Angelman Syndrome Standards of Care
This article is about Angelman Syndrome and how to take care of people who have it. A group of experts led by Dr Jessica Duis came together to create a guide for doctors and caregivers on how to best help these individuals. They looked at all the available research and used their own experience to come up with the best ways to manage the disorder.
Article source: Duis, J., Nespeca, M., Summers, J., Bird, L., Bindels-de Heus, K. G. C. B., Valstar, M. J., de Wit, M.-C. Y., Navis, C., ten Hooven-Radstaake, M., van Iperen-Kolk, B. M., Ernst, S., Dendrinos, M., Katz, T., Diaz-Medina, G., Katyayan, A., Nangia, S., Thibert, R., Glaze, D., Keary, C., … Anderson, A. (2022). A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome. Molecular Genetics & Genomic Medicine, 10, e1843. https://doi.org/10.1002/mgg3.1843
Disclaimer: Note that this page is a significantly simplified version of the original academic publication. Please refer to the source if you require verifiable references. Additionally, standards of care evolve over time and it is important to seek the latest guidance when it comes to rare conditions as scientists and healthcare professionals make new discoveries on a frequent basis.
Angelman Syndrome (AS) is a rare genetic disorder that affects about 1 in 12,000 to 1 in 20,000 people. It is usually diagnosed when a child is between 1 and 2 years old, but sometimes it can be diagnosed later if the symptoms are not typical. Some common symptoms of AS include delays in development (especially in speaking), a happy personality, seizures, problems with movement and coordination, shaking, trouble sleeping, stomach issues, repetitive behaviours, anxiety, and hyperactivity.
Angelman Syndrome is caused by a problem with a gene called UBE3A. This gene is usually active in the brain only on the copy inherited from the mother. If this copy of the gene is missing or not working correctly, it can cause the symptoms of Angelman Syndrome.
For Advanced Readers: The role of E6-AP protein
The content of this section has been adapted from the following source:
Scott V. Dindot, Barbara A. Antalffy, Meenakshi B. Bhattacharjee, Arthur L. Beaudet, The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology, Human Molecular Genetics, Volume 17, Issue 1, 1 January 2008, Pages 111–118, https://doi.org/10.1093/hmg/ddm288
The UBE3A gene is located on a specific region of chromosome 15 called 15q11.2q13. This gene provides instructions for making a protein called E6-AP which has several important functions in the body. If the mother’s copy of UBE3A is missing or not working properly, it can lead to a shortage of E6-AP protein in the brain. However, scientists are still trying to understand how a problem with this protein causes Angelman Syndrome.
Research has found that E6-AP may play an important role in how brain cells communicate with each other. One study found that when E6-AP is not working correctly, it can disrupt the balance between two important signalling pathways in brain cells. Another study found that E6-AP helps to regulate proteins in brain cells by targeting certain proteins for destruction.
These findings suggest that problems with E6-AP can affect how brain cells develop and communicate with each other. This may help to explain why people with Angelman Syndrome have neurological symptoms and problems with movement and balance.
There are four main ways that the UBE3A gene can be affected:
- Deletion of a part of chromosome 15 inherited from the mother (70-75% of cases).
- Mutation of the UBE3A gene inherited from the mother (15%).
- Inheriting two copies of chromosome 15 from the father instead of one from each parent (5-7%). This way is known as UPD or uniparental disomy.
- An imprinting defect (5-7%) where the copy of the UBE3A gene inherited from the mother is not active. This way is known as ICD or imprinting centre defect.
In some cases, a person can have cells with different genetic information. This phenomenon is known as mosaicism. It means that some cells have a normal copy of the UBE3A gene while others do not. Mosaicism can happen when a change in how the gene is controlled affects only some cells. Mosaicism can affect the severity of Angelman Syndrome symptoms.
Symptoms and Diagnosis
The symptoms of Angelman Syndrome can vary depending on which of these mechanisms is involved. Genetic testing can help diagnose Angelman Syndrome and determine which mechanism is involved.
