Etiology and Treatment for Intellectual Developmental Disorders

Learning Objectives

  • Describe common causes of intellectual disability, including fetal alcohol syndrome, Down syndrome, and fragile X syndrome
  • Examine the management and treatment of intellectual developmental disorders


While many causes of intellectual development disorder (intellectual disability) are not known, the etiology of intellectual development disorder mainly divides into genetic abnormalities and environmental exposure. Genetic abnormality can be a single gene mutation, copy number variation, or chromosomal abnormality that causes an inborn error of metabolism, neurodevelopmental defect, and neurodegeneration. Environment exposure can be maternal exposure to toxin/infectious agents, uncontrolled maternal medical conditions, delivery complications, and postnatal trauma and exposure to toxin/infectious agents. The most common known preventable or environmental cause of intellectual development disorder is fetal alcohol syndrome, the most common chromosomal cause is Down syndrome, and the most common genetic cause is fragile X syndrome.

Down Syndrome

Watch this video for an overview of the causes and symptoms of Down syndrome.

You can view the transcript for “Down syndrome (trisomy 21) – causes, symptoms, diagnosis, & pathology” here (opens in new window).


The genetic abnormality may cause an inborn error of metabolism neurodevelopmental defect, or neurodegeneration. An inborn error of metabolism, toxic by-products accumulate, causing intellectual development disorder and other behavioral problems. Phenylketonuria (PKU) is one of the inborn errors of metabolism that occurs in approximately 0.01% of the newborn. Phenylketonuria (PKU) most commonly results from phenylalanine hydroxylase defect inherited in an autosomal recessive fashion. The defect disables the liver from converting phenylalanine to para-tyrosine. The consequent accumulation of phenylalanine is the culprit of intellectual development disorder. Neurological damage from phenylketonuria (PKU) is irreversible but preventable. Therefore, newborn screening of PKU is mandatory in the United States and other countries. Early screening followed by prompt initiation of a low phenylalanine diet before the age of three may prevent intellectual development disorder (intellectual disability). Recently, different rare types of hyperphenylalaninemia were described, including the deficiency of the enzyme dihydropyridine reductase and a deficiency of a cofactor, biopterin.

Lesch-Nyhan syndrome is an X-linked inborn error of metabolism caused by purine metabolism enzyme deficiency. This condition results from a mutation in HGPRT. This mutation leads to a buildup of uric acid, which causes severe self-mutilating behavior of biting mouth and finger as well as intellectual development disorder. Other known inborn errors of metabolism that result in intellectual development disorder are Niemann-Pick disease, Hunter disease, Hurler disease, maple syrup urine disease, Hartnup disease, homocystinuria, and galactosemia.

A neurodevelopmental defect presents in fragile X syndrome, a leading genetic cause of intellectual development disorder (intellectual disability). It results from a single gene mutation in FMR1 (Xq27.3) gene. In most cases, CGG repeat of the FMR1 gene expands to over 200 times. The expansion leads to a phosphorylated CG pattern, causing methylation imprinting of the gene, thereby silencing FMR1 gene expression. FMR1 is a transcription factor of hundreds of genes expressed in the central nervous system, and its disruption causes intellectual development disorder as well as behavioral disturbance, and seizure. Neurodevelopment defect also presents in neurofibromatosis type 1, also known as von Recklinghausen syndrome, an autosomal dominant condition, caused by mutations of NF1. Its characteristic presentation is abnormal neural cell migration leading to cafe au lait spot, movement disorder, and intellectual development disorder.

Fragile X Syndrome

Watch this video for an overview of the causes and symptoms of fragile X syndrome.

You can view the transcript for “Fragile X Syndrome – causes, symptoms, diagnosis, treatment, pathology” here (opens in new window).

Neurodegeneration leading to intellectual development disorder presents in Rett syndrome (RS), an X-linked dominant degenerative condition only seen in female secondary to mutation of the MeCP2 gene. In patients with Rett syndrome (RS), cerebral atrophy (the loss of brain cells over time) occurs at a part of the midbrain known as the substantia nigra, causing defects in the way dopamine is released throughout areas of the brain, starting at six to 18 months of age.

