JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
496
NOVEMBER, 1976
Cytogenetic Studies of Three True Hermaphrodites* D. N. SINGH, Ph.D., SABURO HARA, M.D., CHARLES E. McGRUDER, M.D., JOHN T. ASHHURST, M.D., K. DAVIS, A.B. AND E. P. CRUMP, M.D., Departmnents of Pediatrics, Obstetrics and Gynecology and Pathology, Meliarry Medical College, Nashlville, Tennessee
TRUE hermaphroditism is a condition in which an individual has both ovarian and testicular tissue. The phenotypic appearance may be of either sex depending upon the degree of virilization of the genitalia, even though external genitalia may be ambiguous in some cases. From reported cases, one cannot find differences between male and female sex ratio in true hermaphrodites. Hamerton' has tabulated all reported true hermaphrodites to be 84, and in 68 of these cases, the chromosomes have been studied. Only one case of female phenotype has been reported with 46 XY chromosomes.2 Most of the earlier studies on true hermaphrodites have been ascribed sex chromosomes by studying only the chromatin body. This appears to be inadequate in making any definitive conclusion as to the final chromosomal constitution in the light of recent banding and fluorochrome banding techniques. The present study has utilized the current banding techniques on three black true hermaphrodites, of which, two are phenotypically male with 46 XX and one female with 46 XY chromosomal compliments.
inverted and the breast were infantile. Her weight and height measurements fell within the 50 percentile for her age. Her 24-hour urine specimen was found to have 4.7mg. and 2.9mg. of 17-ketosteroids and 1 7-hydroxy-ketosteroid, respectively. Blood electrolytes were normal. Intravenous pyelogram was normal. There was no history of estrogen intake during pregnancy in the mother. Pregnancy and delivery of the child were uneventful. At the age of 14 years, there was no breast development nor onset of menarche. An exploratory laprotamy revealed thickening of the anterior wall of the vagina, representing rudimentary cervical tissue. The uterus appeared to be a streak; the left gonad and fallopian tube could not be located; and the right gonad and fallopian tube appeared rudimentary. The right gonad was removed, which measured 5.5 x 1.5cm. and microscopic examination revealed infantile atrophic testicular tissue. The tubules were lined irregularly with stratified eosinophilic cuboidal cells on a thick basement membrane and diffuse connective tissue.
CASE HISTORY
Fig. 1. Gonadal tissue showing primordial follicles and seminferous tubules.
Case No. 1. A 10 year-old black female was first seen for an enlarged clitoris. Initial physical examination revealed a 25mm. long clitoris. Labia majoras appeared to be partially fused and underdeveloped. There was a small vagina with a blind pouch 8cm. in depth. The uretheral opening was connected with the bladder. There was no uterine body and cervical os palpable. Her nipples were *Supported by U.S. Public Health Service Grant No. 440 from the Health Services and Mental Health
Administration.
.o
At the age of 17 years, she developed a left inguinal hernia and hernioplasty was performed. At surgery, there was a gonadal mass, 2.1 x 5.0cm., located in the left inguinal canal which was excised. On microscopic examination the left gonad consisted of an infantile ovotestes with seminiferous tubules and a diffuse area of fibrosis. The tubules are solid and devoid of lumina while in others the lumena were widely patent. There was a tunica albuguinea and nests of dilated tubules suggestive of epididymis. There is ovarian
Vol. 68, No. 6
True Hermaphrodites
tissue with poorly developed primordial follicles (Fig. 1). Therefore, she had an abdominal testes on the right side and an ovotestes in inguinal canal on the left. A total of 204 metaphase plates were counted at different times from the peripheral blood cultures. Twenty-two had 45 chromosomes; 179 had 46; and the other three cells had respectively, 47, 48 and 92 chromosomes in each. Karyotypic analysis of cells with 45 chromosomes revealed a random loss of C and G group chromosomes. All cells with 46 chromosomes revealed 46 XY sex chromosome compliments (Fig. 2) except one had 46 XX. Cells with 47 and 48 chromosomes revealed XYY and XYYY chromosomes. The Y chromosomes were identified in each case by quinacrine mustard fluorescence banding tech-
presented to the pediatric service complaining of dribbling on urination of several weeks duration. He had had dysuria and hematuria three days prior to admission. He was catheterized and treated for urinary tract infection. On physical examination, the proband appeared well developed and showed normal height and weight for his chronological age. There was some tenderness over his lower abdomen and a distended urinary bladder was palpated. No other
Fig. 3. Single Y-Body in the buccal
Fig. 2. Q-banding Karyotype showing 46, XY chromosome compliments.
