1. Abnormal development in embryos can be caused by chromosome abnormalities like Turner's syndrome or mutations affecting sex determination. 2. Gonadal abnormalities in both males and females can also disrupt development, leading to ambiguous genitalia or the lack of secondary sex characteristics. 3. Internal and external genitalia can be abnormal due to issues like androgen insensitivity or Mullerian duct abnormalities. Some conditions like congenital adrenal hyperplasia cause virilization of external female genitalia.

1. Abnormal developmentAny aberration in development that results in an unexpected developmental sequence of events may be mediated in a number of ways. 1-Chromosome abnormalitiesIn an embryo that loses one of its sex chromosomes, the total complement of chromosomes-will be reduced to 45, leaving a fetus viable only where this is 45 XO (Turner's syndrome).

2. Here, the absence of the second X chromosome or Y chromosome means there is no testicular development and therefore the phenotype is female , although it initially differentiates to be an ovary, the oogonia are unable to complete their development and at birth only the stroma of the ovary is present (streak ovaries) . Thus, in Turner's syndrome, the absence of a functional ovary means that there is no oestrogen production at puberty, and secondary sexual characteristics cannot develop. As the genes involved in achieving final height areshared by the sex chromosomes, the absence of onesex chromosome will also lead to short stature.

3. In females who have an XY karyotype, a mutation at the site on the short arm of the Y chromosome resulting in failure of production of TDF will mean the re is no testicular development (XY gonadal agenesis). Thedefault phenotypic state is female . In thesecircumstances, the absence of a testis means that the internal genitalia will persist as a result of the development of Mullerian structures, and the Wolffian ducts will regress. The external genitalia will be female.

4. 2-Gonadal abnormalities1- In males, a number of gonadal abnormalities may exist.A- One of these is known as the vanishing testis syndrome:an XY fetus develops testes that then undergo atrophy. The reason for this remains speculative, although torsion,thrombosis and viral infections have been suggested.However, the failure of the development of thetestes leads to a female default state.

5. B- In Leydig cell hypoplasia, the Leydig cells responsible for the production of testosterone either completely fail to produce this or produce it in only small quantities. A range of abnormali ties may result, dependent on the level of androgen produced, and therefore the phenotype may range from female through to the hypospadiac male..

6. C- In XY gonadaldysgenesis, a genetic abnormality leads to an abnormal testicular development. The testis fails to secrete androgen or Mullerian inhibitor, resultingin an XY female. If the genetic abnormality leadsto an enzyme deficiency in the biosynthetic pathway to androgen, testosterone will fail to be secreted by the testis. However, some androgen may be produced,Therefore some effect on the external genitalia may be possible and a varying degree of virilism will occur.If the biosynthetic production of Mulleriainhibitoris deficient, its absence will mean the persistenceof the Mullerillerian duct. This is an extremely rare syndrome.

7. 2-In the female, gonadaldysgenesis may occur, and in this situation (similar to Turner's syndrome) the gonad is present only as a streak. These individuals have been found to have small fragments of a Y chromosome and as a result of this, the gonad may undergo mitoticchange, which leads to the developnent of a gonadaltumour, e.g. a gonadoblastoma. The Mullerian structures remain and the Wolffian structures regress, because of the absence of testes. At puberty, the failure of development of the ovary will mean that there is nopossibility for the production of oestradiol, and a failure of secondary sexual characteristic growth will occur.

8. 3-mixed gonadaldysgenesis,there is a testis and a streak gonad in the same individual. The chromosome complement is typically 46 XX or a mosaic with a Y component. Here, strangely,the Wolffian structures develop only on the side of the testis, but all Mullerian structures regress. The external genitalia in this rare condition may be ambiguous,depending on the functional capacity of the testis.

9. 4-In true hermaphrodites, the gonad may develop into either a testis or an ovary, or a combination of the two known as an ovotestis. .This usually results from a mosaic XX:XYkaryotype, and the predominance of either ovarian or testicular tissue in the gonad depends on the percentage of cell lines in the mosaic. Thus, in the true hermaphrodite, it is possible to get co-existent Mullerian and Wolffian structures in terms of internal development, and varying degrees of masculinization of the external genitalia, depending on the combination of gonads

10. Internal genitalia abnormalitiesIn males there are three fundamental changes that may lead to abnormalities of the internal genitalia.The first of these is1- androgen insensitivity .In this condition the fetus fails to develop androgen receptors due to mutations in the androgen receptor gene. Failure to possess the receptor means that although the testis will be producing testosterone,the androgenic effect cano`t be translated into the end organ as it is not recognized by the cell wall.The result here is that the fetus develops in the default female state

11. This is the commonest type ofXY female and the Wolffian ducts regress, as theyalso have no androgen receptor. However, theMullerian ducts also regress because the testis is normal and produces Mullerian inhibitor. Girls with this abnormality present with primary amenorrhoeaat puberty.2-A further aberration in XY females also exists witha condition known as 5 alfa-reductasedeficiency .As outlined above, this enzyme is responsible for theconversion of testosterone to dihydrotestosteroneresulting in virilization of the cloaca. If this enzyme is absent, the external genitalia will be female but the internal genitalia will be male. The Mullerianductswill regress. Here again, this female will present with primary amenorrhoea.

