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Chromosome Studies in a Chromatin-Negative, XY True Hermaphrodite
Tu.s JorJK,L\L OP UROLOGY Copyright 1I':) 1066 by The ·Williams & \Viikins Co.
KY TRUE
STUDIES I:1\7 A HERl'vfAPHRODITE
WELLINGTON HUNG, CECIL B. JACOBSON, l:-L JOACHIM WIGGER JUDSON G. RANDOLPH
AND
Prom the Departments of n11(1(:n.ru11m,11. Patholo(;y and Children's H ospitol of the Colmnbia and lhe Departrnenis of Pediatrics and F:forgery, Washington Uni1H;rsil11 School of Jk[ ed1:cirw 1 u.,.n,1u11.un D, C.
With '1nYrnnnPrn '·'""t-n,m,o.•.u on diagnosis in the newborn, an increasing number of children ,Yith the intersex phenomenon are recognized at an age, This fact bas the great advantage of m.inirnizing >OV>n>HV,-L•om a,nd psychological pres•• sures which can derive from this group of anom., alies and allows irnrnediate alld accurate sex '"''"'~,L.uucc.uu when proper measures are c;:1rried ouL chromosome studies have been of i.1nrnense help in unraveling this particular group of anomalies, Of the various hermaphrodite synthe t,rue ..... ,.. -,.·-· so designated because of the presence of ovarian and testicular tissue in the 3arne child, is of speeial interest be·· of the µu·~~.w1uc of either a, chronw,tinor chrorn1iti1n1egative (male) Thirty-two case8 of true hermaphroditism have been studied 0 ~,-,rr1ma to sex chromatir.t chrornosome constitution. Of
Accepted for publication November 3, 1965, bv Children's Bureatt Grant of Health, Education and Wel· fa.18, ' SohvaL A. R,: Chrornosomes and sex chroma .. tin in normal and anomafous sexnal developmenL Rev., 43: 306 356, 196:3, LL. and Green. 0. C.: Chromosomal eount in a true hermaphro.dite. J Pecliat., 63: 3::53-335 1H6B. 'Rosenberg, H. S., Clayton, G, W. and Hsu, T. C,: .Familial true hermaphrodisrn, .L Clin. EndocrinoL, 23: 203-206, H/63, ,, R. U., Bregman, E. T., Cushner, F. ]VL: Chromosome analvsis, clinical and endocrine studies a Um!., 89: 47.5-4S2, 1963. W., Everlein, W Briebart, S., P. S, and Mellman, J .. Chromoof multiple tissues from a true hersoma! 1naphroclitc. J. Clin EndocrinoL, 24: 467-469, 1
of
1\)()4 6 Blank. E., Emery, J. L, Dewhurst,
R. B., Bishop, .A.. M., .J. and Bond, J. H .. Chromosome mosaicism in a hermaphrodite. Brit. l\IecL L 2: 1964. D., Mercer, R. D. and McCnllagh,
It is the purpose of our paper i:,ro pr·esent cLromati:n-negative true wi{b XY chromosome constitution who had D assignment contrary to the sex chromatin tern. and sex chromosomal constitution CASE REPORT
R. B., at one week of age cattse of ambiguous external tient was delivered at 40 weeks'
intersex, On physical examination R. B. ·was noted ts:, have ambiguous external phallus measured 2.215 majora were enlarged and sirnulatecl serotmn::;. A urogenital sinus was present, cm. mass was palpable in the righ ,, No niass was palpable on the left. amination a midline structure uterus was palpable. An excretory urogram show1:,d a nonmd Retrograde injection of the ui,,,1,,u,,,u sinus onstrated a nonnal sized in addition a, normal sized bladder, The buccal snimcr consistently chromatir1-negative. No ''drurn,, sticks" were found in on repeated smears of blood Urinary excretion of 17-ketosteroids was 0.6 0.7 mg. per 24 hours on 2 determinations. 17-hydroxycorticosteroid and p,,,;,:,,,.,u,n., tions were 0.4 and 0.2 mg. per 24 . Other studies inch1ding count, urinalysis and blood within normal limits. vv11en the child was 20 K P Tn1e hermaphroditism: \vith chromosomal a1rnlvsis. Quart.,30:207, l963.