nique. Barr body count from buccal smear revealed 2% positive on the right side and negative on the left side. Y-body count from the buccal smear revealed 10% positive on left and 6.5% positive on the right side for single Y-body (Fig. 3). One percent of cells showed two Ybodies on both sides. Eleven percent of neutrophils also were positive for single Y-body. Chromosomal studies on peripheral blood of the mother revealed a normal 46 XX chromosome complement using Q banding techniques. Buccal smear was positive for one X-body and negative for Y-body. Family history was non-contributory. Dermatoglyphic study revealed seven ulnar loops and three whorls with a total ridge count of 180. The atd angles were 360 and 330 on left and right, respectively. There was no pattern on the thenar and hypothenar areas of both palms. Flexian creases were normal on both hands, however, the 5th fingers on both hands were short. The main line formulation is 7(9).7.5'.4.13 and 11.9.7.5'.13 on the left and right palms, respectively. There were both ulnar and radial loops present in the 4th interdigital area of left palm and a radial loop in the 3rd interdigital area of the right palm. Case No. 2 (K.H.). A six year-old black male
497
mucosa
cell.
abdominal organs were palpable. There was a bifid scrotal sac and the left gonad was smaller and firmer in consistency than that on the right side. There was hypospadias with the meatal opening at the dorsal root of the phallus. The relaxed phallus measured 4.5cm in length and 4cm. in circumference. A cystourethragram demonstrated a narrowing of the distal anterior urethra and an excretory urogram revealed the right pyelocaliectasia. 17 keto-steroids and 17 hydroxyketo-steroids were within normal limits for his age. The other physical findings were within normal limits. The patient was a product of a normal pregnancy and uneventful delivery. Microsections of the right testicular tissue revealed well developed seminiferous tubules and hypercellular interstitial tissue. Most of the tubules were without lumens. The specimen was interpreted as infantile testicular tissue. The left side testis showed up to five primordial follicles beneath a fibrous connective tissue capsule and scattered in a spindle cell stroma which also contained several infantile seminiferous tubules. This was interpreted as consistent with ovotestis. Thus, the proband was found to have ovotestis on left side and testes on the right. Chromosomal studies from the lymphocytes cultured cells revealed a normal set of autosomes with normal female sex chromosome compliments. In repeat preparations of the peripheral blood culture, chromosomes were counted in 124 cells revealing a 46 XX chromosome. Quinacrine banding techniques of the chromosomes revealed no trace of Y chromosomes, either in a translocated condition or separately. Barr body count from the buccal smear showed 12% positive on the left and 14% positive on the right side for one Barr body. No Y-body was found in either buccal
498
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
smear or blood smear. The mother and two siblings were found to have normal chromosomal compliments. Dermatoglyphic study revealed nine ulnar loops and one whorl with a total ridge count of 113. The atd angles were 460 and 390 on left and right palm, respectively. There were normal fiexion creases on both palms. The fifth finger on the right hand was shorter. No patterns were evident on the thenar and hypothenar areas on either palm. The main line formulation was 9.7.5'.3.13 and 11.9.7.4.13 on left and right palm, respectively. Both hallucal areas had whorl patterns. Case No. 3 (F.B.). A five year-old black male was seen for ambigous genetalia. Physical examination revealed that his height and weight fell within the 50 percentile for his age. Inspection and auscultation revealed no abnormal findings in the lungs and heart. There was some tenderness over his lower abdomen. There was hypospadias with the external urinary meatal opening at the dorsal root of the phallus. 