Other diseases

Genetic diseases. Prader-Willi syndrome: description, diagnosis, photo, treatment

Prader-Willi syndrome (PWS) is a fairly rare genetic disorder in which 7 genes on the 15th paternal chromosome are deleted (possibly partially) or do not function normally.

The first to study and describe the signs of this disease in 1956, there were Andrea Praderi Heinrich Willi. Also involved in research were Alexis Labhart, Andrew Ziegler and Guido Fanconi, who also studied this chromosomal disorder and contributed.

Prader-Willi syndrome occurs because only the copy of the gene received from the father functions normally. There are irregularities in the mother copy. In organism healthy people there is a copy of the genes, thanks to which it can work without deviations from the norm. In Prader-Willi syndrome, such a copy is absent. Currently, there is a disease that is essentially similar to Prader Willi disease. A similar mechanism of occurrence is observed in Angelman syndrome, only in this case the mutation affects the maternal genetic material. These diseases usually manifest themselves in different forms and have different forms and degrees of severity, but both of them are incurable.

Causes of Prader-Willi syndrome

Quite often, a disease such as Prader-Willi syndrome is discussed on the forum. This is a hereditarily determined pathology that manifests itself only with the development of certain anomalies. In other words, with some chromosomal disorders, parental genes are affected, which, in turn, leads to serious diseases. Specifically, the clinical picture develops when seven genes on chromosome fifteen, which were inherited paternally, are missing or not expressed. That is, the hereditary information contained in DNA is not converted into RNA. When diagnosing and preventing it, it is worth remembering that Prader-Willi syndrome can only be caused by the expression of paternal genes.

Scientists who tried to find out the causes of this hereditary pathology initially believed that it was a homozygote for this deviation. They then concluded that the predominant traits are located in the autosomes, so that the main route of transmission of the disease is inheritance. This version was confirmed by the fact that cases of Prader-Willi syndrome were observed in entire families. But most cases of the disease were isolated, occurring without any prerequisites.

Geneticists conducted a cytogenetic analysis of the pathology. With its help, it was established that the fathers of the newborns had a translocation or mosaicism of the fifteenth chromosome. Then they saw a microdeletion of this chromosome. Only with the advent molecular methods research and genetic testing methods have finally become possible to diagnose chromosomal abnormalities, the presence of which leads to the occurrence of Prader-Willi syndrome.

An interesting fact is that both patients with microdeletion and idiosomy have a similar clinical picture.

It has now been precisely established that this pathology damages the critical region of the fifteenth chromosome in the segment from q11.2 to q13. The same gene aberration occurs in the case of Angelman syndrome, but this disease manifests itself with completely different symptoms. Such dissonance could only be explained in Lately, when they discovered such a phenomenon in genetics as genomic imprinting and uniparental disomy. Genomic imprinting is a completely new phenomenon discovered by molecular geneticists. He says that changes in phenotype occur depending on whether expression occurs on the paternal or maternal chromosomes.

With uniparental disomy, both chromosomes of only one parent are inherited. In order for such a breakdown to occur, the genetic material must be affected by genetic and biochemical factors. This was established using prometaphase analysis and DNA marking of individual loci of the fifteenth chromosome.

Thus, Prader-Willi syndrome is caused by two mechanisms: microdeletion of the fifteenth chromosome, which is received from the father, and idiosomy of the maternal chromosomes (both of them are received from the mother). With Angelman syndrome, everything happens exactly the opposite: maternal microdeletion and paternal idiosomy. Prader-Willi syndrome is caused by a paternal microdeletion.

An interesting fact is that patients with microdeletion and idiosomy show a similar clinical picture.

Prader-Willi syndrome in children

The mechanisms of disorders that occur in the body of a patient with Prader-Willi syndrome have not yet been fully studied, and many open questions remain. However, patients have a number of disorders characteristic of this disease. They are believed to gain excess weight due to increased fat production and decreased lipolysis. In this disease, there is dysfunction of the hypothalamus, which is mainly noted in its two nuclei - the ventromedial and ventrolateral.

This leads to disruptions in the development of secondary sexual characteristics, that is, to hypogonadism, which develops according to the hypogonadotropic type. Decreased tyronase activity in melanocytes and hair follicles causes the skin, hair, and iris to become hypopigmented.

This syndrome can be detected in the early stages of pregnancy. Ultrasound diagnostics will allow you to notice the abnormal position of the fetus and its low mobility. In addition, the level of the hormone gonadotropin, which is produced by chorion cells, changes significantly in a pregnant woman. Intrauterine signs, in addition to decreased fetal activity, also include: normal position and polyhydramnios. Based on these signs, it is impossible to make an accurate preliminary diagnosis, but they are sufficient grounds for further diagnosis.

In infants, Prader-Willi syndrome is expressed in the presence congenital dislocation hip (dysplasia), weakened muscle tone, and poor coordination. There are cases when a child is not able to suck and swallow breast milk on his own, so feeding is carried out using a tube. Breathing problems may also occur, which may be so severe that mechanical ventilation may be required.

In addition to all of the above, there are other symptoms of Prader-Willi syndrome. For example, a child may experience increased drowsiness. Concerning external signs, then he has a developmental delay, so such patients are characterized by short stature, as well as small hands and feet. Strabismus often occurs. To make a diagnosis, there are a number of criteria that are divided into major and minor.

