Medico-Legal Update

(1)Mathur P.N., (2)Saini O.P., (3)Vyas Jyotsana, (4)A. Suman, (5)Saini P.K., (6)Kothari N.S.

(1) Department of Forensic Medicine & Toxicology, S.P. Medical College, Bikaner Rajasthan,
(2) Department of Obst & Gyn, S.P. Medical College, Bikaner Rajasthan.,
(3) Department of Obst& Gyn., J.L.N. Medical College, Ajmer, Rajasthan.

Abstract

A 19 year old Phenotype female with absent uterus, ovaries, pubic, auxiliary hair, primary amenorrhea and chromatin negative buccal smear is presented. This patient is representative of the androgen insensitivity syndrome.

According to highest estimates (Fausto – Sterling et al ,2000) perhaps 1% of live births exhibit some degree of sexual ambiguity and that between 0.1% and 0.2 % of live birth are ambiguous enough to become the subject of specialist medical attention, including surgery to disguise their sexual ambiguity, Other sources (Leonard sax,2002) create a narrower definition of ” True ” intersexual conditions and estimate the incidence as far lower, at approximately 0.018%. The estimated incidence of testicular feminization syndrome varies from 1 in 20,000 (Prader 1957) male births to 1 in 62,400 (Jagiello 1962). This wide variation may be due to the reluctance of some authors to include the incomplete forms in their series.

Isolated cases of malepseudohermaphroditism have been reported during the last 150 years (Ashley 1962) “but it is only since the work of Morris in 1953 that the condition has been recognized as an important clinical entity. He coined the term testicular feminization syndrome.” More recently it has been designated under the term androgen insensitivity syndrome (Timmreck 2003).

Key Words: Male Pseudo Hermaphrodite, Intersex, Testicular Feminization Syndrome.

Case Report

A 19 year old married female (Sex assault no 43/ 5 brought by police on 9 Th December 2005 as F.I.R. was logged against parents under section 420 I.P.C. stating that she does not have uterus and ovaries for examination in forensic medicine and Toxicology O.P.D. She was examined by a panel of doctors. She never had menstruation. Her height and weight were 166.5 cm and 60 kgs respectively. In her family she is the only girl and other are two males. Her mother did not give any history of intake of drugs during pregnancy of the case. She was having long upper extremities (Photograph 1). The dental study revealed second molars erupted in all quadrants and third molars had not erupted in any quadrants of Jaw, Breasts were developed. Pubic and auxiliary hair not appeared. External genitaria were of female with under developed labia minora. Clitoris was not enlarged. Hymen was old torn and admitting two fingers easily, but the vagina ended in blind pouch, about 6.5 cm in depth. Uterus and ovaries were not felt.The ultra sonography (M.L.C.012 dated 10th December 2005) stated that uterus and ovaries are absent (Photograph 2). The case was referred to S.M.S. Hospital Jaipur where in buccal smear bar bodies were not identified and in peripheral blood films drumstick were not found. Her hormonal levels were LH 42.1MIU/ml, testosterone <20.0 ng/dl, insulin 8.90 m.I.U/ml, FSH 65.6 M.I.U. /ml and TSH 2.65 m.I.U/ml. Her blood sugar was 88 mg , Urea 23.0 mg, serum creatinine 0.8 mg and lipid profile within normal limits.

The M.R.I. showed bilateral undescended testes in inguinal canals with absence of uterus and ovaries.

In view of physical findings and investigations it was opined that she is genetically male and phenotype is female but the subject examined can perform sexual intercourse as a female. (Morris 1953) Listed seven features, along with modifications of each, characteristic of testicular feminization:

1. A female habitus with normal appearing female fat deposits (although some patients are eunuchoid with long extremities and large hands and feet).
2. Normal female breasts, at times over-developed, but often with juvenile–type nipples.
3. Absent or scant axillary and pubic hair (there may be slight vulval hair).
4. Female external genitalia (but the labia, particularly the labia minora, may be underdeveloped and the clitoris small or normal).
5. The vagina ends in a blind pouch, but usually is adequate for coitus.
6. Absence of female internal genitalia (except, occasionally a rudimentary uterus and other analogue of the mullerian system).
7. Presence of gonads which may be abdominal or lie within the inguinal canal or labial sacs. Theses gonads consist largely of seminiferous tubules and interstitial cells, and are usually without evidence of spermatogenesis.