17 keto-steroids, 17 hydroxy-keto-steroids, F.S.H. and blood electrolytes were all within normal limits for his age. Bilateral testicular biopsies were performed and three specimens were collected. Microscopic examination of specimen number one, belonging to the lower uterine segment, revealed a rudimentary cervix consisting primarily of endocervix. Microscopic examination of the second specimen revealed ovotestes, there being a clear cut nodular mass of immature seminiferous tubules abutting on ovarian tissue containing ova and follicles. Microscopic examination revealed that the third specimen consisted of a rudimentary corpus uteri, a miniature fallopian tube and an immature ovary containing ova. The final pathological diagnosis was ovotestis on the right, fallopian tube and ovary on the left, and immature rudimentary type uterus and cervix. Cytogenetic study. Chromosome analysis, utilizing peripheral blood cultured cells, revealed 46 XX chromosome constitution. Of the chromosomes, counted in over 100 metaphase cells, 97 showed 46 chromosomes, 2 showed 45 and one showed 44. There was a random loss of chromosomes in cell with 44 and 45 chromosomes. Quinacrine fluorescence banding technique confirms 46 XX karyotypes with complete absence of Y chromosome. Sixteen percent of cells from the buccal smear showed positive for Barr body on both sides. Dermatoglyphic study revealed eight ulnar loops and two whorls with a total ridge count of 129. The atd angles were 45° and 40° on left and right palm, respectively. There were bilateral normal flexion creases and no pattern on the thenar or hypothenar areas. The fifth finger was short on both hands. The main line formulation was 9.7.5'.3.13 and 11.7.9.4.13 on left and right
palm, respectively.
NOVEMBER, 1976
COMMENTS
Merrill and Ramsey classified true hermaphroditism into three groups according to the type of gonad present in the individual.3 Twenty percent of the cases are lateral, in which there is a testis on one side and an ovary on the other; 36% unilateral, with an ovotestis on one side and an ovary or testis on the other; 23% bilateral, with an ovotestis on both sides; and 21 % unknown. More cases of unilateral type have been reported than the other two types combined. Of the present two male true hermaphrodites, both fall within the unilateral type. In one case there was an ovotestis on one side and an ovary on the other side and in the other case a testis. The third case of a phenotypic female with a XY karyotype is another rare unilateral type of true hermaphrodite. Lozzio and his associates have reported a female with ovotestis on side and a testis on other side with a XY karyotype.2 The present case has ovotestis on one side and the testis on other side. A number of hypotheses have been put forth by different scientists regarding the cytogenetic origin of the true hermaphrodite. Gartler and others are of the opinion that the XX/XY mosaicism gives rise to both types of gonads in an individual.4 7 One suggested explanation of the anomaly is that all true hermaphroditism, with an apparent XX sex chromosome constitution, are undetected mosaics in which one of the other cell lines has a Y chromosome. Similarly, with an XY karyotype, the true hermaphrodite may have an undetected mosaicism of an XX cell line. Brogger and Aaefenaes did not find XX/XY mosaicism in lymphocytes, bone marrow and skin cultured cells but found mosaicism in cultured gonadal cells.7 The low percentage of XX cell line in the XY female hermaphrodite in this present study may be a case of mosaicism of XX/XY in gonadal cells lines. We did not find a XY cell line in our other two cases with XX karyotypes. In the XX male case, XY line might have segregated in the early stage of development and localized in
True Hermaphrodites
Vol. 68, No. 6