Large criteria (each corresponds to 1 point)	Small criteria (each corresponds to 0.5 points)
General hypotension with suppression of the sucking reflex In the neonatal period and infancy stop on their own.	Poor fetal motility, infant lethargy, weak cry
Eating disorders in early age, requiring special manipulations and leading to a delay physical development	Hysteria, stubbornness, rigidity, aggressiveness, outbursts of unmotivated anger, obsessive-compulsive disorders
Excessive or rapid weight gain between the ages of one and six years, central obesity	Tendency to steal, pathological dexterity, negativism (more than five signs)
Characteristic facial changes (dolichocephaly, narrow face, almond-shaped eyes, small mouth, thin upper lip, drooping corners of the mouth (more than three signs)	Sleep disturbance or sleep apnea Short stature
General developmental delay, mild mental retardation or medium degree, learning disability	Skin hypopigmentation Small arms and/or legs
Hyperphagia, obsessive eating	Narrow hands
15q deletion or maternal disomy	Speech disturbance, viscous saliva
	Myopia, convergent strabismus

Thanks to these criteria, a diagnosis of Prader-Willi syndrome in newborns is made.

IN further illness characterized by the following symptoms:

curvature spinal column(scoliosis);
caries of baby teeth, increased thickness of saliva;
tendency to eat excess food;
hypofunction of the gonads, which subsequently leads to infertility;
high degree of obesity;
late fine motor skills, delayed speech development.
lagging behind peers in psychomotor development;
delayed puberty.

They are determined visually.

IN adolescence Children suffering from Prader-Willi syndrome exhibit the following symptoms:

delayed speech skills;
overweight; short stature;
unnatural flexibility;
decreased intelligence, learning disability.

Combinations of such signs can serve as the basis for making a final diagnosis.

The psychomotor development of children with the above syndrome always lags behind the age-appropriate norm. Their IQ ranges from 20 to 80 units. The norm for their age is 85 – 115 units. These children have difficulty speaking, significantly reduced lexicon. However, Frimm and Kurff conducted comparative analysis various degrees of mental disabilities and the difficulties that arise when teaching people with Prader-Willi syndrome. They obtained the following results: about five percent of patients have an IQ that exceeds 85 units. Their intelligence level is below average. Twenty-seven percent have mild mental retardation, their IQ ranges from 70 to 85. This is the limit of intellectual activity. Thirty-nine percent of the subjects had slight mental retardation - the IQ of such patients, as a rule, does not exceed 70. Also, 27% of the patients had a slightly more pronounced mental retardation, their IQ was 35-50. And one percent of individuals were diagnosed with severe and profound mental retardation.

According to data obtained by Cassidy, 40% of patients with Prader-Willi syndrome have a fairly low level of intelligence, which is defined as below average or at the limit intellectual abilities. These are people with a transitional level of intelligence.

Children with Prader-Willi syndrome develop a rather unusual cognitive profile. They often have well-developed visual perception, they can read well and have a good vocabulary, but their speech abilities are lower than their understanding of the meaning of what they want to say. Children with Prawer-Willi syndrome are also poor at processing auditory information and lack the ability to do math and calligraphy. These children have poor visual and hearing short term memory and sound concentration. With age, in some cases, an improvement in intellectual abilities has been observed in children who suffer from this disease.

The main mental disorders that occur in patients with Prader-Willi syndrome are manifested by compulsive behavior. It usually appears increased anxiety and tugging at the skin. These psychological problems lead to the fact that such patients have to be forcibly hospitalized in a psychiatric hospital. Videos of patients suffering from Prader-Willi syndrome can be seen on many websites.

In patients, you can visually notice a narrow and high forehead, almond-shaped eyes, a large bridge of the nose and thin lips. They develop infertility due to underdevelopment of the genital organs and obesity, a tendency to hypotension, and increased glucose tolerance. Patients suffering from Prader-Willi syndrome have very thin hair on the pubis and underdeveloped genitals. However, one patient with this syndrome never has more than five signs of the disease.

Genes must be turned on when required. For example, hair growth begins on time and secondary sexual characteristics appear. If this does not happen, then they talk about Prader-Willi syndrome. According to various researchers, it occurs in one case in ten or fifteen thousand newborn babies. There are many photos of children with Prader-Willi syndrome. Obesity is a leading symptom of many hereditary diseases. Prader-Willi syndrome occupies a leading place among them.

Syndromes characterized by obesity

Syndrome name	The nature of obesity	Clinical features
Albright's osteodystrophy (pseudohypoparathyroidism type 1A)	Moderate	Short stature, reduced intelligence, shortening of the fourth and fifth carpals and metacarpals, hypocalcemia, hyperphosphatemia
Lawrence-Moon-Bardet-Biedl	From the first steps	Reduced intelligence, retinal dystrophy, polydactyly, polycystic kidney disease, hypogonadism, short stature
Fragile X syndrome	Early start	Reduced intelligence, macroorchidism, protruding lower jaw, high-pitched voice
Alström syndrome	Since childhood	Hearing loss, retinal degeneration, diabetes mellitus
Boreson-Forsman-Lehman	Moderate, from 6-7 years	Hypotonia, reduced intelligence, developmental delay, hypogonadism, gynecomastia
Tillian syndrome (Techler-Nicolas)	From the first years	Hypotension, tendency to seizures
Cohen's syndrome	Moderate, from 7-8 years	Microcephaly, hypotonia, retinal dystrophy, protruding anterior teeth
Carpenter syndrome	After 12 years	“Tower” shape of the skull, syndactyly, polydactyly, hypogonadism, reduced intelligence
From the first years of life, polyphagia	Hypotension, reduced intelligence, developmental delay
Down syndrome	Uniform, from 12-14 years	Reduced intelligence, heart defects, hypotension

This hereditary pathology can be suspected even during intrauterine development fetus During an ultrasound of a pregnant woman, the doctor sees excess amniotic fluid, reduced fetal mobility and abnormal positioning. In this case, the woman is recommended to undergo prenatal diagnosis, if necessary, it is possible to use invasive methods.