565
·
566
HUNG AND ASS00IA'£ES
laparotomy was undertaken through a Pfannenstiel incision (fig. 2). On the left side of the pelvis a fallopian tube was found and underneath it a gonad measuring 1.5 by 0.5 cm. The gonad was smooth, pale yellow in color and slightly lobulated. The fallopian tube arose from a normal-appearing infant's uterus. On the right side a firm white structure resembling the vas deferens was present, at the end of which, within the confines of the abdomen, a testicular-like structure was found. In contrast to the other gonad, this one was oblong in shape and measured 2 by 2 by 1 cm. Separate biopsies were taken from each gonad. Biopsy of the right gonad revealed testicular tissue composed of tubules ranging in diameter from 30 to 65 microns with an average of 48 microns (fig. 3, A). Most of the tubules contained 2 to 3 layers of pre-Sertoli cells with oval nuclei. Spermatogonia were present in ahnost all of the tubules in a basal position. A few mitoses were noted. The basement membranes and the peritubular sheaths of fibrous tissue were thin. The interstitial tissue consisted of round to oval mesenchymal cells; no sex chromatin bodies were present in these cells. Embedded in the stroma were numerous Leydig cells, usually in clumps. In the area subjacent to the tunica albuginea the tubules were densely packed and there was little interstitial stroma. Some tubules formed structures vaguely reminiscent of coronae radiatae. Other tubules contained very large spermatogonia approaching the appearance of primary spermatocytes or even oogonia. Embedded in the whorly connective tissue of the thick tunica were primordial follicles with large oogonia surrounded by flattened pregranulosa cells.
FIG. l. Photograph of patient's external genitalia
on admission.
FIG. 2. Operati':e findings ~' uterus. B, right vas deferens. C, right ovotest1s. D, left ovary. E, left fallopian tube.
Histological examination of the left gonad showed the presence of only ovarian tissue (fig. 3, B). Primordial follicles were present in large numbers separated by scant stroma. The stromal cells did not contain any sex chromatin bodies. A decision was made to raise the infant as a girl. This selection was based on both the anatomy of the external genitalia and the morphology of the gonads. 8- 1°Complete clitorectomy, including bilateral dissection of the corpora cavernosa was carried out when the child was 1 month old. Reconstruction of the mons veneris and enlargement of the vaginal fourchette were performed concomitantly. The patient was readmitted to the hospital at 7 months of age because of a right inguinal hernia. A standard right inguinal herniorrhaphy was carried out. Small amounts of skin, fascia, muscle and peritoneum were obtained for chromosomal and histological studies. When the hernial sac ,vas opened, a gonad was found which again had the gross appearance of a testicle. A wedge biopsy was taken for chromosomal and histological studies. Chromosomes were studied in cells derived from cultures of leukocytes in the peripheral blood, using a modification of the method of 8 Wilkins, L.: Abnormalities of sex differentiation. Classification, diagnosis, selection of gender of rearmg and treatment. Pediatrics. 26: 846-8.57 1960. ' 9 Wilkins, L.: Embryonic sex differentiation controlling factor~ and abnormalities, diagnosi~ and treatment. Chn. Proc. Child. Hosp. 20: 1-18 ' ' 1964. 10 Randolph, J.: Surgical aspects of intersex, Clin. Proc. Child. Hosp., 20: 33, 1964.
CHROMOSOME STUDIJ~S IN A HERMAPHRODITE
wu11:i,s:-;and
of right ovotestis shows whorly stroma of tunica, serniniferous tubules X 200. photomicrograph of left ovary with large number primordial seant strcmtn except for area of ovarian stroma in center. H & E XlOO.
