X Y sex chromosome complement. REFERENCES
1. Gartler, S. M., Waxman, S. H., and Giblett, E.: An XX/XY human hermaphrodite resulting from double fertilization, Proc. Natl. Acad. Sci. U. S. A. 48" 332, 1962. 2. Overzier, C.: Ein XX/XY hermaphrodit mit einem intratubularen Ei und einem Gonadoblastom (Gonocytom III), Klin. Wochenschr. 42: 1052, 1964. 3. Josso, N., de Grouchy, J., Auvert, J., et al.: True hermaphroditism with XX/XY mosaicism, probably due to double fertilization of the ovum, J. Clin. Endocrinol. Metab. 25: 114, 1965. 4. Brogger, A., and Aegenaes, O.: The human Y chromosome and the etiology of true hermaphroditism with the report of a case with XX/XY sex chromosome mosaicism, Heredltas 53: 231, 1965. 5. Masslmo, L., and Vianello, M. G.: Chromosome studies in two cases of intersexuality, Hum. Chromosome Newsletter 15: 15, 1965. 6. Segni, G., and Grossi-Bianchi, M. L.: Un raro caso di ermafroditismo very di tipo alterno
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con eromosomi XX/XY, Minerva Pediatr. 17: 630, 1965. 7. Manuel, M. A., Allie, A., and Jackson, W. P.: A true hermaphrodite with XX/XY chromosmne mosaicism, S. Afr. Med. J. 39: 411, 1965. 8. Lejuene, J., Berger, R., Rethore, M.-O., Viatatte, J., and Salmon, C.: Sur un cas d'hermaphrodisme XX/XY, Extrait Ann. Genet. 9: 171, 1966.
Elongated short arm of a G-group chromosome associated with similar phenotypic abnormalities in three patients Patricia L. Monteleone, M.D.,* James A. Monteleone, M.D., Donald Rivard, B.S., and Joan A. Grzegocki, B.S., St. Louis, go.
T H E RE have been several reports of a n increase in length of the short arm of an acrocentric chromosome, most of which were unassociated with any phenotypic effect. We have recently studied three males who have small gonads, s/nail phalius, behavioral problems, a n d obesity. I n addition, two of them have hypothyroidism a n d two have gynecomastia. O n e patient was mildly retarded. These patients have been referred for cytogenetic studies with the suspected clinical diagnosis of Klinefelter's syndrome. I n all three patients there was a distinct elongation of the short satellited arm of one of chromosomes n u m b e r 21. From the Department o[ Pediatrics, St. Louis University School of Medicine, and Bidwilt Memorial Research Laboratories, Cardinal Glennon Memorial Hospital [or Children. Presented to Midwest Society [or Pediatric Research, November 3, 1971. ~Address: 1465 S. Grand Ave., St. Louis, Mo. 63104.
Brie[ clinical and laboratory observations
9. Corey, M. J., Miller, J. R., MacLean, J. R., et al.: A case of XX/XY mosaicism, Am. J. Hum. Genet. 19: 378, 1967. 10. Kataki, S., Sharma, T., Udupa, K. N., et al.: A true hermaphrodite with XX/XY mosaicism, Indian J. Med. Res. 59: 104, 1971. 11. Moorhead, P. S., Nowell, P. C., Mellman, W. J., et al.: Chromosome preparations of leukocytes cultured from human peripheral blood, Exp. Cell Res. 20: 613, 1960.
CASE REPORTS Patient 1, a 12-year-old Caucasian boy, had gynecomastia and behavioral problems consisting of inability to make friends at school, difficulty with discipline in the classroom, aggressive behavior, and short attention span. Family history was unrernarkable. He was very obese, in the fiftieth percentile for height, and had gynecomastia (true breast tissue), a small phallus, and extremely small gonads (0.6 x 0.4 cm.). The remainder of the physical examination was within normal limits. Laboratory studies were negative except for plasma thyroxine by column of 2.2 ~g per 100 ml. (normal = 2.9 to 6.4 #g per 100 ml.). All other trophic hormone studies were within normal limits. Intelligence quotient was 85. Patient 2, a 13-year-old Caucasian boy, was referred because of small gonads and gynecomastia. His mother related that he was having difficulty with discipline at school and in relationships with other children. Family history was negative. Intelligence quotient was 90. Physical examination revealed a very obese boy between the fiftieth and seventy-fifth percentiles for height and with a small phallus, very small testes, and gynecomastia (true breast tissue). Serum proteinbound iodine was 5.6 #g per 100 ml. (normal = 4.0 to 8.0 /~g per 100 ml.). Radioactive iodine uptake was 5 per cent at 6 hours and 12 per cent at 24 hours (normal = 7 to 25 per cent at 6 hours and t5 to 40 per cent at 24 hours). After thyrotropin stimulation, radioactive iodine was 25 per cent at 6 hours and 36 per cent at 24 hours. All other trophic hormone studies were within normal limits. Patient 3, a 12-year-old Caucasian boy, was referred for chromosomal studies because of severe behavioral problems. The child would not cooperate in a classroom setting and had a short attention span. On examination, he was found to be obese and to have extremely small gonads