After the baby is born, an experienced geneticist can diagnose Prader-Willi syndrome at the first examination of the baby. These children are so similar that the diagnosis is beyond doubt. However, in order to confirm this hereditary disease, it is necessary to undergo genetic testing, with which an accurate diagnosis can be made. The mother can also donate blood for maintenance human chorionic gonadotropin. The results may be good, which means Prader-Willi syndrome has been ruled out.

Modern geneticists diagnose Prader-Willi syndrome using DNA markers and molecular biological technologies. Thanks to these methods, it is possible to determine both submicroscopic and functional pathology at the DNA level, even in patients who do not have visible chromosome pathology. The diagnosis is made according to the following clinical criteria, How:

reduction in birth weight and height in the case of full-term pregnancy;
incorrect position or breech presentation of the fetus;
some microanomalies of development;
severe muscle hypotonia;
decreased pigmentation of the skin, iris and hair;
obesity, which develops by six months;
delay in psychological, speech and motor development.

Children with Prader-Willi syndrome often hide food, constantly demand food, and do not move much. Due to excessive weight gain, this happens to them serious complication, How sleep apnea. They can die in their sleep.

Genetic screening - photo

Treatment of Prader-Willi syndrome

Doesn't exist to date specific treatment Prader-Willi syndrome in children. If a newborn has breathing problems, he is placed on a ventilator. If he has problems swallowing, he is given a gastric tube through which enteral nutrition is administered. In case of decreased muscle tone, patients with Prader-Willi syndrome are advised to undergo massage and physiotherapy procedures.

Children with Prader-Willi syndrome are given recombinant growth hormone (GH) daily. It maintains a constant increase in muscle mass and may reduce the patient's appetite. Human chorionic gonadotropin is also replaced. With this syndrome, hypogonadism is observed, which means insufficiency of the gonads and disruption of the reproductive system as a whole. In this case, carry out replacement therapy hormones, which allows you to stimulate growth and achieve timely puberty. If a child has undescended testicles, he is first monitored by a pediatric andrologist, and if necessary, the testicles are brought down surgically against the background of hormonal treatment.

Sometimes a familiar psychiatrist may be needed for patients with Prader-Willi syndrome. Children with speech and psychological development delays will need psychological help. Of course, you need to control the amount of food your child consumes. These children can consume incredible amounts of food, leading to severe obesity. If excess weight has already been gained, children with Prader-Willi syndrome are prescribed diet therapy under the supervision of a nutritionist.

Parents should understand the characteristics of their child and in every possible way prevent overeating. IN preschool age the ban on eating food should not be very strict, since a child with Prader-Willi syndrome should receive required quantity proteins, vitamins and minerals. However, nutrition must be balanced. And younger schoolchildren should be provided with a hypocaloric, balanced diet not exceeding a thousand calories per day. It should include enough calcium and vitamins.

Access to food should be limited; the food cupboard and refrigerator should be locked. Children should be provided with maximum physical activity; they should not sit in front of a TV screen or computer monitor. Engage in active sports, stay as much as possible fresh air– the key to weight normalization. The risk of having a second child with Prader-Willi syndrome is very high. Parents should definitely attend a medical genetic consultation, where specialists will conduct a comprehensive examination and calculate the risks.

Children with Prader-Willi syndrome require regular monitoring by endocrinologists and neurologists.

Improvement of general condition in Prader-Willi syndrome

Among people suffering from Prader-Willi syndrome, rates of somatic morbidity increase significantly, and communication is difficult. They have a need for specific medical care, which is determined by the characteristics of their underlying disease. They often do not understand why they need to take care of their health, and do not receive adequate medical care when suffering from severe somatic pathology. There is a large disparity in their health status and that of the rest of the population.

An adequate goal for all people is good health. It should also be a motivation for patients with Prader-Willi syndrome. Such people have impaired learning ability. Their needs are constantly changing, but they require virtually the same medical care. Their health status is influenced to a much greater extent than healthy people by both social and environmental factors. Eliminating such inequalities in the physical health of patients with learning disabilities and the rest of the country's population is an absolute necessity. If the state of somatic health is satisfactory and a person feels well, then both the quality of life and that of his family members improves.

It can be assumed, that somatic condition The health of people with learning disabilities, including those suffering from Prader-Willi syndrome, can be improved by addressing those areas where significant inequalities in both health and physical health care are undeniable. The following factors need to be eliminated:

risk of increased mortality;
likelihood of increased morbidity;
increasing the number of factors that determine health (material well-being);
unequal access to health services;
inequalities in health care.

They can only be eliminated together.

Areas of influence on the quality of life of patients Let's talk about those areas that, by changing them, can improve the health status of patients with Prader-Willi syndrome. First and foremost is health inequality.

Of great importance is the concept of inequality in the state of somatic and mental health persons suffering from Prader-Willi syndrome. It increases public attention to the planning of various services. But at the same time, this concept creates a number of difficulties. This occurs when we attempt to take into account how the causes of an individual's disability contribute to any particular inequality. For example, this happens when trying to find out how the reduction in life expectancy affects patients with deep violations learning abilities. To solve this particular problem, it is necessary to compare individuals within those groups in which participants have exactly the same degree of impairment.

What are the health features of people suffering from Prader-Willi syndrome? This question can be answered by examining the results of a study of such patients in Wales using a special questionnaire. The researchers obtained the following results:

they get sick much more often than the rest of the population;
these people often have low visual acuity;
they are often forced to contact the family doctor;
The vast majority of such patients are overweight or severely obese.

These studies are extremely important to improve the quality of life of these patients.

