Disorder of sexual dysmorphism

Question 1

21-Hydroxylase Deficiency – Congenital Adrenal Hyperplasia (CAH): Genetics

Answer 1

Inheritance: Autosomal recessive
Gene: CYP21A2
Metabolic testing: Elevated serum 17-hydroxyprogesterone

Question 2

21-Hydroxylase Deficiency – Congenital Adrenal Hyperplasia (CAH): Major features

Answer 2

Major features:
●SALT WASTING
●Prenatal virilization in females
●Childhood virilization of males and females
●Ambiguous genitalia in females
●Cortisol deficiency

Treatment: Glucocorticoid replacement therapy, Florinef for salt-wasting
ON NEWBORN SCREENING PANELS

Question 3

Androgen Insensitivity: Genetics

Answer 3

Inheritance: X-linked
Gene: AR

Question 4

Androgen Insensitivity: Major features

Answer 4

●Inability to utilize androgen for virilization due to defective androgen receptor
●46, XY karyotype with “biologically female” appearance
●Individuals with complete androgen insensitivity appear phenotypically female, but are lacking a uterus (Mullerian regression)
oBlind-ending vagina (no cervix)
●Individuals with partial androgen insensitivity may exhibit ambiguous genitalia and/or undervirilzation at puberty
●Increased risk for germ-cell tumors necessitates the removal of undescended testes

Question 5

Kallman Syndrome: Genetics

Answer 5

Inheritance: X-linked, Autosomal Dominant, Autosomal Recessive
Genes: KAL1, KAL2 (FGFR1), KAL3

Question 6

Kallman Syndrome: Major features

Answer 6

Major features:
●Normal sex differentiation at birth
●Failure to start or complete puberty
●Small testicles
●Primary amenorrhea
●Poorly defined secondary sexual characteristics
●Infertility
●Hypogonadotropic hypogonadism
●Anosmia (delineates Kallman from other types of hypogonadotropic hypogonadism)
●Sensorineural hearing problems
●Mirror movement of hands (synkinesis)
●Renal agenesis/aplasia
●Dysmoprhic features:
    oCleft palate
    oCraniofacial defects
    oMicropenis
    oCryptorchidism
    oDental defects

Treatment:
●Hormone replacement therapy

Question 7

X-linked Adrenal Hypoplasia Congenita: Genetics

Answer 7

Inheritance: X-linked recessive
Gene: NR0B1

Question 8

X-linked Adrenal Hypoplasia Congenita: Major features

Answer 8

Major features:
●Acute adrenal insufficiency 
●Adrenal failure
●Hypogonadotropic hypogonadism
●Developmental delay

Treatment:
●Glucocoriticoid and mineralcorticoid replacement therapy