gonadal tissue, one with mosaicism of XX/XY and other with only XY or XX which gave rise to ovotestis on one side and ovary or testis on the other side. Fergusson-Smith has hypothesized a crossover of the male determining gene on the short arm of the Y chromosome onto the short arm of the X chromosome during the first division of spermatogenesis.8 The fertilization of the ovum by a sperm carryin, an X with a "male determining" allel would give a zygote with XX" chromosomes. Due to the random inactivation of the X or the XI sex chromosomes, different types of gonadal tissue would develop during their activation period. Variation in the proportion of the two cell lines will give rise to a range of phenotypes, including persons with ovaries, ovotestis, or testes corresponding to normal female, true hermaphrodite and male phenotype. Dermatoglyphic study in the present three cases, revealed a high incidence of ulnar loops and short fifth fingers. The mean total ridge counts were found significantly higher in males than in females.9'10 In our study, a lower total finger ridge count was found in the two phenotypic males with 46 XX chromosomes than in the female with 46 XY compliments. This suggests that the total finger ridge count may have been influenced by the sex chromosome compliments, rather than the phenotypic sex. SUMMARY
Three black true hermaphrodites were reported. Two were phenotypically male with 46 XX chromosomal compliments in lymphocytes cells. The third case was phenotypically female with 46 XY chromosomes. One of the males was found to have an ovotestis on the right and an ovary and a fallopian tube on the left. The other male had an ovotestis on the left and a testis on the right side. The female had infantile atrophic abdominal testicular tissue on the right and an ovotestis in the inguinal canal on the left. Dermatoglyphic study revealed a high incidence of ulnar loops combined with whorls and short fifth fingers in all
499
three cases. Total ridge count was higher in the female with 46 XY karyotypes than males with 46 XX. This may suggest that a total finger ridge count is influenced by the chromosomal sex rather than the phenotypic sex. ACKNOWLEDGMENT The authors are thankful to Mr. Martin V. Sherrill for microphotography and Miss Wilma J. Lynch for secretarial help in the preparation of this manuscript. LITERATURE CITED
1. HAMERTON, J. L. Human Cytogenetics, Part II. New York, Academic Press, 1971. 2. Lozzio, C. B. and R. MORENO, C. SONNENSCHEIN, M. E. FERREYA, and J. L. VALENCIA. Chromosome Studies in Human Sexual Abnormalities. Hum. Chrom. News Letter, 18: 15-20, 1966. 3. MERRILL, J. A. and J. L. RAMSEY. True Hermaphroditism: Report of a Case and Review of the Literature. J. Ob-Gyn., 22: 505-512, 1963. 4. GARTLER, S. M. and S. H. WAXMAN and E. GIBLETT. An XX/XY Human Hermaphrodite Resulting from Double Fertilization. Proc. Natl. Acad. Sci., USA, 48:332-335, 1962. 5. Josso, N. and J. DEGROUCHY, J. AUVERT, C. NEZELOF, M. E. JAYLE, J. MOULLEE, J. FRIZEL, A. DECASAUBON, and M. LAMY. True Hermaphroditism with XX/XY Mosaicism, Probably due to Double Fertilization of the Ovum. J. Clin. Endocr. Met., 25:114126, 1965. 6. BAIN, A. D. and J. S. SCOTT. Mixed Gonadal Dysgenesis with XX/XY Mosaicism. The Evidence for the Occurrence of Fertilization by Two Spermatozoa in Man. Lancet, 1: 1035-1039, 1965. 7. BROGGER, A. and 0. AAFENAES. The Human Y Chromosome and the Etiology of True Hermaphroditism with the Report of a Case with XX/XY Chromosome Mosaicism. Hereditas, 53:231-246, 1965. 8. FERGUSSON-SMITH, M. A. X-Y Chromosomal Interchange in the Aetiology of True Hermaphroditism and of XX Klinefelter's Syndrome. Lancet, 2:475-576, 1966. 9. HOLT, S. B. The Genetics of Dermal Ridges. Springfield, Illinois, Thomas Press, 1968. 10. Hsu, L. Y. and J. M. KERR, P. WORKMAN, and K. HIRSCHHORN. Total Finger Ridge Count and 45 X Mosaicism with and without Y Chromosome. Am. J. Human. Genet., 24(6):21a, 1972.