The chances of having another child with Angelman Syndrome can vary depending on the mechanism involved. For example, suppose Angelman Syndrome is caused by a mutation of the UBE3A gene inherited from the mother. In that case, there is a 50% chance that another child will also inherit the mutation and have Angelman Syndrome. Genetic counselling is recommended for all families to discuss recurrence risks and help them make informed decisions about future pregnancies.
Infants with Angelman Syndrome may experience low muscle tone and difficulty gaining weight. However, non-invasive medical management, often called conservative treatment, is typically sufficient to assist them. Such treatment may include medication, physical therapy, lifestyle adjustments, and other non-surgical interventions. These infants might struggle with sucking, chewing, and swallowing, including challenges with breastfeeding due to an inability to latch on correctly.
Tongue protrusion and coordination issues between swallowing and breathing during feeding can contribute to weight gain difficulties. Sometimes, silent aspiration could also occur when food or liquid enters the lungs without causing coughing or choking. This condition can lead to aspiration pneumonia, an infection of the lungs caused by inhaling food, liquid, or vomit. To address these concerns, involving a feeding therapist early on is recommended.
A feeding tube might be considered if there’s a history of aspiration pneumonia, but it should be approached with caution. Feeding tubes are more commonly required for individuals with the deletion subtype of Angelman syndrome. Throughout life, choking remains a risk for people with this condition due to improper chewing and a tendency to stuff their mouths with food.
Growth in individuals with Angelman syndrome is generally within the normal range, including their height. However, some may experience slow head growth, resulting in a condition called microcephaly by the age of 2, especially in those with the deletion subtype of Angelman syndrome. Microcephaly is when a person’s head size is significantly smaller than expected (measured as less than or equal to -2 standard deviation scores).
It’s important to note that the absence of microcephaly doesn’t rule out the possibility of Angelman syndrome. This is particularly true for people with non-deletion subtypes of the condition. Therefore, even if the head size is typical, it’s not a reason to dismiss suspicion of Angelman syndrome.
Hormones and puberty
When it comes to puberty and the onset of menstruation, individuals with Angelman syndrome typically experience these changes on a normal timeline. Girls with Angelman syndrome usually have regular periods, much like their peers. However, the hormonal shifts during puberty can impact other aspects, such as epilepsy, anxiety, and behaviour.
Sometimes, managing a girl’s menstrual cycle can be helpful, especially when it comes to hygiene and understanding. Options like oral contraceptives and injectable progestogens can be considered, but remember that the latter might negatively affect bone health. Long-lasting alternatives like subdermal and intrauterine hormonal devices are also available, but they require anaesthesia for placement. Talking to a gynaecologist or endocrinologist about the best option for your loved one is a good idea.
As for permanent sterilisation, this is generally not recommended, and it’s crucial to consult with experts in reproductive ethics before pursuing this route.
For adult males with Angelman syndrome, public masturbation can sometimes be an issue. Behavioural modifications are usually the first step to address this. If needed, medications such as selective serotonin reuptake inhibitors (SSRIs), which can reduce libido as a side effect, might be helpful. However, anti-androgen therapy is not recommended.
Fertility in people with Angelman syndrome is considered normal, but their friendly nature and cognitive challenges can make them vulnerable to abuse. Therefore, regular gynaecological check-ups, including Pap smears, should be done according to general guidelines since the risk of uterine cancer for these individuals is similar to that of the general population.
People with Angelman syndrome don’t seem to have weaker immune systems, so they should follow the standard vaccination schedules to protect them from common illnesses and seasonal germs. Ensure your loved one stays up-to-date with their vaccinations, including the COVID-19 vaccine, to keep them healthy and safe.
Dealing with Heat Intolerance
People with Angelman syndrome often struggle with heat intolerance, which can cause them to become flushed and sweaty. This sensitivity to heat makes them more prone to dehydration, which can increase the risk of seizures. To help manage this issue, it’s a good idea to dress your loved one in breathable clothing, even during sleep, as overheating can affect sleep quality.
