Penetrance

Heterozygous pathogenic variants in NR5A1 that lead to the predicted protein change demonstrated reduced penetrance in 46,XX individuals, with fertile XX phenotypic females described .

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"

Diagnostic Criteria

No consensus clinical diagnostic criteria for nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) have been published. However, algorithms have been developed for the evaluation and diagnosis of DSD, including nonsyndromic 46,XX testicular DSD .

Suggestive Findings

Nonsyndromic 46,XX testicular DSD should be considered in individuals with the following clinical, supportive laboratory, and imaging findings.

Clinical findings

• Male external genitalia that ranges from typical to ambiguous (penoscrotal hypospadias with or without chordee)

• Two testicles, typically smaller than average for age

• Absence of dysmorphic features and congenital anomalies outside of the genitourinary system

• Normal cognitive development

Supportive laboratory findings

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"

Differential Diagnosis

Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) must be differentiated from ovotesticular DSD as their potential outcomes differ, thus affecting management; see . Other disorders to consider in the differential diagnosis of nonsyndromic 46,XX testicular DSD are summarized in . Sex chromosome aneuploidies, which represent the most common disorders in the differential diagnosis, can be distinguished from 46,XX testicular DSD by karyotype and by FISH testing.

Table 4.

Disorders to Consider in the Differential Diagnosis of Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development

DifferentialCategory | Etiology | Phenotype

Sex

chromosome

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"

Management Guidelines

No clinical practice guidelines for nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) have been published. Evaluations Following Initial Diagnosis To establish the extent of the condition and needs in an individual diagnosed with nonsyndromic 46,XX testicular DSD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"

Clinical Guidance

Contraindications to testosterone replacement therapy include prostate cancer (known or suspected) and breast cancer. Oral androgens such as methyltestosterone and fluoxymesterone should not be given (especially for long-term therapy) because of liver toxicity.

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this condition.

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"

Surveillance Guidelines

Table 7. Recommended Surveillance for Individuals with Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development

Source: GeneReviews — "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development"