Angelman syndrome is a chronic neurological disorder produced by a genetic alteration, which causes severe mental retardation, alterations in speech and balance, and a happy appearance and demeanor.

The Angelman syndrome is a genetic neurological disease cause has the following characteristics:

  • Severe mental retardation
  • Severe speech impairment (poor use of words or even complete absence of speech).
  • Ataxia (disorder affecting balance and coordination) and tremors of the extremities.
  • Peculiar conduct and behavior: happy appearance with a permanent smile and frequent laughter, increased excitability.
  • Microcephaly (the head circumference is smaller than usual for the child’s age and sex) and seizures.

It was described for the first time in 1965 by the English pediatrician Harry Angelman, who observed three children who presented similar characteristics that no one had previously explained, thinking that it could be a new syndrome. 

He named these children, because of their physical features, ‘ puppet children. ‘ A couple of years later, Bower and Jeavons observed that others were affected by this syndrome and called it ‘ happy puppet syndrome, a term that 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 precisely, but it is estimated that it affects 1 in 20,000-25,000 newborns, so due to its low frequency, it is considered a rare disease. It affects both sexes equally, and there is no predominance in a specific race. 

People who suffer from this syndrome do not present alterations at birth, and developmental delay can be evident around 6-12 months of age. The most common diagnosis is between three and seven years when characteristic behaviors and clinical features become more apparent. All of these features do not need to be present to make the diagnosis.

Among the various causes of chromosome alteration in Angelman syndrome, the most common is the deletion (loss of a piece of chromosome that separates from the genetic material) of a fragment of chromosome 15 inherited from the mother. This disease does not have a classic inheritance pattern, and the risk of recurrence depends on the causes that gave rise to it. The diagnosis is based on clinical criteria and laboratory findings, although a definitive diagnosis is not always reached. Treatment is very complex and is based on a multidisciplinary treatment, which seeks to reduce or attenuate symptoms.

The degree of involvement of patients with Angelman syndrome is highly variable and depends, among other things, on the genetic alteration that causes the syndrome. For example, when produced by a deletion, the severity of the symptoms is more significant than when the cause is another. On the other hand, the physical and behavioral characteristics of those affected change over time as the individual develops. The symptoms in children are different from those in adults. Thus, treatment and participation in other therapies (physical, occupational, communicative) must be adapted to the other difficulties depending on each stage of life. Apart from the problems described, the sexual development of patients with Angelman syndrome is complete,

Causes of Angelman syndrome

Angelman syndrome is a genetic disease caused by alterations of the UBE3A, located on chromosome 15. All hitherto known mechanisms causing Angelman syndrome produce an involvement of this gene on chromosome 15 from the mother. In all cases, the symptoms are similar (mental retardation, speech impairment, peculiar behavior ), although depending on the cause, the impairment may be more or less severe:

  • The most common cause of Angelman syndrome (up to 70% of cases) is deleting the maternal chromosome in the 15q12 region, where a gene called UBE3A resides. A deletion consists of the loss of a piece of the chromosome, which is broken and separated from the other genetic material. When Angelman syndrome occurs, for this reason, the affectation of the child is quite severe.
  • In a small percentage of cases, Angelman syndrome is caused by inheriting two chromosomes, 15 from the father and none from the mother, known in medical terms as uniparental disomy. In this case, the affectation is usually less severe. Since the physical development is better, there is not as much affectation of the coordination, and the movements and the prevalence of the seizures are smaller.
  • Other causes of Angelman syndrome are defects in the center of the imprint or mutation in the gene for UBE3A, derived from the mother’s chromosome 15. In these cases, the clinical involvement is not usually so severe.