Testicular feminization syndrome

1. TESTICULAR FEMINIZATION
SYNDROME; TFM
Alternative titles
ANDROGEN INSENSITIVITY SYNDROME; AIS
ANDROGEN RECEPTOR DEFICIENCY
AR DEFICIENCY
Ruslan Bayramov .MD
Medical Genetics department Erciyes university.

2. To be MAN or not to be MAN!!!
AZF-
Azoospermia factor
SRY–
Sex d. Region

3. for the SRY gene

4. Sex-determining Region Y (SRY)

5. Genital embryology

6. Pathophysiology
Testicular Feminizing Syndrome
Androgen Insensitivity
Androgen receptor mutations

7. Androgen receptor
Gene/locus:AR(Xq11-q12).

8. Androgen receptor mutations
• Over 400 AR mutations have been reported
• 30% of the time, the AR mutation is a spontaneous
• X-linked recessive

9. Genital embryology

10. SRY MIF

11. SRY MIF
INHIBITED
Female internal structures:
-Fallopian tubes
-Uterus
-Upper portion of

12. SRY Testosterone

13. Genital embryology

14. SRY Testosterone AR(
)
UNDEVELOPED
Male internal structures:
-Seminal vesicles
-Epididymis
-Ejaculatory duct
-Ductus deferens ……

15. … and Male external structures:

16. 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

17. Ais in XX karyotype
• Phenotype Female
• Reduced body hair
• Delayed puberty
• Tall stature
HETEROZYGOTE HOMOZYGOTE
NO CASE
REPORTED

18. Three classes of AIS
• CAIS
Complete androgen insensitivity syndrome
• PAIS
Partial androgen insensitivity syndrome
• MAIS
Mild androgen insensitivity syndrome

19. 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)

20. Expectations
Bilateral
inguinal
hernia
The risk: Malignant germ cell tumors
Testes may be located intra-
abdominally, at the internal inguinal
ring, or may herniate into the labia
majora.

21. 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.

22. • Gynecomastia
• High pitched voice
• Micropenis
Chordee Bifid scrotum

23. 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)

24. 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

25. 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