Treatment of Klinefelter syndrome in men and prognosis for recovery

Klinefelter syndrome is a hereditary disease. The clinical picture of the syndrome was described in 1942 in the works of Harry Klinefelter and Fuller Albright.

Klinefelter syndrome is a genetic disease that is diagnosed exclusively in men. Its characteristic feature is the presence of an additional female sex chromosome in the male XY karyotype. The disease manifests itself through the development of various endocrine disorders. A person with this diagnosis has defective and insufficient production of male sex hormones.

Klinefelter syndrome is not a rare condition. It is diagnosed in 1 in 800 newborn boys per year. Often it is not possible to carry out a full diagnosis of the disease, which later becomes the reason for its severe course. Usually the disease leads to infertility, so we can say that it is not transmitted from generation to generation.

Prevalence of the disease

Klinefelter syndrome is one of the most common genetic diseases. About 0.2% of the male population of the Earth suffers from this pathology. In addition, Klinefelter syndrome is the third most common endocrine pathology in men (after diabetes mellitus and hyperthyroidism).

Today, Klinefelter syndrome is the most common cause of congenital reproductive dysfunction in men. According to statistics, about half of cases of Klinefelter syndrome remain unrecognized. Often such patients seek help for various disorders (infertility, erectile dysfunction, gynecomastia, osteoporosis, etc.

), but the underlying disease remains undiagnosed.

Etiology

Klinefelter syndrome is caused by a gene mutation that leads to the duplication of the female sex chromosome in the male karyotype. Nondisjunction of sex chromosomes during the process of meiosis or mitosis can be caused by various factors. The most common among them are:

• Viruses,
• Inferiority of the immune system of the mother or father,
• Poor ecological state of the environment,
• Children from consanguineous marriages,
• Early or late maternal age
• Hereditary pathologies in previous generations.

Boys with Klinefelter syndrome acquire one Y chromosome and several X chromosomes instead of the normal male XY genotype. Such a change in the genetic makeup leads to the appearance of special external characteristics, a slight decrease in intelligence and the development of a number of concomitant diseases.

An increase in the concentration of follicle-stimulating and luteinizing hormones in the blood leads to fibrosis, hyalinosis and atrophy of the seminiferous tubules. The testicles stop developing and become small and dense. Obliteration of the seminiferous tubules ends with the development of azoospermia and infertility.

Signs and symptoms

Unlike a large number of different diseases with chromosome disorders, the intrauterine development of babies with this diagnosis is quite normal. This suggests that it is impossible to suspect the progression of a genetic disease either in infancy or early childhood. Its first signs may appear in the prepubertal period:

• boys from 5 to 8 years old are tall (relative to their peers);
• high waist;
• legs and arms are elongated;
• impairment of auditory information perception.

Signs of the disease in adolescence:

• gynecomastia - breast enlargement;
• there is little facial hair or it may be completely absent;
• hair in the pubic area grows in a female pattern (triangle);
• there is no hair on the chest and other parts of the body;
• small testicles.

Upon reaching 25 years of age, patients begin to complain of:

• decreased libido and potency;
• male infertility;
• osteoporosis;
• obesity;
• It is also possible to develop diabetes mellitus and rheumatoid arthritis.

Symptoms of the disease directly depend on the formed karyotype. The degree of their expression depends on how many additional chromosomes this same karyotype has. Symptoms of karyotype 48 XXYY:

• high growth. In most cases, the patient’s height is above 182 cm;
• aggressiveness;
• decreased intelligence;
• dysphoria;
• tendency to depression;
• slow speech.

Symptoms of the disease with karyotype 48 XXXY:

• medium or tall height;
• ocular hypertelorism;
• flat bridge of the nose;
• clinodactyly 5 fingers;
• decreased intelligence;
• apathy;
• there is no aggression.

Symptoms of pathology in the case of karyotype 49ХХХХ:

• the bridge of the nose becomes almost flat;
• ocular hypertelorism;
• microcephaly (head small compared to body);
• the palpebral fissure is narrow;
• developmental anomalies of the upper and lower extremities (curvature of the shape of the feet, knee joints);
• outbursts of anger;
• aggressiveness.

The symptoms of the mosaic form of the disease are the same as those of the classic form. The only thing worth noting separately is that with this form the patient still has the opportunity to have children. Of course, it is reduced, but still present.

Treatment

With clinically pronounced Klinefelter syndrome, lifelong replacement therapy with the male hormone testosterone is necessary. Adequate therapy allows not only to improve the appearance and general well-being of the patient, but also to restore the ability to have a normal sexual life.

In addition, replacement therapy prevents osteoporosis and muscle weakness, and if they develop, it can return the patient’s bones and muscles to normal. At a young age, treatment should begin immediately after diagnosis, as this is necessary to prevent gynecomastia.

To prevent concomitant diseases such as obesity and type 2 diabetes, patients are advised to adhere to a diet and monitor their own weight.

Prevention of the syndrome and prognosis

Patients suffering from Klinefelter syndrome have the same life expectancy as other people, although the presence of a tendency to develop chronic diseases may be a factor in early mortality. Most of these patients are infertile.

The only probable option for having children in a family in which the partner is sick is the use of donor seminal fluid.

But, nevertheless, in the presence of a mosaic form of Klinefelter syndrome, a man can still become a father on his own or use assisted reproductive technology, for example, in vitro fertilization.

