Mental retardation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

Intellectual disability (ID) belongs to neurodevelopmental disorders that affect children and adolescents during the developmental period. It is categorized into four subclasses that determine the need for support. This condition is characterized by impairments in both intellectual and adaptive functions. Research involving ID has found that genes that encode cognitive abilities play an essential role in its pathophysiology. An interplay of environment and genetics can cause ID, and comprehensive screening is done in these cases. More importantly, ID has existing co-morbid conditions, which makes treatment and care a challenge.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

Intellectual disability traces its roots back to ancient civilizations. The Egyptians focused on treating disabilities and other ailments, while Greek and Roman Civilizations negatively viewed disability, killing those with disabilities. During the Middle Ages, intellectual disability revolved around religion and superstitions. The Church became a refuge for the individual with disabilities by providing shelter. The Restoration period associated “idiocy” and mental illness with immortality for which having a disability is a punishment. In the 17th century, John Locke differentiated intellectual disabilities from physical ones, where both mental and emotional deficits characterized intellectual disabilities. Oxford Philosopher Willis pinpointed various etiologies for a mental disability such as heredity, trauma, other diseases, and spirits. ^[1]

Previously, intellectual disability is known by the terms mental retardation that included the categories of an idiot, imbecile and moron. These terms are based on IQ test scores. In 2010, President Barack Obama signed Rosa’s law, which removed “mental retardation” and mentally retarded from federal use. This change was also implemented in the DSM5. ^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

There is no established system for the classification of [disease name].

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[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].

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[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3]. [Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].

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Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

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If the staging system involves specific and characteristic findings and features: According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

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The staging of [malignancy name] is based on the [staging system].

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There is no established system for the staging of [malignancy name].

The DSM 5 Classification of Severity for Intellectual disability has veered away from IQ scores and now considers adaptive functioning as the basis for classification.^{[1] [2]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

The exact pathogenesis of intellectual disability is not fully understood but most researches focused on genes that specifically code for cognitive characteristics and are mostly X-linked.

Intellectual disorders with intact cortex have found that most of the known genes influencing cognitive abilities are X-linked. These genes code for different proteins and some are involved in neuronal connectivity and synapse formation and activity. Recent progress in unraveling the pathophysiology of ID involves defects in synaptogenesis and synaptic activities, including neuroplasticity. An important finding that illustrates the importance of synapses in the occurrence of ID involves the FMRP protein that is absent in Fragile X syndrome. The FMRP protein is normally detected in the nucleus, body, and dendrites. It is upregulated by glutamate-mediated stimulation—the specific knockout of Fmr1 results in abnormal morphology of dendrites in Purkinje cells in the cerebellum. Therefore, defects in synaptic structure and overall neuronal connectivity impairs proper information processing. ^{[1] [2]}

The normal physiology of [name of process] can be understood as follows:

• The exact pathogenesis of [disease name] is not completely understood.

OR

• It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
• [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
• Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
• [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
• The progression to [disease name] usually involves the [molecular pathway].
• The pathophysiology of [disease/malignancy] depends on the histological subtype.

[Disease name] is transmitted in [mode of genetic transmission] pattern.

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Genes involved in the pathogenesis of [disease name] include:

• [Gene1]
• [Gene2]
• [Gene3]

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The development of [disease name] is the result of multiple genetic mutations such as:

• [Mutation 1]
• [Mutation 2]
• [Mutation 3]

Conditions associated with [disease name] include:

• [Condition 1]
• [Condition 2]
• [Condition 3]

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

Possible causes for intellectual disability can be divided into genetic causes and environmental factors.

In less than 50% of individuals with mild ID, a specific cause is identified, and it increases to 75% in those with severe ID. ^[1]

Down syndrome (Trisomy 21) is the most common genetic cause of ID, while Fragile X is the most common inherited cause of ID. ^[1]

Alcohol exposure during pregnancy, lead and other heavy metals, iodine deficiency, brain infections, congenital rubella syndrome, and cytomegalovirus infections, as well as hypoxic-ischemic injury, and periventricular hemorrhages all cause brain injury resulting in disability. ^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

Intellectual disability must be differentiated from other diseases that cause cognitive deficits such as neurocognitive disorders or brain injury, specific learning disorders, or genetic conditions that are characterized by mental retardation.

1. Neurocognitive disorders – there is loss of cognitive functioning in these cases.
2. Specific learning disorder and language disorders – compared to individuals with ID, these individuals have deficits in communication and learning aspects but with normal intellect and adaptive function.
3. Autism spectrum disorder – social development and language deficits are the hallmark of autism spectrum patients and have normal motor development.

Possible hearing and visual impairments should be ruled out in diagnosing intellectual disability. ^{[1] [2]}

• Neurocognitive disorders ^[3]
• Communication Disorder ^[4]
• Specific Learning Disorder ^[5]
• Autism Spectrum Disorder ^[6]
• Down Syndrome ^[7]
• DiGeorge Syndrome ^[8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2] Kiran Singh, M.D. [3]

The prevalence of intellectual disability has remained stable over the years. It is noted that it occurs more in males and there is no racial predilection when it comes to the prevalence of this condition.

