TESTICULAR FEMINIZATION SYNDROME; TFM

Alternative titles

ANDROGEN INSENSITIVITY SYNDROME; AIS

ANDROGEN RECEPTOR DEFICIENCY

AR DEFICIENCY

Ruslan Bayramov .MDMedical Genetics department Erciyes university.

To be MAN or not to be MAN!!!AZF-Azoospermia factor

SRY–Sex d. Region

for the SRY gene

Sex-determining Region Y (SRY)

Genital embryology

Pathophysiology

Testicular Feminizing Syndrome

Androgen Insensitivity

Androgen receptor mutations

Androgen receptorGene/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

INHIBITEDFemale internal structures:

-Fallopian tubes

-Uterus

-Upper portion of

vagina

SRY Testosterone

Genital embryology

SRY Testosterone AR( )

UNDEVELOPEDMale 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

• Phenotype Female • Reduced body hair• Delayed puberty• Tall stature

HETEROZYGOTE HOMOZYGOTE

NO CASE

REPORTED

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

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.

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 karyotypeobtained 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