Angelman’s syndrome is a genetic neurological pathology resulting from an intellectual deficit and dysmorphic clinical manifestations (which involve the deformation of one or more limbs).

This disease is rare and its prevalence worldwide (number of cases in a given population at a given time) is estimated at 1: 20 to 000: 1. (10)

Angelman syndrome is the cause of a complex genetic disorder that affects the nervous system. This neurological affectation causes a delay in the intellectual development of the child, significant speech disorders as well as an incoordination of movements (ataxia). Most children with this disease also have seizure disorders and an abnormally small head circumference (microcephaly). The associated intellectual delays are generally visible between the ages of 6 and 12, but other symptoms can appear much earlier. (1)

Children with Angelmon syndrome often exhibit excitable behavior with frequent smiling, laughter, and flapping movements of the hands. Hyperactivity, limited attention span and a fascination with water are also associated with the pathology. Sleep disturbances can be recurrent in these patients with less need to fall asleep than a normal child.

With age, children’s excitability decreases and problems falling asleep tend to improve. Adults with Angelman syndrome have characteristic facial features. These are defined by visible magnifications of the face. Other characteristics may also be visible, such as: abnormally light skin and hair or abnormal curvatures on either side of the spine (scoliosis).

The life expectancy of patients with this pathology is relatively close to that of a normal adult. (1)

Angelman syndrome is a disease that affects a person’s nervous system.

To date, the associated symptoms have been clearly defined.

These physical manifestations are generally absent at the birth of the child and are difficult to identify before the age of one year. Their identifications are most often made between the ages of one and three years. (4)

Despite the fact that the characteristics of the disease are not visible at birth, difficulties in feeding as well as hypotonia (decrease in muscle tone) can be noticed in the first 6 months of a child’s development. In addition, a developmental delay can also manifest between 6 months and 2 years. (3)

The atypical symptoms therefore appear after 1 year and do not result in:

– severe intellectual deficit;

– the absence of language in the child;

– unexplained bursts of laughter;

– abnormal flapping of the hands;

– microcephaly: abnormally small size of the cranial perimeter;

– a macrostomy: significant increase in the slit of the mouth;

– maxillary hypoplasia: deficit in the growth of the upper jaw;

– prognathism: malformation of one or both jaw (s);

– neurological disorders;

– ataxia: deficiency in the coordination of movements;

– epileptic seizures.

Other signs have also been described: cheerful behavior, hyperactivity, decreased attention, hyperexcitability, sleep disturbances, hypersensitivity to heat and a fascination with water.

With age, these signs can evolve by decreasing, we generally observe a thickening of the facial features. Nevertheless, the development of scoliosis and locomotion disturbances may appear later.

Seizures tend to persist into adulthood. Conversely, attention and sleep disorders tend to improve. (3)

Angelman syndrome is a disease of genetic origin. This results from abnormalities in the function of the UBE3A gene.

In the normal context of genetic transmission of this gene, it is inherited from each parent as one copy. These two copies of the gene are in their active form in different parts of the body. However, in certain regions of the body, especially the brain, the active copy of this gene comes exclusively from the mother. This phenomenon is called: genetic fingerprinting. In the case where the maternal copy of the UBE3A gene is not present as a result of chromosomal changes or a genetic mutation, the receptive subject therefore does not hold the active form of the gene for these parts of the brain.

Different mechanisms can be at the origin of the inactivation or absence of the maternal copy of the UBE3A gene. In most cases, this is the absence of a chromosomal segment located on the maternal chromosome 15 and encoding this gene of interest. In other cases, Angelman syndrome results from a mutation in the maternal copy of this gene.

Other cases of the disease can be caused by the inheritance of two copies of this gene from the father and not one copy from the mother and one copy from the father. This phenomenon is called uni-parental disomy.

More rarely, Angelman’s syndrome can also be caused by a chromosomal rearrangement: chromosomal translocation.

The lack of explanation as to the origin of the disease is possible in 10 to 15% of cases. Genetic changes in other genes and / or chromosomes can also be responsible for disorders in these latter cases of the disease.

In most patients with Angelman syndrome, a deficiency in the OCA2 gene is associated with abnormally light hair and skin color. This gene is also located on a fragment of chromosome 15.

Another, non-genetic origin of the pathology has also been put forward. This is characterized by abnormalities in the formation of the egg cell, during reproduction or during embryonic development. (1)

The risk factors associated with the development of Angelman syndrome are genetic.

These risk factors are directly linked to:

– the presence of mutation in the chromosomal segment of ch. Encoding the UBE15A gene;

– an anomaly in the transmission of a copy of this gene from the mother and from the father: notion of genetic imprint, uni-lateral disomy, etc. ;

– an abnormality in the development of the egg cell or embryonic development.

Before the age of one year, the diagnosis of Angelman syndrome is difficult to make. However, if the child presents with tremors before the development of walking, the suspicion of the disease may be expressed.

When the clinical manifestations appear after 1 year, the diagnosis of the disease can then be suggested. It results in a differential diagnosis based on visible symptoms and can be confirmed through genetic testing. These genetic examinations result in the realization of a karyotype, by the use of the FISH technique (Fluorescent in Situ Hybridizationà allowing to detect a possible chromosomal deletion within chromosome 15. (4)

Today, there is no cure for the disease.

However, as soon as the diagnosis of the disease is made, it is essential that the patient has appropriate support as soon as possible. This support is reflected in the mobilization of a multidisciplinary team.

Besides the fact that there is no curative treatment for the disease, other therapeutic means make it possible to improve the lives of patients, and in particular to soothe the associated clinical manifestations. This translates into:

– anti-epileptic drugs;

– support from a psychomotor therapist to improve behavioral disorders visible in children as well as hyperactivity and attention disorders;

– drug and behavioral treatments are also used in the management of sleep disorders;

– drug treatments to prevent gastroesophageal reflux in infants;

– surgical interventions in cases of strabismus, scoliosis and gastroesophageal reflux.