Patients with Prader-Willi syndrome have both general and specific needs that are relevant to their underlying condition. They need treatment for acute or chronic diseases, assistance in promoting health, as well as adequate referral to the hospital. Their needs must be met first and foremost in institutions providing primary medical care. Specialized assistance may consist of the following: treatment of the underlying pathology and somatic diseases that are associated with the underlying disease.

Some syndromes that cause learning disabilities are associated with an increased risk of specific diseases. For example, with Down syndrome there is increased risk development of pathology of cardio-vascular system, organ of vision, leukemia, hypothyroidism. People with fragile X syndrome were significantly more likely to be diagnosed with the disease connective tissue. Particularly severe satiety control disorders occur in patients with Prader-Willi syndrome. They are associated with a risk of developing obesity. This disease leads to a decrease in the life expectancy of patients up to the age of sixty. But in general, the prognosis for the recovery of such patients is disappointing.

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The reason for this rare hereditary disease is the absence of part of the paternal copy in the 15th pair of chromosomes. Prader-Willi syndrome is characterized by wide range clinical signs, the main ones are obesity, short stature, reduced intelligence, hypogonadism. The pathology occurs in 1 out of 12-15 thousand newborns.

Forms of Prader-Willi syndrome

Classic or typical phenotype caused by deletion of the paternal copy of the chromosome.
A mild phenotype that develops with uniparental maternal disomy and is characterized by more developed cognitive function in the child.
A pronounced phenotype, caused by maternal uniparental disomy and mosaic trisomy of chromosome 15, is accompanied by a large number of cardiac pathologies.

Causes of Prader-Willi syndrome

Hereditarily determined pathology occurs as a consequence of disturbances in the q11-13 region in the 15th pair of chromosomes. In 70% of cases, Prader-Willi syndrome is associated with complete loss of the q11-13 locus of the paternal gamete. In 20% of patients, maternal disomy is detected - a duplicated maternal copy of a chromosome section replaces the missing paternal copy in the 15th pair of chromosomes. About 5% of patients suffer from Prader-Willi syndrome due to methylation of the structurally normal region q11-13 of the paternal chromosome, which leads to functional deactivation in the fetus.

Pathogenesis of the disease

To date, the pathogenesis of the disease has been poorly studied. It is believed that obesity, which accompanies the disease, is associated with slow processes of fat breakdown and accelerated (more than 10 times) processes of its accumulation.

Hypogonadism in Prader-Willi syndrome is caused by dysfunction of the hypothalamus. Decreased activity of the enzyme tyrosinase in hair follicles and skin cells that produce melanin, provokes hypopigmentation of the skin and hair. Growth hormone deficiency in such patients is associated with dysfunction of the hypothalamus.

Prader-Willi syndrome is thought to be associated with genes located in the cluster of non-coding small nucleolar RNAs (snoRNAs) or with the SNURF-SNRPN genes, which encode a protein and are located in the region of the imprinting center.

Symptoms of Prader-Willi syndrome

Intrauterine signs of pathology are considered to be a decrease in motor activity fetus and its abnormal position, polyhydramnios. At birth, the disease manifests itself as breech presentation of the fetus, hypotonia, lethargy, breathing problems, feeding difficulties, and hypogonadism.

IN early childhood Prader-Willi syndrome causes delay in physical and intellectual development, accompanied by fatigue, strabismus, and scoliosis. Children with the genetic disease suffer from sleep disturbances, excessive weight gain, hyperphagia, poor physical coordination, and delayed speech development.

Adolescents are characterized by abnormal flexibility, short stature, obesity, and delayed puberty. In adulthood, patients with Prader-Willi syndrome experience:

infertility;
obesity;
tendency to diabetes;
hypogonadism;
thin pubic hair;
abnormal flexibility;
limited intellectual functions.

Diagnosis of Prader-Willi syndrome

At the stage of intrauterine development, diagnose chromosomal disease possible through invasive prenatal testing. Genetic testing is recommended for newborns with hypotonia. If in doubt, a geneticist will refer the parents and child for karyotyping and molecular genetic testing of the 15th pair of chromosomes.

Treatment of Prader-Willi syndrome

There is no specific therapy for genetically determined pathology. If there are breathing problems, the newborn is connected to a ventilator system. If swallowing is impaired, enteral nutrition is administered through a gastric tube. For muscle hypotonicity, massage is prescribed.

Children with Prader-Willi syndrome are prescribed recombinant growth hormone, which helps increase the percentage of muscle mass and reduce appetite. To compensate for the reduced function of the gonads, hormone replacement therapy is prescribed. For patients with delay mental development the help of a psychotherapist is needed. In order to prevent obesity and diabetes, a diet is indicated.

Forecast

Patients with Prader-Willi syndrome live up to 60 years. In general, the prognosis is determined by the severity of the course diabetes mellitus and cardiorespiratory pathologies.

Prevention consists of genetic counseling of families with a proband of Prader-Willi syndrome and molecular cytogenetic studies.

You can undergo genetic testing for chromosomal abnormalities at the Genomed medical genetic center.

Prader-Willi syndrome

^ E.V. Pavlovskaya, T.V. Strokova, A.G. Surkov

Research Institute of Nutrition of the Russian Academy of Medical Sciences

A number of genetic syndromes are accompanied by the development of morbid forms of obesity already in preschool age. Severe obesity in children requires in-depth examination and exclusion genetic reasons diseases. The article examines a case of morbid obesity in a teenager with Prader-Willi syndrome.

Key words: genetic syndromes, Prader-Willi syndrome.

Nikita L., 16 years old, first entered the pediatric dietetics department of the clinic of the Research Institute of Nutrition of the Russian Academy of Medical Sciences in May 2008.