568
HUNG AND ASSOCIATES
FIG. 4. Patient's karyotype showing 46 chromosomes and XY sex chromosome constitution. Moorhead and associates11 adopted to the form of a kit* by Jacobson and Teleford. 12 The following modified technique of Hayflick and Moorhead13 for culturing tissues has been used by one of us (C. B. J.). Tissue specimens were collected in sterile Hanks buffered saline solution (BSS) and minced into a fine cellular suspension. It was found that lymph node, spleen, liver, thym.us, kidney and gonad could be inoculated into reconstituted chromosome culture medium containing phytohemagglutinin. Other tissues were best grown without phytohemagglutinin. All reticulo-endothelial tissues gave satisfactory mitotic response after 3 days of culture. Other tissues were best sacrificed 8 to 16 hours following media change. Colcemide (Ciba) exposure was best at 8 to 12 hours. The cultures were then
* T.C. Chromosome Culture Kit, Difeo Laboratories, Detroit, Michigan. 11 Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M. and Hungerford, D. A.: Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res., 20: 613, 1960. 12 Jacobson, C. B. and Teleford, I. R.: Human cytogenetic techniques using peripheral blood culture. Proc. Amer. Inst. Biol. Science, August
1962. 13 Hayflick, L. and Moorhead, P. S.: The serial cultivation of human diploid cells strains. Exp. Cell Res., 25: 585, 1961.
transferred to conical centrifuge tubes, washed twice in Hanks BSS and treated with 20 per cent hypotonic Hanks BSS for 20 minutes. Cold methanol:acetic acid (3:1) was used for fixation. Slides were then prepared and stained with 10 per cent Giemsa. A minimum of 50 mitotic figures in metaphase was studied. Chromosomal analysis of the peripheral leukocytes as performed during both hospitalizations: The chromosome number of this patient was 46 with an XY sex chromosome constitution (fig. 4). This was the same in the leukocytes as well as in the cultures obtained from skin, fascia, muscle, peritoneum and right gonad. No evidence of sex chrorn.osome n1.osaicism was detected. All of the tissues lacked a chromatin-positive body. DISCUSSION
The histopathologic findings of the gonadal biopsies leave no doubt that our patient is a true hermaphrodite. The chromosomal studies of the four previously reported chromatin-negative true hermaphrodites are summarized in the table. The patient described by Hirschhorn and associates had gonadal biopsies which were compatible with but not conclusive for true hermaphroditism. 14 14 Hirschhorn, K., Decker, W. H. and Cooper, H. L.: Human intersex with chromosome rnosa-
CHROMOSOME STUDIES IN A HEHAIAPHRODITE
Correlatfon between se:;; chromosome wnstilul1.on and tissue sow ce of studied cells in cnnrrrw.,:r.n -·ru,iu.11:1,•w true hermaphrodites*
TABLE.
Ses Chromo.sornes
Authot
Tissue Source
(}nunback and associn,tes 15 Sandberg u.nd
XY
Marrow
associates" lvfiller and asso-
XY /XO
LeL1kocytes
X:{ XY/XO XY
Skin. marrow
Skin
eiates17
Hirschhorn and associates 14 LonsdalP and assoc-iates 7 Present case
LeLtkocytes
Leukocytes, skin, muscle, fascia, peritoneum, right gonad
''' Modified from Solwal. 1
It nn'to•wr,P1".l-'I chrorl'.J0S0IJ18 rnosaicisrn was not detected in our patient. All six tissue showed a consistent cvs,c,1·,,ou1G pattern of 1+6 chromosomes whh a sex chromosome com/JHcrnl\,1.Ll, of XY. 1Vhile it is true that certain biochemical, radioand physical studies allow one to make an diagnosis in cases of infants with genitalia, sufficient doubt remains in many instances which makes laparotomy and gonadal Becaust, of oecafional development of srnall cortical areas of '.ill ovotcstic we feel that bi-
unless the very small. In our is carried out early bipolar gonadal in life 1 as soon as virilizing adrenal and female pseudohermaphroditism the administration of known androgens of case. New E11gL
sex mosomes in sexual anomalies in origin of ihe sex chronmtin. Acta 633, 1960.
