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Intellectual disability (ID), also known as general learning disability, is defined as impaired intellectual ability of conceptual, social, and/or practical domains. ID is identified during childhood development, and can be due to idiopathic, acquired, or genetic causes. Depending on severity, ID can significantly impact adaptive functioning, activities of daily living (ADL), and overall individual independence.


ID is most commonly an idiopathic condition, as 30-50% of all case sources remain unidentified.1 However, brain development can be impaired through congenital malformations or damage during critical prenatal or postnatal developmental stages. Identifiable causes of ID include brain injury, genetic, environmental exposures, obstetric complications (i.e., congenital infections, trauma, alcohol, toxins), nutritional deficiency (i.e., iodine), or malnutrition. Genetic ID may be due to inheritance or de novo mutations. The most common genetic causes of ID include Down syndrome, Fragile X syndrome, and Klinefelter syndrome.

Epidemiology including risk factors and primary prevention

Approximately 1-3% of the global population has ID. In developing countries, the prevalence is 10-15 per 1000 live births.2 ID is often categorized based on mild [intelligence quotient (IQ) 50-69], moderate (IQ 36-49), severe (IQ 20-35), and profound (<IQ 20) severity.3 Approximately 75-90% of individuals are classified with mild ID. Furthermore, there is higher prevalence of males with ID with a 1.5:1 male to female ratio.1,4

Any risk factors that impede normal brain development can be a catalyst to intellectual disability. Threats that affect parental health can have reciprocal effects to the fetus. Complications during pregnancy are common risk factors for ID, including poor parental health, prenatal alcohol or drug exposure, infections and illness, hypoxia during birth, low birth weight, and fetal trauma.5 Furthermore, exposures and trauma during early infant life can have a lasting impact on the child’s intellectual capacity. Lower socioeconomic status (SES) that children are born into is also associated with ID.6 Poverty, dangerous environments, lower income countries, lack of education, and lack of proper resources are all factors of lower SES causing environmental and psychosocial exposures, malnutrition, and poor developmental health. Additionally, individuals with autism spectrum disorder (ASD) or first-degree relatives with ASD tend to have increased association with ID, and about 38% of individuals with ASD have ID.7

Primary prevention of ID is focused on supporting prenatal care with regular newborn screening, dietary regimens, folate supplementation, and maternal vaccinations. Other preventative measures include removing hazardous toxins, improving environmental hygiene, and enhancing safety measures for high risk events like automobile accidents.8


ID can develop during the prenatal, perinatal, and/or postnatal stages of development. Factors that can cause ID include neurodevelopmental disorders and genetics (i.e., Down syndrome, Fragile X syndrome), infections (i.e., HIV, rubella), drugs and toxin exposure (i.e., alcohol), undernutrition (i.e., iodine, folate, cobalamin), and obstetric complications. We briefly discuss the physiology of some of the most common causes of ID.

Genetic mutations are strongly associated with the development of ID. Down syndrome is caused by the presence of an additional chromosome 21. Trisomy 21 is caused from an error in maternal meiosis I (~66%) or meiosis II (~21%); paternal meiosis I (~3%) or meiosis II (~5%); or mitosis, after the zygote is formed (~5%). Mitochondrial dysfunction has been observed in trisomy 21 cells, reducing ATP production and increasing oxidative stress, contributing to ID. Physical traits of Down syndrome include flat facies, upwards slanting palpebral fissures, distinctive epicanthal folds, low-lying small ears, large furrowed tongue, short neck with excess skin, simian palmar crease, Bushfield spots, shortened fifth digit, and widened gap between the first and second toe.9 Fragile X syndrome is a genetic disease that is caused by an abnormal CGG trinucleotide repeat that leads to methylation and silencing of the fragile X mental retardations 1 (FMR1) gene. This silencing leads to a loss of the fragile X mental retardation 1 protein, causing ID. Physical traits of Fragile X include elongated face, broad forehead, large ears, prominent jaw, hyperextensible joints, and post pubertal macroorchidism.10

ID can also result from exposure to infectious agents. HIV and rubella are two widely recognized examples. These two infectious agents can infect various tissues and organs in the developing body, including the brain, causing inflammation and direct damage to neurons.11,12 This can lead to varying degrees of ID.

