Angelman syndrome: What is it? Symptoms, Causes, Treatment and Prognosis

It bears the name of the doctor Harry Angelman, who was the first to delineate the syndrome in 1965.

Angelman syndrome is a genetic disorder with features that include severe language impairment, developmental delay, intellectual disability, and ataxia (movement and balance problems).

Most children with Angelman syndrome have microcephaly (small head size) and epilepsy (recurrent seizures).

The delay in the development of Angelman syndrome usually becomes noticeable at the age of 6 to 12 months.

Adults with Angelman syndrome have facial features that are different and are often described as “thick”.

Some of the characteristics of Angelman syndrome are the result of the loss of function of a gene called UBE3A.

Life expectancy for people with Angelman syndrome seems to be almost normal.

It is a neurobehavioral and genetically determined disorder that affects approximately 1 in 15,000 people. It is caused by various mutations and genetic deletions of the UBE3A gene inherited by the mother, in the chromosomal region 15q11-13.

The UBE3A gene, which encodes E3 ubiquitin ligase, shows tissue-specific imprinting, which is expressed completely from the maternal allele. The diagnosis of Angelman syndrome is confirmed by a methylation test or by mutation analysis.

A more severe clinical picture is related to the deletion phenotype. Patients with Angelman syndrome have a behavioral and motor pattern defined as ” happy puppet” because it is characterized by ataxic jerky movements similar to those of a puppet, a cheerful and sociable disposition and paroxysms of laughter.

Currently there is no cure for Angelman syndrome, and administration is mainly symptomatic. The new therapeutic options are directed towards the possibility of activating the silenced paternal copy of the UBE3A gene.

Angelman syndrome is the result of a mutation in the UBE3A gene, which is located on chromosome 15 and the condition is characterized by developmental delay, lack of speech, seizures and problems walking and balancing.

Patients with Angelman syndrome are very susceptible to seizures and require lifelong care. Currently, neurogenic disorder occurs in approximately 1 in 16,000 live births, and there are no approved therapies for it.

The first signs of Angelman syndrome usually occur when a patient is between 6 and 12 months of age, and seizures usually begin between the ages of 2 and 3 years.

The current standard of care includes medications to control seizure activity and other physical symptoms. Physical and occupational therapies, communication therapy and behavioral therapies are vital to enable people with the disease to reach their full potential for development.

People with Angelman syndrome can not be cured of the condition, however, they are expected to live a normal life.

Angelman syndrome is a genetic disorder that affects the nervous system. It is characterized by severe delays in development, apraxia, epilepsy and lack of functional speech development. AS is late to be noticed and often misdiagnosed.

At birth, there are often no obvious signs of any kind of congenital defect. Normal prenatal and birth records and normal head circumference are not atypical.

Babies with Angelman syndrome will also have normal metabolic, hematological, and chemical laboratory profiles. They will have a normal brain by magnetic resonance or computed tomography.

The delay in development, the first true warning of a diagnosis of Angelman syndrome, is usually not noticed until at least 6 months of age. As time passes, one may notice a delayed or disproportionately slow growth in the circumference of the head.

Seizures also tend to begin before age 3, and it can be seen that an abnormal EEG has a characteristic pattern of Angelman syndrome.

People with Angelman Syndrome are known for their jovial and excitable personalities. They often laugh and show a smiling face. They are also known for their hyperactivity, poor attention span and fascination with water.

Children may have difficulty sleeping, or even need less sleep than expected. Many people with Angelman syndrome become less excitable as they get older, however, intellectual disability, speech disability and epilepsy persist.

symptom

Associated symptoms are stiff, spasmodic movements, microbrizcephaly, hypopigmentation, and unusual motor behaviors, such as flapping hands or lifting arms while walking.

In addition, there are multiple health complications associated with Angelman Syndrome. The difficulty with motor coordination could cause problems feeding babies with Angelman, which could result in a delay in development.

Doctors can recommend a formula for high-calorie babies to compensate. Being incredibly hyperactive, certain restless behaviors can be noticed, such as putting your hands or toys in your mouth.

