Angelman syndrome - history, symptoms and treatment. Sick children look happy and carefree

Angelman syndrome (AS) is caused by a partial deletion of the long arm of chromosome 15 and uniparental disomy. Angelman’s disease does not manifest itself in the first days and weeks of life - its characteristic symptoms are not visible in newborns. In the beginning, there is excessive muscle tension.

What is Angelman Syndrome

In appearance, children with Angelman syndrome initially do not differ from healthy newborns. However, over time, characteristic and concomitant symptoms of the disease appear, which include, among other things, impaired motor development and impaired mental development.

Children suffering from Angelman syndrome develop much more slowly than their healthy peers - they begin to crawl, sit and walk late. Some small patients cannot move independently, but early diagnosis of the disease and intensive rehabilitation can affect mobility.

The first symptoms of Angelman syndrome, causing anxiety in parents, begin to appear in infants at the age of 6 months. The dominant symptom in early life is delayed psychomotor development. The symptoms of Angelman’s disease are sometimes confused with the symptoms of cerebral palsy and also with the symptoms of autism.

In the past, children with Angelman syndrome were called “happy puppet syndrome” because of their characteristic appearance and behavior - puppet movements and fits of laughter for no apparent reason. As a rule, Angelman syndrome is confirmed in early childhood, between the ages of 3 and 6 years. At the stage of diagnosing the causes of violations of the psychomotor development of the child, other neurological diseases should be excluded.

Angelman syndrome - case history

Angelman syndrome was first described in 1965 by pediatrician Harry Angelman, who treated children with a similar set of symptoms, i.e., psychomotor retardation, lack of speech, craniofacial dystrophy, and also with epileptic seizures. These children smiled very often and it was easy to cause fits of laughter in them, and they moved in a specific way - their gait resembled the movements of a puppet. Hence the name “puppet children”.

Just over 200 cases of Angelman syndrome have been described (the name “doll children” is no longer used), but this does not mean that the disease belongs to a group of diseases diagnosed very rarely. Angelman syndrome affects 1 in 15,000 to 20,000 children.

Substrate of Angelman syndrome

Angelman Syndrome is a genetic disorder that can be inherited from one of your parents or developed as a result of a spontaneous mutation on chromosome 15—about 10% of cases, the disease is not due to a mutation passed down from your parents. In most cases, the cause of Angelman syndrome is a maternal chromosome deletion.

The genetically determined Angelman syndrome develops as a result of a deletion of a portion of the 15th chromosome. Psychomotor disorders are caused by dysfunction of the UBE3A gene encoding ubiquitin ligase. The study made it possible to identify 4 mechanisms of the development of the disease that affect its course.

The development of Angelman’s disease can lead to:

• deletion of chromosome 15 of maternal origin in the region 15q11 - q13 - affects 65-75% of sick children,

• mutation in the UBE3A gene - affects 5-11% of sick children,

• uniparental or uniparental disomy (UDP) of paternal chromosome gene copies - affects 2-3% of sick children and is associated with a milder course of Angelman syndrome,

• imprinting defect (ID) - affects about 3% of sick children.

At the diagnostic stage, it is necessary to determine the type of molecular defect that led to the development of the disease. A partial deletion of the long arm of chromosome 15 can also cause Prader-Willi syndrome.

Symptoms of Angelman Syndrome

As already mentioned, the symptoms of Angelman syndrome are initially non-specific. In young children, the disease is manifested by excessive muscle tone and feeding problems resulting from a violation of the sucking reflex. A child with Angelman syndrome does not develop at the right pace - he begins to sit (at the age of 1 to 3 years), crawl (about 2 years) and walk very late (most children do not learn to walk until about 5 years). Some children don’t walk at all.

Other typical symptoms of Angelman syndrome include:

• microcephaly that occurs before about 2 years of age,

• epileptic seizures of varying severity,

• aphasia or severe speech impairment

• behavioral disorders and emotional excitability (attacks of laughter, exaggeratedly cheerful behavior),

• motor hyperactivity,

• eating disorders,

• imbalance,

• sleep disorders.

In this disease, a distinction is made between persistent symptoms, which occur in all affected children, and frequent symptoms (affecting 80% of patients) and concomitant symptoms (affecting 20-80% of patients).

Persistent symptoms of Angelman syndrome include: disturbances in the functioning of the nervous systemwhich are associated with motor and mental retardation, such as impaired coordination of the child’s movements, balance disorders, emotional excitability, speech disorders, sucking disorders and swallowing disorders.

Children with Angelman syndrome may develop characteristic signs over time. phenotypic symptomswhich include, among others:

• flat occiput with occipital furrow,

• big lips,

• widely spaced teeth

• protruding tongue.

Also characteristic is the way of movement of sick children, widely spreading their legs when walking and waving their arms.

In older children, scoliosis in the thoracic region is very common due to weakness of the trunk muscles. As a result of a significant degree of curvature of the spine m.in. to respiratory and other health problems. At the same time, a significant percentage of patients are obese.

Other symptoms of Angelman syndrome include: hypersensitivity to heat and hypopigmentation of the skin, eyes, and hair, which increases sensitivity to sunlight.

How is Angelman syndrome treated?

Treatment of Angelman syndrome is based primarily on rehabilitation. Most patients who have not undergone systematic rehabilitation lose the chance for partial adaptation in adulthood. Early rehabilitation helps prevent progression of the disease. Treatment requires cooperation with many specialists, including a neurologist, ophthalmologist, speech therapist and orthopedist, as well as a specialist in psycho-educational therapy.

Sources:

• Cassidy S.B., Schwartz S.: Prader-Willi and Angelman Syndromes. Violations of genomic imprinting, Medicine 1998, V. 77, No. 2
• Jacek Jaroslaw Bleshinsky: Differential analysis of individual syndromes of autistic disorder. Re-validation scheme; Scientific Publishing House of Nicolaus Copernicus University, Torun, 2010