Overview

Intellectual disability (ID) (formerly known as mental retardation (MR)), is a developmental condition characterised by limitations in intellectual abilities (cognitive functioning), such as learning, judgement, problem-solving, and adaptive behaviour across conceptual, social, and practical domains, such as communication, personal care, and social participation which impacts an individual’s daily activities. These challenges are experienced differently due to differences in intellectual disability. 

Intellectual disability arises from several multifaceted causes including: 

• Genetics changes; alteration or misformation in genetic makeup that leads to genetic disorder and potential intellectual disability.
• Environmental influence; perinatal and childhood exposure to neurotoxic agents (e.g. lead – a naturally occurring element that studies have shown to be associated with the decline in cognitive function when exposed to certain levels) and maternal consumption of intoxicants or illicit drugs (e.g. alcohol, cocaine, and tobacco e.t.c.). Additionally, prenatal conditions such as deprivation of adequate oxygen and nutrients during childbirth, gestation, labour, or delivery cause damage to the foetus's brain cells and subsequently cause developmental delays affecting all areas of the child’s life.
• Physical factors

Virtually all intellectual disabilities are of genetic basis. This is simply because genetic mutation almost directly, if not directly, interrupts the regulation of neurotransmitters that are involved in the functioning and development of the brain and subsequently leads to impaired intellectual ability; It is imperative to discover and understand the aetiology (root cause) of one’s intellectual disability since genetics is not the only cause. This way, strategies to address your needs such as management plans will be easily and specifically implemented for you by your physician. 

However, in the article, primarily, emphasis on the genetic basis of intellectual disability will be discussed.

What are genetic disorders?

Genetic disorders are a set of conditions or diseases caused by changes or abnormalities in a person’s genes (one or more) or by chromosomal alteration.¹ Genes are the basic physical and functional unit of hereditary.² Genetic disorders are assumed to be solely hereditary; however, it is unlikely to be the case for many genetic-related conditions, including intellectual disability.

Understanding genetic disorder 

To fully grasp the complexity of the effect of genetic disorders, we need to first address the gene’s structural and functional aspects. It constitutes a segment of deoxyribonucleic acid (DNA) which is made up of specific proteins – adenine, guanine, cytosine, and thymine, bonded in pairs called base pairs (adenine to thymine; guanine to cytosine) on two strands complementary of each other twisted in the shape of a spiral ladder called DNA helix. It is located in the nucleus of the cell of a chromosome.² 

The human cell contains two sets of chromosomes: 22 sets of autosomes and one sex chromosome (XX and XY), making up a total of 23 human chromosomes in the gene. However, children receive one gene from each parent, making a total of two genes and 46 chromosomes inherited.² 

The gene, ultimately, functions primarily to carry genetic information and instructions required to make specific proteins. Delivering this information to the appropriate protein-making machinery in the cell is a process called gene expression; a complex mechanism that involves tight regulation for proper development and functioning of our cells. Any sort of error in the gene yields undesirable outcomes, in other words–genetic disorders.³ 

Classifications of genetic disorders

Single gene or Mendelian disorder

These are a group of genetic disorders that occur due to a mutation in a single gene. They follow the Mendelian law of inheritance, so, the disorders can be from autosomal genes, others from sex-linked genes.⁴

Chromosomal alterations

These are abnormalities that occur when replicated chromosomes fail to split properly during meiosis which is called nondisjunction. Extra chromosomes are gained or lost sometimes, which is usually fatal and impacts all genes such as Down syndrome and Klinefelter syndrome.⁴ 

Multifactorial disorders

These are disorders that are not caused by genetic mutation but are influenced by multiple genes (polygenic) in combination with other factors–environmental, behavioural (lifestyle) factors such as diabetes. Although multifactorial disorders run in families, their pattern of inheritance remains unclear. 

However, mutations such as cancer, can be acquired through a person's lifetimes, because exposure to toxic agents, or medication, and alteration in behaviour and environment can influence gene traits.^2,5

Mitochondrial inheritance 

This is a maternal genetic disorder caused by a mutation or difference in the mitochondria of the DNA, this is known as a non-nuclear mitochondrial DNA inheritance. Many of our genetic traits can be found in the nucleus of a DNA, but in mitochondrial DNA inheritance, they are found in the mitochondria instead and only mothers can pass any disorders to their child.

