World Autism Awareness Day is commemorated on April 2 every year to spread awareness about this disorder, and the different challenges it imposes on individuals and families. World Autism Awareness Day was first proposed in 2007 at the United Nations (UN), by Her Highness Sheikha Moza bint Nasser, the Chairperson of Qatar Foundation. Since then, April 2 has been declared as World Autism Awareness Day.

At the Qatar Biomedical Research Institute (QBRI) Neurological Disorders Research Center (NDRC), research focuses on investigating neurological disorders of increasing prevalence in Qatar and the region. These disorders are diverse and range from neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), Intellectual Disability (ID) and epilepsy, to neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This edition of QBRI Insights , aims to provide a general collective overview about autism and some of its associated conditions

ASD is a neurodevelopmental disorder of variable severity that affects children before they reach the third year of life, and characterized by:

• Persistent deficit in social communication and social interaction;
• Restricted, repetitive patterns of behavior, interest or activities,
• Symptoms present in early period of developmental life, and limit, or impair everyday functioning;

The term “spectrum” refers to the wide range of symptoms, skills, and levels of disability in functioning that can occur in people with ASD. Some children and adults with ASD are fully able to perform all activities of daily living while others require substantial support to perform basic activities. It is four times common in males than in females.

Many Individuals who are diagnosed withASD have comorbid health problems. Recent large-scale studies have confirmed that several medical conditions are significantly more prevalent in people with ASD compared to the general population. A detailed assessment conducted by the US Centers for Disease Control and Prevention (CDC) demonstrated that children with ASD had much higher than expected rates of all the medical conditions studied, including: ear and respiratory infections, gastrointestinal problems, eczema, allergies, asthma, severe headaches, migraines, and seizures. 

Medical comorbidities are difficult to recognize in individuals with ASD. The failure to identify such comorbidities is due in part to communication impairments and vague symptomatology, but widespread under-diagnosis is also the result of commonly held beliefs that aberrant behaviors and symptoms are ‘just a part of ASD.

Therefore, children and adults with ASDhave an increased need for pediatric and/or specialist services, both for their core functional deficits and concurrent medical conditions. Those different medical conditions and comorbidities associated with ASD increase the complexity of the general picture of autism symptoms, which make it even more difficult to diagnose. Here are some of the medical comorbidities associated with autism:

Conditions caused by genetic disorders:

1. Rett’s Syndrome
2. Fragile-X
3. Tuberous sclerosis
4. Angelman syndrome
5. Down syndrome

Other conditions and disorders:

1. Seizure disorders
2. Attention Deficit Hyperactivity Disorder
3. Intellectual Disability
4. Sleeping disorders
5. Gastrointestinal problems
6. Sensory integration disorders
7. Social anxiety disorders

Fragile-X Syndrome

Fragile X syndrome (FXS) is an inherited genetic disorder characterized by mild to moderate intellectual disability, and is a leading genetic cause of autism. About one third of people with the syndrome also have autism. It affects one in 4,000 boys and one in every 8,000 girls. Boys usually have more severe symptoms than girls.

Some people with FXS have characteristic facial features, such as a long face with a broad forehead, large ears, and prominent jaw. However, not all people with FXS have features like this, and these physical characteristics are not always obvious at birth. Other features may include flexible fingers, and large testicles. About one third of those affected have features of autism, hyperactivity is common, and seizures occur in about 10% of cases. 

Down syndrome

Down syndrome is a genetic disorder caused when abnormal cell division results in an extra full or partial copy of chromosome 21. The term for having an extra copy of a chromosome is ‘trisomy.’ Down syndrome is also referred to as Trisomy 21. This extra genetic material causes the developmental changes and physical features of Down syndrome In the US, one in every 700 babies is born with the condition and 16-19% of individuals with Down syndrome have Autism. 

Older women have an increased chance of having a child with Down syndrome. A 35-year-old woman has aone in 350 chance of conceiving a child with Down syndrome, and this increases to 1 in 100 by age 40 and approximately 1 in 30 at age 45. 

Common physical features of Down syndrome include:

• A flattened face, especially the bridge of the nose
• Almond-shaped eyes that slant up
• A short neck
• Small ears
• A tongue that tends to stick out of the mouth
• Small hands and feet
• A single line across the palm of the hand (palmar crease)
• Poor muscle tone or loose joints
• Shorter in height as children and adults

Some of the more common health problems among children with Down syndrome: 

• Hearing loss
• Obstructive sleep apnea, which is a condition where the person’s breathing temporarily stops while asleep
• Eye diseases
• Heart defects present at birth

At birth, babies with Down syndrome have the same size and weight as other babies, but they then grow at a slower pace. Because they often have less muscle tone, they are sometimes floppy and cannot easily hold their heads up, but such characteristics usually change positively with time. Children with Down syndrome often take longer to reach normal milestones like crawling, walking, and talking. Moreover, in school, they may need extra help with things like learning to read and write.

Intellectual disability:

Intellectual disability (ID), is characterized by below-average intelligence or mental ability and a lack of skills necessary for day-to-day living.

ID affects about 2-3% of the general population, and 75-90% of those affected have mild intellectual disability. Non-syndromic or idiopathic ID accounts for 30-50% of cases. About a quarter of cases are caused by a genetic disorder, although it is more common in males and in low to middle-income countries. Around 50% of individuals with autism have one degree or another of ID, while 10% of individuals with ID have autism.

