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Sections Intellectual Disability
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Presentation

History

Presenting signs/symptoms

The presenting symptoms and signs of intellectual disability (ID) typically include cognitive skills delays, language delay, and delays in adaptive skills. Developmental delays vary depending on the level of ID and the etiology. For example, in mild nonsyndromic ID, delays may not be notable until the preschool years, whereas with severe or profound ID associated with syndromes or extreme prematurity, for example, significant delays in milestones may be noted from birth.

Language delay: One of the first signs of ID may be language delays, including expressive language (speech) and receptive language (understanding). Red flags include no mama/dada/babbling by 12 months, no two-word phrases by age 2, and parents reporting they are concerned that the child may be deaf.
Fine motor/adaptive delay
- Significant delays in activities such as self-feeding, toileting, and dressing are typically reported in children with ID.
- Prolonged, messy finger feeding and drooling are signs of oral-motor incoordination.
Cognitive delay: Children with ID have difficulties with memory, problem-solving and logical reasoning. This may be expressed early on with preacademic difficulties or difficulty following directions (particularly multipart directions).
Social delays: Children with ID may display lack of interest in age-appropriate toys and delays in imaginative play and reciprocal play with age-matched peers. Rather than their chronological age, play reflects their developmental levels.
Gross motor
- Delays in gross motor development infrequently accompany the cognitive, language, and fine motor/adaptive delays associated with ID unless the underlying condition results in both ID and cerebral palsy.
- Subtle delays in gross motor acquisition, or clumsiness, may be identified in the developmental assessment.
Behavioral disturbances
- Even before an age at which psychopathology can be identified, infants and toddlers who go on to have ID may be more likely to have difficult temperaments, hyperactivity, disordered sleep, and colic.
- Associated behaviors may include aggression, self-injury, defiance, inattention, hyperactivity, sleep disturbances, and stereotypic behaviors.
Neurologic and physical abnormalities
- Prevalence of ID is increased among children with seizure disorders, microcephaly, macrocephaly, history of intrauterine or postnatal growth retardation, prematurity, and congenital anomalies.
- In the process of addressing somatic problems, assessment of a child's cognitive abilities is often overlooked.

Diagnoses of ID and autism frequently overlap. Approximately 50-75% of those with autism (autistic disorder) also have ID.^[11]Some literature has suggested diagnostic shifts from ID to autism for unknown reasons.^[12]

Developmental assessment

The American Academy of Pediatrics recommends developmental screening for all children at regular intervals. Methods include several parental surveys, such as the Parents' Evaluation of Developmental Status (PEDS), Ages and Stages Questionnaires (ASQ) and Child Development Inventories (CDI). Other instruments require direct observation, such as the Bayley Infant Neurodevelopmental Screener, Battelle Developmental Inventory, Early Language Milestone Scale, and Brigance Screens.

Key behavioral observations should focus on the child's communicative intent, social skills, eye contact, compliance, attention span, impulsivity, and style of play.

For the diagnoses of developmental delay and intellectual disability (ID), an expanded neurodevelopmental and psychological examination is required. Various tests can be administered to assess language comprehension, language expression, nonverbal cognitive abilities, fine motor and adaptive abilities, attention span, memory, gross motor skills, and adaptive behaviors. The most common psychological tests for children include the Bayley Scales of Infant Development-III, the Stanford-Binet Intelligence Scale, the Wechsler Intelligence Scale for Children-IV, the Wechsler Preschool and Primary Scale of Intelligence-Revised, and the Vineland Adaptive Behavior Scales-II.

Physical examination

See the list below:

Head circumference: Measurement of all growth parameters must include head circumference. Microcephaly correlates highly with cognitive deficits. Macrocephaly may indicate hydrocephalus and is associated with some inborn errors of metabolism and may also be seen early on in some children later diagnosed with autism.^{[1, 2]}
Height: Short stature may suggest a genetic disorder, fetal alcohol syndrome, or hypothyroidism. Tall stature may suggest fragile X syndrome (FraX), Soto syndrome, or other overgrowth syndrome associated with ID.
Neurologic: This examination should include assessments of head growth (for micro/macrocephaly), muscle tone (for hypotonia or spasticity), strength and coordination, deep tendon reflexes, persistent primitive reflexes, ataxia, and other abnormal movements such as dystonia or athetosis.
Sensory: Vision and hearing should always be tested in suspected cases of ID. Children with disabilities and ID are more likely than other children to have visual impairment (refractive errors, strabismus, amblyopia, cataracts, abnormal retinal pigmentation, and cortical blindness) and hearing deficits, particularly among those with severe impairments.
Skin: Cutaneous findings of etiologic interest include hyperpigmented and hypopigmented macules, such as café-au-lait macules (associated with neurofibromatosis type 1), and ash-leaf spots (associated with tuberous sclerosis), fibromas, and irregular pigmentation patterns.
Extremities: Examine for dysmorphic features and organ system dysfunction indicative of syndromes. Although ID with multiple congenital anomalies and major malformations accounts for only 5–10% of all cases, most of these affected individuals have 3–4 minor anomalies, especially involving the face and digits.