To assess the likelihood of having a child with this syndrome during pregnancy monitoring, women are offered prenatal screening. True, even in cases of receiving positive information about the presence of such a syndrome in the fetus, the gynecologist’s insistence that the woman terminate the pregnancy is absolutely unacceptable.

Thus, the decision on the advisability of continuing pregnancy should be made exclusively by future parents. If the parents have a normal karyotype, the risk of having a child with a similar chromosomal abnormality is no more than one percent.

Clinical observation of patients suffering from Klinefelter syndrome is carried out by endocrinologists.

(1

Source: https://osindromah.ru/geneticheskie/sindrom-klajnfeltera.html

Klinefelter syndrome

Klinefelter syndrome is a chromosomal pathology caused by the presence of one or more additional female sex chromosomes in the male karyotype. Klinefelter syndrome is characterized by primary hypogonadism, small testicles, infertility, gynecomastia, and a slight decrease in intelligence. Karyotyping plays a decisive role in the diagnosis of Klinefelter syndrome; phenotypic characteristics are also analyzed, sex chromatin is determined, follicle-stimulating hormone excretion in urine, spermogram, etc. Treatment for Klinefelter syndrome includes hormonal therapy, possibly surgical correction of gynecomastia, but complete cure of the syndrome is impossible.

Klinefelter syndrome is a disomy or polysomy of the female sex chromosome, in which males have at least two X chromosomes and one Y chromosome. Klinefelter syndrome occurs with a frequency of 1 case per 850-1000 newborn boys. Among children suffering from mental retardation, the prevalence of Klinefelter syndrome is 1–2%.

The syndrome was named after the American doctor Harry Klinefelter, who first described it in 1942. The karyotype of such patients with an additional X chromosome was determined in 1959.

Since the leading clinical manifestation of Klinefelter syndrome is primary hypogonadism, such patients are managed by specialists in the field of endocrinology and andrology.

Klinefelter syndrome

As in the case of Down syndrome, chromosomal aberration in Klinefelter syndrome is associated with non-disjunction of chromosomes (in the latter case, sex chromosomes) during meiosis or a violation of zygote division. Moreover, much more often (60%) boys with Klinefelter syndrome receive an extra maternal X chromosome than the paternal one.

Among the possible causes of this kind of chromosomal abnormalities are viral infections, late pregnancy, and inferiority of the regulatory mechanisms of the maternal and paternal immune systems.

In the presence of an extra X chromosome, aplasia of the testicular epithelium develops, their subsequent hyalinization and atrophy, which in adulthood is accompanied by azoospermia and endocrine infertility. Among the causes of male infertility, Klinefelter syndrome accounts for 10%, which specialists in the field of reproductive medicine should always remember.

The most common cytogenetic type is the complete variant of Klinefelter syndrome with karyotype 47,XXY. Mosaicism (46XY/47XXY; 46XX/47XXY) is less common, and polysomy 48,XXXY is even less common; 48,XXYY; 49,XXXXY, etc.

In the mosaic variant (about 10% of cases), some of the cells have a normal karyotype, so men with Klinefelter syndrome can have normally developed and functioning gonads and preserved reproductive abilities.

A child with Klinefelter syndrome is born with normal height and weight, correct differentiation of the external genitalia, and normal testicular sizes. At an early age, boys with Klinefelter syndrome may experience a frequent incidence of ARVI, bronchitis, and pneumonia.

At pre-pubertal age, unilateral or bilateral cryptorchidism may be detected.

Moderate mental retardation, difficulties establishing contact with peers, and behavioral disorders are observed in half of patients with Klinefelter syndrome.

Distinct external signs indicating the presence of Klinefelter syndrome in a child appear in the prepubertal and pubertal periods of development. These include eunuchoid body type, late appearance of secondary sexual characteristics, testicular hypoplasia, small penis, and gynecomastia.

In the postpubertal period of ontogenesis, involution of the testicles is observed, accompanied by loss of fertility. When examining a teenager with Klinefelter syndrome, the absence or scant growth of hair on the face and in the armpits, and female-type pubic hair are revealed.

Most patients have rare emissions, erections, and preserved sexual desire, but due to severe androgen deficiency, on average, by the age of 30, libido decreases and impotence develops.

Klinefelter's syndrome is often accompanied by skeletal abnormalities (chest deformities, osteoporosis), malocclusion, congenital heart defects, etc. The predominance of vagotonic reactions is characteristic: bradycardia, acrocyanosis, sweating of the palms and feet. On the part of the organ of vision, nystagmus, astigmatism, and ptosis of the eyelid are often noted.

Patients with Klinefelter syndrome are predisposed to the development of concomitant diseases: epilepsy, breast cancer, diabetes mellitus, COPD, cholelithiasis, varicose veins, obesity, hypertension, coronary artery disease, rheumatoid arthritis, acute myeloid leukemia. Mental illnesses may occur - manic-depressive psychosis, schizophrenia, etc. There is evidence confirming the tendency of patients with Klinefelter syndrome to alcoholism, drug addiction and homosexuality.

Like other chromosomal abnormalities, Klinefelter syndrome in the fetus can be detected during pregnancy during invasive prenatal diagnostics (amniocetesis, chorionic villus sampling or cordocentesis followed by karyotype analysis or qf-PCR).