People with Angelman syndrome may also exhibit an increased appetite, which can lead to obesity and its complications. Other less common features include:

  • Push the tongue.
  • An outstanding language.
  • An abnormally protruding jaw.
  • A wide mouth or widely spaced teeth.
  • Excessive behaviors of chewing or touching the mouth.
  • Strabismus , a condition that causes crossed eyes.
  • Greater sensitivity to heat.
  • Scoliosis.

Angelman syndrome is caused by a severe reduction of expression in a particular gene (the UBE3a gene) in the brain.

By nature of UBE3a, only one copy of chromosome 15 inherited from the mother is able to function actively. It is unknown what this gene is targeting and how its function is relevant to Angelman syndrome.

There are multiple genetic or chromosomal errors that are known to result in Angelman’s syndrome.

Babies with Angelman syndrome appear normal at birth, but often have feeding problems in the first months of life and have significant delays in development between 6 and 12 months. Seizures often begin between 2 and 3 years of age.

Speech impairment is pronounced, with little or no use of words. People with this syndrome often show the following who may have severe functional impairments:

  • Hyperactivity
  • Small head size
  • Sleep disorders.
  • Movement and balance disorders.

Children with Angelman syndrome usually have a happy and excitable behavior with frequent movements of smiling, laughing and fluttering.

In addition to hyperactivity, a brief attention span and a fascination with water are common.

With age, people with Angelman syndrome become less excitable, and sleep problems tend to improve. However, affected people continue to have intellectual disability, severe speech disability and seizures throughout their lives.

Adults with Angelman syndrome have distinctive facial features that can be described as “thick.”

Other common features include unusually white skin with light hair and an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition seems to be almost normal.

Angelman syndrome results from the absence of a functional copy of the UBE3A gene inherited from the mother.

Causes

Gene deletions

Almost 70% of the cases of Angelman syndrome are caused by the elimination of a particular gene sequence in the maternal copy of chromosome 15. This is a copy error in the DNA replication that ends up eliminating a sequence completely of the new DNA chain.

UBE3a mutations

The next most common cause of AD affects only 11% of cases. The entire UBE3a gene is mutated during replication, resulting in a significant decrease in functional UBE3a in the brain.

Disomía Uniparental

Uniparental disomy is the cause of approximately 7% of cases. With uniparental disomy, an individual would inherit two copies of paternal chromosome 15, unlike a maternal copy and a paternal copy.

Due to genomic imprinting, this means that two inactive copies of the UBE3a gene are inherited, which means that there is no UBE3a present and functional in the brain.

Printing defect

A printing defect is similar, but it is not the same as the problem experienced by uniparental disomy.

In the case of a printing defect, the printing center on the maternal chromosome 15 is damaged in some way, which means that the printing information directed by the UBE3a gene is lost to be active.

There is a significant number of cases of Angelman syndrome, around 11%, that do not have a known cause at present.

All the tests in these individuals show normal results, but still meet the diagnostic criteria for Angelman syndrome.

There may be genetic or chromosomal mutations not yet recognized that are causing Angelman syndrome but are not apparent when using our typical test methods.

Treatment

There is no specific therapy for Angelman syndrome. Medical therapy for seizures is usually necessary. Physical and occupational therapies, communication therapy and behavioral therapies are important in enabling people with Angelman syndrome to reach their full potential for development.

There is no cure for Angelman Syndrome. All the treatment at this time is aimed at managing the medical and developmental difficulties experienced by those diagnosed with Angelman syndrome.

Each individual case is treated taking into account the unique challenges that a team of health professionals can present.

Common treatment methods involve taking anticonvulsant medications, physical therapy, communication therapy to adapt to speech disability, and behavioral therapy to cope with hyperactivity and a shorter period of care.

What is the prognosis of Angelman syndrome?

Most people with Angelman syndrome will have severe developmental delays, speech limitations and motor difficulties.

However, people with Angelman syndrome can have a normal lifespan and, in general, do not show a regression of development as they get older. Early diagnosis and adapted interventions and therapies help improve the quality of life.