Angelman Syndrome Health Article

Definition

Angelman syndrome (AS) is a genetic condition that causes severe mental retardation, severe speech impairment, and a characteristic happy and excitable demeanor.

Description

Individuals with AS show evidence of delayed development by 6–12 months of age. Eventually, this delay is recognized as severe mental retardation. Unlike some genetic conditions causing severe mental retardation, AS is

not associated with developmental regression (loss of previously attained developmental milestones).

Severe speech impairment is a striking feature of AS. Speech is almost always limited to a few words. However, receptive language skills (listening to and understanding the speech of others) and non-verbal communication are not as severely affected.

Individuals with AS have a balance disorder, causing unstable and jerky movements. This typically includes gait ataxia (a slow, unbalanced way of walking) and tremulous movements of the limbs.

AS is also associated with a unique "happy" behavior, which may be the best-known feature of the condition. This may include frequent laughter or smiling, often with no apparent stimulus. Children with AS often appear happy, excited, and active. They may also sometimes flap their hands repeatedly. Generally, they have a short attention span. These characteristic behaviors led to the original name of this condition, the "Happy Puppet" syndrome. However, this name is no longer used as it is considered insensitive to AS individuals and their families.

Demographics

AS has been reported in individuals of diverse ethnic backgrounds. The incidence of the condition is estimated at 1/10,000 to 1/30,000.

Causes and symptoms

Most cases of AS have been traced to specific genetic defects on chromosomes received from the mother. In about 8% of individuals with AS, no genetic cause can be identified. This may reflect misdiagnosis, or the presence of additional, unrecognized mechanisms leading to AS.

The first abnormalities noted in an infant with AS are often delays in motor milestones (those related to physical skills, such as sitting up or walking), muscular hypotonia (poor muscle tone), and speech impairment. Some infants seem unaccountably happy and may exhibit fits of laughter. By age 12 months, 50% of infants with AS have microcephaly (a small head size). Tremulous movements are often noted during the first year of life.

Seizures occur in 80% of children with AS, usually by three years of age. No major brain lesions are typically seen on cranial imaging studies.

The achievement of walking is delayed, usually occurring between two-and-a-half and six years of age. The child with AS typically exhibits a jerky, stiff gait, often with uplifted and bent arms. About 10% of individuals with AS do not walk. Additionally, children may have drooling, protrusion of the tongue, hyperactivity, and a short attention span.

Many children have a decreased need for sleep and abnormal sleep/wake cycles. This problem may emerge in infancy and persist throughout childhood. Upon awakening at night, children may become very active and destructive to bedroom surroundings.

The language impairment associated with AS is severe. Most children with AS fail to learn appropriate and consistent use of more than a few words. Receptive language skills are less severely affected. Older children and adults are able to communicate by using gestures or communication boards (special devices bearing visual symbols corresponding to commonly used expressions or words).

Some individuals with AS may have a lighter skin complexion than would be expected given their family background.

Diagnosis

The clinical diagnosis of AS is made on the basis of physical examination and medical and developmental history. Confirmation requires specialized laboratory testing.

There is no single laboratory test that can identify all cases of AS. Several different tests may be performed to look for the various genetic causes of AS. When positive, these tests are considered diagnostic for AS. These include DNA methylation studies, UBE3A mutation analysis, and fluorescent in situ hybridization (FISH).

Treatment team

Children with Angelman syndrome will need help from a variety of professionals, including a general pediatrician and pediatric neurologist. A child psychiatrist and/or psychologist may be helpful as well, particularly to help design and implement various behavioral plans. Physical, occupational, and speech and language therapists may help support specific deficits. A learning specialist may be consulted for help with an individualized educational plan.