When studying sex chromatin, Bar's bodies are present in the cells of the oral mucosa, which is a marker of Klinefelter syndrome.

Other characteristic signs are special changes in the skin pattern on the fingers. However, a definitive diagnosis of a chromosomal abnormality can only be made after karyotype examination.

Ultrasound of the scrotum reveals a decrease in the volume of the testicles. When studying the androgen profile, the level of testosterone in the blood of patients with Klinefelter syndrome is reduced, but there is an increase in the level of follicle-stimulating and luteinizing hormones.

When analyzing the spermogram, oligo- or azoospermia is revealed.

Morphological examination of the material obtained by testicular biopsy reveals hyalinosis of the seminiferous tubules, Leydig cell hyperplasia, a decrease in the number of Sertoli cells, and lack of spermatogenesis.

Throughout their lives, men with Klinefelter syndrome can consult an andrologist, sexologist, endocrinologist with problems of infertility, impotence, gynecomastia, osteoporosis, etc., but often the underlying disease remains unrecognized.

It is not possible to completely recover from Klinefelter syndrome. However, all patients require symptomatic and pathogenetic therapy. In childhood, prevention of infectious diseases, hardening, exercise therapy, and correction of speech disorders with the help of a speech therapist are necessary.

From adolescence, patients with Klinefelter syndrome are prescribed lifelong sex hormone replacement therapy (intramuscular injections of testosterone propionate, sustanon-250; sublingual administration of methyltestosterone, etc.).

In order to increase working capacity and social adaptation, prevent psychopathization of the individual and its antisocial orientation, psychotherapy is indicated.

Patients with Klinefelter syndrome have a normal life expectancy, but the tendency to develop chronic diseases can be a risk factor for early mortality.

Most patients with Klinefelter syndrome are infertile; the only possible option for having children in families where the partner is sick is the use of donor sperm.

However, with the mosaic form of Klinefelter syndrome, men can become fathers on their own or using assisted reproductive technologies (IVF).

To assess the likelihood of having a child with Klinefelter syndrome during pregnancy, women are offered prenatal screening.

However, even if positive data are received for the presence of Klinefelter syndrome in the fetus, insistence on termination of pregnancy by an obstetrician-gynecologist is unacceptable. The decision on the advisability of prolonging pregnancy should be made by the parents.

With a normal karyotype of the parents, the risk of re-appearance of a child with the same chromosomal abnormality is no more than 1%.

Dispensary observation of patients with Klinefelter syndrome is carried out by an endocrinologist.

Source: https://www.KrasotaiMedicina.ru/diseases/children/klinefelter-syndrome

Experience of using Nebido in a patient with Klinefelter syndrome

Comments

Published in the journal:
“Obesity and Metabolism” 2007, No. 2, p. 32-34

YES. Gusakova, G.Zh. Mskhalaya, Yu.A. Titova, S.Yu. Kalinchenko Ministry of Health and Social Development Federal Center "ROSMED TECHNOLOGIES"

State Institution Endocrinological Research Center, Department of Andrology and Urology

Klinefelter syndrome, being one of the most common congenital endocrine pathologies (prevalence is 1 in 500 newborn boys), is still one of the most common diseases that remain without diagnosis and treatment.

Klinefelter syndrome is a congenital disorder involving cases of sex chromosome polysomy, in which there are at least two X chromosomes and at least one Y chromosome. The most common karyotype in Klinefelter syndrome is 47,XXY.

Despite the high frequency of occurrence, in approximately half of patients this syndrome remains unrecognized throughout their lives [2].

The prevalence of androgen deficiency in patients with Klinefelter syndrome reaches 79% [3,4]. Such patients can be observed by doctors of various specialties with complications associated with the lack of treatment for the underlying disease, i.e.

with symptoms and complications of hypogonadism.

The main clinical manifestations of this pathology and, accordingly, the main complaints of patients are obesity, gynecomastia, impaired spermatogenesis, erectile dysfunction, increased fatigue, and decreased tolerance to physical activity [5].

By the beginning of puberty, characteristic body proportions are formed: patients are often taller than their peers, but unlike typical eunuchoidism, their arm span rarely exceeds the length of the body, and their legs are noticeably longer than the body.

In adolescence, Klinefelter syndrome often manifests as bilateral gynecomastia, although in some cases this symptom may be absent.

It should be noted that 60-75% of adolescents of puberty also experience enlargement of the mammary glands - pubertal gynecomastia, which, however, goes away on its own within 2 years, while in patients with Klinefelter syndrome, gynecomastia persists for life.

Considering the high frequency and prevalence of this disease, there is a need for a targeted search for patients with this pathology for the purpose of early prescription of testosterone replacement therapy.

Clinical symptoms of the disease appear after puberty, which is the reason for late diagnosis and, accordingly, untimely prescription of testosterone replacement therapy.

At the moment, the only pathogenetic treatment method for patients with Klinefelter syndrome is the prescription of hormonal replacement therapy with testosterone preparations.

Replacement therapy should be started as early as possible to prevent the onset of symptoms and consequences of androgen deficiency.

Adequate hormonal therapy eliminates all clinical manifestations of hypogonadism, except infertility, and does not lead to the disappearance of gynecomastia.