12. 3-Finally, a rare condition known as Mullerian inhibitory deficiency may mean that an XY male may have persistent Mullerian structures, due to the absence of Mullerian inhibitory factor, and co-existent male and female internal structures

13. In 46 XX females, a genetic defect that results in failure of development of the uterus, cervix and vagina is known as the Rokitansky syndrome. This is the second most common cause of primary amenorrhoea in women, the first being Turner's syndrome. Here the ovaries are normal, and the external genitalia are normally female. The internal genitalia are either absent or rudimentary..

14. Variations on this may lead to developmentof the vagina without development of theuterus, or development of the uterus without subsequent development of the cervix or vagina, and a functional uterus may result These patients will present at puberty witheither primary amenorrhoea or, in circumstances when a small portion of uterus may be functional, with cyclicalabdominal pain due to retained menstrual blood.

15. External genitalia abnormalitiesIn females, the external genitalia may be virilized, giving a masculine appearance. This is most commonly seen in a condition known as congenital adrenal hyperplasia.In this condition, an enzyme defect in the adrenal gland - usually 21-hydroxylase deficiency - prevents the fetal adrenal gland from producing cortisol. Failure of the production of cortisol means that the feedback mechanism on the hypothalamus leads to an elevation of adrenocorticotrophic hormone (ACTH).

16. This in turn stimulates the adrenal gland to undergo a form of hyperplasia, and the excessive production of steroid precursors (17-hydroxyprogesterone) means that the adrenal gland produces excessive amounts of androgen

18. This androgen enters the fetal circulation and impacts on the developing cloaca, thereby leading to virilization. The female child is then born with a degree of phallic enlargement, and the lower part of the vaginamay be obliterated by the development of a male-type perineum and hence a vaginal orifice is not apparent.

19. Virilization of the cloaca can also occur if the fetus is exposed to androgen in an androgenic drug ingested by the mother or, in many cases, the virilization is idiopathic. The end result in both of these circumstances is known as the intersex state. At birth, investigationof the chromosomes, the endocrine status of the infant and ultrasound of the internal organs will lead to a rapid diagnosis, revealing whether the child is a female with a virilization state, which is most likely to be congenitaladrenal hyperplasia, or a male who has beenunder -masculinized.

20. Abnormal genital tract developmentVagina There may be horizontal septae, vertical septae or the vaginamay be absent.1-Horizontal septae. There may be cryptomenorrhoea with cyclical pain and a haematocolpos. If obstruction is caused simply by the hymen (blood looks blue behind it) then a cruciate incision, usually under anaesthesia, is all that is required. If the septum looks pink rather than blue the situation is potentially more serious and should be referred to a specialist surgeon.

21. If the septum is in the low or midportion of the vagina, total excision and resuturingisnecessary. If the septum is high, a combined abdominal and vaginal approach may be required. Pregnancy rates areexcellent with low septae, but only around 25% for those higher in the vagina.

22. 2-Vertical septae. These may be associated with abnormal uterine development. Although presentation may be with dyspareunia or infertility, they may occasionally present in advanced labour. They can be surgically removed.

23. 3-Vaginal atresia. This is associated with an absent, or only a rudimentary, uterus and is known as the Rokitansky syndrome. Presentation is at puberty with amenorrhoea (or cryptomenorrhoea) in the presence ofnormal secondary sexual characteristics. It is possible to create a vagina with regular use of vaginal dilators, or by one of a variety of surgical techniques. Surrogacy is an option for childbearing.

24. Uterus Abnormal uterine shapes are usually asymptomatic but may present with primary infertility, recurrent pregnancy loss or menstrual dysfunction(oligomenorrhoea, dysmenorrhoea ormenorrhagia). In pregnancy, there maybe miscarriage , preterm labouror an abnormal fetal lie.1-Unicornuate uterus. With this there isa higher miscarriage rate and risk ofpreterm labour.

25. 2-Bicornuate uterus. This may often carry a pregnancy to an adequately advanced gestation, and the chance of thisprobably increases with subsequent pregnancies. A 'Strassman' procedure will correct the defect, but the benefits for pregnancy are unproven. A bicornuate uterus may be asymmetrical with one side hypoplastic Pregnancy in the hypoplastic horn carries a risk of rupture.3-Septate uterus. If appropriate to remove the septum, a hysteroscopic approach is probably the most appropriate.