There are several ways to help keep your loved one with Angelman syndrome cool and comfortable, such as:
- Limiting their time outdoors during hot weather
- Encouraging them to drink cold fluids
- Using fans, water mist, or cool rags to provide relief
- Wearing visors, sunglasses, and UV-protective clothing
These strategies can help maintain their well-being during warm temperatures and reduce the risk of related health issues.
Achieving daytime urinary continence can be a challenge for individuals with Angelman syndrome, with studies reporting success rates ranging from 35% to 75%. Encouraging regular toilet visits, removing diapers, providing positive reinforcement, and closely monitoring progress can help improve continence. All toileting activities, including diaper changes, should take place in the restroom. Techniques such as Applied Behavioral Analysis (ABA) can also be helpful, as they focus on establishing routines and offering rewards for positive behaviour. Nighttime continence is less common but can be supported by limiting fluids after dinner and encouraging toileting before bedtime.
Brushing teeth can be difficult once they erupt in individuals with Angelman syndrome. A double-sided or electric toothbrush may be better tolerated. Factors such as frequent mouthing, chewing, and gastro-oesophageal reflux disease (GORD)—a condition where stomach acid flows back into the oesophagus—can lead to enamel erosion. However, drooling can actually help by continuously rinsing the teeth. Dental examinations and procedures might require sedation or anaesthesia, but it’s essential not to delay dental care.
Although complications from anaesthesia are rare, there are a few specific concerns for people with Angelman syndrome. These include potential interactions with GABA receptors—protein molecules in the brain that help regulate nerve activity—which many intravenous and inhaled anaesthetic agents affect. Other concerns involve malignant bradyarrhythmias, which are abnormally slow and irregular heart rhythms that can be life-threatening, bradycardia due to increased vagal tone—an unusually slow heart rate caused by overstimulation of the vagus nerve—and delayed response to atropine, a medication used to increase heart rate. There have been some reports of atypical responses to benzodiazepines—a class of drugs used for sedation—and complications related to airway management. However, there is not enough evidence to make specific anaesthetic recommendations for individuals with Angelman syndrome, and typical management by an anesthesiologist is generally safe.
Epilepsy and Movement Disorders
Epilepsy affects up to 90% of individuals with Angelman syndrome, with the highest prevalence in those with a genetic deletion. In fact, 80-90% of children with deletions will develop epilepsy. On the other hand, the prevalence of seizures in those with mutations and uniparental disomy (UPD) is up to 75% and up to 50% for those with imprinting centre defects (ICD). On average, seizures start around 1.7 years of age, ranging from 3 months to 5 years old. While seizures are more common in people with deletions, they can also occur in those with other genetic causes of Angelman syndrome.
In about one-third of individuals, the first seizure happens during a fever. Seizures generally improve after puberty, with many people experiencing a significant reduction or resolution around the age of 16. In a case series of 53 adults, 65% showed resolution of seizures beginning at an average age of 16 years. There are various types of seizures in Angelman syndrome, including myoclonic—25%, atonic—23%, generalised tonic-clonic—21%, and atypical absences—12%. Though rare, infantile spasms have also been reported, and up to 30% may have focal seizures.
Non-convulsive status epilepticus (NCSE) is a common issue in Angelman syndrome. It involves periods of decreased responsiveness or alertness, often with a temporary loss of developmental skills, lasting hours to days. NCSE can be challenging to recognise, as it typically has few visible seizures. Recent studies have found that 19% of children with Angelman syndrome experienced NCSE, while 5% experienced convulsive status epilepticus.
Individuals with Angelman syndrome may also have non-epileptic myoclonus (NEM), a movement disorder unrelated to seizures. Myoclonic seizures typically occur in younger children, while NEM is more common in adolescents and adults. Both can be disabling, but myoclonic seizures can be controlled with medication, while NEM is more challenging to treat. Some medications, like levetiracetam, clobazam, and clonazepam, may help with NEM, but the primary focus is minimising triggers, such as poor sleep, gastrointestinal issues, and anxiety.
