Klinefelter's syndrome is one of the most common chromosomal aneuploidies. This anomaly is characteristic only for men and occurs in about every five hundredth newborn boy. The syndrome is not fatal and does not create problems during gestation, childbirth and during childhood until puberty, so there are many people around people who suffer from symptoms of the disease, which they themselves may not even suspect.
The discovery of this chromosomal disease was made by Harry Klinefelter and Fuller Albright, who fully described most of the clinical signs in works dating back to 1942. The anomaly was named after the first of these due to a more significant contribution to research.
Since then, many minds have been trying to solve the problem of Klinefelter's syndrome, but so far genetics are not sufficiently developed to treat chromosomal abnormalities, although various ways have been developed to smooth out the main symptoms and improve the social life of carriers of more than two sex chromosomes.
Klinefelter's syndrome is a sex chromosome polysomy that occurs only in males. Polysomies with different numbers of sex chromosomes occur with different frequencies:
- 47 XXY;
- 47 XYY;
- 48 XXYY;
- 48 XXXY;
- 48 XYYY;
- 49 XXXXY;
- 49 XXXYY.
These cytogenetic variants can be combined in one organism, which is defined in genetics as mosaicism, due to which some clinical manifestations of chromosomal diseases can be smoothed or aggravated. The most common variant is the classic Klinefelter syndrome - 47 XXY. The frequency of manifestation of this disease in one in five hundred to seven hundred boys has been proven. This is much more common than, for example, congenital abnormalities of the adrenal cortex, which occur only in 1 in 10-20 thousand newborns.
Due to the aforementioned frequency in 0.2% of the male population, sex chromosome polysomy can be detected in any patient with the characteristic symptoms of the disease: hypogonadism, erectile dysfunction, infertility and gynecomastia. Therefore, in addition to the genetic nature, Klinefelter's syndrome is ranked among endocrine pathologies, and among them it ranks third in prevalence after diabetes mellitus and various problems with the thyroid gland.
Recent studies of the syndrome provide a basis for the hypothesis that almost half of all patients with sex chromosome polysomy are not registered due to the weak manifestation of symptoms. Such patients are usually registered with doctors of other specialties, undergoing treatment for complications provoked by ignoring and lack of therapy for hypogonadism, its causes and consequences.
- Klinefelter syndrome symptoms
- Causes of Klinefelter syndrome
- Diagnostics of the Klinefelter syndrome
- Treatment for Klinefelter syndrome
Klinefelter syndrome symptoms
At an early age, Klinefelter's syndrome does not give vivid manifestations by which one could detect pathology in a child. The exception is serious mental disorders and mental disorders provoked by Klinefelter's syndrome, due to which the child does not adapt well in society, can show outbursts of aggression, becomes withdrawn and apathetic.
Most of the symptoms appear already during adolescence, during puberty. In boys, the mammary glands can swell and increase in size, the hair is sparse and occurs in the female pattern. The most striking of the symptoms is high growth and a specific body structure with a high waist, narrow shoulders and extended hips.
By itself, gynecomastia is not a symptom that unequivocally indicates the presence of Klinefelter's syndrome - an increase in the mammary glands is observed in more than 60% of male adolescents and goes away on its own after two years. However, in boys with Klinefelter's syndrome, gynecomastia does not disappear on its own, they need hormone replacement therapy.
The most striking symptom of pathology and one of the few signs that allow to determine Klinefelter's syndrome before the patient reaches the age of puberty is growth. Patients with Klinefelter's syndrome are usually taller than 185 cm, while they grow most intensively at 5-8 years old, which is why they stand out among their peers. For some forms of pathology, high growth is uncharacteristic (with two or three additional X chromosomes), but they often have a number of other striking manifestations.
Patients with Klinefelter's syndrome have a characteristic appearance: high waist, long arms and legs, arm span rarely exceeds height, and the upper body is shorter than the lower one.
Other symptoms of the disease:
- Rare and weak hair growth - in men, hair on the face and in the armpits does not grow well, pubic hair is located according to the female type;
- An atypical structure of the face with features characteristic of pathology - wide-set eyes, maybe squint, a wide flattened nose and a half-open large mouth. The auricles are deformed, set low;
- Bone anomalies - Many of the defects in bone tissue can manifest at birth. Sunken or misshapen sternum, micrognathia, high palate, and clinodactyly (curvature of the fingers).
- The appearance of the genitals - the penis is underdeveloped, one or both testicles may be missing in the scrotum due to cryptorchidism, their size does not correspond to the norm for healthy men of the same age.
- Sexual impairment, a significant deterioration in potency in 70% of patients over the age of 25.
The mental manifestations of Klinefelter syndrome can be very diverse - some children are characterized by unstable behavior, often show aggression and anger, while others, on the contrary, are in a cheerful and elated state of mind most of the time.