People with ID can learn new skills, but they do so slowly. There are varying degrees of ID from mild to profound. It could take longer for a child with ID to learn to speak, walk, dress, or eat without help, and learning in school could be challenging for them.

An individual with ID has limitations in two main areas:

• Intellectual functioning: This refers to a person’s ability to learn reason, make decisions, and solve problems.
• Adaptive behaviors: These are skills necessary for every day, like communicating effectively, interacting with others, and taking care of oneself.

Levels of ID

Intellectual disability can be divided into four levels, based on IQ and degree of social adjustment: 

1) Mild intellectual disability (IQ range of 50 to 69) 

Some symptoms might include:

• Taking longer to learn to talk, but communicating well once they know how.
• Being fully independent in self-care when they get older.
• Having problems with reading and writing.
• Social immaturity.
• Increased difficulty with the responsibilities of marriage or parenting.
• Benefiting from specialized education plans.

2) Moderate ID (IQ range of 35 to 49) 

Affected persons may exhibit some of the following symptoms:

• Slow in understanding and using language.
• Some difficulties with communication.
• Can only learn basic reading, writing, and counting skills.
• Generally unable to live alone.
• Can only get around on their own to familiar places.

3) Severe ID (IQ range of 20 to 34)

Symptoms of severe ID include:

• Noticeable motor impairment.
• Severe damage to, or abnormal development of, their central nervous system.

4) Profound ID (IQ of less than 20)

Symptoms of profound ID include:

• Inability to understand or comply with requests or instructions.
• Possible immobility.
• Incontinence.
• Very basic nonverbal communication.
• Inability to care for their own needs independently. 
• The need for constant help and supervision.

Seizure disorders (Epilepsy)

Seizures are unexpected quick and uncontrolled electrical disturbances that occur to the brain. Sometimes seizures can cause alterations in the behavior, movements, feelings, and in levels of consciousness of individuals. If a person is subjected to two or more consecutive seizures, or a tendency to have recurrent seizures, he/she is considered to have epilepsy.

There are many types of seizure, which vary by where and how they begin in the brain. Most seizures can last up to two minutes. If a seizure lasts for longer than five minutes this is considered to be a medical emergency.

Seizures are more common than one might think; and can happen after a stroke, a closed head injury, an infection such as meningitis or febrile illness. The direct cause of a seizure is unknown on many occasions.

Most seizure disorders can be controlled with medication, but can still have a significant impact on the affected person’s daily life. Around 18-20% of individuals with autism have seizures.  

Types of Seizures 

There are two main types of seizure based on how and where abnormal brain activity begins; classified as either focal or generalized:

1) Focal seizures: 

Abnormal electrical activity in one area of the brain can be a reason for focal seizures, this can occur with loss of consciousness or without.

2) Generalized seizures: 

Seizures that appear to involve all areas of the brain are called generalized seizures.

Causes of seizures

• Genetic causes:

Genetics is believed to be involved in the majority of cases, either directly or indirectly. Some epilepsies are due to a single gene defect (1–2%), but most are due to the interaction of multiple genes and environmental factors. More than 200 genes and many chromosomal abnormalities are involved in the causation of epilepsy; most genes involved affect ion channels, either directly or indirectly.

Most of those genes are also involved in different neurodevelopmental disorders and conditions, like Tuberous sclerosis, Rett’s, FXS, Autism, Down syndrome, Angelman syndrome, and others.

• Brain tumor:

Brain tumors are a collection of cancer cells that either start in the brain (primary tumors), or somewhere else in the body and then spread to the brain (called secondary, or metastatic). Brain tumors sometimes might cause swelling and pressure which disrupt the brain's normal electrical activity and result in seizures.

• Head trauma:

This can cause bleeding and scars inside the brain, which interferes with the normal activity in the brain and causes seizures. 

• Stroke:

Strokes cause tissue damage in small or large areas of the brain, and this damage may cause seizures, for example strokes that affect certain areas of the brain like the temporal lobe, are more likely to cause a seizure disorder than in other areas, such as the brainstem.

• Meningitis:

An infection of the protective membranes that surround the brain, called the meninges, may cause seizures by disrupting brain activity. Luckily, most seizures associated with meningitis resolve once the underlying infection is treated.

• Encephalitis/Brain Abscess:  

Encephalitis (brain inflammation) and brain abscesses (a collection of pus in the brain) are serious conditions that may produce immediate seizures, as well as lasting epilepsy.

• High fever:

When associated with an infection such as meningitis, a very high fever can provoke seizures in some predisposed young children and babies. These types of seizures are called febrile seizures and require prompt medical attention.

Diagnosis of seizures

The diagnosis of epilepsy is typically based on observation of the seizure onset and the underlying cause. 

An electro-encephalogram to look for abnormal patterns of brain waves and neuroimaging (CT scan or MRI) to look at the structure of the brain, will usually form part of the diagnostic examination of a patient. 

Contributed by: Dr. Fouad Alshaban, (Senior Scientist at QBRI’s Neurological Disorders Research Center) 

Editors: Dr. Adviti Naik (Postdoctoral Researcher, QBRI), Dr. Prasanna Kolatkar (Senior Scientist, QBRI)