IQ alterations can also occur as part of a clinical picture in other genetic syndromes. In many cases, the intellectual deficit appears to be limited and can occur at different stages of neurodevelopment, also in terms of cognitive decline. For example, in chromosome 22q11.2 deletion syndrome, DiGeorge syndrome, or velocardiofacial syndrome, which is one of the most common multiple anomaly syndromes in humans, it is usually described as a cognitive decline rather than an early onset intellectual development disorder.


Environmental exposure during pregnancy may lead to intellectual development disorder (intellectual disability), which can be caused by maternal exposure to a toxin, infectious agent, uncontrolled maternal condition, and birth complications. One common toxic substance that leads to an intellectual development disorder during pregnancy includes alcohol. Alcohol exposure, indeed, commonly causes intellectual development disorder along with other developmental abnormalities, in a condition known as fetal alcohol syndrome.

One study looked at the effects of moderate alcohol exposure by studying pregnant rats who were given 5% ethanol for four hours per day; the results showed that the rats born to mothers exposed to ethanol had deficiencies in various aspects of social behavior, tongue protrusion, and issues with cognitive processes.[1] Fetal exposure to alcohol inhibits the production of retinoic acid, which is an essential, signaling molecule for the development of the nervous system. Even a small amount of alcohol at any trimester of pregnancy may cause fetal alcohol syndrome. Exposure to opioids, cocaine, and teratogenic medications may also lead to intellectual development disorder.

Fetal Alcohol Syndrome

This video introduces us to Natalie, who lives with fetal alcohol syndrome.

You can view the transcript for “Living with Fetal Alcohol Syndrome” here (opens in new window).

To learn more about living with FAS, watch this story of Iyal and his family.

Common, well-known infectious agents that causes intellectual development disorder (intellectual disability) are rubella and HIV. Maternal rubella infection in the initial trimester of pregnancy leads to intellectual development disorder approximately 10 to 15% of the time; it can rise to above 50% with infection during the first month. Immunization may prevent the mother from rubella infection. HIV may be transferred vertically from mother to infant. Infants with HIV may develop encephalopathy, seizures, and intellectual development disorder within the first year of life secondary to microcephaly, immunosuppression, and Pneumocystis jiroveci pneumonitis (PCP) infection. Excessive neuro-inflammation causes overstimulation of the N-methyl-D-aspartate type receptor (NMDAR) system that leads to neuronal injury. Antiretroviral therapy to the mother and prophylactic treatment with zidovudine to newborn exposed to HIV has significantly reduced the transmission. Other known infectious exposures to mothers that may cause intellectual development disorder in the newborn are cytomegalic inclusion disease, syphilis, and toxoplasmosis.

Uncontrolled maternal medical conditions may lead to intellectual development disorder. Pregnancy hypertension, asthma, urinary tract infection, pre-pregnancy obesity, and pre-gestational diabetes were shown to increase the risk significantly. Furthermore, uncontrolled maternal diabetes, malnutrition, and obstetrical complications causing anoxia (placenta previa, placenta abruption, and umbilical cord prolapse) may also cause intellectual development disorder. An intellectual development disorder is acquirable during early childhood. Causes include infection (notably encephalitis and meningitis), head trauma, asphyxia, intracranial tumor (either directly or indirectly through seizure, surgery, and chemotherapy), malnutrition, and exposure to toxic substances.

Key Takeaways: Intellectual Disability

Treatment and Management of Intellectual Development Disorder

Management of intellectual development disorder (intellectual disability) must begin promptly with the goals to prevent further worsening, minimize the symptoms of the development disorder, and improve the quality of everyday life. When initiating therapy, a healthcare provider must be aware of the various avenues of treating intellectual development disorder to orchestrate a multidisciplinary and individually tailored treatment appropriately. This section will discuss some examples of the multiple interventions available.

A special education teacher working on an activity with a young student.

Figure 1. Students with intellectual development disorders should be placed in less restrictive environments.