A.
G. F,, Crosswhite,
L, II. and Hauschlrn, . S chromosome constitiition of hrnnan marrow in various developmental and blood disorders, AmeL J. Hmnan 12: 19GO. 0. J., , I-L L and Hirschhorn, cleveloprnen1s in cytogcnetics. Eugenic C}nart , 8: 2;3-:3;3, 19Gl.
and progesti.ns to the pregnant mother have ruled out. This prompt action allows men1, in life and minimizes the stress for the fam.ily child. Thereafter, indicated cedures can be carried out basis once the infant's onnv.r.n,·,-o
the various anatomical and features to be considered in the newborn with is However, it should emphasized that the anatomical features and for gonadal must take dence in the important der,ision of It may thus be wiser to select. sex assignment that sex which is coutrnry to sex chromosoma.l pattern of the individtml br,cause of certain physical and lw,,,,nlnn· charac teristics. This report, based on c·xtensive chromosmnal studies in a herniaphrodite with an XY sex chromosome c(,rJ . emphasizes diagnostic consideration,; and demonstrates factors upon ,rhich sex ment is made. It was felt wise to make a ~ex rnent which was contrary to the sex chromoH,.rr18 constitution and sex chromatin pattern. f,Ui\l'VIAR.Y
_\ chromatin-negative newborn infant clini(:al and histological e,cidence of true maphroclitism is presented. Chromosomal e,:arn ination of peritoneum and right gonad revealed the pre,encc of 46 chromosomes and an XY sex chromoH)rnc complement. No evidence of "ex chnimo~rnHe mosaicisrn. was deteckd. The cases of four reported u11w1ur ucsca, true l1crmaphrodi tes with XY sex chromornnrn constitutions are sumrnarizecl. Our n·\HH"t ernpirnsizerl th, considerations upon which H'X ment is made . It was felt wise, on the bas1., o; existing anatomy and the morphology of gonads, to make a sex '"'"""P'"'' ,rhich contrary to the sex chromosomal constituti.on sex chromatin pattern. "\Ve are indebted to for us.
KY TRUE
STUDIES I:1\7 A HERl'vfAPHRODITE
WELLINGTON HUNG, CECIL B. JACOBSON, l:-L JOACHIM WIGGER JUDSON G. RANDOLPH
AND
Prom the Departments of n11(1(:n.ru11m,11. Patholo(;y and Children's H ospitol of the Colmnbia and lhe Departrnenis of Pediatrics and F:forgery, Washington Uni1H;rsil11 School of Jk[ ed1:cirw 1 u.,.n,1u11.un D, C.
With '1nYrnnnPrn '·'""t-n,m,o.•.u on diagnosis in the newborn, an increasing number of children ,Yith the intersex phenomenon are recognized at an age, This fact bas the great advantage of m.inirnizing >OV>n>HV,-L•om a,nd psychological pres•• sures which can derive from this group of anom., alies and allows irnrnediate alld accurate sex '"''"'~,L.uucc.uu when proper measures are c;:1rried ouL chromosome studies have been of i.1nrnense help in unraveling this particular group of anomalies, Of the various hermaphrodite synthe t,rue ..... ,.. -,.·-· so designated because of the presence of ovarian and testicular tissue in the 3arne child, is of speeial interest be·· of the µu·~~.w1uc of either a, chronw,tinor chrorn1iti1n1egative (male) Thirty-two case8 of true hermaphroditism have been studied 0 ~,-,rr1ma to sex chromatir.t chrornosome constitution. Of
Accepted for publication November 3, 1965, bv Children's Bureatt Grant of Health, Education and Wel· fa.18, ' SohvaL A. R,: Chrornosomes and sex chroma .. tin in normal and anomafous sexnal developmenL Rev., 43: 306 356, 196:3, LL. and Green. 0. C.: Chromosomal eount in a true hermaphro.dite. J Pecliat., 63: 3::53-335 1H6B. 'Rosenberg, H. S., Clayton, G, W. and Hsu, T. C,: .Familial true hermaphrodisrn, .L Clin. EndocrinoL, 23: 203-206, H/63, ,, R. U., Bregman, E. T., Cushner, F. ]VL: Chromosome analvsis, clinical and endocrine studies a Um!., 89: 47.5-4S2, 1963. W., Everlein, W Briebart, S., P. S, and Mellman, J .. Chromoof multiple tissues from a true hersoma! 1naphroclitc. J. Clin EndocrinoL, 24: 467-469, 1