Anamnesis of life. The child was born from a second normal pregnancy, a second term pregnancy rapid labor. Body weight at birth was 2850 g, height 49 cm. The early neonatal period proceeded without pathology, and was discharged from the maternity hospital on the 5th day. Breast-feeding up to 1 month, after which, due to hypogalactia in the mother, he was transferred to an adapted formula. Preventive vaccinations were carried out according to an individual schedule. Neuropsychic development with a lag. From the age of 1.5 he suffers from bronchial asthma, from the age of 5 - atopic dermatitis. Drug allergy for penicillins, cerebrolysin.

Heredity is burdened by allergic pathology (bronchial asthma in the maternal grandfather, hay fever and atopic dermatitis in an older brother), metabolic pathology (obesity, arterial hypertension and cirrhosis of the liver in a paternal grandmother); rheumatoid arthritis from my maternal grandmother.

History of the disease. At the age of 2 weeks there was a deterioration general condition, which was manifested by decreased appetite, lethargy, suppressed reflexes, and decreased body weight. The condition was

Contact information: Pavlovskaya Elena Vyacheslavovna, [email protected]

initially assessed as exogenous intoxication (the apartment was undergoing renovations). At the age of 3 months, a neurologist first suspected Prader-Willi syndrome (PWS) based on phenotypic characteristics. From the age of 10 months, the boy’s appetite sharply increased; according to his mother, there was no feeling of satiety. The diagnosis was confirmed at the age of 1 year 8 months in Children's City Clinical Hospital No. 13 named after. N.F. Filatova. From an early age, excessive weight gain, inactivity, increased appetite, tendency to constantly search for food. In 2000 and 2001 it was carried out surgical correction cryptorchidism. Over the past 2 years, there has been a sharp increase in body weight: in 2006 - 92 kg, in 2007 - 122 kg. Does not follow a diet (adult supervision is insufficient), physical activity is low. Blood pressure is not controlled. In 2007, he was hospitalized at the Tushino Children's City Clinical Hospital with a diagnosis of exogenous constitutional obesity of IV degree; Prader-Willi syndrome; hypogonadotropic hypogonadism; bronchial asthma, interictal period.

Upon admission, he complains of increased appetite, pain in the back and legs, fatigue, shortness of breath, and poor tolerance to physical activity. State moderate severity. Body weight 154.6 kg, height 163 cm, body mass index

58.3 kg/m2 (99th percentile), circumference

Appearance of patient L.

waist 160 cm, hip circumference 133 cm. Noteworthy are the phenotypic features (picture): small hands and feet, narrow bridge of the nose, almond-shaped eyes.

Skin pale pink, on the stomach and in the axillary areas - purple striae, in the lower part of the anterior abdominal wall- hyperemia and thickening of the skin. The skin on the legs is dry, hyperemic, with signs of atrophy. On hundredMedicine 4.2009---------------------

groin, in the interdigital spaces - skin hyperemia, lamellar peeling. Subcutaneous fat is overdeveloped and evenly distributed. Severe swelling in the lower part of the anterior abdominal wall, on the anterior surface of the legs. The musculoskeletal system is not changed, muscle tone is reduced.

In the lungs, breathing is vesicular, there are no wheezes, the respiratory rate is 20 per minute. Heart sounds are muffled, clear, pulse characteristics are satisfactory. Heart rate 100/min, blood pressure 128/70 mmHg. Art. The tongue is pink, covered with a yellow coating, and moist. The pharynx is not hyperemic. The abdomen is increased in volume due to subcutaneous fatty tissue; upon palpation it is soft and painless in all parts. Palpation parenchymal organs difficult. There is no dysuria, the urine is yellow and transparent. The stool is decorated, colored, up to 3-4 times a day. Sexual development with delay.

Score according to the diagnostic criteria for Prader-Willi syndrome (see below) - 9 points (including 7 major criteria).

Laboratory and instrumental examination data. Biochemical analysis blood: glucose 5.0 mmol/l, total cholesterol 3.41 mmol/l, triglycerides 1.06 mmol/l, total bilirubin 14.1 µmol/l, alanine aminotransferase 27 U/l, aspartate notransferase 32 U/l. Glucose tolerance test: fasting glucose - 5.7 mmol/l, after 120 minutes - 6.0 mmol/l.

14.3 µIU/l, testosterone 1.1 ng/ml, luteinizing hormone<0,7 мМЕ/л, фолликулостимулирующий гормон <0,05 мМЕ/л.

During ultrasound examination of organs abdominal cavity and kidneys there are signs of pancreatitis and fatty hepatosis. Ultrasound of the thyroid gland and adrenal glands is unremarkable. Ultrasound of the testicles: the testicles are identified in the inguinal canals in the form of hypoechoic structures with distinct

Prschra-Vim syndrome

with a similar contour without differentiation of layers, their volume is 0.8 and 0.72 ml.

Echocardiography: the structures of the heart are formed correctly. The cavities of the heart are expanded. Prolapse mitral valve with regurgitation of the second degree. Eccentric hypertrophy of both ventricles. The function of contraction and relaxation of the myocardium is impaired.

X-ray of the hands and wrist joints: bone age corresponds to 15.5-16 years. X-ray of the cervical and lumbar spine: straightening of the cervical lordosis. The bodies of the cervical vertebrae, arches and articular processes are not changed. It is not possible to take a photograph of the lumbar lordosis in the lateral projection due to obesity. In a direct projection, the body, arches and articular processes of the vertebrae appear unchanged.

