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Renowned Cantopop artists Fred Cheng Chun-wan and Stephanie Ho Ngan-si have revealed in a media interview that their son is diagnosed with Angelman Syndrome, a rare genetic disorder [1]. This disclosure has sparked widespread discussion and concern within the community. According to statistics from the Hong Kong Angelman Syndrome Foundation, there have been about 3 to 5 new confirmed cases in Hong Kong each year for the past 5 years [2]. Since the development of the disease is not obvious in early infancy, most diagnoses are not usually confirmed until 9 months to 6 years of age [3]. In this article, we will take an in-depth look at Angelman Syndrome, exploring its symptoms, causes, diagnosis and potential treatments.
1. What is Angelman Syndrome?
Angelman Syndrome (AS) is a neurological genetic disorder characterized by severe learning disabilities, specific facial features and behaviors. The disorder usually manifests itself in early childhood (onset at 6-12 months) with severe delays in speech and mental development, and is accompanied by specific behaviours, such as excessive laughter and involuntary tics [4].
2. What are the symptoms of Angelman Syndrome?
Developmental Delay | Easily excitable |
Speech and Language Disorder | Seizures |
Movement or Balance Disorder | Sleep disorders |
Feeding problems | Strabismus |
Facial features : smaller than average head circumference, short broad skull, large lower jaw, wide mouth, widely spaced teeth, large tongue, light skin color and hair color
3. What are the causes of Angelman Syndrome？
The main cause of the disease is a defect in the long arm of the 15th pair of chromosomes at segment 15q11.2-q13 in the child’s maternally inherited chromosome, and there are several possible causes:
Causes | Proportion |
| 68% |
2. Both copies of chromosome 15 are inherited from the father (Uniparental Disomy; UPD) | 7% |
3．Mutation in the UBE3A gene of the maternally inherited chromosome 15 | 11% |
4．Mutation at the imprinting centre of the maternally inherited chromosome 15, causing UBE3A gene silence | 3% |
Source： Codex Genetics
4. How is Angelman Syndrome diagnosed?
In addition to clinical assessment, Whole Genome Sequencing (WGS) technology allows for the analysis of the child’s and parents’ DNA changes. This advanced testing can identify deletions within the 15q11-q13 region, pathogenic mutations in the UBE3A gene, or determine if both copies of chromosome 15 in the patient are paternally inherited. Furthermore, it can check if the symptoms are due to other genetic causes, and help with family planning. For further information about our testing services, please contact our customer support team.
4. What are the treatments and preventive measures for Angelman Syndrome?
Treatments
Clinical assessment and diagnosis by a doctor is required before seeking for advice on any treatment. For the time being, the disease can only be treated symptomatically, e.g. antiepileptic medication is prescribed to control seizures, while abnormalities in gait and movement, speech and learning disabilities can be improved with physical, occupational, and speech therapies, among others [5]. Overseas research has been conducted on the treatment of Angelman Syndrome, including the use of antisense oligonucleotides (ASOs) to activate the normal UBE3A gene from the father, or gene therapy or to inject a healthy UBE3A gene directly into the body [6].
Prevention
According to GeneReviews® , less than 1% of cases can be detected by karyotyping [7], and although abnormalities caused by deletions (cause 1) may be detected by chromosome microarray analysis (CMA) , more precise prenatal testing is required to detect other causes of abnormalities, but it is important to note that there are limits to the accuracy of each test. Please ask your healthcare professional for details.
References:
[1] 健康旦 HiEggo
[7] Dagli AI, Mathews J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2021 Apr 22]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
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