Prader-Willi syndrome (PWV) 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 investigate and describe the signs of this disease in 1956 were Andrea Praderi Heinrich Willy. Alexis Labhart, Andrew Ziegler and Guido Fanconi, who also studied and contributed to this chromosomal abnormality, also did research.
Prader-Willi syndrome occurs due to the fact that only the copy of the gene received from the father functions normally. There are violations in the parent copy. In the body of healthy people there is a copy of genes, thanks to which it can work without deviations from the norm. With Prader-Willi syndrome, this copy is missing. Currently, there is a disease that is inherently similar to Prader Willi’s disease. A similar mechanism of occurrence is observed in Angelman syndrome, only in this case, the mutation affects the maternal genetic material. These diseases, as a rule, manifest in a different form and have different forms and severity, but both are incurable.
Causes of Prader-Willi Syndrome
Quite often, the forum discusses the disease, such as Prader-Willi syndrome. This is a hereditarily determined pathology, which manifests itself only with the development of certain anomalies. In other words, with some chromosomal abnormalities, the parental genes suffer, which, in turn, leads to serious diseases. In particular, the clinical picture develops when the seven genes in the fifteenth chromosome, which was inherited from the paternal line, are missing or not expressed. That is, the genetic information contained in the DNA is not converted into RNA. In the diagnosis and prevention it is worth remembering that the cause of Prader-Willi syndrome can only be the expression of paternal genes.
Scientists who tried to find out the reasons for the emergence of this hereditary pathology, at first believed that it formed a homozygote for this deviation. They then concluded that the predominant traits are located in autosomes, so inheritance is the main mode of transmission of the disease. This version was confirmed by the fact that cases of Prader-Willi syndrome were observed in whole families. But most cases of the disease were isolated, occurring without any prerequisites.
Genetics conducted a cytogenetic analysis of pathology. With its help, it was established that the fathers of newborns had a translocation or mosaicism of the fifteenth chromosome. Then they saw the microdeletion of this chromosome. It was only with the advent of molecular research methods and genetic testing methods that finally there appeared an opportunity to diagnose chromosomal disorders, the presence of which leads to the appearance of Prader-Willi syndrome.
An interesting fact is that a similar clinical picture is observed in both patients with microdeletion and idiosomies.
Prader-Willi syndrome: a genetic mechanism
It has now been established that with this pathology, the critical region of the fifteenth chromosome in the segment from
In uniparental disomy, both chromosomes of only one parent are inherited. In order for such a breakdown to occur, genetic and biochemical factors must act on the gene material. This is established by prometaphase analysis and DNA labeling of individual loci of the fifteenth chromosome.
Thus, Prader-Willi syndrome causes two mechanisms: the microdeletion of the fifteenth chromosome, which was obtained from the father, and the idiosomy of the maternal chromosomes (both of them were received from the mother). In Angelman syndrome, everything happens exactly the opposite: the maternal microdeletion and paternal idiosomy. The cause of Prader-Willi syndrome is paternal microdeletion.
An interesting fact is that patients with microdeletion and idiosomy have a similar clinical picture.
Prader-Willi syndrome in children
The mechanisms of disorders that occur in the patient’s body 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. It is believed that they are gaining excess weight due to increased fat formation and lower lipolysis. In this disease, there is dysfunction of the hypothalamus, which is mainly noted in its two nuclei – 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. The reduced activity of tyronase in the melanocytes and hair follicles causes the skin, hair and iris to become hypopigmented.
Prader-Willi syndrome: symptoms of the disease
This syndrome can be detected in early pregnancy. Ultrasound diagnostics will notice the wrong location of the fetus and its low mobility. In addition, the level of the hormone gonadotropin, which is produced by the cells of the chorion, varies significantly in the pregnant woman. To intrauterine signs, in addition to the reduced activity of the fetus, also include its abnormal position and polyhydramnios. On the basis of these signs it is impossible to make an accurate preliminary diagnosis, however, they are sufficient grounds for conducting further diagnostics.