Body composition assessment (bioimpedance analysis):

Basic metabolism - 1881 kcal;

Fat mass - 77.3 kg (increased);

Lean mass - 73.4 kg (increased);

Active cell mass - 40.0 kg (increased);

The proportion of active cell mass is 54.6% (reduced);

Total liquid mass - 53.7 kg (increased);

Waist-to-hip ratio - 1.2 (increased);

Classification by percentage of fat mass - 51.3% (obesity).

Consultation with a cardiologist: chronic

pulmonary heart; chronic heart failure (III functional class).

Consultation with a neurologist: organic damage to the central nervous system against the background of diencephalic-cerebrasthenic syndrome; delayed mental and physical development.

Consultation with a psychotherapist: mild mental retardation with behavioral disorders and emotional instability

tew in adolescence against the background of genetic pathology; hyperphagia.

Treatment was carried out: individual diet No. 8, verapamil, isosorbide mononitrate, trimetazidine, spironolactone, hofi-tol, allochol, lipoic acid, fluvox-min, pyritinol, chlorprothixene. Physical therapy was not performed due to low exercise tolerance.

Final clinical diagnosis: Prader-Willi syndrome; obesity III degree, morbid; hypogonadotropic hypogonadism; fatty hepatosis; biliary dyskinesia; secondary changes in the pancreas; chronic pulmonary heart disease, chronic heart failure (III functional class); organic damage to the central nervous system against the background of diencephalic-cerebrasthenic syndrome; delayed mental and physical development; bronchial asthma; mycosis of the skin of the feet.

During his stay in the department, the patient's condition improved. Manifestations of heart failure decreased, swelling on the anterior abdominal wall was reduced, and tachycardia decreased. In general, there was a positive trend in the form of a decrease in body weight by 10.8 kg (body weight at discharge 143.8 kg, body mass index 54.9 kg/m2).

Diagnosis and treatment of Prader-Willi syndrome

Prader-Willi syndrome occurs with a frequency of 1: 10,000-1: 15,000 births. The majority (about 70%) of cases of PWS are caused by microdeletion of the long arm of chromosome 15 (15d11-r13). The remaining cases are associated with uniparental disomia - in this case, with the inheritance of both 15th chromosomes from the mother.

Clinical manifestations

Low fetal mobility and/or pathological position of the fetus during labor may

Large criteria (each corresponds to 1 point)

Small criteria (each corresponds to 0.5 points)

General hypotension with suppression of the sucking reflex in the neonatal period and infancy, which gradually resolves on its own.

Eating disorders at an early age, requiring special manipulations and leading to developmental delays.

Excessive or rapid weight gain at the age of 1-6 years, central obesity.

Characteristic facial changes: dolichocephaly, narrow face, almond-shaped eyes, small mouth, thin upper lip, drooping corners of the lips (>3 signs). Hypogonadism.

Hypoplasia of the genitals.

Delayed puberty.

General developmental delay, mild to moderate mental retardation, learning disability. Hyperphagia, obsessive attitude towards food.

Deletion 15d11-13 or maternal disomy.

Low fetal mobility, infant lethargy, weak cry.

Hysteria, stubbornness, rigidity, outbursts of unmotivated anger, obsessive-compulsive disorders, theft, pathological deceit, negativism (>5 signs).

Sleep disturbances or sleep apnea. Short stature.

Skin hypopigmentation.

Small hands and/or feet.

Narrow hands.

Convergent strabismus, myopia.

Viscous saliva.

Speech disorders.

be prenatal manifestations of hypotension associated with PWS. In the neonatal period, hypogonadism can be detected (in the form of scrotal hypoplasia and cryptorchidism in boys). Newborns with PWS have a weak sucking reflex and difficulty feeding, which can lead to developmental delays.

Hyperphagia and food-seeking behavior appear between 1 and 6 years of age. Pathology of the hypothalamus in PWS leads to a lack of feeling of satiety, which, combined with a decrease in calorie expenditure due to muscle hypotension and insufficient activity, causes the development of obesity. Fat deposition is observed predominantly on the trunk and proximal limbs. Ghrelin levels (a hormone evoking feeling hunger) in plasma is increased in patients with PWS, regardless of body weight.

Phenotypic manifestations of PWS include a narrow face, dolichocephaly, almond-shaped eyes, low-set ears and microacria

(small hands and feet), 50% of children have skin hypopigmentation. Growth retardation and growth hormone deficiency may occur. Manifestations of hypogonadism include small genitalia and incomplete or late puberty.

There is always a delay in motor development with late formation of skills, and varying degrees of speech and cognitive delay. Behavioral disorders in the form of hysteria, stubbornness, obsessive-compulsive manifestations and rigidity of thinking are common. 5-10% of patients experience mental illness(psychosis, bipolar disorders, obsessive-compulsive disorders). Specific characteristics of PWS are a high pain threshold, increased viscosity saliva and a high threshold for vomiting.

Diagnostics

Examination to exclude Prader-Willi syndrome is necessary for children with

Přčra-Viyaš syndrome

obesity, delay mental development, muscle hypotonia, hyperphagia and eating disorders with a history of eating disorders and a weak sucking reflex.

Classic diagnostic criteria PPVs are presented in the table. Currently, the number of criteria has been increased for the purpose of early diagnosis and correction. The diagnosis is likely in children under 3 years old with a score >5 (including 3 major criteria), in children over 3 years old - with a score >8 (including 4 major criteria). Despite the high sensitivity of this scale (about 90%), in all cases, karyotyping and molecular genetic testing of the 15th pair of chromosomes are required to confirm the diagnosis of PWS. The specificity of these methods reaches 100%.