of
1\)()4 6 Blank. E., Emery, J. L, Dewhurst,
R. B., Bishop, .A.. M., .J. and Bond, J. H .. Chromosome mosaicism in a hermaphrodite. Brit. l\IecL L 2: 1964. D., Mercer, R. D. and McCnllagh,
It is the purpose of our paper i:,ro pr·esent cLromati:n-negative true wi{b XY chromosome constitution who had D assignment contrary to the sex chromatin tern. and sex chromosomal constitution CASE REPORT
R. B., at one week of age cattse of ambiguous external tient was delivered at 40 weeks'
intersex, On physical examination R. B. ·was noted ts:, have ambiguous external phallus measured 2.215 majora were enlarged and sirnulatecl serotmn::;. A urogenital sinus was present, cm. mass was palpable in the righ ,, No niass was palpable on the left. amination a midline structure uterus was palpable. An excretory urogram show1:,d a nonmd Retrograde injection of the ui,,,1,,u,,,u sinus onstrated a nonnal sized in addition a, normal sized bladder, The buccal snimcr consistently chromatir1-negative. No ''drurn,, sticks" were found in on repeated smears of blood Urinary excretion of 17-ketosteroids was 0.6 0.7 mg. per 24 hours on 2 determinations. 17-hydroxycorticosteroid and p,,,;,:,,,.,u,n., tions were 0.4 and 0.2 mg. per 24 . Other studies inch1ding count, urinalysis and blood within normal limits. vv11en the child was 20 K P Tn1e hermaphroditism: \vith chromosomal a1rnlvsis. Quart.,30:207, l963.
565
·
566
HUNG AND ASS00IA'£ES
laparotomy was undertaken through a Pfannenstiel incision (fig. 2). On the left side of the pelvis a fallopian tube was found and underneath it a gonad measuring 1.5 by 0.5 cm. The gonad was smooth, pale yellow in color and slightly lobulated. The fallopian tube arose from a normal-appearing infant's uterus. On the right side a firm white structure resembling the vas deferens was present, at the end of which, within the confines of the abdomen, a testicular-like structure was found. In contrast to the other gonad, this one was oblong in shape and measured 2 by 2 by 1 cm. Separate biopsies were taken from each gonad. Biopsy of the right gonad revealed testicular tissue composed of tubules ranging in diameter from 30 to 65 microns with an average of 48 microns (fig. 3, A). Most of the tubules contained 2 to 3 layers of pre-Sertoli cells with oval nuclei. Spermatogonia were present in ahnost all of the tubules in a basal position. A few mitoses were noted. The basement membranes and the peritubular sheaths of fibrous tissue were thin. The interstitial tissue consisted of round to oval mesenchymal cells; no sex chromatin bodies were present in these cells. Embedded in the stroma were numerous Leydig cells, usually in clumps. In the area subjacent to the tunica albuginea the tubules were densely packed and there was little interstitial stroma. Some tubules formed structures vaguely reminiscent of coronae radiatae. Other tubules contained very large spermatogonia approaching the appearance of primary spermatocytes or even oogonia. Embedded in the whorly connective tissue of the thick tunica were primordial follicles with large oogonia surrounded by flattened pregranulosa cells.
FIG. l. Photograph of patient's external genitalia
on admission.
FIG. 2. Operati':e findings ~' uterus. B, right vas deferens. C, right ovotest1s. D, left ovary. E, left fallopian tube.
