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The prevalence is unknown.

46,XY partial gonadal dysgenesis (46,XY PGD) is characterized by ambiguous external genitalia with or without Müllerian structures. The degree of genital ambiguity varies along a spectrum, ranging from an almost female phenotype with clitoromegaly at one extreme to an almost male phenotype with isolated hypospadias at the other. Many patients present ambiguous genitalia or severe micropenis and cryptorchidism associated with complete regression of testicular tissue in one or both sides. Testicular regression syndrome (ETRS) is considered as part of the clinical spectrum of 46,XY PGD. Patients with NR5A1 variants can have adrenal insufficiency. Gonadoblastomas or dysgerminomas may occur in a significant proportion of patients, but may depend on the genetic origin.

46,XY PGD is a heterogeneous disorder associated with partial absence of both Leydig cell and Sertoli cell function that may result from a variety of genetic events. Rarely, deletions or point mutations in the SRY gene or dose sensitive sex locus (NR0B1) duplication on the X chromosome have been described. Most SRY mutations are de novo mutations, however some cases of X-linked inheritance have been observed. More important are mutations in steroidogenic factor 1 (NR5A1; SF-1). SF-1 is a nuclear receptor and regulator of multiple genes involved in adrenal and gonadal development, steroidogenesis, and the reproductive axis. Therefore, affected patients may also have adrenal insufficiency. 46,XY PGD may be a feature of many syndromes (e.g Denys-Drash syndrome) and other genetic conditions.

Diagnosis is made on the basis of clinical findings with cytogenic analysis, endocrine investigations, molecular genetic studies, and sometimes surgical exploration with biopsy.

Differential diagnoses include all forms of syndromic 46,XY gonadal dysgenesis (for example, Denys-Drash syndrome, campomelic dysplasia and 46,XY DSD with adrenal insufficiency) and similar phenotypes that can also result from a 45,X/46,XY karyotype, known as 45,X/46,XY mixed gonadal dysgenesis (45,X/46,XY MGD). The absence of a 45,X lineage is of importance for the management and prognosis.

Antenatal diagnosis is possible if a genital malformation is suspected with imaging and if a familial background exists.

Genetic counseling is mandatory.

Management of patients requires a multi-disciplinary team in a designated DSD centre. Psychological evaluation and counseling of parents is necessary. The determination of social sex should consider etiological diagnosis, clinical evaluation, ethnic traditions, sexual identity and the acceptance of assigned social sex by the parents. Hormone therapy in patients with female social sex at the time of puberty is based on estrogen and progesterone for those patients where uterus is present in order to induce menses, and estrogen alone in patients without a uterus. Androgen replacement, including testosterone injections, may be appropriate for patients who choose a male social sex in adolescence. Surgery may be considered to allow sex appropriate functionality. This may require legal approval in some countries. Previously, gonadectomy was widely performed in children assigned to female sex, but is nowadays often postponed to allow an informed consent policy. However, due to the increased risk for the development of gonadal tumors, regular clinical assessment and diagnostic visualization of the gonads should be recommended.

With early diagnosis, surgery and hormone treatment can result in good outcome, both functionally and phenotypically. Infertility is almost always present.