Patients with PWS require observation and therapy in the following areas:

Treatment of muscle hypotonia and feeding problems at an early age;

Detection and correction of hypogonadism or hypopituitarism;

Treatment of obesity;

Scoliosis monitoring;

Correction behavioral disorders. Impaired circulation bile acids in patients with PWS leads to a deficiency of fat-soluble vitamins, which necessitates their additional administration. If there is significant growth retardation, therapy with growth hormone drugs is indicated, which allows you to increase muscle mass, eliminate osteopenia, normalizes secondary sexual characteristics, but in some patients it causes sharp deviations in behavior.

Patients with PWS may need surgery cryptorchidism, scoliosis, obstructive sleep apnea. Because of

Low pain sensitivity and inability to vomit in these patients makes it difficult to diagnose cholecystitis, appendicitis and other acute pathology abdominal cavity.

Patients with PWS have hyperphagia and decreased basal metabolic rate. Most obesity treatment programs are ineffective in these patients. Nutrition should be based on the following principles:

At primary school age, a hypocaloric balanced diet (1000 calories per day with the addition of vitamins and calcium) under the supervision of a nutritionist is indicated;

Limiting the availability of food at home and at school (including using locked cabinets and refrigerators, small plates).

Patients with PWS are characterized by muscle hypotonia, which leads to the need for additional physical exercise and physical therapy to develop motor skills, strengthen skeletal muscles, and prevent scoliosis. Promotion physical activity plays at home and at school important role in body weight correction.

There are currently no effective medications to correct hyperphagia, so reducing caloric intake and food availability is the only available strategy to prevent or limit weight gain in PWS. Children with PWS are characterized by a constant desire to search for food and consume it. They may beg and hide food, ask strangers for food, and eat without feeling full. Parents and family members need to know

about these features and provide proper nutrition and sufficient activity of the child. Supporting parents and caregivers, monitoring portion sizes and food availability, and planning for long-term care are critical aspects of treating this group of patients.

Kazantseva L.Z., Novikov P.V., Semyachkina A.N.

Prader-Willi syndrome in children: new in etiology, pathogenesis and treatment // Ros. Vestn. perinatol and pediatrician. 1999. No. 4.

Peterkova V.A., Vasyukova O.V. Rare forms obesity // Treatment. doctor. 2008. No. 3. P. 29-33.

Prader-Willi Syndrome E.V. Pavlovskaya, T.V. Strokova, and A.G. Surkov

Many of genetic syndromes are accompanied by the development of morbid forms of obesity even at preschool age. Sharply expressed obesity demands the profound investigation and excluding of the genetic reasons of disease in children. The case of severe obesity in adolescents with Prader-Willi syndrome is detailed in the article.

Key words: genetic syndromes, Prader-Willi syndrome.

Books of the Publishing Holding “Atmosphere”

Obesity in modern civilized society has become an epidemic. More and more more people suffer from lack of exercise and excess weight. Among obese patients separate group made up of children and adolescents. The reasons for the development of the disease in this case are not only sedentary life and unbalanced nutrition, but also in genetic abnormalities. Similar pathologies include Prader-Willi syndrome.

Hereditary obesity: definition and likelihood of development

All information about a person’s appearance, character metabolic processes in the body is contained in the deoxyribonucleic acid (DNA) molecule. Sections of DNA that encode certain characteristics (hair, eye, skin color) are called genes. All human hereditary material is grouped into forty-six chromosomes, clearly visible in the cell nucleus through a microscope. Half of them unborn child

receives from his father, the other from his mother. Chromosomes are initially contained in germ cells - the egg and sperm.

The human chromosome set contains all the information about the structure and functioning of the body Any damage to a DNA molecule of varying length (a gene, a section of a chromosome) is likely to affect either the external features of a person or the nature of metabolism. Prader-Willi syndrome is a medical term describing characteristic changes

the appearance of the patient in combination with hereditary obesity and metabolic characteristics.

Prader-Willi syndrome is a combination of obesity, altered facial features and body proportions of a hereditary nature

The syndrome was first described by scientists Andreas Prader and Heinrich Willi in 1956. The prevalence of the pathology is one case in ten to twenty thousand newborns. The disease is equally common among boys and girls. Family cases of Prader-Willi syndrome have been described in the literature.

The main reason for the development of Prader-Willi syndrome is a disorder in the structure of genes located on the fifteenth chromosome. Two types of defects lead to the formation of the disease:

loss of a large section of the DNA molecule (microdeletion) of paternal origin;
inheritance of both fifteenth chromosomes from the mother (isodisomy).

Prader-Willi syndrome develops due to genetic defects of the fifteenth chromosome

About two thirds of cases of pathology are caused by microdeletion, the rest by maternal isodisomy.

There is a genetic opposite defect: microdeletion of maternal origin or paternal disomy. Both causes lead to the development of a hereditary pathology called Angelman syndrome. The clinical picture of this disease is characterized by a slowdown in physical and intellectual development, impaired coordination of movements, and epileptic seizures.

Before development molecular genetics It was generally accepted that inheritance of both pairs of chromosomes from one parent was impossible. However, with the advent modern methods analysis not only proved this fact. In the process of ongoing genetic research, the assertion about the equal influence of paternal and maternal hereditary information on the external features and nature of the child’s metabolism was refuted.

Clinical aspects of genetic diseases - video

Features of the pathology

The main consequence of genetic abnormalities in Prader-Willi syndrome is an unusual metabolism of fats in the body, leading to a tenfold prevalence of their deposition in subcutaneous fat over breakdown. One more important mechanism development of the disease is a violation of the exchange of sex hormones, as a result of which reproductive system has many anomalies of anatomical structure.

In addition, with Prader-Willi syndrome, the risk of developing malignant tumors is significantly increased due to genetically programmed weak system protecting the DNA molecule from damage.

Symptoms of the disease

Clinical picture of Prader-Willi syndrome in children of different ages varies significantly.