Moreover, drug and toxin exposure, the most common being fetal alcohol syndrome, can cause ID through various mechanisms, especially when alcohol is consumed during critical periods of brain development. Alcohol can directly damage brain cells and interfere with neurotransmitter systems, affecting cognitive processes such as learning memory, attention, and executive functioning. Moreover, alcohol can induce epigenetic changes, altering gene expression pathways in ways that affect brain development and function. Alcohol abuse can also lead to nutritional deficiencies, such as folate, cobalamin, and iodine, required for brain development and function. Physical characteristics include craniofacial abnormalities (i.e. short palpebral fissures, epicanthal folds, facial hypoplasia, smooth philtrum, thin upper lip, underdeveloped jaw), microcephaly, heart defects, and growth defects.13

Obstetric complications that lead to hypoxic-ischemic events in the newborn or birth trauma can also cause ID. Hypoperfusion or inadequate oxygen during pregnancy or delivery places the newborn at increased risk for brain damage. Birth trauma through difficult or traumatic deliveries can result in physical injuries to the brain and manifest as ID. 

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

The disease progression of ID can vary depending on the underlying mechanism and individual factors. ID refers to a lifelong condition characterized by reduced ability to understand complex information with onset occurring during childhood or adolescence. Generally, the progression of ID occurs in the following order:

  • Identification and Screening: ID is often identified during infancy or early childhood through developmental screening and assessments. Diagnostic criteria typically include assessments of intellectual functioning (developmental quotient testing) and adaptive behavior, considering factors such as communication, self-care, social skills, and independence. Language comprehension is best correlated with intelligence, so delayed language development can often be the earliest sign of an overall developmental problem.2,14
  • Developmental Milestones: Children with ID may experience delays in reaching developmental milestones, such as sitting up, crawling, walking, talking, and social interactions.15
  • Educational and Support Needs: As children with ID grow, they often require specialized educational interventions and support services. Individualized Education Programs (IEPs) are commonly developed to tailor educational goals and accommodate each child’s abilities.15
  • Transition to adulthood: Adults with ID will need to navigate adulthood through vocational training, social integration, healthcare management, and developing independent living skills.
  • Lifelong Challenges and Support: ID is typically a lifelong condition where adults face ongoing challenges and require continuous adaptation and support that may evolve over time.

Specific secondary or associated conditions and complications

ID can affect different aspects of an individual’s functioning and may require additional support and management. Depression, anxiety, and behavioral disorders, such as attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), can occur alongside ID. These mental health conditions may require specialized assessments and interventions, including counseling, therapy, and medication management. Moreover, individuals with ID may be at increased risk of physical health issues, such as obesity, diabetes, and cardiovascular disease.2,16 Physical health issues pose a substantial threat to livelihood and well-being.

Essentials of Assessment


A complete history includes the following:

  • Developmental history, including milestones and any delays or concerns noted by caregivers
  • Medical history, including the patient’s prenatal, perinatal, and postnatal history. Inquire about pregnancy complications and any exposures to environmental toxins or infections. Explore any genetic conditions, psychiatric disorders, neurological disorders, and chronic health conditions. Ask about previous surgeries, hospitalizations, medications, and allergies.
  • Family history, specifically related to ID.
  • Social history, including current education, school accommodations, and living situation. 

Physical examination

A full neurological exam should be done to assess for any neurological deficits that may mimic ID. Visual and hearing tests are also important because abnormalities can cause delay in communication, which can be mistaken for ID. It is also important to observe the physical characteristics of the patient because many specific conditions can be diagnosed this way. For example, individuals with down syndrome often have slanted eyes, a single palmar crease, epicanthal folds, and low-set small ears. Patients with Fragile X syndrome typically present with a prominent forehead and long, narrow face with a prominent chin.2

Functional assessment

A functional assessment for ID involves evaluating an individual’s functional skills, adaptive behavior, and level of independence in daily life activities. The key components of a functional assessment for intellectual disability include addressing ADLs, instrumental activities of daily living (IADLs), and adaptive function. ADLs refer to basic self-care tasks, such as dressing, grooming, bathing, toileting, and feeding. IADLs describe more complex daily living skills related to independent living, such as meal preparation, housekeeping, managing finances, and medication management. Adaptive function can be measured using the Adaptive Behavior Assessment System, which examines a patient’s ability to communicate, participate socially, and live independently.2