496
NOVEMBER, 1976
Cytogenetic Studies of Three True Hermaphrodites* D. N. SINGH, Ph.D., SABURO HARA, M.D., CHARLES E. McGRUDER, M.D., JOHN T. ASHHURST, M.D., K. DAVIS, A.B. AND E. P. CRUMP, M.D., Departmnents of Pediatrics, Obstetrics and Gynecology and Pathology, Meliarry Medical College, Nashlville, Tennessee
TRUE hermaphroditism is a condition in which an individual has both ovarian and testicular tissue. The phenotypic appearance may be of either sex depending upon the degree of virilization of the genitalia, even though external genitalia may be ambiguous in some cases. From reported cases, one cannot find differences between male and female sex ratio in true hermaphrodites. Hamerton' has tabulated all reported true hermaphrodites to be 84, and in 68 of these cases, the chromosomes have been studied. Only one case of female phenotype has been reported with 46 XY chromosomes.2 Most of the earlier studies on true hermaphrodites have been ascribed sex chromosomes by studying only the chromatin body. This appears to be inadequate in making any definitive conclusion as to the final chromosomal constitution in the light of recent banding and fluorochrome banding techniques. The present study has utilized the current banding techniques on three black true hermaphrodites, of which, two are phenotypically male with 46 XX and one female with 46 XY chromosomal compliments.
inverted and the breast were infantile. Her weight and height measurements fell within the 50 percentile for her age. Her 24-hour urine specimen was found to have 4.7mg. and 2.9mg. of 17-ketosteroids and 1 7-hydroxy-ketosteroid, respectively. Blood electrolytes were normal. Intravenous pyelogram was normal. There was no history of estrogen intake during pregnancy in the mother. Pregnancy and delivery of the child were uneventful. At the age of 14 years, there was no breast development nor onset of menarche. An exploratory laprotamy revealed thickening of the anterior wall of the vagina, representing rudimentary cervical tissue. The uterus appeared to be a streak; the left gonad and fallopian tube could not be located; and the right gonad and fallopian tube appeared rudimentary. The right gonad was removed, which measured 5.5 x 1.5cm. and microscopic examination revealed infantile atrophic testicular tissue. The tubules were lined irregularly with stratified eosinophilic cuboidal cells on a thick basement membrane and diffuse connective tissue.
CASE HISTORY
Fig. 1. Gonadal tissue showing primordial follicles and seminferous tubules.
Case No. 1. A 10 year-old black female was first seen for an enlarged clitoris. Initial physical examination revealed a 25mm. long clitoris. Labia majoras appeared to be partially fused and underdeveloped. There was a small vagina with a blind pouch 8cm. in depth. The uretheral opening was connected with the bladder. There was no uterine body and cervical os palpable. Her nipples were *Supported by U.S. Public Health Service Grant No. 440 from the Health Services and Mental Health
Administration.
.o
At the age of 17 years, she developed a left inguinal hernia and hernioplasty was performed. At surgery, there was a gonadal mass, 2.1 x 5.0cm., located in the left inguinal canal which was excised. On microscopic examination the left gonad consisted of an infantile ovotestes with seminiferous tubules and a diffuse area of fibrosis. The tubules are solid and devoid of lumina while in others the lumena were widely patent. There was a tunica albuguinea and nests of dilated tubules suggestive of epididymis. There is ovarian
Vol. 68, No. 6
True Hermaphrodites
tissue with poorly developed primordial follicles (Fig. 1). Therefore, she had an abdominal testes on the right side and an ovotestes in inguinal canal on the left. A total of 204 metaphase plates were counted at different times from the peripheral blood cultures. Twenty-two had 45 chromosomes; 179 had 46; and the other three cells had respectively, 47, 48 and 92 chromosomes in each. Karyotypic analysis of cells with 45 chromosomes revealed a random loss of C and G group chromosomes. All cells with 46 chromosomes revealed 46 XY sex chromosome compliments (Fig. 2) except one had 46 XX. Cells with 47 and 48 chromosomes revealed XYY and XYYY chromosomes. The Y chromosomes were identified in each case by quinacrine mustard fluorescence banding tech-
presented to the pediatric service complaining of dribbling on urination of several weeks duration. He had had dysuria and hematuria three days prior to admission. He was catheterized and treated for urinary tract infection. On physical examination, the proband appeared well developed and showed normal height and weight for his chronological age. There was some tenderness over his lower abdomen and a distended urinary bladder was palpated. No other
Fig. 3. Single Y-Body in the buccal
Fig. 2. Q-banding Karyotype showing 46, XY chromosome compliments.