In infants, Prader-Willi syndrome is expressed in the presence of congenital hip dislocation (dysplasia), weakened muscle tone, as well as a lack of coordination. There are cases when a baby is unable to suck and swallow breast milk on its own, so that food is provided with a probe. There may also be breathing problems that may be so severe that artificial lung 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 sleepiness. With regard to external signs, then he has a delay in development, so for these patients is characterized by low growth, as well as small hands and feet. Often there is squint. For diagnosis, there are a number of criteria that are divided into large and small.
Thanks to such criteria, Prader-Willi syndrome is diagnosed in newborns.
Further, the disease is characterized by such symptoms:
- spinal curvature (scoliosis);
- caries of milk teeth, increased saliva density;
- propensity to eat excess food;
- hypofunction of the genital glands, which further 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 in children suffering from Prader-Willi syndrome, the following symptoms are detected:
- speech delay;
- overweight; short stature;
- unnatural flexibility;
- decrease in intelligence, inability to learn.
Combinations of such signs can serve as the basis for statement of the final diagnosis.
Prader-Willi syndrome in adolescents
The psychomotor development of children with the above syndrome always lags behind the age-appropriate rate. They have an intelligence development factor ranging from 20 to 80 units. The norm for their age is 85 – 115 units. These children have difficulty speaking, vocabulary is significantly reduced. However, Frim and Kurf conducted a comparative analysis of the various degrees of mental abnormalities and the difficulties that arise in training people with Prader-Willi syndrome. They obtained such results: about five percent of patients have an IQ factor that exceeds 85 units. Their level of intelligence is below average. In the twenty-seven percent, unexpressed mental retardation is noted, their IQ is between 70 and 85. This is the limit of intellectual activity. Thirty-nine percent of the subjects had a slight mental retardation – IQ of such patients, as a rule, did not exceed 70. Also, 27% of patients had slightly more pronounced mental retardation, their IQ was 35-50. And one percent of people had severe and profound mental retardation.
According to data obtained by Kessidy, 40% of patients with Prader-Willi syndrome have a rather low level of intelligence, which is defined as below average or at the limit of intellectual abilities. These are people with a transient level of intelligence.
In children with Prader-Willi syndrome, a rather non-standard cognitive profile is formed. They have quite often well developed visual perception, they can read well and have a good vocabulary, but their speech abilities are lower than understanding the meaning of what they want to say. Children with Praver-Willi syndrome can also process hearing information, they do not have the ability to do mathematical science and calligraphy. These children have poor visual and auditory short-term memory and sonic concentration. With age, in some cases there was an improvement in the intellectual abilities of children who suffer from this disease.
The main mental disorders that occur in patients with Prader-Willi syndrome, manifest compulsive behavior. It is usually manifested by increased anxiety and twitching of the skin. These psychological problems lead to the fact that these patients have to be forcibly hospitalized in a psychiatric hospital. Videos of patients suffering from Prader-Willi syndrome can be seen on many sites.
Photos of children with Prader-Willi syndrome
In patients, a narrow and high forehead, almond-shaped eyes, large nose bridge and thin lips can be visually observed. They develop infertility due to underdevelopment of the genital organs and obesity, a tendency to hypotension, and an increased tolerance to glucose. In patients suffering from Prader-Willi syndrome, very pubic hair and genital organs are underdeveloped. However, in one patient with this syndrome more than five signs of the disease are never observed.
Phenotype of a child with Prader-Willi syndrome
Genes should be included in the work when it is required. So, for example, in time begins the growth of hair, there are secondary sexual characteristics. If this does not happen, then they talk about Prader-Willi syndrome. He, according to different researchers, is found in one case of ten or fifteen thousand newborn babies. There are many photos of children with Prader-Willi syndrome. Obesity is the leading symptom of many hereditary diseases. Prader-Willi syndrome is among them leading place.