If gynecomastia bothers the patient, you can resort to a mastectomy, performed by an experienced specialist in a plastic surgery clinic.

It is necessary to start replacement therapy as early as possible. As shown, in particular by Nielsen et al. [6], early testosterone replacement therapy not only relieves symptoms such as anemia, osteoporosis, muscle weakness and sexual dysfunction, but also promotes the social adaptation of patients and their integration into public life.

For Klinefelter syndrome, it is better to use long-acting testosterone preparations.

At the moment, the drug of choice for long-term hormone replacement therapy for primary hypogonadism, including Klinefelter syndrome, is Nebido (Bayer Schering Pharma AG). Nebido is a depot drug with a slow release of the active substance, injections of which are given once a day. 3 months, t.

Yes, only 4 times a year.

The following is a clinical case study of a patient with Klinefelter syndrome, in whom untimely prescribed therapy led to the development of metabolic syndrome and osteoporosis.

Patient K., 27 years old, first applied to the Andrology Department of the State Research Center of the Russian Academy of Medical Sciences with complaints of periodic pain in the back and legs, enlarged mammary glands, general weakness, and decreased performance.

Drawing. Patient K., 27 years old, before treatment

From the anamnesis: he was always ahead of his peers in height. At the age of 15, the mother began to notice enlargement of the mammary glands; around the same time, complaints of general weakness, decreased performance, and periodic pain in the back and legs began to appear.

The diagnosis of “Klinefelter syndrome” was established in 2004 (25 years old), when the patient was examined due to complaints of pain in the back, legs, enlarged mammary glands, and small testicles. During examination: karyotype - 47.XXY, height - 193 cm, weight - 103 kg.

Hormonal examination revealed high levels of LH - 24.3 U/l (2.5 - 11.0), FSH - 39 U/l (1.55 - 9.74), low concentration of total testosterone - 2.1 nmol/ l (11-33.5), increased levels of triglycerides - 2.29 mmol/l (0.1-2.2), total cholesterol - 5.4 mmol/l (3.3-5.2); as well as impaired glucose tolerance: fasting glucose - 4.5 mmol/l, at 120' against the background of OGTT - 8.5 mmol/l. Dynamic monitoring was recommended. For two years the patient remained without treatment. In May 2006, the patient sought consultation at the Andrology Department of the State Research Center of the Russian Academy of Medical Sciences.

At the initial examination, the general condition is satisfactory. Height - 193 cm, weight - 115 kg, BMI = 31.1 kg/m2, WC - 117 cm, VR - 120 cm, WC/VR = 0.98, BP 144/86 mm Hg, st. The hair growth line above the forehead is straight, on the face and chest it is absent, in the armpits there are no features.

Bilateral true gynecomastia. Pubic hair growth is female type. Sexual status: Testis dexter = Testis sinister = 5 ml, flabby consistency. Penis - appropriate for age.

According to the results of the questionnaire: AMS (Aging Male Scale) questionnaire aimed at identifying symptoms of hypogonadism - 45 points, which corresponds to a moderate degree of severity of symptoms of androgen deficiency, IIEF-5 (International Index of Erectile Function) - 0 points, the patient is not sexually active, due to decreased libido and severe erectile dysfunction.

According to the results of the hormonal examination: FSH - 37 U/l (1.55-9.74); LH - 25 U/l (2.5-11.0); total testosterone - 3.0 nmol/l (normal 11-33).

According to the results of a biochemical blood test: an increase in cholesterol levels to 6.0 mmol/l, LDL - 4.0 mmol/l, triglycerides - 3.2 mmol/l; HDL level - 1.14 mmol/l and glucose - 5.8 mmol/l within normal values, against the background of OGTT - 9.6 mmol/l.

According to the results of densitometry: osteoporosis of the lumbar spine (T-criterion L2-L4 - 3.0), initial osteoporosis of the proximal femur (T-criterion - 2.5).

Based on the clinical picture and examination data, a diagnosis was made: “Klinefelter syndrome” (hypergonadotropic hypogonadism) 47,XXY. Metabolic syndrome: Abdominal obesity. Dyslipidemia. Impaired glucose tolerance; osteoporosis of the lumbar spine, initial osteoporosis of the proximal femur.

The patient was prescribed therapy with Nebido 4 ml IM according to the following schedule: second injection after 6 weeks, then 4 ml IM once every 10 weeks; Ca D3 Nycomed 1 tablet 1 time per day, a rational balanced diet with limited consumption of fats and easily digestible carbohydrates.

A repeat examination was carried out after 8 months. On examination: general condition is satisfactory; height - 193 cm, weight - 101 kg, BMI = 25.2 kg/m2, blood pressure 128/80 mm Hg. Art. There is a noticeable decrease in abdominal obesity: WC - 102 cm, TB - 108 cm, WC/TB = 0.94.

Facial hair is moderate. Hair growth on the chest is a single hair, in the armpits there are no features. Male pattern pubic hair.

According to the results of the questionnaire, positive dynamics: AMS - 22 points, indicating the absence of symptoms of hypogonadism, IIEF-5 - 21 points (beginning of sexual activity), indicating complete normalization of erectile function.

As can be seen from Table 1, normalization of hormonal parameters, in particular total testosterone, has been achieved.

