Pediatric Medical Genetics - S.I. Smiian 2003

Chromosomal diseases
Klinefelter syndrome

Klinefelter syndrome is a distinct clinical symptom complex in males, which in some cases is accompanied by neuropsychiatric disorders. The incidence of the syndrome among newborn boys is 0.2%. The condition was first described in 1942 by Klinefelter in males presenting with delayed sexual development. In 1959, Jacobs and Strong demonstrated the presence of a pathological sex chromosome complex — XXY — in these patients.

The underlying cause of the disease is a pathological set of sex Chromosomes. Instead of a normal karyotype with 46 chromosomes, individuals with Klinefelter syndrome have 47 chromosomes. Specifically, affected males possess two X chromosomes (instead of the normal one X and one Y), resulting in an XXY sex chromosome Complement. Additionally, this syndrome can present with various cytogenetic variants and their combinations. Several types of X and Y chromosome polysomy have been identified in males: 47 XXY; 48 XXXY; 49 XXXXY; 47 XYY; 48 XYYY; 48 XXYY; 49 XXXYY. The most common form is the X-polysomic Klinefelter syndrome (XXY). The overall incidence of this syndrome ranges between 2 and 2.5 per 1000 newborn boys.

Affected men typically present with tall stature, elongated limbs, an eunuchoid body habitus, poorly developed musculature, as well as testicular atrophy and underdeveloped secondary sexual characteristics. Gynecomastia (enlargement of the breast tissue) frequently develops during Puberty. As a rule, varying degrees of intellectual disability and psychiatric disorders are observed, including Schizophrenia-like states, manic-depressive psychosis, and others. Individuals with 3 to 4 X chromosomes exhibit skeletal abnormalities, more pronounced Hypogenitalism, cryptorchidism, and severe mental deficiency, sometimes bordering on idiocy. No Metabolic Disorders have been associated with this condition. Cardiovascular function remains unimpaired. Elevated levels of chorionic gonadotropin are noted. Diagnosis is based on clinical findings and the determination of a pathological karyotype, which can be confirmed by examining sex Chromatin in Cells. Due to the presence of an additional X chromosome, sex chromatin is detected, which is normally absent in male cells.

Patients are viable.

There is no specific Treatment. Replacement therapy is administered to promote The Development of secondary male sexual characteristics: methyltestosterone (5–25 mg daily); tocopherol (100–200 mg daily); and for patients aged 14 to 20 years, prolonged-action androgens (500–1000 mg daily). However, patients remain infertile even after hormone replacement therapy.

A distinct variant of Klinefelter syndrome is Y-chromosome polysomy (XYY). It was first described by J.S. Hauschka in 1962 in phenotypically normal men. The incidence of this syndrome in the general population is estimated at 0.1–0.15%, although it is significantly higher among psychiatric populations (ranging from 0.45 to 15%).

Clinically, XYY syndrome resembles Klinefelter syndrome. However, men with the XYY chromosomal complement are significantly taller, averaging over 180–185 cm in height. Intelligence is preserved, though cognitive development falls within the low-to-average normal range. Some individuals exhibit aggressive behavior and oligophrenia. Most of these individuals lack any specific somatic abnormalities, which is why they rarely come to medical attention. As with Klinefelter syndrome, patients with the XYY symptom complex experience Infertility, endocrine imbalance, and testicular hypoplasia. Histological examination reveals a reduction in terminal Cells of the seminiferous tubules, hyalinization, and thickening of the basement membranes.

There is no radical cure.