Electroencephalogram (EEG) tests evaluate seizures in individuals with Angelman syndrome. These tests can help determine if a behavioural episode is a seizure or a non-epileptic event. Blood tests can exclude metabolic triggers and provide a baseline for treatment. Lumbar puncture and brain imaging are typically only needed if other causes are considered.
There are no specific guidelines for selecting anticonvulsant drugs (ACDs) to treat seizures in Angelman syndrome, so treatment is based on case studies. Clobazam, levetiracetam, and clonazepam are considered beneficial with limited adverse effects. Dietary interventions, like the ketogenic diet or low glycemic index therapy, may also help control seizures. If seizures are not well controlled with medication and diet, referral to an epilepsy specialist is recommended. Medications like phenobarbital, primidone, carbamazepine, phenytoin, and vigabatrin, should be avoided. CBD medication, like Epidiolex, shows promise for treating seizures and possibly NEM. Valproic acid should be used cautiously due to the high rate of motor side effects.
Seizure alarm devices can be an option, but they might not be effective for detecting less obvious seizure types, such as atonic and atypical absence seizures. It’s crucial for caregivers to learn about managing seizures, especially recognising non-convulsive status epilepticus. Some individuals with Angelman syndrome might eventually stop taking anticonvulsant drugs, but no specific guidelines exist for this process. Although around 65% of adults may become seizure-free, many adolescents and adults continue using ACDs like clobazam and clonazepam to manage other symptoms, such as sleep issues, anxiety, and non-epileptic myoclonus.
Acid Reflux and Vomiting
Acid reflux, also known as gastro-oesophageal reflux disease (GORD), is a condition in which stomach acid flows back into the oesophagus, causing irritation. GORD is common in people with Angelman Syndrome and may persist or reoccur in adulthood. Symptoms include gagging, frequent swallowing, and pain or discomfort during and after feeding.
For infants, treatment often starts by feeding them in an upright position and maintaining this position for at least 30 minutes after feeding. Additionally, adjusting posture (e.g. side-lying position), technique, and formula can help. Considering thickening feeds and modifying the diet might also be beneficial. If needed, seek a referral to specialised feeding therapy. Unfortunately, uncontrolled GORD can lead to inflammation in the oesophagus (oesophagitis) and upper gastrointestinal bleeding.
In older individuals, vomiting could indicate gastroparesis, a condition where the stomach takes longer than normal to empty its contents. Symptoms such as back arching, poor sleep, gagging, food regurgitation, and unexplained discomfort should prompt the use of medications like proton pump inhibitors (which reduce stomach acid production) or H2 blockers (which decrease the amount of acid released in the stomach). If symptoms persist, prokinetic medication, which helps to improve stomach contractions, might offer relief.
Several factors can cause vomiting, such as severe constipation, migraine variants, rumination (a repetitive behaviour that involves bringing up swallowed food and re-swallowing or spitting it out), urinary tract infections, medication side effects, and anxiety. In some cases, vomiting may develop into a behavioural issue, requiring further attention and management.
Constipation is a common issue in Angelman Syndrome, affecting around 80% of individuals. Treating constipation is crucial, as it may lead to increased seizures, sleep disturbances, and behavioural changes. The first step in addressing constipation involves assessing fluid and fibre intake and considering adding dietary fibre when needed.
Moreover, incorporating magnesium, probiotics or medium-chain triglyceride oil into the diet might provide relief. If dietary changes are insufficient, stool softeners are usually the next option. In more stubborn cases, stimulant medications can be helpful. For those experiencing persistent constipation, intermittent or regular suppositories may be necessary.
Some individuals with Angelman Syndrome may experience cyclic vomiting, which consists of persistent episodes of vomiting followed by periods without symptoms. These episodes can be distressing and often lead to dehydration. The underlying cause could be a migraine variant, although anxiety and gastro-oesophageal reflux disease (GORD) might also contribute.