During therapy, normalization of the lipid spectrum was observed: a decrease in the level of total cholesterol, LDL, triglycerides; a decrease in glucose levels against the background of OGTT, which indicates the normalization of carbohydrate metabolism (Table 2).

Table 1. Hormonal blood test indicators before and during treatment.

Hormonal indicators	Reference values	Before treatment	After treatment
Testosterone	11–33 nmol/l	3,0	23,1
LH	2.5–11.0 U/l	25	4,1
FSH	1.55–9.74 U/l	37	7,4

Table 2. Indicators of biochemical blood analysis before and during treatment.

Biochemical indicators	Reference values	Before treatment	After treatment
Cholesterol	3.3–5.2 mmol/l	6,0	4,8
HDL	0.9–2.6 mmol/l	1,14	1,32
LDL	0.0–3.7 mmol/l	4,0	2,8
Triglycerides	0.1–2.2 mmol/l	3,2	1,6
Glucose	3.05–6.38 mmol/l	5,8	5,1
Glucose against the background of OGTT	9,6	7,2

• Thus, after 8 months of therapy, the patient was diagnosed with metabolic syndrome.
• It is recommended to continue therapy with Nebido and Ca D3 Nycomed, a repeat consultation after 6 months with the results of repeat densitometry.
• Considering the need for lifelong androgen therapy, the drug of choice in this case is the long-acting drug Nebido.

REFERENCES 1. Dedov I.I., Melnichenko G.A., Fadeev V.V. Endocrinology. – M.: Medicine, 2000. 2. Abramsky L., Chapple J. 47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counseling. Prenat Diagn. 1997; 17: 363–368. 3. Buckler KL, Hoffman DL, Albert A., Underdahl LO, Mason HL

Klinefelter's syndrome. Arch. Int. Med 1966. 118: 314–21. 4. Gordon DL, Krmpotic E., Thomas W., Gandy HM, Paulsen CA Pathologic testicular findings in Klinefelter`s syndrome 47,XXY vs 46,XY/47,XXY. Arch. Int. Med 1972. 130: 726–9. 5. Jockenhovel F., Nieschlag E. Primare testikulare Erkrankungen. In: Hesch RD: Endocrinology. Urban&Schwarzenberg, Munich.

1989; 928–51.

6. Nielsen J., Pelsen B., Sornensen K. Follow-up of 30 Klinefelter males treated with testosterone. Clin. Genet. 1988; 33:262–269.

Source: https://medi.ru/info/6424/

Klinefelter syndrome: treatment, causes, symptoms, signs

There are many reasons for male infertility. One of them is Klinefelter syndrome. As a result of the pathology, a lack of the hormone testosterone occurs. This results in a man having more female hormones. It is important to identify the pathology as early as possible and begin its treatment.

Now let's look at this in more detail.

What is Klinefelter syndrome?

Klinefelter syndrome is a genetic disease that occurs exclusively in men. A characteristic sign of the disease is the presence of an additional female sex chromosome on the male karyotype. The disease is manifested by the presence of endocrine disorders. A man who has a similar pathology has insufficient production of male sex hormones.

The disease was first described in 1942. This was done by a doctor from the USA, Harry Klinefelter. In the seventies, American scientists began to conduct active research into pathology. They studied the chromosome sets of all newborn boys.

Klinefelter syndrome is not a rare disease. Pathology is diagnosed in 1 out of 800 boys. In practice, it is often not possible to conduct a full diagnosis of the disease. In the future, this becomes the reason for its severe course. The disease causes infertility. Therefore, we can say that the disease is not transmitted from generation to generation.

A healthy person has 46 chromosomes. 22 of them are somatic. Pair 23 contains sex chromosomes. It is thanks to it that the fetus belongs to one sex or another.

In women, the chromosome set looks like xx, and in men, it looks like xy. If the disease progresses, the man must have a male chromosome and two additional female chromosomes.

That is why an individual always remains a man.

In the case of the development of Klinefelter syndrome, the individual's karyotype undergoes significant changes. He may not even have one additional chromosome included, but several at once. Depending on their number, types of pathology are distinguished. The list includes

1. A classic type of disease. It has 1 extra chromosome. The karyotype becomes 47xxy.
2. The second most common pathology is the development of which a man has 2 additional chromosomes. The karyotype in this case takes the form 48xxxx.
3. The most rare situation occurs when a person has three additional chromosomes at once. The karyotype in this case looks like 49xxxxx.

Experts also classify male karyotypes as Klinefelter syndrome, which have not only a female additional chromosome, but also a male one. In this case, the karyotype takes the form 48xxy. And another variation of the pathology will be the presence of a normal set of chromosomes and part of an additional chromosome. Which karyotype looks like this: 46XY/47XXY.

The first signs of Klinefelter syndrome

Diseases caused by abnormalities in the number of sex chromosomes lead to the fact that the gonads do not develop as expected.

Klinefelter syndrome has a similar effect on the human body. That is why the clinical picture of the pathology becomes most clear during puberty.

However, some signs of the presence of pathology can be detected before this period.

1. Significant increase in height. Boys diagnosed with the disease are usually significantly taller than their peers.
2. The presence of a characteristic disproportionate physique. Patients with Klinefelter syndrome have long arms and legs.
3. The torso of patients is short. At the same time, the waist is located quite high.
4. The patient has a narrow, flat chest.

In some cases, a disturbance in the process of mental development and psyche may be observed.