nique. Barr body count from buccal smear revealed 2% positive on the right side and negative on the left side. Y-body count from the buccal smear revealed 10% positive on left and 6.5% positive on the right side for single Y-body (Fig. 3). One percent of cells showed two Ybodies on both sides. Eleven percent of neutrophils also were positive for single Y-body. Chromosomal studies on peripheral blood of the mother revealed a normal 46 XX chromosome complement using Q banding techniques. Buccal smear was positive for one X-body and negative for Y-body. Family history was non-contributory. Dermatoglyphic study revealed seven ulnar loops and three whorls with a total ridge count of 180. The atd angles were 360 and 330 on left and right, respectively. There was no pattern on the thenar and hypothenar areas of both palms. Flexian creases were normal on both hands, however, the 5th fingers on both hands were short. The main line formulation is 7(9).7.5'.4.13 and 11.9.7.5'.13 on the left and right palms, respectively. There were both ulnar and radial loops present in the 4th interdigital area of left palm and a radial loop in the 3rd interdigital area of the right palm. Case No. 2 (K.H.). A six year-old black male
497
mucosa
cell.
abdominal organs were palpable. There was a bifid scrotal sac and the left gonad was smaller and firmer in consistency than that on the right side. There was hypospadias with the meatal opening at the dorsal root of the phallus. The relaxed phallus measured 4.5cm in length and 4cm. in circumference. A cystourethragram demonstrated a narrowing of the distal anterior urethra and an excretory urogram revealed the right pyelocaliectasia. 17 keto-steroids and 17 hydroxyketo-steroids were within normal limits for his age. The other physical findings were within normal limits. The patient was a product of a normal pregnancy and uneventful delivery. Microsections of the right testicular tissue revealed well developed seminiferous tubules and hypercellular interstitial tissue. Most of the tubules were without lumens. The specimen was interpreted as infantile testicular tissue. The left side testis showed up to five primordial follicles beneath a fibrous connective tissue capsule and scattered in a spindle cell stroma which also contained several infantile seminiferous tubules. This was interpreted as consistent with ovotestis. Thus, the proband was found to have ovotestis on left side and testes on the right. Chromosomal studies from the lymphocytes cultured cells revealed a normal set of autosomes with normal female sex chromosome compliments. In repeat preparations of the peripheral blood culture, chromosomes were counted in 124 cells revealing a 46 XX chromosome. Quinacrine banding techniques of the chromosomes revealed no trace of Y chromosomes, either in a translocated condition or separately. Barr body count from the buccal smear showed 12% positive on the left and 14% positive on the right side for one Barr body. No Y-body was found in either buccal
498
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
smear or blood smear. The mother and two siblings were found to have normal chromosomal compliments. Dermatoglyphic study revealed nine ulnar loops and one whorl with a total ridge count of 113. The atd angles were 460 and 390 on left and right palm, respectively. There were normal fiexion creases on both palms. The fifth finger on the right hand was shorter. No patterns were evident on the thenar and hypothenar areas on either palm. The main line formulation was 9.7.5'.3.13 and 11.9.7.4.13 on left and right palm, respectively. Both hallucal areas had whorl patterns. Case No. 3 (F.B.). A five year-old black male was seen for ambigous genetalia. Physical examination revealed that his height and weight fell within the 50 percentile for his age. Inspection and auscultation revealed no abnormal findings in the lungs and heart. There was some tenderness over his lower abdomen. There was hypospadias with the external urinary meatal opening at the dorsal root of the phallus. 