Furthermore, allergies or acute illnesses causing congestion and post-nasal drip may result in persistent vomiting. In such cases, antiemetics and fluid replacement therapy may be necessary. To manage cyclic vomiting effectively, treatments for chronic migraines, such as amitriptyline, cyproheptadine, and topiramate, could be helpful. Additionally, addressing anxiety and GORD as needed may also provide relief.
Hyperphagia or Excessive Hunger
Hyperphagia, a condition in which an individual cannot recognise the feeling of fullness and displays related behaviours, is observed in some people with Angelman Syndrome. This condition might have an obsessive-compulsive component and can be triggered by anxiety, changes in routine, or transitions in general. Individuals with uniparental disomy or imprinting defects are at a higher risk of experiencing hyperphagia.
Effective management strategies for hyperphagia involve:
- Setting scheduled mealtimes with a visual schedule.
- Using partitioned and smaller plates.
- Adopting a diet that is higher in protein and lower in carbohydrates.
In some cases, it may be necessary to lock up food, and avoiding using food as a reward is recommended.
A study involving 100 parents of children with Angelman Syndrome found that 32% reported hyperphagia in their children, ranging from not knowing when to stop eating to searching for food and even consuming non-food items. Up to 50% of adults with Angelman Syndrome may experience hyperphagia, and it has been associated with an elevated body mass index (BMI).
Food Allergy and Eosinophilic Esophagitis
If a child with Angelman Syndrome experiences challenging gastrointestinal symptoms, it’s worth considering food allergy testing. Sometimes, even when allergy tests come back negative, food sensitivities, such as those to dairy and gluten, could still be present. In such cases, an elimination diet, which involves removing one food at a time for around two weeks, may help identify foods that exacerbate gas, bloating, and constipation.
Some children with food allergies may develop eosinophilic esophagitis (EoE), an inflammatory condition affecting the oesophagus, the tube that carries food from the mouth to the stomach. EoE typically necessitates an elimination diet and treatment with medications prescribed by gastroenterologists or allergists. A small percentage of children with Angelman Syndrome, particularly those with deletions or uniparental disomy, have been diagnosed with EoE.
Drooling in individuals with Angelman Syndrome can result from open-mouth behaviour, less frequent swallowing, or issues related to the oral phase of swallowing. While there’s no need for treatment if there’s no aspiration (accidental inhalation of food or liquid into the airways), social acceptance might be a concern. Using bibs and absorbent wristbands for mouth wiping can be helpful. Encouraging mouth closure and active swallowing can also be beneficial.
Anticholinergic therapies, such as glycopyrrolate (a medication that reduces saliva production) or sublingual administration of atropine eye drops (an eye drop placed under the tongue to decrease saliva production), or parotid botulinum toxin injections (injections into the salivary glands to reduce saliva flow) may be used to manage drooling. However, it’s important to consider the potential adverse effects of reduced saliva on dental health. Side effects like constipation, dry eyes, and thickened mucus might limit the use of these treatments.
Further research is needed to determine the best dietary recommendations for individuals with Angelman Syndrome. The Ketogenic Diet (KD) and Low Glycemic Index Treatment (LGIT) are dietary approaches mainly used for treating epilepsy that doesn’t respond well to medication. Still, they may offer other advantages as well.
The classic Ketogenic Diet is a high-fat, low-carbohydrate diet that derives 90% of its calories from fat. It’s designed with a specific ratio of fat to protein and carbohydrates. A 3:1 or lower ratio can be used to increase protein or carbohydrate intake, making it suitable when starting the diet.
On the other hand, LGIT is a diet that allows for a more relaxed carbohydrate intake of 40-60 grams per day but still focuses on consuming carbohydrates with a low glycemic index (under 50). A low glycemic index means that these carbohydrates cause more minor fluctuations in blood sugar levels.
