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Clinical Findings

A. Symptoms and Signs

Features of Turner syndrome are variable and may be subtle in girls with mosaicism. Turner syndrome may be diagnosed in infant girls at birth, since they tend to be small and may exhibit severe lymphedema. Evaluation for childhood short stature often leads to the diagnosis. Girls and women with Turner syndrome have an increased risk of aortic coarctation and bicuspid aortic valves; these cardiac abnormalities are more common in patients with a webbed neck. Typical manifestations in adulthood include short stature, hypogonadism, webbed neck, high-arched palate, wide-spaced nipples, hypertension, and kidney abnormalities (Table 28-16. Manifestations of Turner Syndrome). Emotional disorders are common. Affected women are also more prone to autoimmune disease, particularly thyroiditis, IBD, and celiac disease.

Hypogonadism presents as "delayed adolescence" (primary amenorrhea, 80%) or early ovarian failure (20%); girls with 45,XO Turner (blood karyotyping) who enter puberty are typically found to have mosaicism if other tissues are karyotyped.

B. Laboratory Findings

Hypogonadism is confirmed in girls who have high serum levels of FSH and LH. A blood karyotype showing 45,XO (or X chromosome abnormalities or mosaicism) establishes the diagnosis. GH and IGF-1 levels are normal.

C. Imaging

A transthoracic ultrasound and MRI scan of the chest and abdomen should be done in all patients with Turner syndrome to determine whether cardiac, aortic, and renal abnormalities are present.

Treatment

For short stature, GH therapy should be started early, ideally by age 4-6 and before age 12 years. GH is given subcutaneously in doses of 50 mcg/kg/day or 4.5 IU/m2 /day; the GH dose is titrated to keep the serum IGF-I levels within 3 SD above the mean for age. Rarely, GH treatment causes pseudotumor cerebri. The oral androgen oxandrolone (0.03-0.05 mg/kg/day) is added after age 10 for girls whose growth is inadequate with GH therapy alone. After age 12 years, estrogen therapy is begun with low doses of transdermal estradiol, with a gradual increase in dose over 2-3 years. Progesterone is added after 2 years of estrogen therapy or if menstrual bleeding occurs. For girls age 12 years or older with Turner mosaicism and spontaneous menses, early oocyte retrieval and cryopreservation should be considered, while weighing the risks of pregnancy.

Complications & Surveillance

Women with Turner syndrome have a reduced life expectancy due in part to their increased risk of diabetes mellitus (types 1 and 2), hypertension, dyslipidemia, and osteoporosis. Patients are prone to keloid formation after surgery or ear piercing. Annual surveillance should include a blood pressure determination and laboratory evaluations that include 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 over age 18 years.

Bicuspid aortic valves are common and are associated with an increased risk of infective endocarditis, aortic valvular stenosis or regurgitation, and ascending aortic root dilation and dissection. The risk of aortic dissection is increased more than 100-fold in women with Turner syndrome, particularly those with pronounced neck webbing and shield chest. Patients with aortic root enlargement are usually treated with beta-blockade and serial imaging.

About 5% of women with Turner syndrome experience natural pregnancy and even more can become pregnant with oocyte donation. Such pregnancies are very high-risk, with increased fetal morbidity and preeclampsia. During pregnancy, women with Turner syndrome have a 2% risk of aortic dissection or rupture, so they require close monitoring with repeated echocardiography; those with aortic root diameter 4 cm or more are delivered by elective caesarean section, whereas those with an aortic root diameter less than 4 cm may deliver vaginally.

Partial anomalous pulmonary vein connections can lead to left-to-right shunting of blood. Adults with Turner syndrome also have a high incidence of ECG abnormalities, such as long QT syndrome.

Patients with the classic 45,XO karyotype have a high risk of renal structural abnormalities, whereas those with 46,X/abnormal X are more prone to malformations of the urinary collecting system.