Histological examination of the left gonad showed the presence of only ovarian tissue (fig. 3, B). Primordial follicles were present in large numbers separated by scant stroma. The stromal cells did not contain any sex chromatin bodies. A decision was made to raise the infant as a girl. This selection was based on both the anatomy of the external genitalia and the morphology of the gonads. 8- 1°Complete clitorectomy, including bilateral dissection of the corpora cavernosa was carried out when the child was 1 month old. Reconstruction of the mons veneris and enlargement of the vaginal fourchette were performed concomitantly. The patient was readmitted to the hospital at 7 months of age because of a right inguinal hernia. A standard right inguinal herniorrhaphy was carried out. Small amounts of skin, fascia, muscle and peritoneum were obtained for chromosomal and histological studies. When the hernial sac ,vas opened, a gonad was found which again had the gross appearance of a testicle. A wedge biopsy was taken for chromosomal and histological studies. Chromosomes were studied in cells derived from cultures of leukocytes in the peripheral blood, using a modification of the method of 8 Wilkins, L.: Abnormalities of sex differentiation. Classification, diagnosis, selection of gender of rearmg and treatment. Pediatrics. 26: 846-8.57 1960. ' 9 Wilkins, L.: Embryonic sex differentiation controlling factor~ and abnormalities, diagnosi~ and treatment. Chn. Proc. Child. Hosp. 20: 1-18 ' ' 1964. 10 Randolph, J.: Surgical aspects of intersex, Clin. Proc. Child. Hosp., 20: 33, 1964.
CHROMOSOME STUDIJ~S IN A HERMAPHRODITE
wu11:i,s:-;and
of right ovotestis shows whorly stroma of tunica, serniniferous tubules X 200. photomicrograph of left ovary with large number primordial seant strcmtn except for area of ovarian stroma in center. H & E XlOO.
568
HUNG AND ASSOCIATES
FIG. 4. Patient's karyotype showing 46 chromosomes and XY sex chromosome constitution. Moorhead and associates11 adopted to the form of a kit* by Jacobson and Teleford. 12 The following modified technique of Hayflick and Moorhead13 for culturing tissues has been used by one of us (C. B. J.). Tissue specimens were collected in sterile Hanks buffered saline solution (BSS) and minced into a fine cellular suspension. It was found that lymph node, spleen, liver, thym.us, kidney and gonad could be inoculated into reconstituted chromosome culture medium containing phytohemagglutinin. Other tissues were best grown without phytohemagglutinin. All reticulo-endothelial tissues gave satisfactory mitotic response after 3 days of culture. Other tissues were best sacrificed 8 to 16 hours following media change. Colcemide (Ciba) exposure was best at 8 to 12 hours. The cultures were then
* T.C. Chromosome Culture Kit, Difeo Laboratories, Detroit, Michigan. 11 Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M. and Hungerford, D. A.: Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res., 20: 613, 1960. 12 Jacobson, C. B. and Teleford, I. R.: Human cytogenetic techniques using peripheral blood culture. Proc. Amer. Inst. Biol. Science, August
1962. 13 Hayflick, L. and Moorhead, P. S.: The serial cultivation of human diploid cells strains. Exp. Cell Res., 25: 585, 1961.
transferred to conical centrifuge tubes, washed twice in Hanks BSS and treated with 20 per cent hypotonic Hanks BSS for 20 minutes. Cold methanol:acetic acid (3:1) was used for fixation. Slides were then prepared and stained with 10 per cent Giemsa. A minimum of 50 mitotic figures in metaphase was studied. Chromosomal analysis of the peripheral leukocytes as performed during both hospitalizations: The chromosome number of this patient was 46 with an XY sex chromosome constitution (fig. 4). This was the same in the leukocytes as well as in the cultures obtained from skin, fascia, muscle, peritoneum and right gonad. No evidence of sex chrorn.osome n1.osaicism was detected. All of the tissues lacked a chromatin-positive body. DISCUSSION
The histopathologic findings of the gonadal biopsies leave no doubt that our patient is a true hermaphrodite. The chromosomal studies of the four previously reported chromatin-negative true hermaphrodites are summarized in the table. The patient described by Hirschhorn and associates had gonadal biopsies which were compatible with but not conclusive for true hermaphroditism. 14 14 Hirschhorn, K., Decker, W. H. and Cooper, H. L.: Human intersex with chromosome rnosa-
CHROMOSOME STUDIES IN A HEHAIAPHRODITE
Correlatfon between se:;; chromosome wnstilul1.on and tissue sow ce of studied cells in cnnrrrw.,:r.n -·ru,iu.11:1,•w true hermaphrodites*
TABLE.