Some common side effects of the Ketogenic Diet and LGIT include gastrointestinal disturbances (upset stomach, indigestion), temporary increases in blood lipid levels (fats in the blood), metabolic acidosis (too much acid in the body), and occasionally kidney stones (small, hard deposits that form in the kidneys).
Children with epilepsy resistant to treatment have a higher risk of poor bone health due to long-term exposure to anti-seizure medications, which can negatively impact calcium and vitamin D metabolism, as well as motor impairments that impact weight-bearing activities.
The Ketogenic Diet can further increase this risk due to its high “acid load,” which comes from the ketone bodies produced during fat metabolism, alterations in vitamin D levels, and the reduction of growth factors essential for bone health. As a result, it is recommended that children on the Ketogenic Diet for over two years undergo a bone density screening using a dual-energy X-ray absorptiometry (DEXA) scan to evaluate for signs of reduced bone density.
Supplementing with vitamin D, calcium, and B vitamins at the recommended daily allowance and taking a multivitamin with minerals is advised. While on dietary therapy, monitoring levels of various nutrients and compounds such as carnitine, selenium, magnesium, zinc, phosphorus, iron, copper, and beta-hydroxybutyrate is essential.
For individuals with Angelman Syndrome who experience excessive hunger, more liberalised versions of the Ketogenic Diet, such as the Modified Atkins Diet or LGIT, may be beneficial.
Sleep problems are common in individuals with Angelman Syndrome, affecting up to 80% of them. These issues include trouble falling asleep, frequent awakenings during the night, and waking up too early. Sleep for those with Angelman Syndrome is often shorter and more fragmented. Although sleep difficulties tend to decrease with age, many adolescents and adults continue to experience disrupted sleep and share their bed with others.
Poor sleep quality and reduced periods of REM sleep (a stage of sleep characterised by rapid eye movements, increased brain activity, and muscle relaxation, which plays a crucial role in learning, memory consolidation, and overall brain function) can negatively affect behaviour and worsen seizures. When there are changes in behaviour, it’s essential to consider the possibility of new sleep disorders. Factors such as epilepsy, anti-seizure medications, acid reflux, scoliosis, and constipation can further disrupt sleep. People with Angelman Syndrome should be screened for sleep problems, and if any are detected, a thorough assessment of their sleep and wake routines should be conducted.
Overnight sleep studies (polysomnography) are recommended for individuals with sleep-related breathing problems, nighttime seizures, or unusual behaviour during sleep. However, due to anxiety in unfamiliar environments, polysomnography can be challenging for those with Angelman Syndrome. Sleep diaries and actigraphy, a non-invasive way to monitor sleep and wake patterns, can be useful alternatives. Video polysomnography can also be used to observe sleep patterns objectively.
In order to address sleep disorders, it’s crucial to treat any contributing factors such as acid reflux, epilepsy, and behavioural issues like anxiety. Specific sleep disorders, like obstructive sleep apnea, should be managed with the help of appropriate specialists. Sleep problems are initially treated with behavioural therapies and by promoting good sleep hygiene, which involves maintaining a regular sleep-wake rhythm, having a bedtime routine, and creating a calm, cool, and dark bedroom environment.
People with Angelman Syndrome often benefit from safety beds, and it’s recommended to consider an enclosed bed early on when transitioning from a crib. Behavioural therapies typically involve managing parent-child interactions at night, with intensive coaching for parents to support these interventions. Medicinal treatments targeting sleep difficulties can be beneficial if behavioural therapies are ineffective. These include low-dose melatonin, alpha agonists (such as clonidine or guanfacine), benzodiazepines (like clonazepam), gabapentin or pregabalin, antihistamines (promethazine or diphenhydramine), antidepressants (mirtazapine or trazodone), and in resistant cases, antipsychotics (for example, quetiapine).
Cognitive and Behavioural Characteristics
People with Angelman Syndrome often experience severe intellectual disabilities, significant developmental delays, and an absence of speech. Delays can occur in all areas of development, with cognitive skills typically falling below the 24-30 months developmental level. The severity of these delays may depend on the specific genetic cause of Angelman Syndrome, seizure control, choice of anticonvulsant drugs, access to therapy, and individual genetic factors.