Children with a similar syndrome sometimes experience speech impairment, lack of attention, excessive suggestibility, memory problems, attachment to family members, lack of independence, and high subordination. The patient may experience mood swings, which sometimes lead to outbursts of aggression.

Depending on the presence of additional X chromosomes in the karyotype, the manifestation of clinical signs may become more pronounced. In some boys, the presence of pathology is detected even at an early age.

Symptoms of Klinefelter syndrome

The pathology is characterized by a number of clinical manifestations. However, the severity of symptoms varies. Thus, the presence of the disease can be indicated by the characteristic proportions of the body.

They appear in the form of two body types - asthenic or eunuch-like. In the first case, men are tall. They are skinny. Patients have long arms and legs. The chest is narrow.

The muscles are poorly developed. The genitals appear normal in appearance.

If there is a eunuch-shaped physique, the patient has female-type fat deposition. The man has narrow shoulders and a wide pelvis. The limbs are long. Men with a eunuch-like physique are prone to obesity. The genitals are relatively small in size.

A patient suffering from pathology may exhibit gynecomastia. This is the name given to breast enlargement. It can be unilateral or bilateral. The process is not associated with pain.

Body hair growth in men is weak. A similar rule applies to the face and armpits. Baldness in the pubic area occurs according to the female pattern. Sometimes it may be completely absent. The hair on the head also grows characteristically. On the forehead the process is carried out in the form of a straight line.

The size of the testicles in patients decreases. They have a characteristically dense consistency. Sexual desire and potency begin to fade at a fairly early age. The man develops infertility.

Mental retardation may occur. However, it does not manifest itself in all persons faced with pathology. According to statistics, only 25% of men with the syndrome have mental retardation. Its degree can vary from practically normal to significant debility. Pathology is often combined with deviations in the emotional sphere.

There is a decrease in the amount of testosterone in the blood. This in turn leads to the development of osteoporosis and muscle weakness. Often, patients with the syndrome develop diabetes mellitus, thyroid disease, and an autosomal disease.

The clinical manifestation of the pathology has a high degree of variation, which relates to physique, mental and mental development, and the appearance of the genital organs. All types of pathology are characterized by infertility.

Causes and prevention of Klinefelter syndrome

The main cause of the disease is gene mutation. The process takes place during intrauterine development of the fetus. As a result, the female chromosome is doubled or tripled in the male karyotype.

The exact reasons leading to the occurrence of this phenomenon have not been established. However, experts were able to identify risk groups. In children of people at risk, the likelihood of developing pathology increases.

Factors that provoke the disease are:

• age of the child's mother;
• unfavorable environmental conditions in the area where the pregnant woman lives;
• the birth of a child in a marriage between close relatives;
• in previous generations there were hereditary pathologies.

As in the case of other pathologies resulting from gene mutations, there is no specific prevention against Klinefelter syndrome. You can only try to reduce the risk of pathology.

So, if there are genetic disorders in the family, it is recommended to plan pregnancy and monitor its course. The child needs to be examined on time.

The earlier the pathology is identified, the easier it is to treat.

Klinefelter syndrome is not a death sentence. It has a satisfactory prognosis with adequate early diagnosis and timely initiation of hormone replacement therapy.

The pathology does not affect life expectancy, except in particularly severe cases, during which the patient has several additional X chromosomes.

There are quite a lot of categories of men who have no idea about their diagnosis. They continue to lead a full life, without even knowing about infertility. This feature indicates a favorable prognosis during the disease.

However, one must remember about possible deviations in the intellectual and mental sphere, the vulnerability of men included in this category, a tendency to depression and psychological trauma, and sometimes to antisocial behavior.

The manifestation of possible complications and their clinical expression is directly dependent on the start of the course of treatment. The psychological state of the patient will be better if he is surrounded by the care of loved ones.

Treatment of Klinefelter syndrome

Before starting treatment, a diagnosis is performed. First of all, a special test is carried out to determine the level of hormones. We can talk about the presence of pathology if there is a decrease in testosterone. Additionally, densitometry can be performed.

It is used to determine the density of human bone tissue. Then a spermogram is performed. With its help, sperm activity is determined. If Klinefelter syndrome is suspected, an ECG of the heart is performed and blood pressure is constantly monitored.

The patient will have to visit a therapist and a geneticist.

It is impossible to completely get rid of the pathology. However, therapy allows you to get rid of the clinical manifestations of the disease. Treatment is symptomatic. Its essence lies in the use of hormone replacement therapy. The patient is prescribed medications containing testosterone.

The drug is used to treat conditions caused by low testosterone levels. Such a pathology, for example, is osteoporosis.

The effectiveness of hormonal therapy directly depends on the age at which treatment is started. The sooner the diagnosis is made, the sooner therapy is started, the fewer symptoms indicating testosterone deficiency will subsequently arise.

It should be borne in mind that hormonal medications are prescribed for life. With their help, it is possible to eliminate many clinical manifestations of pathology. Treatment is aimed at correcting hormonal deficiency.

With its help, sexual characteristics are normalized and sexual function is enhanced. The treatment also has a beneficial effect on the patient’s mental state. There is a significant improvement.

Therapy helps the patient adapt to society.

