TESTICULAR FEMINIZATION

SYNDROME; TFM

Alternative titles

ANDROGEN INSENSITIVITY SYNDROME; AIS

ANDROGEN RECEPTOR DEFICIENCY

AR DEFICIENCY

Ruslan Bayramov .MD

Medical Genetics department Erciyes university.
 To be MAN or not to be MAN!!!
SRY– AZF-
Sex d. Region Azoospermia factor
for the SRY gene
Sex-determining Region Y (SRY)
Genital embryology
 Pathophysiology
Testicular Feminizing Syndrome

Androgen Insensitivity

Androgen receptor mutations

Androgen receptor
Gene/locus: AR (Xq11-q12).
 Androgen receptor mutations
• Over 400 AR mutations have been reported
• 30% of the time, the AR mutation is a spontaneous
• X-linked recessive
Genital embryology
SRY MIF
SRY MIF

INHIBITED
Female internal structures:
-Fallopian tubes
-Uterus
-Upper portion of
SRY Testosterone
Genital embryology
SRY Testosterone AR (
)
UNDEVELOPED
Male internal structures:
-Seminal vesicles
-Epididymis
-Ejaculatory duct
-Ductus deferens ……
… and Male external structures:
Androgen insensitivity syndrome

- Condition that results in the partial or

complete inability of the cell to
respond to androgens

-Clinically significant only when it occurs

in genetic males

- X-linked recessive
 Ais in XX karyotype

HETEROZYGOTE HOMOZYGOTE

• Phenotype Female NO CASE

• Reduced body hair REPORTED
• Delayed puberty
• Tall stature
 Three classes of AIS
• CAIS
Complete androgen insensitivity syndrome
• PAIS
Partial androgen insensitivity syndrome
• MAIS
Mild androgen insensitivity syndrome
 Complete androgen
insensitivity syndrome
• Phenotypically female
• Symptoms do not appear until puberty
• Absent menses
• External genitalia is normal
• Vaginal depth is short
• Not ovaries - atrophic testes
• Slightly longer limbs and larger hands and feet,
minimal or no acne, larger teeth, well developed
breasts.
• Greater incidence of meibomian gland
dysfunction (dry eye syndromes and light
sensitivity)
 Expectations
Testes may be located intra-
abdominally, at the internal inguinal
ring, or may herniate into the labia
majora.

Bilateral
inguinal
hernia

The risk: Malignant germ cell tumors

 Partial androgen insensitivity syndrome

• Significant in 46,XY karyotype

• Partially prevented masculinization of the
genitalia: penis diminished size, hypospadias,
enlarged clitoris.
• Wolffian structures are typically partially or
fully developed. (SEED)
• The prostate is small.
• Müllerian remnants are rare, but have been
reported.
• Gynecomastia
• High pitched voice
• Micropenis

Chordee Bifid scrotum

 Mild androgen insensitivity syndrome
• Impaired virilization or spermatogenesis
• Normal male genital
• Retractile testes
Kennedy Disease

A variant of MAIS

Spinal and bulbar muscular atrophy (SBMA)

 Differential diagnoses
• Klinefelter syndrome
• Turner syndrome
• Smith-Lemli-Opitz syndrome (associated with
intellectual disability
• Androgen excess in 46,XX individuals
• Mayer-Rokitansky-Küster-Hauser syndrome
• Kallmann syndrome (often associated with anosmia)
• Frasier syndrome (associated with progressive
glomerulopathy)
• Denys-Drash syndrome (associated with nephropathy
and Wilms tumor
 A diagnosis of CAIS or Swyer syndrome can be
made in utero by comparing a karyotype
obtained by amniocentesis with the external
genitalia of the fetus during a prenatal
ultrasound.
Swyer syndrome has been estimated to occur in
approximately 1 in 30,000 people.
CAIS affects 2 to 5 per 100,000 people who are
genetically male.
Reference: 1. Tables from First Aid USMLE step 1 book
2. Wikipedia