Laboratory studies

Laboratory studies can help identify underlying factors contributing to ID. Genetic testing may include chromosomal analysis, but typically starts with microarray or SNP array, gene panel, and exome or genome sequencing based on the individual’s presentation. Biochemical testing, including a complete blood count, electrolytes (basic metabolic panel), thyroid function (TSH), vitamin levels, and enzyme activities, can help confirm or rule out suspected conditions. Additionally, toxicology screening can be used to detect substance abuse or poisoning, such as alcohol or lead, by identifying drugs or toxic substances that may impact neurological function.2


Neuroimaging can be useful in identifying malformations, developmental anomalies (ie. microcephaly, cerebral developmental delay, cerebral palsy), and ruling out other potential diagnoses. MRI is useful because of its ability to produce a comprehensive image of brain structure and evaluate for signs of brain injury. CT scan is also useful for evaluating brain structure and assessing for acute intracranial conditions. Moreover, EEG can be used to detect abnormal patterns of electrical activity in the brain that may suggest epilepsy or another seizure disorder.2 All of these conditions may present with some form of cognitive impairment.

Supplemental assessment tools

The IQ test is widely used to measure a person’s cognitive abilities in relation to their age group and is an important assessment tool for identifying deficits in intellectual function. Derived from Stanford-Binet Intelligence Scales, scores are reported using the formula “mental age” divided by chronological age, multiplied by 100. An IQ lower than 70 (two standard deviations below the mean), suggests a diagnosis of ID. An IQ of 50 to 69 suggests mild ID, 36 to 49 suggests moderate ID, 20 to 35 suggests severe ID, and below 20 suggests profound ID. It’s important to note that ID is not diagnosed using IQ score alone; adaptive function, which assesses an individual’s ability to communicate socially and live independently, is also considered. Neuropsychological testing can also evaluate cognitive function to identify specific learning strengths and weaknesses, such as problem-solving and memory.2

Early predictions of outcomes

Predicting outcomes for individuals with ID varies depending on the individual’s abilities and environmental factors that influence development and quality of life. The individual’s cause of ID and severity of ID play a crucial role in predicting outcomes for individuals with ID. Early identification of ID is important for initiating interventions early on. Furthermore, severity of ID, as assessed using the IQ test, can predict the individual’s outcome.2 Individuals with milder impairments may achieve greater independence and functional skills. Monitoring developmental milestones can also provide insight into an individual’s potential.


Given the varying degrees of ID and resulting array of individual abilities, environmental needs vary. Potential challenges for patients include difficulty in understanding and learning complex information, and limited verbal and nonverbal communication. These barriers can lead to difficulty forming and maintaining social relationships, and challenges in the academic and work environments. IEPs, structured work environments, and support in performing daily routines are important for providing successful care.

Social role and social support system

The sense of social isolation and incompetence weighs heavily on individuals with ID. Educating social support systems about the importance of fostering environments that help to improve the individual’s social skills and self-esteem is extremely beneficial. For example, engagement with the Special Olympics International program provides opportunities for social interactions and building friendships. Educating family members that individuals with ID are more prone to experience failures and require a supportive environment is an essential aspect of care.2

Professional issues

Individuals with ID are at greater risk for abuse, bullying, and discrimination. Raising awareness and establishing policies that promote inclusivity of those with ID are important steps to support equality and accessibility to education and work. Moreover, ethical considerations are crucial for ensuring respect for an individual’s autonomy in the healthcare setting. Encouraging self-expression, active participation, and input in decision-making processes help to recognize and respect choices of individuals with ID.

Rehabilitation Management and Treatments

Available or current treatment guidelines

As intellectual disability is considered a heterogeneous condition, there is not a single comprehensive set of guidelines for rehabilitation management of ID. However, there are several organizations and resources that provide recommendations for supporting individuals with ID in the rehabilitation setting. While rehabilitative interventions for ID may not aim to restore individuals to their previous level of functioning, goals include improving skills to maximize adaptive functioning in various domains, such as daily living skills, communication, and socialization.17 Often, enhancing cognitive function is paramount to the rehabilitative process. 

