What Are Some Etiologies for Intellectual Disability?

Patient Presentation
A 4-year-old male came to clinic with his mother to establish care after they moved to the area. He was a former 26 week premature infant, who was known to have problems related to retinopathy of prematurity, global developmental delay after bilateral grade IV intraventricular hemorrhages and lung problems due to bronchopulmonary dysplasia. They were in the process of re-establishing his specialty medical and service care. They had already contacted the local school district and had appointments with the occupational, physical and speech therapists. The mother needed additional referrals to Developmental Disabilities, Ophthalmology, Orthopaedics and Pulmonary to continue his followup. “The neonatologists had already transitioned him to the Developmental Disabilities people to continue to monitor him, so I need to get that arranged too,” his mother noted. “He needed a feeding tube before but he has been eating fine and gaining weight, so I don’t think we need GI at this time, and I already have appointments with Neurology and Neurosurgery to followup on his seizures and VP shunts,” she stated. “He’s well controlled on his medications and so far has only needed one shunt revision,” she explained.

The pertinent physical exam showed a smiling thin male who was polite but spoke little during the visit. His weight was in the 10% and height was 25% and was tracking from his previous records. He wore glasses and had some caps on his teeth. Bilateral ventriculoperitoneal shunts were in place. His abdomen showed previous surgerical scars. His neurological examination had increased tone throughout and increased DTR +2/+2 but his strength was normal. His ankle-foot orthoses appeared to fit well without skin breakdown.

The diagnosis of a child with global developmental delay secondary to prematurity and its complications was made. “I will order those consultations. He also will need a dentist and I can refer you to one in the area who works with lots of children who need special care. There’s also recreational services for families with a family member with special needs and I can tell you more about those too,” the pediatrician offered.

“Intellectual disability (ID) is a neurodevelopmental disorder that is characterized by deficits in both intellectual functioning and adaptive function whose onset is in the development period.” Global developmental delay (GDD) is used to describe children from 0-5 years old with significant delays in 2 or more developmental areas. These delays may be transient but up to 2/3 of children with GDD will have ID. Overall 1-3% of the general population has ID which makes it very common.

Most children with GDD/ID are identified because of delays in meeting milestones or general academic achievement. ID patients who have more severe problems are usually identified earlier. Each person with ID is individual and their strengths and weaknesses will be different. There are different ID severity levels which are grouped as:

  • Mild
    • 85% of ID population
    • Associated IQ score: 55-70
    • Described as having: academic problems, communication/thinking more concrete, more immature socially, may live and work independently and provide own personal care but may also need intermittent support often with complex daily activities
    • Projected academic achievement: up to 6th grade
  • Moderate
    • 10% of ID population
    • Associated IQ score: 40-55
    • Described as having: academic problems, more problems with providing own personal care, can live and work in a supervised environment
    • Projected academic achievement: up to 2nd grade
  • Severe
    • 3-4% of ID population
    • Described as having: severe academic problems, limited communication, needs extensive oversight and supervision for all activities of daily living
    • Projected academic achievement: up to Preschool level
  • Profound
    • 1-2% of ID population
    • Associated IQ score: < 25
    • Described as having: severe problems understanding language but may understand basic instructions, is dependent for personal care and needs constant supervision
    • Projected academic achievement: very limited

When trying to identify a potential cause of ID, during physical examination the skin should be examined for possible neurocutenaous disorders. Head size, especially microcephaly but also macrocephaly, is commonly associated with ID. Evidence of dysmorphic features are also helpful but are not necessarily specific. It is important to remember that it is usually a constellation of findings that may help to distinguish an etiology.

A review of the causes of microcephaly can be found here.
A review of the causes of macrocephaly can be found here.

Evaluations can be helpful for the patient and family as then they can understand the natural history, obtain condition-specific medical surveillance and treatment, and obtain genetic counseling for future pregnancies and family members.
Recommended testing will depend on the history and physical examination.
Review of prior testing such as the neonatal screening testing may be helpful. Additionally testing for TORCH or Zika infections, neuroimaging, hearing and vision testing may be helpful. Other testing such as creatinin kinase, thyroid function, and baseline biochemistry and hematology labs, and urine metabolic screening can be helpful. Genetic testing currently often includes a chromosomal microarray analysis and may also include karyotyping and Fragile X testing. Specific genetic testing for certain syndromes or because of family history are also considered.

Individualized services for education and life functioning are important along with education and support for family members. Early intervention services for young children and school based services with appropriate goals for vocation and education along with individual preferences, strengths and weakness should be considered. For teenagers, transition planning for after school is important to start early.

Learning Point
Potential etiologies for ID include:

  • Unknown – a very common reason
  • Environment
    • Fetal alcohol syndrome
    • Hypoxic-ischemic encephalopathy
    • Infections – TORCH, Zika, meningitis
    • Toxin – lead
    • Traumatic brain injury
  • Genetic – a very common reason
    • Chromosomal – Down syndrome, Neurofibromatosis
    • Continuous gene deletions – 22q11 deletion, Angleman syndrome, Cri-du-chat, Prader-Willi, Smith-Magenis syndrome, Williams syndrome
    • Single gene deletion – Fragile X syndrome, Rett syndrome, Rubenstin-Taybi syndrome, Tuberous sclerosis
  • Inborn errors of metabolism – congenital hypothyroidism, phenylketonuria
  • Neurologic disorders – Brain malformations, central nervous system disorders
  • Nutritional deficiency – iron deficiency, severe malnutrition

The differential diagnosis for ID includes:

  • Autism spectrum disorder
  • Language disorder
  • Psychiatric problems
  • Specific learning disorders
  • Sensory deficits – vision, hearing
  • Trauma – adverse childhood experiences, post-traumatic stress disorder, abuse/neglect

It should be noted that many of these conditions could be co-morbid or overlap. For example, autism spectrum disorder often does not have ID but can. About 30% of people with ID have co-morbid conditions.

Questions for Further Discussion
1. What are some of the clinical features of Fragile X syndrome? A review can be found here
2. What is the classification of intraventricular hemorrhage? A review can be found here
3. What information should be in a health care plan for special needs children? A review can be found here
4. What is the role of the primary care provider for families with a special needs child?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Developmental Disabilities

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Purugganan, Oscar. Intellectual Disabilities. Pediatrics in Review. June;39(6):299-309.

Amor DJ. Investigating the child with intellectual disability. J Paediatr Child Health. 2018;54(10):1154-1158. doi:10.1111/jpc.14202

Bass N, Skuse D. Genetic testing in children and adolescents with intellectual disability. Curr Opin Psychiatry. 2018;31(6):490-495. doi:10.1097/YCO.0000000000000456

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa