Angelman syndrome is a genetic disorder resulting in severe intellectual disability. It affects one in 12,000 to 20,000 children, and accounts for 6% of severely mentally disabled children who also have epilepsy.
Symptoms and signs
Children with this condition often show developmental delay which becomes apparent by 6-12 months, and progress to be eventually classified with severe developmental delay. Symptoms include; ataxia with trembling limbs, impaired expressive speech and a typically happy hyperactive temperament, with a short attention span, laughing, and sleep disturbances.
It was once known as “happy puppet syndrome”. It is notable that the characteristic features of the syndrome are usually apparent only after the age of one year. Less universal findings of Angelman syndrome include:
- microcephaly
- flat neck
- pale skin and fair hair
- widely spaced teeth
- tongue protrusion and open mouth
- scoliosis
- constipation
- feeding difficulties.
Genetic basis of Angelman syndrome
The disease is the result of a missing UBE3A gene on chromosome 15q. In over 70% of patients it is due to maternal deletions of 15q11-13, which also produces the most severe form of the syndrome. Other forms of the syndrome are due to uniparental disomy, imprinting center mutations and UBE3A mutations. This gene is part of a cluster of genes coding for GABA-receptor subunits. About 20% show no detectable mutation.
Diagnosis and treatment
Diagnosis is based on the typical physical and developmental features, EEG changes, especially large-amplitude slow-spike waves, and genetic testing. DNA methylation testing detects the condition in about 80% of patients.
Treatment involves seizure control with anticonvulsants like sodium valproate, benzodiazepines and ethosuximide. Other components of therapy include physiotherapy, speech therapy and special education, which are required to improve the patient’s physical and mental skills, and prevent scoliosis and immobility.
Genetic counseling is necessary to assess the risk to siblings or other members of the extended family. The risk of the condition is more than 50% when the mechanism is via UBE3A mutations, but much less with other mechanisms of chromosomal loss.
References
- http://www.ncbi.nlm.nih.gov/pubmed/23622177
- http://www.ncbi.nlm.nih.gov/pubmed/14510623
- http://www.ncbi.nlm.nih.gov/pubmed/20445456
- http://www.ncbi.nlm.nih.gov/books/NBK1144/
Further Reading
- All Angelman Syndrome Content
Last Updated: Aug 23, 2018
Written by
Dr. Liji Thomas
Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.
Source: Read Full Article