Educational support is a crucial component of intellectual development disorder management. Upon diagnosis of intellectual development disorder in children, healthcare providers must contact the school promptly to set up special education arrangements. What special education entails may vary slightly among schools, but it typically aids comprehensively with providing academic modifications as well as transition planning from childhood to adulthood with a focus on promoting self-sufficiency. It also teaches them how to seek assistance, behavioral skills, vocational skills, communication skills, functional living skills, and social skills based on individual needs in the least restrictive environment. Creating the least restrictive environment for students with an intellectual development disorder means to place them in general classrooms as much as tolerated. While segregated classrooms for special needs may be helpful for those who need it, implementing the least restrictive environment policy has been shown to improve student outcomes. It is important to monitor the patients’ progress in school because education solely from classroom settings may not be sufficient. If an individual with an intellectual development disorder requires assistance beyond what is available at school, the family can meet the need at home through family education or other outside resources. For example, a disabled student who needs extra attention with social skills may be referred to participate in the Special Olympics programs that have been shown to improve social competence in intellectual development disorder subjects. Lastly, other causes of learning difficulties need to be ruled out, and appropriate hearing and vision screenings are necessary for individuals with intellectual development disorders.

Behavioral intervention is another important aspect of intellectual development disorder management, and it can occur in a few different ways. Behavioral therapy aims to encourage positive behaviors while discouraging undesirable behaviors. Providing positive reinforcement and benign punishments (e.g., time-outs) is an effective method of behavioral training. Other supplemental methods may include avoiding triggers of negative demeanor, shunning misconduct, and redirecting to prevent or curtail any troublesome behavior. Cognitive therapy is another mode of behavioral training that has been effective for eligible intellectual development disorder patients. Cognitive therapy has its basis on a principle that one’s behavior, emotions, and cognitions are connected, and it aims to correct one’s negative behaviors by identifying and adjusting negative thoughts and emotional stress. Although many other approaches to behavioral intervention exist, the implementation of behavioral therapy, cognitive therapy, or a combination of the two is the most widely used method that has shown to be an effective means of behavioral intervention for intellectual development disorder patients.

Vocational training helps teenagers and young adults to obtain the necessary skills to enter the labor market. In vocational training, patients carry out pre-scheduled activities under the supervision of a multi-disciplinary team consisting of a social worker, occupational therapist, teacher, counselor, and psychologist. Patients learn to keep themselves clean, wear appropriate clothes, and carry out their responsibilities. A study has shown that patients who underwent vocational training had reduced support requirements compared to their peers.

Family education is an essential service provided by healthcare providers for family members of intellectually disabled patients. The first part of this education is assisting the family members in understanding intellectual development disorder: definition, management, and prognosis. Then, healthcare providers can help the family through placement decisions, refer them to appropriate services and equipment, and provide caregiver training. In addition to preparing the family for the patient, physicians must recognize that family members also often bear a significant amount of stress as well. The medical team must support the whole family through psychosocial problems such as the need for respect, feeling helpless, depression, and anxiety. There are also outside resources to which the family can obtain a referral. American Association on Intellectual and Developmental Disabilities (AAIDD), The Arc of the United States, and Family-to-Family Health Information and Education Centers are some of the nationally available resources, and social workers can help with connecting the families with local resources. Establishing strong support for the family, in turn, creates a caring home environment for the patient.

Government resources are available for patients with intellectual development disorders (intellectual disabilities) and their families. Patients with intellectual development disorders are eligible to benefit from social security income. Patients also may benefit from various community services that provide housing and food delivery. The government also provides education and employment opportunities as outlined under the “Disability Resources” section of the U.S. Department of Labor website.

Psychopharmacologic interventions may not be the main component of intellectual development disorder (intellectual disability) treatment, but they play a significant role in treating behavioral abnormalities associated with intellectual disorder and comorbid conditions. Aggressive behavior is not uncommon among individuals with intellectual development disorders (intellectual disabilities) and causes admission to institutional settings. Risperidone is a well-documented treatment of disruptive, aggressive, and self-injurious behaviors in children with intellectual development disorder with good safety and tolerability profile.[25] Risperidone is an atypical antipsychotic that is less likely to cause tardive dyskinesia, which commonly results in a typical antipsychotic. Aripiprazole is another atypical antipsychotic used to manage aggression.