Hormone therapy does not eliminate infertility. Testosterone-based drugs also do not combat gynecomastia. The only way to get rid of this phenomenon is to undergo surgery or mastectomy. Strict adherence to the recommendations of specialists will significantly improve the quality of life of a man suffering from Klinefelter syndrome.

Source: https://zdorrov.com/drugie/sindrom-klajnfeltera.html

Klinefelter syndrome: a man with a female chromosome

Elena Shvedkina about one of the most common genetic diseases - patients complain of infertility, erectile dysfunction, gynecomastia and osteoporosis

Klinefelter syndrome is a genetic disease characterized by an additional female sex chromosome X (one or even several) in the male karyotype XY . At the same time, insufficient sex hormones are produced in the male gonads - the testicles.

As you know, the human genetic set has 46 chromosomes, of which 22 pairs are called somatic, and the 23rd pair is called sexual.

Klinefelter syndrome requires the presence of a male Y chromosome, so despite the additional X chromosomes, patients are always male.

Classification: types of karyotypes in Klinefelter syndrome

Based on the number of additional X chromosomes, the following variants of Klinefelter syndrome are distinguished:

• 47,XXY - the most common
• 48,ХХХY
• 49,XXXXY

In addition, Klinefelter syndrome also includes male karyotypes that include, in addition to additional X chromosomes, an additional Y chromosome - 48,XXYY . And finally, among patients with this syndrome there are individuals with a mosaic karyotype 46,XY / 47,XXY (that is, some of the cells have a normal chromosome set).

History of the discovery of the syndrome

The syndrome got its name in honor of Harry Klinefelter, a doctor who first described the clinical picture of the disease in 1942. Klinefelter and colleagues published a study of 9 men with common symptoms such as low body hair, eunuchoid body type, tall stature, and small testicles.

Later, in 1956, geneticists Plunkett and Barr (E.R. Plunkett, M.L. Barr) discovered sex chromatin bodies in the nuclei of cells of the oral mucosa in men with Klinefelter syndrome, and in 1959 Polanyi and Ford (P.E. Polanyi, SE

Ford and his colleagues showed that patients have an extra X chromosome in their chromosome set.

Active research into this pathology was conducted in the 70s in the USA. Then all newborn boys were subjected to karyotyping, as a result of which it was possible to reliably identify the prevalence and genetic characteristics of Klinefelter syndrome.

Interestingly, mice can also have XXY sex chromosome trisomy, making them useful models for studying Klinefelter syndrome.

Prevalence of the disease

Klinefelter syndrome is one of the most common genetic diseases: for every 500 newborn boys, there is 1 child with this pathology.

In addition, Klinefelter syndrome is the third most common endocrine pathology in men (after diabetes mellitus and thyroid pathology) and the most common cause of congenital reproductive dysfunction in men.

To date, about half of cases of Klinefelter syndrome remain unrecognized. Often such patients seek help for infertility, erectile dysfunction, gynecomastia, osteoporosis, anemia, etc. without a previously established diagnosis.

Etiology and causes of the disorder

Klinefelter syndrome is a genetic disease that is not inherited because patients, with rare exceptions, are infertile.

Pathology, as a rule, occurs as a result of a violation of chromosome divergence in the early stages of the formation of eggs and sperm. At the same time, Klinefelter syndrome, which occurs due to a disorder in female reproductive cells, occurs three times more often.

The reasons for nondisjunction of sex chromosomes and disruption of cell division at the earliest stages of embryogenesis are still poorly understood. Unlike other chromosomal diseases, the effect of parental age is absent or only slightly expressed.

Early signs

Unlike most diseases associated with a violation of the number of chromosomes, the intrauterine development of children with Klinefelter syndrome proceeds normally, and there is no tendency to premature termination of pregnancy.

So in infancy and early childhood it is almost impossible to suspect pathology. Moreover, clinical signs of classic Klinefelter syndrome usually appear only in adolescence.

However, there are symptoms that suggest the presence of Klinefelter syndrome in the prepubertal period:

• high growth (peak height increase occurs between 5–8 years);
• long legs (disproportionate physique);
• high waist.

Some patients experience some delay in speech development.

In adolescence, the syndrome often manifests itself as gynecomastia, which with this pathology has the appearance of bilateral symmetrical painless enlargement of the mammary glands. Since this type of gynecomastia is often observed in completely healthy adolescents, this symptom often goes unnoticed.

Normally, teenage gynecomastia disappears without a trace within several years, but in patients with Klinefelter syndrome, reverse involution of the mammary glands does not occur.

In some cases, gynecomastia may not develop at all, and then the pathology manifests itself as signs of androgen deficiency already in the postpubertal period.

Symptoms of androgen deficiency in Klinefelter syndrome

Androgen deficiency in Klinefelter syndrome is associated with gradual testicular atrophy, which leads to decreased testosterone synthesis. The degree of androgen deficiency varies dramatically.

First of all, the external signs of hypogonadism attract attention:

• scanty facial hair or its complete absence;
• female-pattern pubic hair growth;
• there is no hair on the chest or other parts of the body;
• small volume of the testicles (2–4 ml) and their dense consistency (pathognomonic sign).

Since degeneration of the gonads, as a rule, develops in the postpubertal period, in most patients the size of the male genital organs, with the exception of the testicles, corresponds to age norms.

Patients may complain of weakened libido and decreased potency.