Signs and symptoms of genetic disorders 

Genetic disorders can present in different, yet similar symptoms. The following are a few symptoms you can look out for:

• Developmental problems (e.g. intellectual disability, seizure, low muscle tone, autism spectrum disorders etc.) 
• Sensory deficit (e.g. hearing loss, vision impairment)
• Birth defects (e.g. spina bifida, glaucoma, cleft lips, cataracts, misshapen skull etc.)
• Chronic diseases (sickle cell disease, thalassemia, bleeding disorders, stunted growth etc.)

Some physical signs include:

• Misshapen teeth 
• Excessive body hairs 
• Webbed limbs 
• Distinctive facial features 
• Body odour 
• Excessive sweating 
• Unusual eye colour or different coloured eyes 
• Stiff or loose joints

Diagnosing genetic disorders

• Physical examination 
• Personal medical history 
• Family health history 
• Genetic testing 

Genetic disorders associated with intellectual disability 

Fragile-X syndrome (FXS)

It is an inherited condition that causes intellectual disability and physical, behavioural, and emotional problems. FXS is caused by a change in a gene called FMR1 and it is found on the X chromosome.⁶ FXS affects both males and females, but it affects males more than it affects females, who have milder symptoms. This is because there is only one X chromosome in males(XY), whereas in women there are two X chromosomes (XX); only one X chromosome is affected. It is estimated that about 1 in 7000 males and about 1 in 11,000 females have been diagnosed with FXS.⁷

Down syndrome 

Down syndrome is a genetic condition that occurs when there is an addition of chromosome 21. Generally, humans have 46 chromosomes (23 pairs inherited from each parent). There are three types of down syndrome. In conditions such as intellectual disability, a type of down syndrome is involved called trisomy 21 where there is an extra copy of chromosome number 21 in the gene. The disruption causes reduced development and affects the overall health of an individual. The presence of that mutated gene usually presents itself with certain physical features after birth and plays a role in intellectual challenges.⁸

Phenylketonuria (PKU)

It is an inherited autosomal recessive metabolic disorder of a faulty gene. It is caused due to protein-rich foods not broken down properly from a deficit in a liver enzyme, phenylalanine hydroxylase (PAH). PAH is responsible for breaking down a specific protein called phenylalanine and converting it into tyrosine. But because of the deficit in PAH, it is unable to carry out its function, thus causing excess accumulation of phenylalanine in the blood, consequently, damaging the brain and nervous system.^9,10

Rett syndrome (RTT)

Rett syndrome is a rare genetic disorder that causes neurodevelopmental problems caused by a mutation on the X-linked gene, methyl-CpG-binding protein 2 (MeCP2). MeCP2 is considered to affect the function of neurons and other brain cells. It is characterised by early development followed by regression of acquired skills after a period of development accompanied by severe impairment such as loss of speech, learning disabilities, breathing abnormalities, and deceleration in head growth.^11,12

Prader-Willi syndrome (PWS)

Prader-Willi syndrome (PWS) is a genetic disorder associated with deletion or disruption of the paternal genes in chromosome number 15.¹³ It is associated with alteration of metabolism, development, intellectual disability, and an insane insatiable hunger. PWS is characterised by life-threatening obesity, diminished foetal activity, short stature, behavioural problems, defective sexual development, and low muscle tone.

Causes of intellectual disability 

Genetic factors

These are factors that occur due to mutations or abnormalities in the inherited genes or chromosomes or errors in the combination of genes. Examples are down syndrome, Fragile X syndrome, and phenylketonuria. 

Environmental factors

These are non-genetic factors, (external influences) that can impact gene expression or interact with genetic predispositions and cause intellectual disability. Examples below:-

• Prenatal (during pregnancy) exposure to neurotoxic substances and infections during pregnancy can affect the development of the brain and lead to intellectual disability. A common example of a disorder is foetal alcohol syndrome, caused by consumption or exposure of alcohol during pregnancy
• Perinatal (during childbirth) complications such as deprived oxygen can result in brain damage and consequently develop intellectual disability. Low birth weight and premature birth also play a role in the manifestation of intellectual disability
• Postnatal (afterbirth) factors as in the case of traumatic brain injury (TBI) and shaken baby syndrome affect the developing brain. Additionally, degenerative disorders such as Rett Syndrome

Physical factors 

This involves infections and diseases, malnutrition, inadequate medical care and exposure to toxic substances like lead and mercury. In a few cases; statistically, malformation in the central nervous system (CNS) is identified at about 10-15%. The malformation presents itself in neural tube defects and microcephaly. Other examples include: meningitis, measles, or whooping cough.¹⁴

Other environmental/physical influences such as near-drowning could potentially cause the onset of intellectual disability.