Signs of Prader-Willi syndrome in different age groups - table

Age groups	Newborns	12–18 months	Preschoolers and teenagers
Indicators	Newborns	12–18 months	Preschoolers and teenagers
Physical development	Prematurity; breech birth.	Marked decrease muscle tone	Obesity with preferential localization on the torso and upper sections limbs; short stature.
Neuropsychic development	Age appropriate	Weakening of reflexes	Delayed intellectual development
Sexual development		Age appropriate, possible absence of testicles in the scrotum (cryptorchidism)	Underdevelopment of the genital organs, cryptorchidism
Anatomical abnormalities		Slightly increased skull size	High forehead; narrow palpebral fissures; eversion of the eyelid; underdevelopment of teeth and ears; rachiocampsis; reduction in limb length.

During intrauterine development, a fetus with Prader-Willi syndrome has minor anatomical features in the form of a narrow facial skeleton.

Appearance of patients with Prader-Willi syndrome - photo

A genetic defect on the fifteenth chromosome leads to multiple external manifestations of the disease
Obesity in Prader-Willi syndrome mainly affects the trunk, shoulders and hips Obesity is the most characteristic external feature of the disease
Wide bridge of nose, narrow eyes and lips - character traits faces of patients with Prader-Willi syndrome

Diagnostic methods

To establish a diagnosis, the following methods are used:

Differential diagnosis is carried out with the following diseases, in which the main symptoms are obesity, low muscle tone, and delayed intellectual development:

Down syndrome;
myopathy;
spinal amyotrophy;
Lawrence-Moon syndrome;
Bardet-Biedl syndrome;
Alström syndrome;
Opitz-Frias syndrome.

Hereditary syndromes - photo gallery

Down's disease - genetic defect associated with changes in the number of chromosomes
Patients with Lawrence-Moon syndrome have a characteristic appearance
Alström syndrome is accompanied by the development of obesity

Treatment of hereditary obesity

Treatment of the disease is aimed at improving the patient’s quality of life, since the genetic defect is modern stage the development of medicine cannot be corrected. Therapy for Prader-Willi syndrome is complex, including correction of nutrition and weight, muscle tone, sexual development, as well as initial intellectual abilities.

Drug treatment

Medicines are used to achieve an acceptable level of growth, as well as the correct formation of the genital organs during puberty.

The hormone somatotropin promotes muscle and skeletal growth. The drug is used until the cartilaginous zones of the long bones of the shoulder, femur, tibia and forearm are closed. Correct sexual development in Prader-Willi syndrome is achieved by administering the hormone gonadotropin. The drug provides normal process

It is important to remember that only a doctor can decide what the duration of the course of treatment will be and prescribe the appropriate medications.

To develop secondary sexual characteristics, adolescents with Prader-Willi syndrome are prescribed human chorionic gonadotropin.

Physiotherapy

Physiotherapeutic procedures used at an early age to correct muscle tone:

electrical stimulation;
electrophoresis.

These methods are based on the beneficial effects electric current different shapes and polarities. Massage allows you to create a harmonious tone in various muscle groups. Physiotherapy - necessary event in the treatment of patients with Prader-Willi syndrome. Greatest effect achieved through swimming and water aerobics. A sufficient level of physical activity is vital for the patient in the fight against excess weight.

Swimming is an ideal sport for a patient with Prader-Willi syndrome

Diet

Rational nutrition is the main way to correct the special metabolism of fats in patients. First of all, it is necessary to teach the child not to overeat, so parents need to exclude free access to food.

whole grain bread;
brightly colored berries;
fresh juices;
dairy products;
sea fish;
seafood;
green tea;
fresh vegetables and fruits;
sea kale.

Whole grain bread is a source of valuable carbohydrates
Fruit natural juices contain many various vitamins
Seafood - source valuable protein
Green tea contains a large number of antioxidants
Seaweed is an ideal source of iodine to support thyroid function
Dairy products contain calcium necessary for bone growth

Foods to avoid:

sugar;
carbonated drinks;
fast food;
fatty meats and fish;
White bread;
potato;
chocolate;
confectionery with cream;
fresh bakery.

Photo gallery: foods to avoid

Simple carbohydrates contained in sugar accelerate the process of fat deposition
Fast food is not the healthiest food and is very high in calories.
White bread made from premium flour is very high in calories
Potatoes are a source of large amounts of simple carbohydrates (starch)
Confectionery have a high sugar content
Carbonated drinks contain excess sugar and calories

Correction of a child’s intellectual development

An adequate level of intelligence is the key to the socialization of patients with Prader-Willi syndrome. The development of initial abilities in classes with a speech therapist-defectologist and teacher allows children to be accepted into any team.

Development correct pronunciation and figurative speech is very important for a child with Prader-Willi syndrome

Complications and prognosis of the disease

Timely diagnosis and adequate therapy allows patients with Prader-Willi syndrome to achieve an acceptable level of quality of life. If the course of the disease is unfavorable, the following complications develop:

diabetes;
severe forms of stopping breathing during sleep (apnea);
pronounced curvature of the spine;
destruction of cartilage tissue of joints under the influence of excess weight;
heart failure;
malignant neoplasms.

Prevention

The only effective method of prevention is prenatal genetic diagnostics with determination of the characteristics of the chromosomal set of fetal cells obtained from amniotic fluid. Subsequently, consultation with a geneticist is carried out.

Genetic counseling is the only effective method prevention of Prader-Willi syndrome

Prader-Willi syndrome - serious genetic disease. To maintain the proper quality of life, long-term persistent cooperation between the child, his parents and doctors is necessary. Only disciplined implementation of all recommendations will make the patient a full-fledged member of modern society.