Gonadal Dysgenesis (complete or partial)

Gonad is the generic term used to indicate the organs that produce sperm and egg cells, i.e., the testicles and the ovaries, respectively. These organs also produce sex hormones (testosterone, oestrogen, progesterone). Gonadal dysgenesis is a condition characterized by an alteration, either partial or complete, in the embryonic development of the gonads. In its complete form, the newborn with a 46,XY karyotype exhibits typically female internal and external genitalia (in some cases with a slight enlargement of the clitoris); there is no development of secondary sexual characteristics or no onset of the first menstrual cycle during adolescence; in adulthood, height is as expected or greater. The gender identity of persons with complete gonadal dysgenesis is reported as female in the vast majority of cases.
Typically, complete gonadal dysgenesis also includes the embryonic testicular regression syndrome, characterized by atypical genitalia –considered neither typically male nor female– or a micropenis, and one or no testicles. Specifically, the degree of virilization of the external genitalia depends on how long the testicle produces male hormones before it stops working, which usually occurs for reasons as yet unknown.
The partial form is characterized by testicles with altered morphology and function, atypical genitalia, and occurs in widely different forms. For example, some people may show the same characteristics as in Turner syndrome, while others may have a typically masculine appearance at birth and after puberty. The internal reproductive organs also exhibit a variable degree of development along the male or female line. The gonads can be two dysgenetic (malformed) testicles, or a streak (underdeveloped) gonad and a partially or fully formed testicle.
In some cases, complete or partial gonadal dysgenesis is associated with malformations in other organs, resulting in syndromic conditions.
This form of Variation of Sex Characteristic (VSC)/Difference of Sex Development (DSD) has an incidence of approximately 1/80,000 births.

Genetic traits
Individuals with complete gonadal dysgenesis usually have a 46,XY karyotype. Cases of familial forms of gonadal dysgenesis have been reported, in many of which the responsible genetic alteration is undefined. Probably, the mutation of each gene involved in the process of gonad development is potentially responsible for a form of gonadal dysgenesis (the ones most studied to date are ARX, ATRX, CBX2, DHH, DMRT1, GATA4, MAMLD1, MAP3K1, NR0B1, NR5A1, SOX9, SRY, WNT4, WT1 and WWOX).
Partial gonadal dysgenesis may be associated with mosaicism in the karyotype, i.e., the presence of partly male and partly female sex chromosomes (most commonly 45,X0/46,XY; less frequently 45,X0/47,XYY) in the different cells of the body.

Identification
Complete gonadal dysgenesis is rarely identified in pre-adolescence, since the internal and external genitalia look typically female at birth. Suspicion can arise if the mother has carried out a karyotype examination during pregnancy, revealing a male chromosomal sex inconsistent with the female appearance of the newborn's genitalia. More often, the person seeks medical attention because there is no pubertal development and/or no onset of the first menstrual cycle. As for the hormonal structure, complete gonadal dysgenesis is characterized by markedly reduced testosterone levels –comparable to those found in childhood–, while in the partial form there may be standard, or slightly lower, levels in adults with karyotype 46,XY. Instead, there are high values of luteinizing hormone (LH) and follicle stimulating hormone (FSH), hormones that stimulate the testicular function as a compensating mechanism for the reduced functioning of the gonads. Ultrasonography can be helpful in identifying dysgenetic gonads, which are frequently found in the abdomen rather than the scrotum.

Medical options
Complete gonadal dysgenesis is associated with a markedly increased risk of gonadal cancer, and  cases in pre-pubertal age have been reported. Therefore, removal of the gonads is generally recommended as soon as the condition is recognised, especially if the person has a stable female gender identity. Whereas in cases of partial gonadal dysgenesis, given the low risk of gonadal cancer before puberty –and if it is possible to surgically position the gonads in the scrotum– close medical monitoring can be considered instead. Thus, lesions can be promptly identified, and a gonadectomy postponed until the person can express a more informed consent, also based on their gender identity.
Nevertheless, hormone replacement therapy is required for individuals with complete gonadal dysgenesis to induce puberty, maintain secondary sexual characteristics, and support bone and overall health.
Despite the absence of functioning ovaries, after adequate hormonal stimulation the uterus is usually capable of carrying out a pregnancy, and several cases of pregnancy resulting from medically assisted procreation techniques with egg donation have also been reported.

Bibliography
King, T. F., & Conway, G. S. (2014). Swyer syndrome. [Abstract]. Current Opinion in Endocrinology, Diabetes and Obesity. 2014 Dec; 21(6), 504-510
Lee PA et al. Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care. Hormone research in paediatrics. 2016;85:158-180 
McCann-Crosby et al. (2014). State of the art review in gonadal dysgenesis: challenges in diagnosis and management. International journal of pediatric endocrinology. 2014;(1),1-17

Further Links 
Orphanet. 46,XY partial gonadal dysgenesis
Orphanet. 46,XY complete gonadal dysgenesis