Partial androgen insensitivity syndrome

Alternative names

Reifenstein syndrome; Incomplete male pseudohermaphroditism

Definition

Reifenstein syndrome is an inherited disorder that causes underdevelopment of the male reproductive tract and sexual dysfunction in males, which includes an inability to make sperm, undescended testicles (the testicles do not descend into the scrotum), and development of breasts.

Causes, incidence, and risk factors

Reifenstein syndrome is one of a group of diseases in which the body is unable to respond appropriately to the male sex hormones (androgens), which include testosterone.

In this genetic disease, the affected gene codes for the androgen receptor, which is the key protein that allows cells to respond to androgens. This particular mutation makes the cells less responsive to these hormones - hence the alternative name, Partial Androgen Insensitivity Syndrome.

By default, human babies develop female genitalia. It is only when androgens are made by the testes of male fetuses that male sexual organs arise. As a result, boys with the most severe cases of Reifenstein syndrome may appear to be girls at birth even though they are genetically male, or they may have very small penises.

The disease is inherited in an x-linked recessive manner, which means that women are not affected but may carry the gene, and males who inherit the gene from their mothers will have the condition.

Symptoms

• Abnormal male genitals, including undescended testes; a small scrotum, with a line down the middle (bifid) or incompletely closed; a small penis; and hypospadias (the urethra exits the body on the side of the penis, not the tip)
  
• Breast development in males at time of puberty
  
• Infertility
  
• Decreased body hair and beard with normal pubic and armpit hair
  

Signs and tests

• Male chromosomes - X,Y
  
• High testosterone and luteinizing hormone level in blood
  
• Low or absent sperm count
  
• Testicular biopsy shows no mature sperm despite normal precursors
  
• Decreased or absent vas deferens (the tubes through which sperm exit the testes)
  
• Partial development of female gonads/sex organs
  
• Decreased ability to bind androgen in cell culture tests
  
• Mutations in the androgen receptor gene