The prevalence is 1% in the general population, with 6 per 1000 persons having a severe mental disability. During 2014–2016, the prevalence of children ever diagnosed with any developmental disability significantly increased, from 5.76% in 2014 to 6.99% in 2016 while the prevalence of children ever diagnosed with intellectual disability did not significantly change from 2014 to 2016. ^[1]

The prevalence of intellectual disability was lower among younger children than older children: 0.73% among children aged 3–7 years, 1.45% among children aged 8–12 years, and 1.40% among children aged 13–17 years. ^[2]

The prevalence of children diagnosed with intellectual disability did not differ significantly by race and Hispanic ethnicity. The difference in the prevalence of intellectual disability between non-Hispanic black children (1.53%) and non-Hispanic other children (0.86%) was not statistically significant (p = 0.21). ^[3]

Males are more likely to have a mental disability with a ratio of 2:1. During 2014–2016, the prevalence of children ever diagnosed with intellectual disability was 1.48% among boys and 0.90% among girls. ^{[4] [5] [6]}

In the United States, individuals with a severe intellectual disability are at 0.3-0.5% and 9.21 per 1000 people in developed countries. ^{[7] [5]}

Prevalence is at 16.41 per 1000 people in developing countries. ^{[8] [5]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2] Kiran Singh, M.D. [3]

The risk factors for intellectual disability are divided into three categories which are pre-natal, perinatal, and post-natal risk factors.

Prenatal causes ^[1]

1. Genetic syndromes
2. Inborn errors of metabolism
3. Brain malformations
4. Maternal disease
5. Environmental factors such as the history of alcoholism, teratogens, and other drugs

Perinatal causes include events during labor and delivery that ultimately lead to ischemic injury to neonates’ brains. ^[2]

Postnatal causes ^[3]

1. Hypoxic-ischemic injury
2. Traumatic brain injury
3. Infections
4. Demyelinating disorders
5. Infantile spasms
6. Severe and chronic social deprivation
7. Heavy metal poisoning
8. Toxic metabolic syndromes

Risk factors for mental retardation include genetic syndromes, hypoxic ischemic injury, and seizure disorders among others.^[1]

• Genetic syndromes (e.g., sequence variations or copy number variants involving one or more genes; chromosomal disorders)
• Inborn errors of metabolism
• Brain malformations
• Maternal disease (including placental disease)
• Environmental influences (e.g., alcohol, other drugs, toxins, teratogens)
• Variety of labor and delivery-related events leading toneonatal encephalopathy
• Hypoxic ischemic injury
• Traumatic brain injury
• Infections
• Demyelinating disorders
• Seizure disorders (e.g., infantile spasms)
• Severe and chronic social deprivation
• Toxic metabolic syndromes and intoxications(e.g., lead, mercury)^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

Screening for patients with a suspected intellectual disability includes standardized intelligence assessments, adaptive functioning, genetic tests, and neuroimaging modalities.

Evaluation is dependent on age at onset, the severity of signs and symptoms, and the need to determine the underlying etiology of ID. A comprehensive screening includes clinical assessment paying particular attention to prenatal and perinatal history and family pedigree, psychological testing, karyotyping and metabolic screening, as well as neuroimaging tests. ^{[1] [2] [3]}

Intelligence Quotient (IQ) is the standard for estimating intellectual function. Standardized tools such as the Wechsler scale is administered to children 6-16 years old, while a brief assessment tool such as the Kauffman Brief Intelligence Test is an alternative if the Wechsler test is not possible. The mean value of IQ is 100, and 70-75 represents the upper limit of two standard deviations below the mean. Several factors may influence intelligence assessment, and this includes measurement error, Flynn effect, practice effects, outliers, and test selection, to name a few. ^{[3] [4]}

The Vineland Adaptive Behavior Scale evaluates communication, ability to perform activities of daily living (ADL), motor and socialization. Another assessment tool is AAIDD’s Diagnostic Adaptive Behavior Scale (DABS), administered to individuals 4-21 years old. This tool focuses on the “cut-off” area for ruling in a diagnosis of ID to determine eligibility for special education services, social security benefits, and home and community-based waiver services. ^{[5] [6]}

Newborn screening programs screen for inborn errors of metabolism with a yield of < 1%, and chromosomal analysis is required in children with unknown causes of ID with a yield of 12%. While genetic tests help discern the prognosis and treatment plan, it should be taken into account that these are expensive, and the findings may not reflect the phenotype of an individual. ^[7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Chelsea Mae Nobleza, M.D.[2]

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

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Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

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Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

ID often is accompanied by other mental, medical, and physical conditions like epilepsy and cerebral palsy. The most common comorbid conditions are attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder, anxiety disorder, autism spectrum disorder, and stereotypical movement disorder. ^[1]

People with mild to moderate ID are able to live independently and be successful at jobs requiring simple tasks while people with severe ID will require lifetime support. ^[2]

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