Angelman Syndrome - Description

Page Contents

• ICD-9
• Description
• Genetics
• Prognosis
• Prevalence
• Pearls And Alerts

ICD-9

759.89, Angelman syndrome

Description

Angelman syndrome (AS) is a genetic disorder that causes severe developmental delay/intellectual disability and an unusual behavior pattern of frequent smiling, laughing, hyperactivity, and decreased communication skills. Although children with AS are typically social, delays in language and other features, such as decreased eye contact, are reminiscent of autism. Seizures are usually present, and acquired microcephaly, gait ataxia, tremor, scoliosis, and speech impairment are also common. Sleep and eating problems are frequently observed. Children with AS appear normal at birth, then show progressive developmental delays. It isn't until 2 or 3 years of age, or even later, that the typical syndrome phenotype becomes obvious. The diagnosis of AS is based on clinical features and genetic testing, which confirms the diagnosis in approximately 90% of individuals with the typical phenotype. Because Angelman syndrome is a clinical diagnosis, individuals who meet clinical criteria but whose genetic testing is negative continue to carry the diagnosis. Angelman Syndrome (GeneReviews)

Genetics

Genetics: Individuals with AS are missing a functional copy of the UBE3A gene from their mother. Individuals with Prader-Willi syndrome (PWS) are missing a functional copy of the UBE3A gene from their father. AS and PWS are examples of a genetic phenomenon called imprinting, where the clinical phenotype of a gene abnormality depends on the parent of origin of the gene defect. Gene abnormalities leading to AS may result from:

1. deletions in the 15q11-q13 region of chromosome 15 in the mother (most common)
2. paternal uniparental disomy, where both copies of the gene derive from the father
3. mutations in the UBE3A gene

75-80% of abnormalities in the UBE3A gene can be found by performing a gene methylation test, which detects deletions, uniparental disomy, and imprinting center mutations. [Guerrini: 2003] If methylation testing is negative, UBE3A sequence analysis will detect abnormalities in another 10-15%.

The UBE3A gene produces a protein involved in targeting selected proteins for degradation in the ubiquitin pathway. It is unknown whether the clinical phenotype results from failure of degradation of these proteins, decreased new protein due to accumulation of old proteins, or other mechanisms. Angelman Syndrome (GeneReviews)

Prognosis

Most children with AS will have clinically significant seizures and will need antiepileptic therapy. Children with AS do not show developmental regression and, with good proactive care, should have normal life expectancies. They are, however, at risk for early death due to seizures, aspiration pneumonia, and chronic and restrictive lung diseases.

Prevalence

1 in 12,000 births. [Steffenburg: 1996]

Pearls And Alerts

Angelman Syndrome Module Authors

The authors listed above are responsible for the overall Angelman Syndrome Module. Authors contributing to individual pages in the module are listed on those pages.

Page Bibliography

Guerrini R, Carrozzo R, Rinaldi R, Bonanni P.
Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms.
Paediatr Drugs. 2003;5(10):647-61. PubMed abstract

Steffenburg S, Gillberg CL, Steffenburg U, Kyllerman M.
Autism in Angelman syndrome: a population-based study.
Pediatr Neurol. 1996;14(2):131-6. PubMed abstract