Mild androgen insensitivity syndrome is a condition that results in a mild impairment of the cell’s ability to respond to androgens. The degree of impairment is sufficient to jeopardize spermatogenesis and/or the development of secondary sexual characteristics at puberty in men, but does not affect genital differentiation or development, it is also known as: Mild androgen insensitivity syndrome (MAIS).
The clinical phenotype associated with MAIS is a normal male type with mild spermatogenesis defects and/or secondary terminal hair reduction.
It should not be confused with the complete androgen insensitivity syndrome, in which case the external genitals will be those of a normal woman (already commented on in another post in this blog, see Morris Syndrome), in the mild androgen insensitivity syndrome the external genitals are those of an almost normal male, and in the partial androgen insensitivity syndrome the external genitals are partially masculinized (PAIS), but not totally.
Signs and symptoms:
People with mild androgen insensitivity syndrome are born phenotypically male, with fully male genitals; this category of androgen insensitivity is diagnosed when the degree of androgen insensitivity in an individual with a karyotype 46, XY is large enough to endanger virilization or spermatogenesis, but not large enough to affect normal male genital development, although there may be micropenis and in some cases hypospadias.
MAIS is the mildest and least known form of androgen insensitivity syndrome, although there are more than 600 mutations that can cause it, the gene is located on the long arm of the X chromosome, and is inherited with an X-linked recessive pattern, which accounts for 2/3 of the cases, transmitted by carrying mothers, the rest of the cases are de novo mutations, produced at the beginning of fetal development.
Cases of phenotypically normal males with isolated spermatogenic defect due to AR mutation were detected for the first time as the result of male infertility evaluations. It is estimated that 2-3% of infertile men have AR gene mutations.
Examples of MAIS phenotypes include isolated infertility, mild gynecomastia in adulthood, secondary terminal hair loss, acute voice, or mild hypospadias that appear in childhood. External genitalia are otherwise normal in individuals with MAIS.
Internal genitalia, including the Wolff structures and prostate, is also normal, although the bitesticular volume of infertile men is decreased, male infertility is associated with lower bitesticular volume, varicocele, retractile testes, low volume of ejaculate, infections of the male accessory glands, and mumps orchitis . The incidence of these characteristics in infertile men with MAIS is similar to that of infertile men without MAIS and is not associated with muullerian remains.
Kennedy’s disease, also known as spinal muscular atrophy and bulbar, is a severe neurodegenerative syndrome that is associated with a particular polyglutamine mutation of the androgen receptor called a trinucleotide repeat expansion, occurs when the length of polyglutamine exceeds 40 repeats, is technically a variant of MAIS, but is not typical of this androgen insensitivity and is often confused with amyotrophic lateral sclerosis.
In affected genealogies polyglutin tends to increase in length over generations, a phenomenon known as «anticipation», leading to an increase in the severity of the disease, as well as a decrease in the age of onset for each subsequent generation of a family affected by this syndrome. All forms of androgen insensitivity are associated with infertility, although there are exceptions for both mild and partial forms.
They are people with partial AIS (PAIS), also known as incomplete male pseudohermaphroditism that is to say a more accentuated form of androgenic insensitivity that can have both male and female characteristics and these include:
Abnormal male genitalia, for example, with the urethra at the bottom of the penis, small penis, small scrotum (with a line in the middle or with incomplete closure), or undescended testes. Breast development in men during puberty. Decreased body hair and beard, but with normal pubic and axillary hair and sexual dysfunction in males and infertility.
MAIS is only diagnosed in phenotypically (appearance) normal men, and is not normally investigated, except in cases of male infertility. MAIS has a light presentation that often goes unnoticed and untreated and therefore confirmation of an AR gene mutation is necessary.
The androgen sensitivity index (ASI), which is defined as the product of luteinizing hormone (LH) and testosterone, is frequently elevated in individuals with all forms of AIS (androgen insensitivity), including MAIS, although many individuals with MAIS have an index in the normal range. Testosterone levels may be elevated despite normal levels of the hormone LH.
The conversion of testosterone to dihydrotestosterone may be affected, although to a lesser extent than that seen in 5a-reductase deficiency. A high ASI in a normal phenotypic male, especially when combined with azoospermia or oligospermia, when there is a deterioration of T to DHT conversion, may be indicative of MAIS, and may justify genetic testing.
Suprafisiological doses of testosterone are sometimes needed to correct secondary sexual characteristics in men with MAIS, as well as to reverse infertility due to low sperm count.