Many men with Klinefelter syndrome do not experience sexual desire at all, while some, on the contrary, start a family and live a normal sex life.

The most constant sign of pathology is infertility; it is this that most often becomes the reason for such patients to consult a doctor. 10% of men with azoospemia have Klinefelter syndrome.

All patients with spermatogenesis disorders must have their karyotype determined to exclude or confirm the diagnosis of Klinefelter syndrome.

Androgen deficiency leads to the development of osteoporosis, anemia and skeletal muscle weakness. In a third of patients, varicose veins of the legs can be observed.

Androgens affect metabolism, so patients with Klinefelter syndrome are prone to obesity, impaired glucose tolerance and type 2 diabetes.

The predisposition of such patients to autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid diseases and others) has been proven.

Psychological characteristics

The IQ of patients with classic Klinefelter syndrome varies from below average to well above average.

However, in all cases there is a disproportion between the general level of intelligence and verbal abilities, so that patients with a fairly high IQ often experience difficulties in perceiving large volumes of material by ear, as well as in constructing phrases containing complex grammatical structures.

Such features cause patients a lot of trouble during the training period and often continue to affect their professional activities.

There is evidence that patients with Klinefelter syndrome are prone to homosexuality, alcoholism and drug addiction.

It is difficult to say whether the mental characteristics of such patients are caused by the direct influence of a chromosomal abnormality, or whether it is a reaction to problems in the sexual sphere.

With regard to different cytogenetic variants of Klinefelter syndrome, the rule is true that with an increase in the number of additional X chromosomes, the number and severity of pathological symptoms increases.

Diagnosis of Klinefelter syndrome

In many countries, Klinefelter syndrome is often diagnosed before the birth of a child, since many women of late childbearing age, due to the high risk of genetic defects in future offspring, use prenatal genetic diagnosis of the fetus. Often, prenatal detection of Klinefelter syndrome is a reason for termination of pregnancy, including on the recommendation of doctors. In Russia, analysis of the karyotype of an unborn child is extremely rare.

If Klinefelter syndrome is suspected, a laboratory blood test is performed to determine the level of male sex hormones. Differential diagnosis with other diseases that occur with manifestations of androgen deficiency is necessary. An accurate diagnosis of Klinefelter syndrome is made based on studying the karyotype (set of chromosomes) of the patient.

Tests needed to confirm the diagnosis

Analyzes	results
Karyotype	47,ХХY (80% of cases) 48,ХХYY 48,ХХХY 49,ХХХY 46,ХY/47,ХХY
Concentration of LH, FSH	Increased, especially FSH
Total testosterone concentration	Most often reduced (in some cases normal due to an increase in sex steroid-binding globulin SSSG or at the initial stage of disease development)

In all men with sharply increased concentrations of gonadotropins, it is necessary to exclude Klinefelter syndrome, since often the first laboratory sign of this genetic pathology is an increase in the concentration of gonadotropins in the blood with normal levels of total testosterone.

Klinefelter syndrome must be differentiated from other forms of primary hypogonadism. In any case, if the level of FSH in the blood increases, it is necessary to determine the karyotype to exclude, first of all, Klinefelter syndrome.

Treatment

Treatment goals for Klinefelter syndrome:

• Restoring normal testosterone levels
• Restoration of sexual function
• Elimination of metabolic disorders

In case of clinically pronounced pathology, lifelong replacement therapy with testosterone preparations is necessary.

Adequate therapy allows not only to improve the appearance and general well-being of the patient, but also to restore the ability to have a normal sexual life. In addition, replacement therapy prevents the development of osteoporosis and relieves muscle weakness. At a young age, treatment should begin immediately after diagnosis.

For Klinefelter syndrome, it is better to use long-acting testosterone drugs:

• a mixture of testosterone esters in the form of an oil solution, injections of which must be done 2-3 times a month;
• testosterone undecanoate in the form of an oil solution - a depot preparation with a slow release of the active substance - injections once every 3 months.

Hormone treatment for the presence of the X chromosome in men should be permanent. The dose of the drug is selected individually under the control of testosterone and LH levels in the blood serum.

1. Already developed gynecomastia in Klinefelter syndrome does not undergo involution even with adequate treatment, so it is often necessary to resort to surgical correction (mastectomy).
2. To prevent concomitant diseases such as obesity and type 2 diabetes, patients are advised to adhere to a diet and monitor their own weight.
3. Patients with Klinefelter syndrome should be monitored at least once every 6–12 months. It should include the following studies:

• complete blood count to assess hemoglobin and hematocrit levels;
• hormonal blood test, including determination of testosterone and LH (carried out against the background of drug therapy 1–2 days before the next testosterone injection);
• densitometry (all patients who had osteopenia or osteoporosis at the time of diagnosis).

The introduction of intracytoplasmic sperm injection (ICSI) and data on the possibility of the presence of germ cells in the testes in patients with Klinefelter syndrome predetermined the use of artificial insemination for this category of patients, some attempts were successful.

Forecast

The prognosis for life and work in patients with classic Klinefelter syndrome is generally favorable. Early replacement therapy and psychological work with patients and their parents allow patients to fully adapt to modern society.

Source: https://www.katrenstyle.ru/articles/journal/medicine/syndrome/sindrom_klaynfeltera_muzhchina_s_zhenskoy_hromosomoy