17 keto-steroids, 17 hydroxy-keto-steroids, F.S.H. and blood electrolytes were all within normal limits for his age. Bilateral testicular biopsies were performed and three specimens were collected. Microscopic examination of specimen number one, belonging to the lower uterine segment, revealed a rudimentary cervix consisting primarily of endocervix. Microscopic examination of the second specimen revealed ovotestes, there being a clear cut nodular mass of immature seminiferous tubules abutting on ovarian tissue containing ova and follicles. Microscopic examination revealed that the third specimen consisted of a rudimentary corpus uteri, a miniature fallopian tube and an immature ovary containing ova. The final pathological diagnosis was ovotestis on the right, fallopian tube and ovary on the left, and immature rudimentary type uterus and cervix. Cytogenetic study. Chromosome analysis, utilizing peripheral blood cultured cells, revealed 46 XX chromosome constitution. Of the chromosomes, counted in over 100 metaphase cells, 97 showed 46 chromosomes, 2 showed 45 and one showed 44. There was a random loss of chromosomes in cell with 44 and 45 chromosomes. Quinacrine fluorescence banding technique confirms 46 XX karyotypes with complete absence of Y chromosome. Sixteen percent of cells from the buccal smear showed positive for Barr body on both sides. Dermatoglyphic study revealed eight ulnar loops and two whorls with a total ridge count of 129. The atd angles were 45° and 40° on left and right palm, respectively. There were bilateral normal flexion creases and no pattern on the thenar or hypothenar areas. The fifth finger was short on both hands. The main line formulation was 9.7.5'.3.13 and 11.7.9.4.13 on left and right
palm, respectively.
NOVEMBER, 1976
COMMENTS
Merrill and Ramsey classified true hermaphroditism into three groups according to the type of gonad present in the individual.3 Twenty percent of the cases are lateral, in which there is a testis on one side and an ovary on the other; 36% unilateral, with an ovotestis on one side and an ovary or testis on the other; 23% bilateral, with an ovotestis on both sides; and 21 % unknown. More cases of unilateral type have been reported than the other two types combined. Of the present two male true hermaphrodites, both fall within the unilateral type. In one case there was an ovotestis on one side and an ovary on the other side and in the other case a testis. The third case of a phenotypic female with a XY karyotype is another rare unilateral type of true hermaphrodite. Lozzio and his associates have reported a female with ovotestis on side and a testis on other side with a XY karyotype.2 The present case has ovotestis on one side and the testis on other side. A number of hypotheses have been put forth by different scientists regarding the cytogenetic origin of the true hermaphrodite. Gartler and others are of the opinion that the XX/XY mosaicism gives rise to both types of gonads in an individual.4 7 One suggested explanation of the anomaly is that all true hermaphroditism, with an apparent XX sex chromosome constitution, are undetected mosaics in which one of the other cell lines has a Y chromosome. Similarly, with an XY karyotype, the true hermaphrodite may have an undetected mosaicism of an XX cell line. Brogger and Aaefenaes did not find XX/XY mosaicism in lymphocytes, bone marrow and skin cultured cells but found mosaicism in cultured gonadal cells.7 The low percentage of XX cell line in the XY female hermaphrodite in this present study may be a case of mosaicism of XX/XY in gonadal cells lines. We did not find a XY cell line in our other two cases with XX karyotypes. In the XX male case, XY line might have segregated in the early stage of development and localized in
True Hermaphrodites
Vol. 68, No. 6
