Angelman Syndrome

Angelman syndrome is a genetic disorder characterized by neurological problems like delayed development, intellectual disability, and problems with movement and coordination. The initial symptoms can be noticed in children when they are about 6-12 months old. 

Patients with this syndrome have a normal life expectancy. These children have a cheerful and excitable demeanor which gradually reduces with age. Adults with this syndrome have characteristic facial features, often referred to as ‘coarse’. 

In most of the cases, it is not inherited but caused by a mutation that occurs around the time of conception. Treatment strategies include management of the medical and developmental problems.

Children with Angelman syndrome appear to be normal during the first few months, except for feeding problems and the initial symptoms are noticed by around 6-12 months. The common symptoms include: 

• Delay in development – children miss important milestones like crawling or babbling within 6-12 months. 
• Intellectual disability
• Lack of speech
• Problems with walking and coordination
• Cheerful demeanor
• Frequent smiling and laughter
• Seizures that start at 2-3 years of age
• Small head size
• Sleep disorders
• Hyperactivity
• Thrusting of tongue
• Light colored skin, hair, and eyes

They may also show unusual behaviors like flapping or lifting of hands while walking. The distinctive facial features of the people with this syndrome is described as ‘coarse’. Many adults with Angelman syndrome show a curvature of spine. 

Loss of function of ubiquitin protein ligase E3A (UBE3A) gene causes Angelman syndrome. This gene is located in chromosome 15. One copy of the gene is inherited from each parent. In many of the tissues, both the gene copies are active. But in some parts of brain only one copy of the gene, the one received from mother, is active. 

This process where only one of the copies of the gene is activated is called genomic imprinting. But, if the maternal copy of the gene is lost or mutated, some parts of the brain will not have any active copies of the gene.

 In some cases, a person may inherit both the copies from father, resulting in this syndrome. 

The actual cause of the genetic changes is not clear. In most of the cases, it is not seen running in families. In some rare cases it may be inherited, thus increasing the risk of children born with this syndrome. 

Angelman syndrome is diagnosed based on developmental delay and other characteristic features of the syndrome. Small head, problems in movement and coordination, and frequent laughter indicates presence of this syndrome. 

Confirmatory diagnosis is based on genetic studies. 

• DNA methylation test is a genetic test which identifies the genetic mechanism that result in this disorder
• Fluorescence in situ hybridization (FISH) test is another genetic test that screens for deletions in chromosome. Comparative genomic hybridization test (CGH test) is also suggested to screen for chromosomal deletions. 
• UBE3A gene mutation test is useful to look for mutation in maternal gene. 

Doctors from different fields work together to chalk out a treatment strategy for managing symptoms of Angelman syndrome. Some of the common treatment methods used are:

• Anti-epileptic medications are recommended to control seizures, one of the symptoms of this syndrome. This includes sodium valproate, clonazepam, or ethosuximide.
• Problems in walking, balance, and coordination are managed by physiotherapy. This also helps to prevent stiffening of joints as the child gets older. 
• Curvature of the spine is treated by using a back braces or spinal surgery. 
• Ankle or lower leg braces are useful to aid in walking without difficulty.
• Communication therapy is recommended to control speech delay and to help with other modes of communication like sign language.
• Behavioral issues are treated with behavioral therapy. 

As the condition is caused by genetic mutations, there are no standard preventive measures for Angelman syndrome. Genetic counseling will help in assessing the risks of a child to be born with this condition.

Several alternative remedies are being tried to manage the symptoms of Angelman syndrome. But none of them are supported by scientific evidence. 

Phosphorous, Ferrum phos, and Nux vomica are used in homeopathy to treat specific symptoms of the condition. Ketogenic diet is used to control seizures in children.

Lifestyle modifications are necessary in order to cope with Angelman syndrome.

Parents of a child with Angelman syndrome may have to work with different specialists to treat the developmental delays. Connecting with support groups or other families with children suffering from this syndrome help to discuss and share experiences. 

Support groups provide emotional support and share educational and community resources to cope with the condition.

Hyperactivity, sleep disorders, curving of spine, and obesity are the main complications associated with Angelman syndrome.