Angelman Syndrome > Health and Wellness.

Angelman Syndrome is a neurological disease of genetic cause that has the following features:
  • Severe mental retardation.
  • Severe impairment of speech (use small words or even complete absence of speech).
  • (Disorder affecting balance and coordination) ataxia and/or tremors of the extremities.
  • Conduct and peculiar behavior: happy with permanent smile and frequent laughter appearance, increased excitability.
  • Microcephaly (the circumference of the head is smaller than normal for the age and the sex of the child), and seizures.
It was first described in 1965 by English pediatrician Harry Angelman, who observed three children who had similar characteristics that nobody had described so far, thinking that it could be a new syndrome. He called these children by their physical characteristics, 'puppet children'. A couple of years later, Bower and Jeavons, observed that there were others affected by this syndrome, and called it 'happy puppet syndrome', a term which would be used until 1982, when it was replaced by Angelman Syndrome, in honor of its discoverer.
The exact incidence of Angelman syndrome is not known with accuracy, but it is estimated to affect 1 in every 20,000-25,000 newborns, which, due to its low frequency, is considered a rare disease. It affects both sexes equally and there is no dominance in a particular race. People who suffer from this syndrome not present alterations at birth, and retardation of the development can start to be seen around 6-12 months of age. The most common age at diagnosis is between three and seven years, when the characteristic behaviors and the clinical features are made more obvious. All of these traits do not need to be present to be able to make the diagnosis.
Among the various causes of chromosomal alteration in Angelman Syndrome, the most common is the deletion (loss of a piece of chromosome spreading of genetic material) from a fragment of chromosome 15 inherited from the mother. This disease does not have a classic inheritance pattern, and the risk of that again depends on the causes that gave origin. The diagnosis is based on clinical and laboratory findings, but a definitive diagnosis is not always achieved. The treatment is very complex and is based on a multidisciplinary treatment, which seeks to reduce or lessen the symptoms.
The degree of involvement of the patients presenting with Angelman syndrome is highly variable and depends, among other things, the genetic alteration that causes the syndrome. For example, when it is caused by a deletion the severity of the symptoms is greater than when the cause is another. On the other hand, the physical characteristics and behavior of the affected change over time, as the individual will develop, so that symptoms in children are different from the adult. In this way, the treatment and participation in different therapies (physical, occupational, communication) you should mold to different difficulties according to every stage of life. Apart from the described problems, sexual development of patients with Angelman syndrome is complete, health status is good and they have a normal life expectancy.

Causes of Angelman Syndrome

Angelman Syndrome is a genetic disease caused by alterations of the UBE3A gene, located on chromosome 15. All mechanisms known so far to cause Angelman Syndrome produces an affectation of this gene on chromosome 15 from the mother. In all cases, the symptoms are similar (mental retardation, impairment of speech, peculiar behavior...), although depending on the cause, involvement may be more or less severe:
  • The most frequent of Angelman Syndrome (up to 70% of cases) is deletion of the maternal chromosome in the region 15q12, where resides a gene called UBE3A. A deletion is the loss of a piece of chromosome, which breaks down and is separated from the rest of genetic material. When Angelman syndrome occurs for this reason, the involvement of the child is severe enough.
  • In a small percentage of cases, Angelman syndrome is caused by inheriting two chromosomes 15 from the father and no mother, what is known in medical terms as uniparental disomy. In this case, the involvement tends to be less severe, because physical development is better, there is no such involvement and coordination of movements and the prevalence of seizures is less.
  • Other causes of Angelman Syndrome are defects in the center of the stamp or the mutation in the gene of the UBE3A, derived from chromosome 15 from the mother. In these cases the clinical involvement is generally not so severe.

Angelman Syndrome signs and symptoms

Angelman Syndrome is a neurological disorder that is associated with mental retardation. It has a genetic origin, and causes in the development, learning and behavior disorders.

Physical symptoms of Angelman Syndrome

From a physical point of view, children with Angelman Syndrome usually present the following characteristic (though not necessarily all) features:
  • The size of the head is usually small in proportion to the rest of the body, what is known in medical terms as microcephaly. It occurs in 80% of cases.
  • The mouth is large, wide and separated, teeth and is usually an exaggerated protrusion of the tongue and jaw (prognathism). These changes tend to be more evident from the 12 months of life.
  • Hypopigmentation: the color of hair, skin and eyes presents a clearer hue in comparison with their family of origin, and may suggest the presence of albinism in the most severe cases.
  • Occasionally there may be visual impairments such as strabismus, atrophy of the optic nerve or presence of known as the 'Brushfields 'spots in the iris.