Diagnosis and identification of intellectual disability

Signs and symptoms 

• Learning difficulty
• Difficulty socialising 
• Forgetfulness 
• Slow development than other children 
• Inability to think logically 
• Lower than average IQ scores
• Inability to perform daily tasks 
• Lack of sense of action and consequence 

Diagnostics

• Genetic testing – this refers to laboratory tests that require special genetic techniques to analyse human genetic materials to detect any abnormality with the composition and/or structures and positions of your genes. Human genetic materials may include your DNA, chromosomes, and RNA
• Neuroimaging – this is a noninvasive medical imaging technique used to view the structure and detect the functionality of the brain in healthy and impaired individuals. It falls into two categories; functional neuroimaging and structural neuroimaging – both valuable for understanding the function and disorders of the brain
• Functional neuroimaging deals with imaging the brain function in real time i.e. looks to see or view and measure your brain activities
• Structural neuroimaging involves viewing the anatomy of the brain to help identify any abnormalities in the structure of your brain
• Developmental screening – this is the assessment of your child’s development to identify any potential delays in areas that include: cognitive abilities, communication, motor skills, and social-emotional development

Management and treatment of intellectual disability

Early intervention 

Responding to the complications of intellectual disability can gradually reduce their course and lessen the disability. For instance, in phenylketonuria, dietary control – decreased intake of protein-rich foods, can manage the effects of the disorder and ultimately increase cognitive function. 

Gene therapy

In gene therapy, genetic manipulation (replacement of defective gene) is used in the cases of genetics causing intellectual disabilities to correct abnormal or mutated genes.¹⁵

Therapeutic interventions 

• Physical therapy – this is a type of therapy that focuses on helping you with mobility and physical function.
• Occupational therapy – this involves engaging you in meaningful and purposeful activities, domestic activities, employment skills, and leisure activities. 
• Speech and language therapy – aims to improve your speech articulation, receptive and expressive language, and communication skills. 

Pharmacological treatments 

Pharmacotherapy helps to manage behavioural and mood changes that come with the disability, but not to treat intellectual disability as no medication has been proven effective to treat intellectual disability.¹⁶

Educational strategies and support 

Education for individuals with intellectual disabilities should be specialised to meet the needs of the individual with disability and inclusive across academics and training in adaptive skills, social skills, and vocational skills. Specialised education and individual programs are crucial for the improvement of individuals with disabilities.¹⁷

FAQ’s

How common is intellectual disability? 

Very common. It is estimated that approximately 200 million people have intellectual disability. 

Can intellectual disability be from an unknown cause?

Yes, the cause, other than the identified ones, of intellectual disability in most patients remains unknown.

When should I see a doctor? 

Once you suspect a delay in your child’s development, it is advised you see a healthcare professional or consult a doctor. Early intervention is key to tackling this concern. You should not hesitate. By doing this, a developmental assessment will be done to evaluate your child and guidance on how management and preventative care will be given in order for your struggling child to reach their full potential.

Is Intellectual disability the same as developmental disorder?

No, developmental disorder is an umbrella term for conditions that limit the functions and development of a person in areas of life, INCLUDING intellectual disability – intellectual disability is a TYPE of developmental disorder.

Summary

Intellectual disability (ID) is a developmental disability that can interfere with the daily activities of an individual across intellectual and adaptive domains. ID stems from many influential factors including physical, environmental, and genetic factors. The genetic basis of ID refers to cellular changes in genes or chromosomes. These changes manifest into genetic disorders that affect the brain’s neural activity during development.

Early interventions and gene therapy, pharmacological, and educational strategies are ways to prevent, manage, and essentially improve the quality of living of the intellectually handicapped population. By incorporating and addressing these strategies, ID’s progressive potential can be reduced.