Angelman syndrome

What is it?

Angelman syndrome (AS) is a neurological disorder first described in 1965 by an English physician named Dr. Harry Angelman.  Symptoms are usually evident after the age of three, and are characterized by severe congenital mental retardation, unusual facial appearance, and muscular abnormalities.

Who gets it?

While an exact count of cases of Angelman Syndrome in the United States is not available, the Angelman Syndrome Foundation has knowledge of around 1000 cases in the U.S. and Canada.  Angelman Syndrome is found among all racial groups.

What causes it?

Researchers have found a very small deleted area in chromosome 15 in patients with Angelman Syndrome.  This deleted area contains genes that are activated or inactivated (turned on or off) depending upon which parent the chromosome was inherited from.  The Angelman Syndrome gene is called UBE3A.  When this gene is turned on, Angelman Syndrome does not occur.  However, when it is turned off or missing, Angelman Syndrome occurs.  In patients with Angelman Syndrome, a missing UBE3A gene only occurs in the chromosome given by the mother.  For this reason, it seems that the UBE3A gene is turned on only on the chromosome inherited from mother.  Researchers have also found that Angelman Syndrome is caused when a child inherits both chromosomes 15 from the father.  This condition is called paternal uniparental disomy (UPD).  In this case, both chromosomes have turned off UBE3A genes on them.  There is a control region, called the Imprinting Center (IC), that can control or turn on or off the action of the UBE3A gene.  Mutations in the area of the Imprinting Center can also cause Angelman Syndrome.

What are the symptoms?

Symptoms of Angelman syndrome include a stiff, unstable jerky gait, absent or diminished speech skills, hand flapping, excessive laughter/unusually happy demeanor, developmental delay, and small head size (microcephaly).  Some patients may also develop epilepsy and have problems with balance.

How is it diagnosed?

Because it is difficult to detect the developmental problems associated with Angelman syndrome during infancy, children are usually diagnosed with the disorder between the ages of three and seven. Parents and doctors may notice a developmental delay between the ages of 6 and 12 months, but because the child does reach most developmental milestones during this stage, a diagnosis cannot be made.  Brain scans are also normal at this time. By the age of two, however, the child with Angelman Syndrome will begin to show signs of microcephaly.  By age three, clinical features of Angelman Syndrome are present, including speech impairment, movement or balance disorder, frequent laughter and smiling, easily excitable personality, hand flapping movements, and short attention span.  Seizures may begin after the age of three.  An abnormal electroencephalograph (EEG), a painless procedure in which wires are pasted to the scalp to record the brain's electrical activity, will also be found at this time.  Some children with Angelman Syndrome will also have symptoms related to the mouth and jaw, including protruding tongue or  tongue thrusting, sucking/swallowing disorders, feeding problems during infancy; a jaw that projects forward (prognathia), a wide mouth with wide-spaced teeth, frequent drooling, and excessive chewing/mouthing behaviors.  Children may also have an imbalance of eye muscles so that one eye cannot focus with the other, called strabismus; under-pigmented skin, hair, and eye color; hyperactive lower limb deep tendon reflexes; uplifted, flexed arm position especially during movement; increased sensitivity to heat; sleep disturbances; and an attraction to/fascination with water.

What is the treatment?

Treatment of Angelman Syndrome is focused on providing physical therapy and adaptive devices to assist with gait and balance problems.  Speech therapy is recommended for language problems.  Patients with epilepsy are prescribed anticonvulsant medications.