Philip, in 1965 added three characteristics to the syndrome which appear pertinent;

1. The high malignancy rate of gonads left in the patient after the age of 30.
2. The hereditary nature of the syndrome.
3. The X Y karyotype and chromatin negative cells.

Bergada et al 1962 confirmed some of these findings in a series of 8 patients, all of whom had adequate structures. Four of the 8 were first seen after puberty and all were well feminized.

Nunez 1960 & Prader 1957 have described a similar clinical picture with clitoral enlargement. These authors suggested that this type be called “partial “or “incomplete” testicular feminization. Moris, 1953 also recognized the existence of this entity, but felt that such patients should not be included with those having a normal–sized clitoris, for the following reason:

1. Secondary sex characteristics, even with slight enlargement of the clitoris, are phenotypically unpredictable–they may resemble those characteristics of the testicular feminization syndrome, they may be essentially male, they may be intermediate with sexual hair and breast development or there may be no hair and no breast development.
2. While it appears that both syndromes are hereditary, the complete feminization syndrome and the syndrome with clitoral enlargement, as a rule, do not occur in the same family.
3. The complete form, with no clitoral hypertrophy and no sexual hair development will not respond to exogenous testosterone whereas the incomplete form may. Despite this plea for separation of these groups in complete testicular feminization, the term testicular feminization syndrome today encompasses all persons with an XY chromosomal complement, female appearing external genitalia and testicular gonads.

There is general agreement that testicular feminization is hereditary in nature, but much speculation exists regarding the genetic mechanism. Three mechanisms have been proposed:

1. An inconsistent non disjunction of X chromosomes. (Taillard, et al 1957).
2. A male limited autosomal dominant gene.
3. A sex linked mutant recessive gene. (Morris, & Mahesh 1963).

The latter mechanism is, at present, most widely accepted. (Ashley 1962) as it best explains the ratio of 2 normal females to 1 testicular feminization syndrome to 1 normal male found in hereditary studies.

The etiology of testicular feminization syndrome is yet to be explained adequately. Many of the theories proposed are based on Jost, 1947 work on sex differentiation. He postulated that the meduallary components of the developing gonad produced fetal masculinizing hormone, and that if a male fetus is castrated prior to the development of gonadal differentiation, he will develop along female lines with a mullerian duct system and female external genitalia. Jost 1947 felt that the fetal masculinizing hormone inhibits mullerian duct development. He did not feel that this inhibiting substance was testosterone, because if testosterone is injected into a female fetus, it will show external genitalia masculinization, but the mullerian system continues to develop. Bergada et al, 1962 agree with this theory and feel that the difference in anatomic structure sometimes found is based on the degree of deficiency of the masculinizing hormone or the stage of development at which the deficiency occurs. They feel that there may be at least two different substance from the fetal testes, one causing masculinization of the ductal system and/or genitalia and the other causing regression of the mullerian system. Moris and Mahesh 1963 concur and state that along with the mullerian inhibiting substance, there is also a “nonacting androgen” which is responsible for normal male testosterone levels, the inaction of which is responsible for the lack of secondary sexual characteristics at the end-organ sites. They feel that this lack of secondary sexual characteristics is not an inherent end-organ failure, but the result of an inability of the androgenic substance to make the end organs respond-thus, the designation nonacting androgen. Van de Wiele and Jailes 1954 disagree with this theory and state that the lack of response is probably on the basis of either end-organ failure or a peripheral conversion of testosterone to estrogen. This latter theory is not borne out by the work of Bagett and Stone 1962. They injected (Van De Wiele & Jailes 1954) C-labeled testosterone into such patients and recovered no labeled estrogenic metabolic products, but only androsterone and etiocholanolone, therefore suggesting that there was no peripheral conversion of testosterone to estrogen.