From the moment any delays are noticed, it’s crucial to refer the individual to early intervention services for physical, occupational, and speech and language therapy. These therapies should continue throughout their lives. People with Angelman Syndrome might benefit from alternative therapies, such as hydrotherapy (due to their love for water) and hippotherapy (horse riding therapy), which can help improve their behaviour, social interaction, and physical abilities.
Individuals with Angelman Syndrome are often described as happy, with frequent smiling and laughter. However, this laughter can sometimes be a sign of anxiety or discomfort. Hyperactivity and impulsive behaviour are also common. High rates of disruptive behaviours have been reported, which may serve as a way to communicate feelings like pain, fatigue, or anxiety. These individuals can also show features similar to autism spectrum disorders, such as repetitive behaviours and restricted interests.
When new behavioural concerns or changes in sleep habits occur, exploring possible underlying medical issues, such as infections, constipation, menstrual pain, acid reflux, dental problems, or scoliosis, is essential. Behavioural therapies like Applied Behaviour Analysis (ABA) can be beneficial in addressing these concerns, as can augmentative and assistive communication (AAC) devices.
Educators may have little experience with Angelman Syndrome, so it’s crucial to develop an appropriate individualised education plan (IEP) that builds on the person’s social skills while focusing on personalised one-on-one learning and instruction. It will help improve communication and motor skills. The IEP should include intensive physical, occupational, and speech therapy. Parents, teachers, and caregivers should be trained and supported in using AAC devices to ensure consistency between school and home environments. A functional behavioural assessment can help identify triggers and create a management plan if a child has behavioural challenges.
Eye Health and Vision Care
Regular eye examinations by an ophthalmologist are recommended for people with Angelman Syndrome, starting from the time of diagnosis and then annually. Strabismus, or misaligned eyes, is a common issue in these individuals. However, conservative treatments like eye patching or corrective lenses can be difficult to implement due to challenges in cooperation. Around 30% of people with Angelman Syndrome may require surgery for strabismus.
Astigmatism, an imperfection in the eye’s curvature, is the most frequent vision problem in individuals with Angelman Syndrome. Many of these individuals could benefit from corrective lenses, but wearing glasses can be difficult, and amblyopia (lazy eye) rates have not been reported.
Eye health assessments should consider both the physical condition of the eyes and the person’s visual behaviour. Some individuals with Angelman Syndrome may have severe eye conditions, such as optic and chorioretinal atrophy, leading to poor visual function. In some cases, the first symptom might be cortical visual impairment, which can improve over time. This condition has many characteristics, from complete blindness to altered visual perception. Nystagmus, or involuntary eye movement, has been reported in a small percentage of individuals with Angelman Syndrome.
Referrals for occupational and physical therapy, as well as vision and mobility services, are crucial to maximising visual function. Additionally, oculocutaneous albinism – a condition affecting skin, hair, and eye colour – should be considered in those with Angelman Syndrome who display specific eye-related symptoms. Identifying children with this condition is crucial because it affects their overall care, including the use of sunscreen, low vision management, regular eye check-ups, and cancer screening.
Orthopaedics and Bone Health
Individuals with Angelman Syndrome may experience lower bone density than those without developmental delays. Factors such as anti-epileptic drugs, a ketogenic diet, immobility, reduced exposure to sunlight, and late puberty can contribute to this issue. Consequently, low-impact fractures may occur. A DEXA scan, a test that measures bone density, is recommended every two years, depending on risk factors. In females over 65 years old, yearly screening is advised. Vitamin D supplements, daily physical activity (particularly in a standing position), and 15-30 minutes of sunlight exposure daily can help maintain bone health.