Neurological symptoms of Angelman Syndrome

From a neurological point of view, these children may suffer, among others, the following demonstrations:
  • Alterations of the March with strange postures of the upper extremities which, according to the form, remember to a puppet or a chandelier (hence the name that drew them initially those affected by Angelman Syndrome: 'puppet boys').
  • Abnormal limb movements (trembling or shaking), appearing more frequently in the first months of life. These incoordinados movements hamper the child performing basic tasks as walking, eating or pick up objects with the hands. For this reason, the development of children with Angelman syndrome is slower that in healthy children (for example, begin to sit 12 months of life and to walk around 3-5 years).
  • Seizures of different types that, in some cases, do not respond well to conventional medication. Most of these crises begin from three years of age, while in 25% of cases they may appear before the 12 months of life. The severity of seizures decreases with age, but they persist throughout adulthood. Electroencephalogram (medical test that records the brain bioelectrical activity in different conditions) presents a characteristic pattern in 80% of cases, regardless of the child affected by Angelman Syndrome to any seizure or not. This may allow to make an early diagnosis, especially in the early stages of the disease.
  • Sleep disorders.
  • Communication disorders: oral language tends to be incoherent, without issue in many cases more than two consecutive words. The gestural ability also tends to be impaired. Compression remains something better, in fact, children affected by Angelman syndrome tend to have good memory for faces. These difficulties to communicate make affected children to resort to other types of behaviors to express their emotions and needs, as pulling hair, biting, hitting, or push others. Therefore it is working on other routes of communication learning to improve the quality of life of these patients and help them to communicate as an alternative.
  • Other signs: stiffness, instability, stature, sudden movements or small limbs.

Psychological symptoms of Angelman Syndrome

Psychological characteristics most frequently associated with Angelman Syndrome are:
  • Severe mental retardation, which causes that the people affected by this syndrome do not reach the minimum skills of personal autonomy.
  • Characteristic behavior: people suffering from Angelman syndrome have affective behaviors and happy child's appearance. They have interest in establishing relationships with other people. They are friendly and have good social attitude. Degree of hyperactivity and attention deficit can also be observed. A curious feature of these children is his fascination with water and plastic.
Other alterations that can be found in these children are difficult to suck, swallow and even tendency to spit out food (probably in relation to the uncoordinated movements of the tongue). These alterations in food can trigger problems with weight and growth.
Another curious feature of those affected by Angelman syndrome is the presence of excessive sweating and poor tolerance to heat. Moreover, children with this syndrome have a normal physical and sexual development, although puberty may be delayed in 1-3 years.

Diagnosis of Angelman Syndrome

The diagnosis of Angelman Syndrome may be confirmed by clinical and laboratory findings. It is difficult to do it at the time of birth or in the first months of life, since at that time the problems of development are not very obvious. The age range in which Angelman syndrome is diagnosed normally is between three and seven years of age.
To make the diagnosis there are diagnostic criteria collecting clinical characteristics, development and examinations. The definitive diagnosis is achieved by conducting a genetic study.
  • Clinical criteria: are grouped, according to their frequency of appearance, in:
    • Consistent (100%): delayed psychomotor development, impairment of speech, movement or balance and special behavior disorders.
    • Frequent (80%): delay disproportionate growth of the size of the head, seizures and abnormal electroencephalogram.
    • Associated (20-80%): flat occiput and occipital Groove, strabismus, prognathism, wide-mouth, hypopigmentation of skin and eyes, increased sensitivity to heat, sleep disorders, problems of food, etc.
  • Features of development.
  • Complementary tests:
    • Analysis of blood and urine normal.
    • (Cerebral resonance and computed tomography) imaging unaltered tests.
    • Characteristic electroencephalogram in some cases.
The confirmation of Angelman Syndrome diagnosis is made by a genetic study, making a karyotype (study of the chromosomes) that allows to detect the characteristic anomalies causing this syndrome. Other tests can also be performed as the test of hybridization in situ (FISH) or the test of DNA methylation, allowing to study alterations in chromosome 15.
With the diagnostic criteria and the genetic study gets to diagnose the vast majority of those affected, however, on some occasions (around 20% of cases) a definitive diagnosis is not reached.

Treatment of Angelman Syndrome

There is no curative treatment for Angelman Syndrome, but yes a treatment of its symptoms can be and, depending on each case, can be offered special support measures. Therefore, treatment of Angelman Syndrome is a multidisciplinary treatment, with individualization according to each case.
From a medical point of view, different alterations associated with Angelman Syndrome such as hyperactivity, epilepsy, disorders of sleep or scoliosis (spine deviation) can be treated:
  • In hyperactivity, some affected can benefit from treatment with methylphenidate.
  • Seizures usually require treatment with anticonvulsant drugs, although it appears that no drug there is more effective than another (importantly, identify in each case). Conducting reviews by the neuropaediatrician is important.
  • For sleep disorders may be helpful melatonin and behavioral therapies, but in more severe cases may be used even to sedatives.
  • Scoliosis physiotherapy, is important to facilitate the child's motor development.
It is also important that treatment encompasses the psychological field. To do this, relaxation techniques (for controlling the excitability and improve care), should work as well as behavior modification therapies (appears to be effective in the correction and modification of behavior and inappropriate behaviours). In addition, should encourage participation in social activities, to enhance relations with the environment as well.
Measures should be taken to enhance perception, motor skills, attention, intelligence, cognition or language. Communication therapies are one of the pillars of the treatment. The speech therapists work both the non-verbal and verbal communication with an emphasis in the latter due to the characteristics of this disease. Educational programs must be flexible and adapt to the needs and abilities of these children.
Finally, if other types of alterations have to be treated in a specific way in each case
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