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Phelan-McDermid syndrome is a very rare neurodevelopmental disorder characterized by hypotonia, developmental and language delay, autism spectrum disorder, and dysmorphisms. It is produced by loss of chromosomal material.
Phelan-McDermid syndrome is a set of signs and symptoms resulting from a neurodevelopmental or neurodevelopmental disorder. From a clinical point of view, it manifests with severe hypotonia (decreased muscle tone) from birth, global developmental delay, absence or severe delay of language, autism spectrum disorders, intellectual alterations and abnormalities in the body anatomy (dysmorphia) .
This syndrome is very rare, genetic in origin and usually occurs randomly. Its diagnosis is very cumbersome and molecular. There is currently no specific treatment.
What is Phelan-McDermid syndrome?
Phelan et al. were the first to describe it in 1988. They identified it as a product of the loss of genetic material at the terminal end of the long arm of chromosome pair 22, in the 22q13.3 band. This is why it is also known as 22q13.3 deletion or 22q13.3 monosomy.
In the world only have been described about 1200 cases. Its prevalence is not exactly known, because the diagnosis is very complicated and expensive. The clinical manifestations are not specific and, in daily clinical practice, genetic studies are not usually performed.
Phelan-McDermid syndrome can be caused by deletion (loss of genetic material) of the terminal end of chromosome 22 or by mutations that specifically affect the SHANK3 gene, in different areas of the brain.
For the precise diagnosis, a study of the genetics of the cells is carried out, with different methods: karyotype (study of the chromosomes), hybridization in situ fluorescent, comparative genomic hybridization, MLPA and microarray.
At present, it is considered that the first study on suspicion is the karyotype to show the loss of genetic material. Then it is confirmed with microarray.
Clinical manifestations of Phelan-McDermid syndrome
From a clinical point of view, there are many and not very specific symptoms of this syndrome. They include global developmental delay, language delay or absence, body dysmorphia, hypotonia, intellectual disturbances, and autism spectrum disorder.
Phelan-McDermic syndrome is a cause of autism spectrum disorders worldwide.
Central nervous system involvement
The SHANK3 gene is found in multiple systems, predominantly in the central nervous system. The affection of the cerebral cortex manifests with severe hypotonia from birth. This is usually the most relevant clinical data.
Hypotonia delays the development of motor skills, ranging from holding the head to gait without assistance. Toilet training is not usually achieved until approximately 7 years of age.
Language is also affected, being more characteristic the difficulty in the capacity to express itself. Children generally have very little communication, utter a few words, and follow only simple commands. The ability to speak is permanently lost after 4 years.
When imaging studies such as brain MRI are done, atrophy of the cerebral cortex is evidenced, a hypoplastic corpus callosum, alterations in the myelination of nerve fibers, arachnoid cysts and dilation of the ventricles.
Body dysmorphia
Body dysmorphisms are usually minor and include flattening of the back of the head, long, full eyelashes, prominent lips, pointed beard, large hands, malformed nails, bulbous nose tip and enlarged ears.
Genitourinary system
There may be agenesis or renal dysplasia. Have also been registered multiple cysts in the kidneys and hydronephrosis.
Heart malformations
Cardiac malformations can occur in up to 25% of cases and atrial septal defect, heart valve insufficiency, patent ductus arteriosus, and pulmonary artery reflux are more common.
Decreased immune system response
Recurrent infections, especially of the upper airways, are common. There may be allergies, dermatitis, autoimmune hepatitis, and cellulite.
Other manifestations
Other manifestations include seizures, which are more common after puberty, behavioral disorders, altered pain perception, and lymphedema. Gastroesophageal reflux, constipation, diarrhea, and recurrent vomiting can occur.
On rare occasions, alterations in weight growth are associated, such as short stature or a head that is smaller than expected. There may be visual disturbances, such as myopia and hyperopia.
Behavioral disorders include the presence of stereotyped movements (tics), repetitive behaviors, sleep / wake cycle disturbances, intolerance to changes in routine and aggressiveness.
There is no specific treatment and the prognosis is reserved
No specific treatment has been developed for the syndrome, because there is no cure for the loss of genetic material. The assistance of those who suffer from it requires the performance of multiple specialties.
Management is usually required by the area of psychology or psychiatry, neurology, physical therapy and rehabilitation, as well as speech therapy. Although its manifestations do not represent a risk to life, it is not known exactly how patients will evolve.
Phelan-McDermid syndrome is a very rare disease and its diagnosis cannot be made during pregnancy, since there is no specific alteration that is shown in the ultrasound. However, genetic studies can be performed during pregnancy with a sample of chorionic villi or amniotic fluid.
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