section name header

General Reference

Nejm 2004;351:1227

Pathophys and Cause

Cause:Genetic mutation or transmitted as? "X-linked or autosomal dominant expressed only in male". No incr w advanced maternal age.

Pathophys:Part of mixed gonadal dysgenesis (see above); XO, X with partial X or Y deletion, isochromosome of X or Y, ring chromosome with deletion of X or Y. Lymphatic hypoplasia causes edema

Epidemiology

Rare, incid = 1/1500-2500 females, prevalence = 50-75 000 in US; more common in miscarriage fetuses

Signs and Symptoms

Sx:Short stature (90% are <5 ft); primary amenorrhea; multiple moles appear between age 4 and 15 yr

Si:Normal female genitalia; ankle edema; low hairline at base of neck; neck webbing (20%); multiple nevi and nail anomalies; increased carrying angle of elbow, short 4th metacarpal

Complications

Diabetes mellitus; Hashimoto's thyroiditis in up to 50%; congenital cardiovascular abnormalities, esp coarctation of the aorta (15%) and bicuspid aortic valve; renal and gi congenital abnormalities occasionally; tumors in streak gonads if present; renal HT; scoliosis (10%); OM from malformations of mouth/nose; hypothyroidism (20%); stabismus

Lab and Xray

Lab:

Path:Streak gonads w gonadal dysgenesis

Chromosome preps are Barr body-negative; get full karyotype to r/o XO-XY mosaicism with increased gonadal cancer incidence

Chem:FSH and LH increased (unlike hypogonadotrophic hypogonadism)

Xray:

Prenatal ultrasound may show lymphedema, thickened nuchal fold, cystic hygroma, horseshoe kidney

Knee films show overgrowth of medial tibial condyle

Treatment

Rx:

Growth hormone rx in late childhood (Nejm 1999;340:502, 557); ERT and cycled progresterone in adults; pregnancy possible esp w donated ova

Surgical removal of any streak gonad in all mosaics