Mental development in Klinefelter's syndrome can be impaired - in many patients, there is a decrease in verbal intelligence, which leads to difficulties in assimilating school material. The manifestations of the disorder can range from mild difficulties in perceiving and memorizing information by ear to severe developmental delays with peers. Cognitive activity suffers less than verbal, therefore, in general, the IQ of such patients may have average or even much higher than normal values.
Children with Klinefelter's syndrome may be apathetic, prone to depressive states, and have problems with adaptation in society. They may experience abrupt mood changes, mental lability - from a calm and balanced child, suddenly becomes angry and aggressive, after which it can just as suddenly become cheerful and full of enthusiasm. In most cases, friends and relatives of patients describe them as modest, vulnerable and sensitive people who have a hard time making contact with others.
Causes of Klinefelter syndrome
The synthesis of extra chromosomes, as in any polysomy, occurs due to the nondisjunction of already formed chromonemes during meiotic division of gametes (germ cells), or during mitotic division of embryonic cells at the stage of zygote and blastulation of the embryo. According to statistics, distortion of the genetic material is most often observed in the first variant. Approximately two thirds of all cases of the disease are provoked by an error during oogenesis (the formation of the mother's egg and follicular bodies), the other third is due to nondisjunction during spermatogenesis (the formation of paternal sperm).
The only link that can be traced in the study of the anamnesis of thousands of patients with Klinefelter syndrome was established with the age of the mother (the older, the higher the likelihood of the disease). The age of the child's father, as it turned out, does not affect the chance of the syndrome. Therefore, prenatal screening is mandatory for older mothers, although the reason for this is not so much the polysomy of sex chromosomes, but other aneuploidies that are associated with an increased risk of miscarriage and a possible lethal factor. Unlike most chromosomal diseases, Klinefelter's syndrome does not affect the birth process and the viability of a newborn, which is why a statistical doubling of the number of patients in the world is assumed due to the impossibility of registering all patients.
Diagnostics of the Klinefelter syndrome
As already mentioned, many (about half) of all cases of sex chromosomal polysomy remain undiagnosed due to the neglect of prenatal screening due to the positive results of fetal ultrasound. Such patients are found in adulthood when visiting a doctor with problems such as impotence, infertility and enlargement of the mammary glands (although often even these disadvantages are not considered worthy of a hospital visit due to obesity and various prejudices).
The only reliable way to detect a chromosomal abnormality is karyotyping. It is recommended for infertile men with developed mammary glands, as well as for boys with mental disabilities.
Other symptoms of the syndrome are detected through the following procedures:
- Biochemical blood test to detect a decrease in testosterone levels and an increase in follicle-stimulating and luteinizing hormones;
- Spermogram to detect reduced sperm activity or defectiveness (azoospermia);
- Ultrasound examination of the heart to fix its malformations;
- Densitometry to look for osteoporosis;
- Histological examination of obesity, if any.
Diagnosis of Klinefelter's syndrome in the prenatal period is made by one of two invasive methods: chorionic biopsy (from 9.5 to 12 weeks) or amniocentesis (from 16 to 18 weeks of gestation).
If a sex chromosome polysomy is detected in an unborn child, the doctor must not influence the mother's decision and fully describe the possible problems of a person with this syndrome and methods for solving them. With early diagnosis of the disease, thanks to well-planned treatment of hormonal imbalance and other symptoms, significant results can be achieved - to ensure a normal life for a patient with a chromosomal abnormality.
In some cases, when using modern IVF methods, a patient with Klinefelter syndrome may have children. Practice and research results show that children from fathers with sex chromosome polysomy are born healthy.
Treatment for Klinefelter syndrome
There is no cure for Klinefelter's syndrome, as is the case with other chromosomal abnormalities. But patients can undergo surgical correction of some external signs of the disease, such as a cleft lip, and they also need hormone replacement therapy due to the lack of natural androgens in the desired concentration.
In general, the standard of living of patients with Klinefelter's syndrome does not differ in quality from that of healthy people. However, patients with this pathology are more prone to the development of obesity and type 2 diabetes, osteoporosis, diseases of the cardiovascular system associated with congenital heart defects.
In some patients, mental problems are observed, which, with progression, can reduce intelligence to the stage of debility.
The common manifestation of Klinefelter's symptom for almost all patients is male infertility due to lack of sperm or low sperm viability. At the same time, men with a mosaic form of the disease can have children if they use IVF technologies.
Therapy for patients with Klinefelter's syndrome should include medications that prevent bone fragility and other pathologies of the musculoskeletal system, hormonal drugs that reduce the risk of developing malignant tumors against the background of gynecomastia.
Article author: Mochalov Pavel Alexandrovich | d. m. n. therapist
Education: Moscow Medical Institute. IM Sechenov, specialty - "General Medicine" in 1991, in 1993 "Occupational Diseases", in 1996 "Therapy".