Author: Christine Ma
Editor: Leah Farquharson
Angelman Syndrome (AS) is a rare neurological disorder with varying subtypes (Madaan & Mendez, 2021). Angelman Syndrome has many symptoms including difficulty sleeping, movement disorders, seizures, cognitive disability, and speech impairment (Margolis et al., 2015). Angelman Syndrome may be difficult to diagnose in some individuals due to the symptoms overlap with other neurological disorders (Madaan & Mendez, 2021). Currently, treatment for Angelman Syndrome is generally based on the individual’s symptoms (Madaan & Mendez, 2021).
What causes Angelman Syndrome?
Angelman Syndrome is generally caused by a genetic mutation occurring before birth (Margolis et al., 2015). The mutations can occur as a deletion mutation (missing sequence(s)) or imprinting defect (incorrect genetic copying) (Margolis et al., 2015). The majority of cases, around 70-100%, are due to a mutation from the DNA inherited from the mother (Margolis et al., 2015). The cases involving a deletion mutation are generally more severe in presentation than those involving a nondeletion mutation (Margolis et al., 2015).
Symptoms of Angelman Syndrome
Symptoms may be reported as early as 6 months, and some symptoms may become progressively severe over time (Wheeler et al., 2017).
- Severe cognitive disability
- Frequent seizures (majority of individuals have onset of seizures prior to age 3)
- Speech impairment (may entirely lack speech or can speak few words)
- Receptive language may or may not be impaired
- Motor dysfunction (tremors, jerkiness, ataxia)
- Short attention span
- Happy demeanor with easily provoked or excessive laughter
- Mouthing of objects
- Attraction to water
- Decreased sleeping (Margolis et al., 2015)
- Aggression and irritability (Wheeler et al., 2017)
- Protruding tongue, tongue thrusting, suck/swallowing disorders
- Wide mouth with widely spaced teeth
- Frequent drooling
- Hypopigmented (fair skin, light hair, light eyes)
- Hyperactive lower extremity deep tendon reflexes
- Increased sensitivity to heat
- Strabismus (eyes do not seem to align/ focus)
- Abnormal food behaviors
- Truncal hypotonia
- Prognathism (underbite) (Madaan & Mendez, 2021)
- Genetic predisposition: the mutation causing AS is usually inherited, especially from the maternal side (Madaan & Mendez, 2021)
- Subfertile couples (couples with a time to pregnancy greater than 2 years and/or fertility treatment) have an increased risk of birthing an individual with the imprinting phenotype of AS (Ludwig et al., 2005).
How does my Doctor Know it’s Angelman Syndrome?
There are two main ways to diagnose AS, the first being before birth in the prenatal stage (Madaan & Mendez, 2021). This can be done through non-invasive prenatal testing (NIPS) techniques that can determine growth restrictions (Madaan & Mendez, 2021).
After birth, AS is usually first suspected by a healthcare practitioner, then further testing is performed to confirm the diagnosis (Madaan & Mendez, 2021). If some symptoms listed above are present, the healthcare practitioner may suspect AS and may perform some of the following tests:
- Methylation studies
- fluorescence in situ hybridization (FISH) technique
- molecular studies
- DNA sequencing and marker analysis (Madaan & Mendez, 2021).
An EEG may also be used to show seizure activity (Madaan & Mendez, 2021). Sleep studies may be useful for individuals with sleep impairment (Madaan & Mendez, 2021).
Currently, treatment for AS is primarily based on the symptoms presented, so individuals with different symptoms may receive different treatments (Madaan & Mendez, 2021). Physical and occupational therapy can be helpful for individuals with movement disorders such as difficulty walking (Wheeler et al., 2017). Increasing communication output, while increasing both verbal and nonverbal communication may also be helpful for individuals with speech impairments (Wheeler et al., 2017). Behavioral interventions and pharmacological treatments may be required for other symptoms (Wheeler et al., 2017).
Ludwig, M., Katalinic, A., Gross, S., Sutcliffe, A., Varon, R., & Horsthemke, B. (2005). Increased prevalence of imprinting defects in patients with Angelman syndrome born to subfertile couples. Journal of medical genetics, 42(4), 289–291. https://doi.org/10.1136/jmg.2004.026930
Madaan, M., & Mendez, M. D. (2021). Angelman Syndrome. In StatPearls. StatPearls Publishing.
Margolis, S. S., Sell, G. L., Zbinden, M. A., & Bird, L. M. (2015). Angelman Syndrome. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 12(3), 641–650. https://doi.org/10.1007/s13311-015-0361-y
Wheeler, A. C., Sacco, P., & Cabo, R. (2017). Unmet clinical needs and burden in Angelman syndrome: a review of the literature. Orphanet journal of rare diseases, 12(1), 164. https://doi.org/10.1186/s13023-017-0716-z