Androgen insensitivity syndrome: a review.

Area of Science:

• Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Androgenic insensitivity syndrome (AIS) is a primary cause of disorders of sexual differentiation in 46,XY individuals.
• It stems from mutations in the androgen receptor (AR) gene, leading to resistance to androgens.
• AIS manifests in three main phenotypes: complete (CAIS), partial (PAIS), and mild (MAIS).

Purpose of the Study:

• To review the genetic basis, clinical presentation, diagnosis, and management of androgenic insensitivity syndromes.
• To highlight the challenges and open issues in the clinical care of individuals with AIS.
• To emphasize the poor genotype-phenotype correlation observed in AIS.

Main Methods:

• Review of literature on androgen receptor gene mutations and their impact on sexual differentiation.
• Analysis of diagnostic criteria, including hormonal levels (LH, testosterone) and virilization status.
• Examination of current treatment strategies based on phenotype and social sex.

Main Results:

• Androgen receptor gene variants occur across all domains and exons, showing a weak correlation with specific phenotypes.
• Diagnosis typically involves elevated LH and testosterone with minimal virilization.
• Treatment decisions are individualized, considering phenotype, social sex, and potential long-term outcomes.

Conclusions:

• Management of AIS involves complex decisions regarding sex assignment, gonadectomy timing, fertility, and psychological support.
• Genetic counseling is crucial for affected individuals and families.
• Further research is needed to address unresolved issues in AIS management.