Leydig cell agenesis has been proposed a cause of male pseudho hermaphroditism (Francois et al 1978)

Allen, 1976 proposed that patient with inadequate virilization of the external genitalia of a varying degree due to deficient biosynthesis of TST, inadequate conversion of TST to DHTST (lack of 5a-reductase) or inadequate androgen (TST/DHTST) utilization (lack of androgen receptors). This category also includes patients with AMH deficiency who exhibit adequate male external genitalia with retained Mullerian structures, i.e. tubes and uterus (hernia uteri inguinalis)

Espiner, 1970 observed the patients with Androgen Insensitivity Syndrome (AIS) present at puberty with normal onset of breast development, but menses is absent. Instead of a 46 XX karyotype these patients have 46 XY chromosomes Brown et al, 1989 are of the opinion that instead of having ovaries that produces estrogen, they have testes, which primarily produce testosterone. Because of androgen receptor gene mutations, these patients are unable to respond to the testosterone signal with masculinization at puberty. The androgen receptor gene is x linked with large number of affected individuals, these gene mutations can also arise de novo (Nitsche &Hiort 2000) As per Mc phaul et al, 1993 it was hoped that AIS could be diagnosed by identifying one of a few specific androgen receptor gene mutations, However, most of the mutations identified are unique to family in which they are found these mutations are present in all parts of the gene and this explains the differences in results previously published for androgenbinding assays. Mutation in the steroid-binding domain are associated with normal binding of androgens to the receptor. Androgen insensitivity is caused by mutations in the androgen receptor (AR) gene on the proximal long arm of the X chromosome (Xq11). Over 300 mutations have been reported, including single nucleotide substitutions resulting in amino acid substitutions or premature stop codons; nucleotide deletions or insertions leading to frameshifts and premature stop codons; partial or complete gene deletions; and intronic mutations that affect splicing. (BRINKMANN 2001) At birth, these patients have a normal female phenotype with a small, blind ending vaginal pouch. At puberty, their increasing levels of androgens are converted to estrogens with normal female breast development. Patients with complete androgen insensitivity have almost complete absence of pubic hair. Because of the presence of Y chromosome and its associated height genes patients with AIS are tall. These patients also have a risk of developing malignances of gonads. Because gonads are testes rather than dysgenetic gonads, the risk of transformation does not increase until after puberty and usually involves the development of seminomas, unlike the germ cell tumors of a dysgenetic gonads. Unless these testes are inguinal in location, they are usually left in place until after breast development is complete. The resistance to androgen in these patients help us to understand the role androgen play in process such as masculinization.

Intersexuals in Society

Intersexual individuals are treated in different ways by different cultures. In same cultures intersexuals were included in larger “Third gender” or gender bending. Social roles along with other individuals. In most societies intersexes individuals have been expected to select one sex, and conform to its gender role. (Wikipedia 2006). Persons with testicular feminization syndrome are reared as females psychosexually because they have female behaviour; often they have a normal female libido. However, in all intersexes there is a high incidence of suicide. (Wilson et al 1968)

It is very possible for a child born with both sex organs to grow up to have healthy view of sexuality and successful relationships. From early on, the child should be taught how valuable, loved and accepted they are by their family and also by god. He or she is not a victim of divine.

Judgement but god has a plan for each one of us that will bring him glory as we can learn from a man who was healed by Jesus Christ.

“Teacher! his disciples asked him, why was this man born blind? was it a result of his own sins or those of his parents?, it was not because of his sins or his parents, sins, Jesus answered, “He was born blind so the power of god could be seen in him (John 9:2-3).”

(The authors apologizes for not having recognized many important contributors due to lack of knowledge about such contributions).

References

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Reprint requests: Dr. Mathur P.N.
S.P. Medical College,
Bikaner Rajasthan