gonadal tissue, one with mosaicism of XX/XY and other with only XY or XX which gave rise to ovotestis on one side and ovary or testis on the other side. Fergusson-Smith has hypothesized a crossover of the male determining gene on the short arm of the Y chromosome onto the short arm of the X chromosome during the first division of spermatogenesis.8 The fertilization of the ovum by a sperm carryin, an X with a "male determining" allel would give a zygote with XX" chromosomes. Due to the random inactivation of the X or the XI sex chromosomes, different types of gonadal tissue would develop during their activation period. Variation in the proportion of the two cell lines will give rise to a range of phenotypes, including persons with ovaries, ovotestis, or testes corresponding to normal female, true hermaphrodite and male phenotype. Dermatoglyphic study in the present three cases, revealed a high incidence of ulnar loops and short fifth fingers. The mean total ridge counts were found significantly higher in males than in females.9'10 In our study, a lower total finger ridge count was found in the two phenotypic males with 46 XX chromosomes than in the female with 46 XY compliments. This suggests that the total finger ridge count may have been influenced by the sex chromosome compliments, rather than the phenotypic sex. SUMMARY
Three black true hermaphrodites were reported. Two were phenotypically male with 46 XX chromosomal compliments in lymphocytes cells. The third case was phenotypically female with 46 XY chromosomes. One of the males was found to have an ovotestis on the right and an ovary and a fallopian tube on the left. The other male had an ovotestis on the left and a testis on the right side. The female had infantile atrophic abdominal testicular tissue on the right and an ovotestis in the inguinal canal on the left. Dermatoglyphic study revealed a high incidence of ulnar loops combined with whorls and short fifth fingers in all
499
three cases. Total ridge count was higher in the female with 46 XY karyotypes than males with 46 XX. This may suggest that a total finger ridge count is influenced by the chromosomal sex rather than the phenotypic sex. ACKNOWLEDGMENT The authors are thankful to Mr. Martin V. Sherrill for microphotography and Miss Wilma J. Lynch for secretarial help in the preparation of this manuscript. LITERATURE CITED
1. HAMERTON, J. L. Human Cytogenetics, Part II. New York, Academic Press, 1971. 2. Lozzio, C. B. and R. MORENO, C. SONNENSCHEIN, M. E. FERREYA, and J. L. VALENCIA. Chromosome Studies in Human Sexual Abnormalities. Hum. Chrom. News Letter, 18: 15-20, 1966. 3. MERRILL, J. A. and J. L. RAMSEY. True Hermaphroditism: Report of a Case and Review of the Literature. J. Ob-Gyn., 22: 505-512, 1963. 4. GARTLER, S. M. and S. H. WAXMAN and E. GIBLETT. An XX/XY Human Hermaphrodite Resulting from Double Fertilization. Proc. Natl. Acad. Sci., USA, 48:332-335, 1962. 5. Josso, N. and J. DEGROUCHY, J. AUVERT, C. NEZELOF, M. E. JAYLE, J. MOULLEE, J. FRIZEL, A. DECASAUBON, and M. LAMY. True Hermaphroditism with XX/XY Mosaicism, Probably due to Double Fertilization of the Ovum. J. Clin. Endocr. Met., 25:114126, 1965. 6. BAIN, A. D. and J. S. SCOTT. Mixed Gonadal Dysgenesis with XX/XY Mosaicism. The Evidence for the Occurrence of Fertilization by Two Spermatozoa in Man. Lancet, 1: 1035-1039, 1965. 7. BROGGER, A. and 0. AAFENAES. The Human Y Chromosome and the Etiology of True Hermaphroditism with the Report of a Case with XX/XY Chromosome Mosaicism. Hereditas, 53:231-246, 1965. 8. FERGUSSON-SMITH, M. A. X-Y Chromosomal Interchange in the Aetiology of True Hermaphroditism and of XX Klinefelter's Syndrome. Lancet, 2:475-576, 1966. 9. HOLT, S. B. The Genetics of Dermal Ridges. Springfield, Illinois, Thomas Press, 1968. 10. Hsu, L. Y. and J. M. KERR, P. WORKMAN, and K. HIRSCHHORN. Total Finger Ridge Count and 45 X Mosaicism with and without Y Chromosome. Am. J. Human. Genet., 24(6):21a, 1972.