At different disease stages

Infancy/Early Childhood

Seeking the potential origin of ID, such as through genetic testing, is essential for guiding initial interventions. A close eye should be kept on growth metrics to catch developmental delays early. Efforts should be prioritized to prevent and lessen impairments, address medical conditions, and manage psychiatric disorders that could complicate long-term well-being. Early intervention programs offer vital support by teaching developmental skills and addressing fundamental needs.2


Caregivers, service providers, and clinicians should maintain ongoing monitoring of growth metrics and associated health conditions. Local agency support systems offer crucial services for personalized development and rehabilitation. Additional management strategies may involve enrollment in specialized education programs, speech-language therapy, and psychotherapeutic interventions.


Continued support services are based on the individual’s specific needs with the emphasis on improving their ability to live as independently as possible. Transitional care can help individuals adapt to adult situations. Specialized care may include appropriate adult services, vocational training, employment support, community and social support, and pharmacological management for medical complications, especially for psychiatric disorders.

Coordination of care

Optimal management of patients with ID involves a collaborative interprofessional team. Adopting an interprofessional approach is essential for serving patients’ best interests, proven to reduce healthcare costs by minimizing the need for diagnostic tests and hospitalizations related to ID. Key members of the interprofessional team include psychiatrists, psychologists, neurologists, speech pathologists, special nurse educators, social workers, and pharmacists.2 Effective communication among team members is vital for maintaining collaborative care. Successful collaboration ensures prompt and accurate diagnoses, establishing timely services, and medication and therapeutic compliance.

Patient & family education

This involves aiding family members in comprehending ID, management strategies, and long-term outlook. Families should be advised to focus on fostering independence and encourage learning in their child while setting appropriate expectations. Subsequently, healthcare professionals guide patients and families in making decisions, facilitate referrals to relevant services, and provide training for caregivers. Because of the considerable stress often borne by family members, social workers play a vital role in connecting families with local resources. Families can access external resources through referrals to organizations such as the American Association on Intellectual and Developmental Disabilities, The Arc of the United States, and Family-to-family Health Information and Education Centers.2

Measurement of treatment outcomes

Measurement of treatment outcomes for ID involves assessing the effectiveness of interventions in various domains, such as functional abilities, cognitive function, and progress in education and vocation. Improvements in functional abilities include improvements in daily living skills (eg. self-care, household tasks), social skills, communication abilities, adaptive behaviors, and independent living. ADL independence can be measured by using functional assessment tools, such as the Functional Independence Measure for Children. Standardized assessment tools, such as the Vineland Adaptive Behavior Scales and Adaptive Behavior Assessment System, can be used to track functional abilities over time.18 Assessing changes in cognitive skills, such as attention, memory, problem-solving, reasoning, and executive functions, can be measured by using cognitive assessment tools, such as the Wechsler Intelligence Scale for Children and Stanford-Binet Intelligence Scale.19 Progress in education and vocation can be tracked by evaluating academic and vocational achievements, and through feedback from educators, supervisors, and peers.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Conduct a thorough and multidimensional assessment to identify ID early on
  • Tailor interventions and support strategies to the unique needs, abilities, and developmental stage of everyone with ID
  • Foster collaboration among healthcare professionals, educators, therapists, caregivers, and community resources to provide comprehensive and coordinated care
  • Involve the patient and families as partners in care, providing education, support, resources, and empowerment to enhance the well-being of both the individual with ID and their family members
  • Assess the effectiveness of interventions using validated assessment tools that can be used to track changes in an individual’s functional abilities, cognitive function, and progress in education and vocation

Cutting Edge/Emerging and Unique Concepts and Practice

Emerging research is focused on deeper understanding of genetic and metabolic etiologies of ID in hopes of developing novel therapeutics to improve cognitive function.20 Small-molecule, genetic, and cell therapies are beginning to be explored at an increased pace in recent years. Currently, approved treatments are available for certain conditions, such as metachromatic leukodystrophy, which necessitate early or even pre-symptomatic diagnosis.

Gaps in the Evidence-Based Knowledge

Outside of preventative screening and correcting metabolic abnormalities, there is no definitive curative treatment for patients with ID. Despite best efforts to understand the complex multifactorial condition, the cause of many cases remain unknown. Future research into the etiologies of ID may prove useful for understanding and potentially developing new treatment modalities and technologies to help remedy preventable forms of ID.


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Author Disclosures

Sunil K Jain, MD
Nothing to Disclose

Tyler Shick
Nothing to Disclose

Maxwell Li, MD
Nothing to Disclose

Matthew Nguyen, BS
Nothing to Disclose