Angelman Syndrome - Pattern of Inheritance, Clinical Features, and Treatment Modalities

Introduction:

It is a rare type of genetically inherited neurological disorder. Children born with Angelman syndrome exhibit several developmental and intellectual disabilities, including lack of speech, inability to walk properly, and more. The typical feature of the syndrome is that the affected individual has a happy and affectionate disposition almost all the time. They also tend to suffer from frequent seizure attacks. The affected individual requires physical therapy, behavior modifications, and special education to compensate for the disabilities.

How Is Angelman Syndrome Inherited?

The gene causing Angelman syndrome is called UBE3A. When this gene on chromosome 15 is genetically mutated and gets passed on to the children, they stay active in the body. When it is active in certain parts of the brain, one develops Angelman syndrome. If one of the children is affected by Angelman syndrome, chances are there for the next child to be born with it. It affects people of every race from either gender. Angelman syndrome is not a life-threatening condition, and the majority of the affected have a normal lifespan. Although they may require support in daily tasks. According to the statistics, about one in twenty thousand individuals may get affected with Angelman syndrome.

What Are the Symptoms of Angelman Syndrome?

This is also known as ‘happy puppet syndrome’ pertaining to the child's excited demeanor and jerky movements. The characteristic symptoms are:

Physical Features:

1. Developmental delays, especially in motor activities like sitting up, crawling, and walking.

2. Have a habit of flapping one’s arms in the air while walking.

3. Peculiar walking style with legs held wide and stiff with jerky movements of the body. The child has issues with balancing while moving (ataxia) and coordination.

4. Most children develop seizures by the age of two to three. Apart from typical epilepsy cases, those affected with Angelman syndrome might encounter a combination of different types of seizures.

5. Sideways curvature in the spine (scoliosis).

6. A typically small-sized head, which is relatively flat in the back.

7. A broad face, deep-set eyes, and wide mouth with widely spaced teeth.

8. Frequent drooling due to the inability to swallow the saliva.

9. The skin, eyes, and hair can be a shade lighter than the others in the family.

10. Each eye points in different directions (crossed eyes).

11. Outwardly projected lower jaw.

12. Issues with feeding as a baby may persist later on. Shows trouble sucking and swallowing in the infant stage.

13. Tongue thrusting habit.

Intellectual Features:

1. Significant lack of attention and focus. Switch activities frequently without sticking to one.

2. Severe learning disabilities and low intellect.

3. Lack of speech or scanty speech. Most affected children, later on, adapt to non-verbal skills of communication.

4. Hyperactive behavior; may decrease as the child grows.

5. Socializing personality with a happy disposition.

6. Problem getting sleep or showing minimal sleep requirement.

7. Laughing and smiling a lot frequently, the laughter may be inappropriate and out of context.

8. Gets excited easily.

9. Increased hunger; may lead to obesity.

10. Often exhibit characteristic stubbornness and determination towards certain things. Trying to grab food and people around, and hair pulling are a few among them.

11. Some children tend to keep mouthing random things and chewing clothes.

12. A peculiar fascination with water and water-based activities.

How Is Angelman Syndrome Diagnosed?

In most cases, the child is brought to the doctor's attention around the age of six months to one year when parents notice delays in obtaining developmental milestones. They usually complain that the baby is not crawling or babbling as one is supposed to. Parents seek consultation following a seizure episode as well. The doctor looks for a history of Angelman syndrome in the family and specific clinical features such as - a small head that is flat at the back, frequent bouts of laughter, and trouble with walking and balancing oneself. The most important test for confirming the diagnosis of Angelman syndrome is genetic analysis, where one looks at the genetic units of the affected individual and family members (chromosomes and DNA) to identify the UBE3A gene. The electroencephalogram (EEG) study also shows typically different electrical activities in the brain.

What Is the Treatment for Angelman Syndrome?

There is no cure for Angelman syndrome, as chromosomal errors cannot be repaired. Treatment mainly focuses on compensating the developmental delays and functional disabilities. Additionally, doctors may prescribe medications to help with general medical ailments. The following are the available treatment modalities:

• Anticonvulsive drugs like Sodium valproate (Epilim), Clobazam, and Levetiracetam (Keppra) help with frequent seizure attacks.

• Doctors might prescribe Melatonin hormone supplements to help with sleep issues.

• Laxatives like Movicol help with frequent constipation.

• An ophthalmologist can help with surgical correction of the cross-eye (strabismus) and prescribe glasses if necessary.

• Physical therapy helps with walking, mobilizing the joints, and improving motor activities.

• Speech therapy helps with developing effective communication. A speech and language therapist can help the individual learn nonverbal forms of communication, such as hand gestures, sign language, understanding facial expressions, recognizing symbols, etc. Training the affected to use augmentative and alternative communication (AAC) devices such as tablets and laptops can be beneficial too.

• Occupational therapy can improve functional abilities to help lead an independent life. A therapist can advise the family on special equipment and house modifications to better suit the necessities of the affected individual.

• Approaching orthotic services helps deal with mobility issues and posture improvement. For example, one can use leg braces, custom-made shoes, splints, and insoles to walk and balance better.

• Behavioral therapy, social skills training, and special education are needed too.

• Talking to a genetic counselor is helpful in understanding the chances of the next child getting born with Angelman syndrome so that parents can make informed decisions.

Conclusion:

Angelman syndrome is very rare. Compared to many other conditions with intellectual disabilities, those affected with Angelman syndrome love to socialize and have interpersonal interactions. The desire to connect with others encourages the majority of the affected to develop their own ways of communicating. With the proper support and encouragement, they can learn new skills and household tasks to live in a community. A qualified healthcare professional can advise the child’s family on the various treatment strategies.