Treatment of comorbid conditions is an important aspect of adequate therapy. ADHD, depression, and movement disorders are some of the comorbid conditions accompanying intellectual development disorder that require evaluation and treatment. Methylphenidate, clonidine, and atomoxetine are shown in randomized control trials to reduce ADHD symptoms. Methylphenidate significantly improved the maintenance of attention to complete a task; however, there was no long-term improvement in learning and social skills.

Depressive symptoms can be easily overlooked in individuals with intellectual development disorders when other behavioral problems are prominent; thus symptoms require careful evaluation. Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, and sertraline were shown in multiple studies to help with depressive symptoms in this patient population.

Involuntary movements, repetitive self-stimulatory behaviors, and obsessive-compulsive symptoms may be harmful to the patients. Antipsychotic medications have been anecdotally reported to diminish these symptoms, although there was no observation of improvement in adaptive behavior. SSRIs are useful in treating obsessive-compulsive symptoms and stereotyped motor movements.

Studies have shown that patients with intellectual development disorders (intellectual disabilities) are at risk for polypharmacy, and providers should be cautious when prescribing medications as some patients may be at a higher risk of side effects and may need lower dosages.

Differential Diagnosis

Several diseases or conditions can be mistaken for intellectual development disorder (intellectual disability):

  • child abuse. Childhood abuse may cause developmental delays in language and socialization, causing a defect in adaptive function. The child may have difficulty communicating their needs and developing trust and social responsibility. Unlike intellectual development disorder (intellectual disability), symptoms are often reversible when the environment improves.
  • debilitating medical disease. Individuals with normal intelligence may experience depression and delay in the development of chronic, debilitating medical illness.
  • cerebral palsy. Poor muscle coordination and problems with vision, hearing, and speaking may imitate symptoms of intellectual development disorder.
  • sensory disability. Deafness or blindness may lead to a flaw in diagnostic testing, causing a false-positive diagnosis of intellectual development disorder.
  • speech disorder. Expressive and receptive aphasia may be mistaken for intellectual development disorder.


Father smiling at his son who has Down syndrome.

Figure 2. With the right support, many individuals with ID can have a higher quality of life.

The cognitive deficit of intellectual development disorder (intellectual disability) is permanent damage; thus, the prognosis of intellectual development disorder depends on the severity of cognitive impairment and the supportive environment provided. If provided adequate support, individuals with mild intellectual development disorders may achieve adequate language and social competency to live independently and raise their own families. Individuals with moderate intellectual development disorders are not likely to achieve academic levels greater than second grade; however, they may acquire language and communicate their needs. They may be able to get a job under supervision. Individuals with a severe intellectual development disorders usually have difficulty acquiring language. They may be able to develop alternative communication skills and recognize words that are critical to functioning. Adults with a severe intellectual development disorder usually require supervised living situations, such as group homes, and supervision to perform any work-related tasks. Individuals with profound intellectual development disorders have significant difficulty with communication and social functioning.


Most of the individuals with intellectual development disorder have comorbid psychiatric conditions. Individuals are at higher risk of developing depression because they are prone to developing negative self-images as they have difficulty interacting with others and meeting social expectations. Other psychiatric comorbid symptoms frequently observed in these individuals are hyperactivity, self-injurious behaviors, and repetitive stereotypical behaviors.

Try It


Down syndrome: also known as trisomy 21, a genetic disorder caused by the presence of all or part of a third copy of chromosome 21

fetal alcohol syndrome: a disorder caused by environmental factors due to ethanol exposure while developing in the womb

fragile X syndrome: a genetic disorder resulting from a single gene mutation in FMR1

  1. Hamilton, D. A., Barto, D., Rodriguez, C. I., Magcalas, C. M., Fink, B. C., Rice, J. P., Bird, C. W., Davies, S., & Savage, D. D. (2014). Effects of moderate prenatal ethanol exposure and age on social behavior, spatial response perseveration errors and motor behavior. Behavioural brain research, 269, 44–54.