Hip dysplasia, a misalignment of the hip joint, can be caused by external rotation of the legs, decreased muscle tone, and delayed walking. Standard hip screening and X-rays should be performed, particularly for non-walking children, followed by an orthopaedic referral if needed. Early physical therapy is recommended to maintain or improve joint movement. Using standing devices can help increase bone density.
Around 80% of children with Angelman Syndrome achieve independent walking, with an average age of 3.7 years for those with genetic deletions. Their walking pattern is characterised by reduced step length and continues throughout childhood, despite adjustments for delayed walking onset. Walking patterns and mobility change as individuals age, but reported muscle stiffness is poorly described. Initial treatment should involve physical therapy and bracing to maintain joint movement and prevent permanent muscle shortening. Gait analysis is recommended when considering an orthopaedic intervention, as many patients develop inappropriate walking patterns that may worsen with incorrect lengthening procedures. Some individuals may benefit from orthotic devices to treat misaligned or pronated ankles. Corrective surgery for significant fixed angular deformity remains controversial, as recovery after the procedure is often poor. Botulinum toxin injections should be used with caution, as they may worsen walking patterns and contribute to muscle weakness.
Scoliosis is a condition where the spine curves sideways, and it occurs in 10-30% of children with Angelman Syndrome and 30-70% of adults. Most of these spinal curves are in the upper part of the spine (thoracic). Still, up to 20% have an increased inward curve in the lower back (lumbar lordosis), which can be associated with weakness in the trunk muscles, forward tilt of the pelvis, and a crouch walking pattern. Regular spine screening, monitoring with X-rays, and orthopaedic referrals are advised for walking patients. In non-walking patients, early use of thoracolumbosacral orthoses (TLSO) – a type of supportive brace – should be considered to promote better hand use and social interaction. Continued monitoring of curve progression and its effect on heart and lung function, as well as the quality of life, should guide interventions. Surgical intervention for scoliosis may improve quality of life, but it has a high complication rate, so a thorough discussion of risks and benefits is necessary before proceeding.
Orthopaedic concerns for adults with Angelman Syndrome include maintaining joint movement and managing body weight. Over time, hip and knee muscle shortening, scoliosis, and decreased stamina may develop. However, 64-75% of all adults with Angelman Syndrome are able to walk independently. Physical therapy may be needed intermittently throughout life to address changes in function, walking patterns, posture, joint movement, and strength.
Adults with Angelman Syndrome and Transition of Care
Adults with Angelman Syndrome face unique challenges, such as reduced mobility, a more sedentary lifestyle, difficulty chewing and swallowing, gastro-oesophageal reflux disease (GORD), constipation, anxiety, and behavioural concerns. However, sleep issues, seizures, and hyperactivity may improve over time. Transitioning to adulthood requires careful planning to ensure ongoing educational and therapeutic support, including access to behavioural therapy, augmentative and alternative communication (AAC) devices, disability benefits, local authority funding programmes, and help with decision-making.
Early planning should involve the use of community support resources, such as Mencap and Rare Disease UK, as well as patient support organisations like Angelman UK and ASF. Financial planning is vital and may include establishing trust for the person with Angelman Syndrome. Early on, consider enrolling in vocational or recreational opportunities, such as adaptive sports or vocational training programmes.
Caregiver and Family Health
Caregivers of individuals with Angelman Syndrome are at high risk of experiencing negative consequences. Therefore, it is essential to conduct ongoing research to understand the specific needs of caregivers throughout their lives. Healthcare professionals should be aware of the stressors associated with caregiving, which can negatively impact social networks, family dynamics, and financial security, leading to or worsening mental and physical health challenges for caregivers. Professionals can offer much-needed relief, such as respite care, which can have long-term positive impacts on the person with Angelman Syndrome and their support system.
The relationship between siblings of individuals with Angelman Syndrome is unique and requires family-based approaches. It is crucial to provide regular, individualised attention to siblings, allowing them an outlet to share their concerns and challenges. Connecting with local and national support groups and linking with other families can help create valuable support networks. Tools for siblings may include children’s books and support groups.