Pediatric Medical Genetics - S.I. Smiian 2003

Chromosomal disorders
Turner syndrome

Turner syndrome is a clinical symptom complex observed in females, characterized by distinctive physical development and delayed sexual maturation. The incidence among newborn girls is approximately 1 in 3,000. X-chromosome monosomy occurs in about 1% of all conceptuses and in 18–20% of spontaneous abortions. Nearly 95% of all zygotes with an XO chromosome Complement perish prenatally. The condition was first described in 1925 by the endocrinologist N.A. Shereshevsky, who believed it was associated with hypoplasia of the anterior pituitary and Ovaries combined with other congenital developmental anomalies. The classic description belongs to H.H. Turner (1938). In 1954, Polani and co-workers established the absence of female sex Chromatin in these patients and hypothesized that the sex chromosome complement corresponded to the male type, XY. The cytogenetic Discovery of the XO syndrome was made by C.E. Ford in 1959.

Turner syndrome in males was described by Flavell. Patients with male Turner syndrome are phenotypically dwarfed boys with short stature, short neck, testicular aplasia, tubular dysgenesis, and reduced intelligence. The Y chromosome retains its activity to some extent. Furthermore, girls with gonadal dysgenesis, boys with Hermaphroditism, and those with frequent gonadal tumors exhibit a mosaic XO/XY chromosomal makeup; all of them are chromatin-negative, similar to other variants of Turner syndrome with chromosome complements such as XO, 46,XY, XO/XY, etc.

In Various Forms of mosaicism, clinical manifestations in these patients are less pronounced than in classical XO syndrome (lymphedema at birth and webbed neck folds are observed only in isolated cases, patient height may remain within the normal range, and spontaneous menstruation occurs more frequently).

Chromatin-positive variants of Turner syndrome are represented by XO/XX/XXX and XO/XXX karyotypes, prechromosomal mosaicism of XX₁ and XX/XX₁, karyotypes with a ring X chromosome: XO/XX₂, XO/XX/XX₂, XO/XX₂/XX₂/X₂, and a sex chromosome with long-arm deletion X₁XO/XX. The Gonads of such patients are underdeveloped, and marked infantilism is present.

The disorder is rooted in a pathological chromosomal complement (45 Chromosomes). The sex chromosomes are represented by a single X chromosome (designated as the XO complement). In some cases, morphological alterations in the X chromosome may occur despite a normal quantitative karyotypic ratio. Additionally, there are patients with a karyotype characteristic of Turner syndrome where XO chromosomes are detected only in a fraction of Cells, while other cells show different karyotypes such as XX, XY, XXX, XXY, etc. About 80% of these patients are chromatin-negative. Such patients are referred to as "mosaics."

The absence or alteration of the X chromosome disrupts protein and enzyme synthesis, which impairs metabolic processes in the body and leads to numerous congenital anomalies.

The Clinical presentation of the disease is highly variable.

The most frequent symptom is short stature. Even in childhood, these patients lag behind their peers, and by the time they reach Puberty, their height is only 130–145 cm. Data indicate a high incidence of Turner syndrome among short girls in Japan. The second characteristic feature is sexual infantilism, which is particularly evident during puberty in the form of Amenorrhea, hypoplasia of the genitalia, and underdeveloped secondary sexual characteristics. Streak gonads are found in place of the ovaries. Histological examination reveals Connective Tissue containing isolated ovarian tissue islands with primordial follicles and, very rarely, developed follicles. These patients are infertile. Body proportions are abnormal, with the upper half of the torso being significantly longer than the lower half. The ears are deformed and low-set. The hard palate is sometimes high and narrow ("gothic"), and dental malocclusion is observed. The neck is broad and short, with a low posterior hairline. Wide Skin folds extending from the mastoid processes to the shoulders give the neck its typical webbed appearance (pterygium coli). Hand anomalies manifest as shortening of the fourth fingers (due to short metacarpals) and clinodactyly of the fifth fingers. The third, fourth, and fifth toes are also shortened and deformed. The space between the First and Second toes is often increased. Persistent lymphedema of the extremities is observed. Turner syndrome is also associated with various internal organ abnormalities, including Congenital Heart defects and Anomalies of the great vessels (coarctation of the aorta, ventricular septal defect, pulmonary valve stenosis), as well as renal anomalies (Horseshoe Kidney, duplicated renal pelves or Ureters).

Neurological examination reveals no pathological changes. In 50% of cases, patients with Turner syndrome present with intellectual disability. They are passive and asthenic, with a tendency toward psychogenic reactions and reactive psychoses. Hearing impairment is common (in about 40%), often accompanied by otitis media. This is attributed to the abnormal position of the auditory tube resulting from maldevelopment of the caudal portion of the external acoustic meatus.

Diagnosing Turner syndrome in newborns is difficult because the characteristic features are not yet fully apparent. However, the most distinctive signs—such as a short neck with excess skin and folds, and lymphedema of the feet, lower legs, hands, and forearms—are present, allowing this chromosomal pathology to be suspected. In school-aged children, and particularly in adolescents, growth retardation, poor development of secondary sexual characteristics, amenorrhea, and the characteristic phenotype become evident. In older individuals, the Diagnosis is based on the clinical picture and sex chromatin analysis. The detection of an abnormal karyotype (45 chromosomes with an XO sex chromosome complement, etc.), along with the absence or reduced count of sex chromatin bodies, confirms the diagnosis.

Complete recovery is not observed, although therapeutic interventions can significantly improve the patients' condition.

Treatment for Turner syndrome is symptomatic, aiming to stimulate growth and correct secondary sexual characteristics. Anabolic Steroids (methylandrostenediol, nerobol) are used to promote linear growth.

Estrogen therapy is initiated at 13–15 years of age. Stilbestrol is prescribed at 1–2 mg every other day for 20 days. Estradiol benzoate is administered intramuscularly at 1 mg every 2–3 days for 6–12 months. Estrogen therapy is often highly effective, resulting in breast enlargement, the appearance of secondary sexual characteristics, and occasionally regular menstruation.