Shereshevsky-Turner syndrome.

Turner syndrome (Shereshevsky-Turner syndrome, Bonnevie-Ulrich syndrome, Syndrome 45, X0) is a consequence of the complete or partial absence of one of the two sex chromosomes, phenotypically determined to be female. Diagnosis is based on clinical manifestations and is confirmed by karyotype examination. Treatment depends on manifestations and may include surgery for heart defects, and often growth hormone therapy for short stature and estrogen replacement therapy in the absence of puberty.

It was first clinically described by the Russian endocrinologist N. A. Shereshevsky in 1926. The syndrome was cytogenetically verified in 1959. The population frequency is 1:5000 females.

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Epidemiology of Shereshevsky-Turner syndrome

Turner syndrome occurs in approximately 1/4000 live births and is the most common sex chromosome abnormality in women. At the same time, 99% of pregnancies with a 45, X fetal karyotype end in spontaneous abortion.

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What causes Turner syndrome?

Approximately 50% of patients with Turner syndrome have a 45,X karyotype; in about 80% of cases, the paternal X chromosome is lost. Most of the remaining 50% are mosaic (eg, 45,X/46,XX or 45,X/47,XXX). Among mosaic patients, the phenotype can range from typical for Turner syndrome to normal. Occasionally, girls with Turner syndrome may have one normal X chromosome and one X ring chromosome; to form a ring chromosome, it must lose a portion of both the short and long arms. Some girls with Turner syndrome may have one normal X chromosome and one isochromosome, consisting of the two long arms of the X chromosome that formed when the short arm was lost. Such girls tend to have many of the phenotypic features of Turner syndrome; Thus, it seems that divisions of the short arm of the X chromosome play an important role in the formation of the phenotype of Shereshevsky-Turner syndrome.

Pathogenesis of Shereshevsky-Turner syndrome

The absence or alteration of a sex chromosome leads to impaired ovarian maturation, absent or late partial puberty and infertility.

Symptoms of Shereshevsky-Turner syndrome

Many neonates have only very mild manifestations; however, some have marked dorsal lymphedema of the hands and feet and lymphedema or skin folds on the back of the neck. Other common abnormalities include webbed neck folds, a broad chest, and inverted nipples. Affected girls have short stature compared to family members. Less common features include a low hairline on the back of the neck, ptosis, multiple pigmented nevi, short fourth metacarpals and metatarsals, prominent finger pads with whorls at the ends of the fingers, and hypoplastic nails. Cubitus valgus (a hallux valgus) is also noted.

Common cardiac abnormalities include coarctation of the aorta and bicuspid aortic valve. Hypertension often develops with age, even in the absence of coarctation. Renal abnormalities and hemangiomas are common. Telangiectasia is sometimes found in the gastrointestinal tract, with subsequent gastrointestinal bleeding or protein loss.

Gonadal dysgenesis (ovaries are replaced by bilateral strands of fibrous stroma with no developing germ cells) is observed in 90% of patients, leading to the absence of puberty, absence of breast enlargement, and amenorrhea. At the same time, 5-10% of affected girls spontaneously undergo menarche, and very rarely affected women are fertile and have children.

Mental retardation is rare, but many patients have a decline in some perceptual abilities and, as a result, low scores on nonverbal tests and in mathematics, even though scores on the verbal component of intelligence tests are average or even high.

• Growth retardation, often from birth (100%).
• Gonadal dysgenesis with amenorrhea and sterility.
• Lymphatic edema of the dorsum of the hands and feet (40%).
• Broad chest with combined deformation of the sternum.
• Widely spaced, hypoplastic and inverted nipples (80%).
• Abnormally shaped and protruding ears (80%).
• Low hair growth rate.
• Short neck with excess skin and wing-like folds (80%).
• Cubitus valgus (70%).
• Narrow, hyperconcave and depressed nails (70%).
• Congenital kidney defects (60%).
• Hearing loss (50%).
• Congenital heart and aortic defects (coarctation of the aorta and valve pathology, dilation and dissection of the aorta) (20-40%).
• Idiopathic arterial hypertension (AH) (27%).

Diagnosis of Shereshevsky-Turner syndrome

In neonates, the diagnosis may be suspected by the presence of lymphedema or alar fold of the neck. In the absence of these changes, the diagnosis is detected later in some children based on short stature, amenorrhea, and absence of puberty. The diagnosis is confirmed by karyotype testing. Echocardiography or MRI is indicated to detect congenital heart defects.

Cytogenetic analysis and Y-probe studies are performed in all individuals with gonadal dysgenesis to exclude mosaicism with a cell line with a 46, XY (45, X/46XY) karyotype. These patients usually have a female phenotype with various features of Turner syndrome. They are at increased risk for developing gonadal malignancies, especially gonadoblastoma, so gonadectomy should be performed prophylactically immediately after diagnosis.

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Physical examination

The diagnosis is made on the basis of the characteristic clinical picture: a short neck with excess skin and alar folds in newborn girls, lymphedema of the hands and/or feet, congenital defects of the left heart or aorta (especially coarctation of the aorta ), delayed growth and sexual development during puberty in girls.

Laboratory research

Cytogenetic testing verifies the absence of the X chromosome or its structural changes.

Treatment of Shereshevsky-Turner syndrome

There is no specific treatment for the genetic disorder. Coarctation of the aorta is usually treated surgically. Other heart defects are treated with dynamic observation and surgical correction if necessary. Compression stockings are used for lymphedema.

Recombinant human growth hormone therapy may be initiated if height is less than the 5th percentile, with an initial dose of 0.05 mg/kg subcutaneously once daily. Typically, estrogen replacement therapy with conjugated estrogens 0.3 mg orally or micronized estradiol 0.5 mg once daily is needed to initiate puberty at age 12 to 13 years. Progestin-only oral contraceptives are then given to maintain secondary sexual characteristics. Growth hormone is continued along with sex hormone therapy until the growth plates have closed, at which time growth hormone therapy is stopped. Continuation of sex hormone replacement therapy helps to achieve optimal bone density and skeletal development.

Turner syndrome is treated by correcting short stature through courses of human somatropin, as well as by developing secondary sexual characteristics through the administration of estrogens.

What is the prognosis for Turner syndrome?

Shereshevsky-Turner syndrome has a favorable prognosis for life and intellectual development. Unfavorable for childbearing.