Angelman syndrome (AS) is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements especially hand-flapping, frequent laughter or smiling, and usually a happy demeanour. An older, alternative term for this syndrome, happy puppet syndrome, is generally considered pejorative and stigmatizing and is no longer in current use.

Etio- pathology

• AS is a classic example of genetic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15.
• The sister syndrome, Prader-Willi syndrome, is caused by a similar loss of paternally-inherited genes.
• Other causes include uni-parental disomy, translocation, or single gene mutation in that region.
• Angelman syndrome can also be the result of mutation of a single gene. This gene (Ube3a, part of the ubiquitin pathway) is present on both the maternal and paternal chromosomes, but differs in the pattern of methylation (Imprinting).

Signs and symptoms

Consistent (100%)

• Developmental delay, functionally severe
• Speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
• Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
• Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span

Frequent (more than 80%)

• Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
• Seizures, onset usually < 3 years of age
• Abnormal EEG, characteristic pattern with large amplitude slow-spike waves

Associated (20 - 80%)

• Strabismus
• Hypopigmented skin and eyes
• Tongue thrusting; suck/swallowing disorders
• Hyperactive tendon reflexes
• Feeding problems during infancy
• Uplifted, flexed arms during walking
• Prominent mandible
• Increased sensitivity to heat
• Wide mouth, wide-spaced teeth
• Sleep disturbance
• Frequent drooling, protruding tongue
• Attraction to/fascination with water
• Excessive chewing/mouthing behaviors
• Flat back of head

The diagnosis of Angelman syndrome is based on:

• A history of delayed motor milestones and then later a delay in general development, especially of speech
• Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait
• Characteristic facial appearance (but not in all cases)
• A history of epilepsy and an abnormal EEG tracing
• A happy disposition with frequent laughter

• A deletion on chromosome 15

Treatment

• There is currently no cure available. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications.
• Early intervention with physiotherapy is important to encourage joint mobility and prevent stiffening of the joints.
• Occupational therapy, speech therapy, hydrotherapy and music therapy are also used in the management of this condition.