Angelman syndrome Q93.5

Harry Angelman (1915-1996), British paediatrician. He described the syndrome named after him in 1965 and called it "Happy Puppet Syndrome" because of the children's conspicuous movement pattern and frequent laughter.

mutation on chromosome 15 (microdeletion on the maternal chromosome or uniparental disomy 15q11-13). The maternal chromosome section is not functional and the UBE3A gene on the paternal chromosome is silenced by imprinting; thus the gene product is completely missing. If not the maternal but the paternal chromosome section is defective, this leads to Prader-Willi syndrome (see also Hypomelanosis Ito). The Angelman syndrome can have a hereditary component. The parents are not affected, but have certain chromosomal peculiarities that are hereditary.

Skeletal deformities: Microcephaly, large mouth with protruding upper jaw, comparatively small teeth that are spaced apart. Unusual protrusion of the tongue (in about 50% of the patients). There are also growth disorders, scoliosis, small hands and feet, feet turned outwards.

Skin: Pigment disorders: Often only weakly pigmented skin, light hair and blue eyes (hypopigmentation, partly parallel to albinism). Hyperhidrosis, particular sensitivity to heat.

Eyes: Strabismus with a frequency of 50 %.

Movement disorders: In infancy often very limited ability to articulate. Movement and balance disorders, ataxias, (mostly a stiff, awkward, swaying gait, with jerky, choppy (running) movements can be observed. Delay in motor development.

Mental developmental disorders: Characteristic of the syndrome are frequent, often objectively unfounded laughter (unmotivated laughter), sometimes downright laughing fits, often during excitement and stress, cognitive disabilities, often hyperactivity, concentration difficulties; pronounced sleep disorders; often good memory for faces, good spatial orientation.

Neurological disorders: About 75% of the people affected suffer from epileptic seizures (between the 3rd and 36th month of life). They involve a constant risk of injury, as they can lead to falls in the middle of movement. The seizures often disappear in adolescence. Special features can be detected in the EEG, even independently of epilepsy and also during sleep.

The diagnosis is made on average between the 3rd and 7th year of life, usually on the basis of abnormal EEG values: a positive genetic test confirms the diagnosis.

The Angelman syndrome is not causally curable. Medically relevant is the adequate treatment of the frequently occurring epilepsy, strabismus and scoliosis. Otherwise, early remedial education, mototherapy, physiotherapy, occupational therapy, speech therapy, sensory integration therapy and therapeutic riding are useful.

People with Angelman syndrome remain dependent on the help of others for their entire lives. They are intellectually capable of development to varying, but usually very limited degrees. They usually need special help and above all permanent personal support in learning and in coping with everyday life.

1. Bonello D et al (2017) Angelman Syndrome: Identification and Management. Neonatal Netw 36:142-151.
2. Buiting K et al (2016) Angelman syndrome - insights into a rare neurogenetic disorder. Nat Rev Neurol 12:584-593.
3. Margolis SS et al (2015) Angelman Syndrome. Neuro therapeutics 12:641-650.
4. Spruyt K et al (2018) Sleep in Angelman Syndrome: A review of evidence. Sleep Med Rev 37:69-84.