Angelman syndrome
Updated : 2024 08 19:12pm
By M.k.karikalsozhan blog Reporter
Angelman syndrome is a congenital genetic disorder often resulting from the absence or malfunction of the UBE3A gene on chromosome 15. The most frequent cause is the deletion of this gene, but it can also stem from mutations or improper activation.
The syndrome is characterised by a range of features: distinctive facial traits, intellectual disability, speech impairments, a jerky gait, and a notably happy demeanour with hyperactivity. Historically referred to as "happy puppet syndrome" due to the child's cheerful disposition and movements, the condition was renamed after Dr. Harry Angelman, who first described it in 1965.
Typically diagnosed between the ages of two and five, Angelman syndrome affects approximately one in every 10,000 to 20,000 children.
Causes of Angelman Syndrome
Angelman syndrome is primarily caused by the loss of function of the UBE3A gene. Typically, individuals inherit one copy of this gene from each parent, with both copies active in most tissues. However, in the neurons of the brain and spinal cord, only the maternal copy is active due to a process known as genomic imprinting. If the maternal copy is inactivated or deleted due to a genetic alteration, the individual will lack active copies of UBE3A in these regions, leading to the characteristic features of Angelman syndrome.
There are several genetic mechanisms that can result in the loss of the maternal UBE3A gene function:
1. **Chromosomal Deletion**: The most common cause, accounting for about 70% of cases, is the deletion of a segment of the maternal chromosome 15 that contains the UBE3A gene.
2. **Gene Variants**: In 10 to 20% of cases, Angelman syndrome arises from a variant in the maternal copy of the UBE3A gene.
3. **Paternal Uniparental Disomy**: This rare occurrence involves the inheritance of two copies of chromosome 15 from the father, instead of one copy from each parent.
4. **Chromosomal Rearrangements and Translocations**: These structural changes can disrupt the region controlling the activation of UBE3A, leading to its inactivation.
5. **Unknown Causes**: In 10 to 15% of cases, the precise genetic cause is unidentified, suggesting that other genes or chromosomal changes might be involved.
Additionally, the deletion of the OCA2 gene, which is located on the same segment of chromosome 15 often deleted in Angelman syndrome, can result in lighter hair and fair skin. However, the loss of OCA2 does not contribute to the neurological symptoms of Angelman syndrome. The OCA2 gene is responsible for pigmentation, affecting the colouring of skin, hair, and eye.
Angelman syndrome is predominantly not inherited. In most cases, the condition arises from a deletion on the maternal chromosome 15 or from paternal uniparental disomy, where both copies of chromosome 15 are inherited from the father. These genetic anomalies typically occur randomly during the formation of reproductive cells (eggs and sperm) or in the early stages of embryonic development, leading to the
disorder in individuals with no prior family history of Angelman syndrome.
In rare instances, however, Angelman syndrome can be inherited. For example, a mutation in the UBE3A gene or in an adjacent DNA region responsible for regulating gene expression can be passed down from one generation to the next.
Care your Family
Key symptoms include:
- Delayed motor development such as difficulties in sitting, crawling, and walking
- Severe speech impairments or absence of speech
- Ataxia, or balance and coordination issues
- Puppet-like movements and stiff-legged walking
- Hand flapping and hyperactivity
- A sociable, happy, and affectionate nature, with frequent laughter
- Intellectual disability, often severe
Some children may also exhibit:
- Microcephaly (a smaller head size)
- Abnormal brainwave patterns
- Epilepsy, affecting over 80% of individuals with the syndrome
Physical traits, which may become more apparent as the child grows, include a flattened back of the head, deep-set eyes, a wide mouth with frequent smiling, a prominent jaw, widely spaced teeth, and lighter hair, skin, and eyes.
Common behavioural challenges are feeding difficulties, disrupted sleep, delayed toilet training, and a very short attention span.
The genetic basis of Angelman syndrome involves the loss or mutation of the maternal UBE3A gene on chromosome 15. This can occur through several mechanisms:
- Deletion of the maternal UBE3A gene region (68% of cases)
- Mutation of the UBE3A gene (11% of cases)
- Inheritance of two copies of chromosome 15 from the father, leading to the absence of maternal UBE3A gene expression (7% of cases)
- Other chromosomal deletions affecting UBE3A gene expression (3% of cases)
- Unknown causes (11% of cases)
Diagnosis involves clinical evaluation and genetic testing. It is crucial to differentiate Angelman syndrome from other conditions with similar symptoms, such as autism, Rett syndrome, Lennox-Gastaut syndrome, and non-specific cerebral palsy.
atOptions = { 'key' : 'fe05809f2859f4df91db847e5f11b228', 'format' : 'iframe', 'height' : 300, 'width' : 160, 'params' : {} }; >While there is no cure for Angelman syndrome, various therapies can help manage symptoms. These include speech and communication therapy, behavioural therapy, occupational therapy, physical therapy, special education, social skills training, and medication for epilepsy.
Despite the challenges, individuals with Angelman syndrome generally have a normal lifespan and can lead fulfilling lives with appropriate support and interventions.
Support for parents of children with Angelman syndrome includes:
- Support organisations, such as the Angelman Syndrome Association Australia
- Genetic counselling
- Family therapy
- Respite care
The Genetic Support Network of Victoria (GSNV) is connected with a wide range of support groups throughout Victoria and Australia and can connect you with other individuals and families affected by Angelman syndrome.
Genetic Counselling and Angelman Syndrome
If a family member has been diagnosed with Angelman syndrome, or this genetic condition runs in your family, it can be helpful to speak to a genetic counsellor.
Genetic counsellors are health professionals qualified in both counselling and genetics. As well as providing emotional support, they can help you understand Angelman syndrome, including its causes, inheritance patterns, and the implications of a diagnosis for your child's health and your family.
Genetic counsellors offer information and support that is sensitive to your family’s circumstances, culture, and beliefs.
If Angelman syndrome runs in your family, a genetic counsellor can explain the available genetic testing options for you and other family members. You may choose to visit a genetic counsellor if you are planning a family – to understand your risk of passing the condition on to your child, or to arrange for prenatal tests.
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.