Ses Chromo.sornes
Authot
Tissue Source
(}nunback and associn,tes 15 Sandberg u.nd
XY
Marrow
associates" lvfiller and asso-
XY /XO
LeL1kocytes
X:{ XY/XO XY
Skin. marrow
Skin
eiates17
Hirschhorn and associates 14 LonsdalP and assoc-iates 7 Present case
LeLtkocytes
Leukocytes, skin, muscle, fascia, peritoneum, right gonad
''' Modified from Solwal. 1
It nn'to•wr,P1".l-'I chrorl'.J0S0IJ18 rnosaicisrn was not detected in our patient. All six tissue showed a consistent cvs,c,1·,,ou1G pattern of 1+6 chromosomes whh a sex chromosome com/JHcrnl\,1.Ll, of XY. 1Vhile it is true that certain biochemical, radioand physical studies allow one to make an diagnosis in cases of infants with genitalia, sufficient doubt remains in many instances which makes laparotomy and gonadal Becaust, of oecafional development of srnall cortical areas of '.ill ovotcstic we feel that bi-
unless the very small. In our is carried out early bipolar gonadal in life 1 as soon as virilizing adrenal and female pseudohermaphroditism the administration of known androgens of case. New E11gL
sex mosomes in sexual anomalies in origin of ihe sex chronmtin. Acta 633, 1960.
A.
G. F,, Crosswhite,
L, II. and Hauschlrn, . S chromosome constitiition of hrnnan marrow in various developmental and blood disorders, AmeL J. Hmnan 12: 19GO. 0. J., , I-L L and Hirschhorn, cleveloprnen1s in cytogcnetics. Eugenic C}nart , 8: 2;3-:3;3, 19Gl.
and progesti.ns to the pregnant mother have ruled out. This prompt action allows men1, in life and minimizes the stress for the fam.ily child. Thereafter, indicated cedures can be carried out basis once the infant's onnv.r.n,·,-o
the various anatomical and features to be considered in the newborn with is However, it should emphasized that the anatomical features and for gonadal must take dence in the important der,ision of It may thus be wiser to select. sex assignment that sex which is coutrnry to sex chromosoma.l pattern of the individtml br,cause of certain physical and lw,,,,nlnn· charac teristics. This report, based on c·xtensive chromosmnal studies in a herniaphrodite with an XY sex chromosome c(,rJ . emphasizes diagnostic consideration,; and demonstrates factors upon ,rhich sex ment is made. It was felt wise to make a ~ex rnent which was contrary to the sex chromoH,.rr18 constitution and sex chromatin pattern. f,Ui\l'VIAR.Y
_\ chromatin-negative newborn infant clini(:al and histological e,cidence of true maphroclitism is presented. Chromosomal e,:arn ination of peritoneum and right gonad revealed the pre,encc of 46 chromosomes and an XY sex chromoH)rnc complement. No evidence of "ex chnimo~rnHe mosaicisrn. was deteckd. The cases of four reported u11w1ur ucsca, true l1crmaphrodi tes with XY sex chromornnrn constitutions are sumrnarizecl. Our n·\HH"t ernpirnsizerl th, considerations upon which H'X ment is made . It was felt wise, on the bas1., o; existing anatomy and the morphology of gonads, to make a sex '"'"""P'"'' ,rhich contrary to the sex chromosomal constituti.on sex chromatin pattern. "\Ve are indebted to for us.