Turner Syndrome (Gonadal Dysgenesis)

Key Features

• Group of X chromosome disorders associated with spontaneous pregnancy loss, primary hypogonadism, short stature, and other phenotypic anomalies

• Manifestations include

  • Short stature with normal growth hormone levels

  • Primary amenorrhea or early ovarian failure

  • Epicanthal folds, webbed neck, short fourth metacarpals

  • Renal and cardiovascular anomalies

• Incidence: 1 in 2500 live female births

• Diagnosis suspected: at birth, small newborns, often with lymphedema; in childhood, short stature

• Reduced life expectancy due to increased risk of diabetes mellitus, hypertension, dyslipidemia, and osteoporosis

Clinical Findings

• Features variable and may be subtle if mosaicism

• Short stature

• Webbed neck

• Aortic coarctation and bicuspid aortic valves (more common in patients with a webbed neck)

• High-arched palate

• Short fourth metacarpals

• Wide-spaced nipples

• Hypertension

• Kidney abnormalities

• Emotional disorders

• Autoimmune disease, particularly thyroiditis, inflammatory bowel disease, and celiac disease

• Hypogonadism presents as delayed adolescence (80%) or early ovarian failure (20%)

• Adults with Turner syndrome have a high incidence of ECG abnormalities

Diagnosis

• Serum FSH and LH levels elevated

• Karyotype shows 45, XO (or X chromosome abnormalities, or mosaicism)

• Serum growth hormone and IGF-I levels normal

• Transthoracic ultrasound and MRI scan of the chest and abdomen to determine presence of associated cardiac, aortic, and renal abnormalities

Treatment

• Growth hormone therapy

  • For short stature: start early, ideally by age 4–6 years and before age 12

  • Dosage: 50 mcg/kg/day subcutaneously, or 4.5 international units/m²/day

  • Oxandrolone (0.03–0.05 mg/kg/day) is added after age 10 for girls whose growth is inadequate with growth hormone therapy alone

• Estrogen therapy

  • Low doses of transdermal estradiol after age 12, with a gradual increase in dose over 2–3 years

  • Progesterone is added after 2 years of estrogen therapy or if menstrual bleeding occurs

• Annual surveillance should include

  • Blood pressure determination

  • Laboratory evaluations, including a serum TSH, liver enzymes, BUN, creatinine, and fasting serum lipids and glucose

• Celiac disease screening (serum TTG IgA Ab) is warranted every 2–5 years for school-age girls and then whenever indicated clinically

• Audiology exams are recommended every 1–5 years

• Bone mineral densitometries should be measured periodically for women > age 18 years

• Patients with aortic root enlargement are usually treated with β-blockade and serial imaging

• Pregnancy

  • Very high-risk, with increased fetal morbidity and preeclampsia

  • Patients have a 2% risk of aortic dissection or rupture, so they require close monitoring with repeated echocardiography

  • Delivery

    • Elective caesarean section if aortic root diameter ≥ 4 cm

    • Vaginal if aortic root diameter < 4 cm

• Early oocyte retrieval and cryopreservation should be considered for girls ≥ 12 with Turner mosaicism and spontaneous menses