Prenatal conditions (genetic)

Trisomy 21 or Down syndrome

This disorder accounts for 25–50% of persons with severe intellectual disability (ID); Down syndrome occurs in approximately 1 per 600–800 live births.
In infancy, this disorder is recognized by specific facial features, including flat facial profile, brachycephaly, up-slanted and narrow palpebral fissures, and anomalous auricles.
Hypotonia, joint hyperextensibility, neonatal jaundice, simian crease, shortened digits, and excess skin on the back of the neck contribute to the clinical features.
Congenital heart disease is present in approximately 40%. GI malformations are present in 5%. Congenital cataracts are found in 3%, and as many as 35% require treatment for strabismus or refractive error. Infantile spasms may develop in 5%.
The IQ score ranges from 25 to 50. Generally, verbal-linguistic skills lag behind visual-spatial skills and social performance is usually above the mental age.
In trisomy 21, gene expression of chromosome 21 is increased in a dosage-dependent fashion that varies by tissue type. While some trisomic 21 genes are not expressed at elevated levels, many are. Of those significantly increased, several encode proteins critical for mitochondrial function and for neurogenesis.
Other chromosomal abnormalities (eg, deletions, duplications, translocations) may be present in as many as 25% of individuals with severe ID.
- The most commonly occurring abnormalities of this class, detectable at the 500 band level of chromosomal analysis, are 5p- (ie, Cri du chat syndrome) and 4p- (ie, Wolf-Hirschhorn syndrome).
- Cryptic subtelomeric deletions are diagnosed with increasing frequency as fluorescently tagged molecular DNA probes allow detection of deletions below the microscopic resolution of a standard karyotype.
- Cryptic subtelometric rearrangements now account for 5–6% of cases of idiopathic mental retardation.
- Chromosomal analysis is undergoing further refinement with the application of gene array hybridization techniques that may detect abnormalities in up to 20% of cases of idiopathic ID.

Fragile X syndrome

The population prevalence of this disorder is approximately 1 in 3500 males, giving a prevalence within the ID population of about 1 in 76. For males with severe ID, the prevalence rises to about 1 in 13. Other studies have found in populations of those with ID-positive fragile X studies in 5.9% of males and 0.3% of females.^[13]About 1 in 2000 females carries the fragile X (FraX) gene. Current studies suggest that FraX is the most prevalent form of inherited ID.

Males with the full FMR1 trinucleotide repeat expansion (ie, the full mutation) usually function in the moderate to severe range of ID.^[14]Other features include testicular enlargement in the postpubertal period and minor facial anomalies (eg, large forehead, elongated face, protuberant auricles, prominent chin).

Females with the full FMR1 trinucleotide repeat expansion may have no symptoms, although some have mild learning disabilities or even mild to moderate ID.

Mitral valve prolapse and seizures may occur.

Up to 20% of FraX males meet criteria for autism; autistic-like behaviors can be present in affected females as well.

Direct DNA analysis of the FMR-1 gene is the method of choice for diagnosing both affected individuals with the full trinucleotide repeat expansion (>200 repeats) and unaffected carriers with the premutation (60–200 repeats).

Contiguous gene deletion syndromes

Although less common, some of these syndromes can be readily identified clinically. The following syndromes often can be confirmed by utilizing a fluorescence in situ hybridization (FISH) probe to the deleted region in question.

Prader-Willi syndrome

The Prader-Willi syndrome (PWS) involves deletion at 15q11-q13 (deletion of the paternally derived region).
Classic clinical features include neonatal and infantile hypotonia, feeding problems or failure to thrive in infancy, excessive weight gain with hyperphagia beginning between ages 12 months and 6 years, food compulsions, hypogonadism, global developmental delay, almond-shaped eyes, thin upper lip, and down-turned corners of the mouth.
The candidate gene within the Prader-Willi gene region is SNRPN, which encodes a ribonucleoprotein involved in mRNA splicing. How SNRPN contributes to the hypothalamic dysfunction that defines many clinical features of PWS is unclear.
It is the first known human disorder of genomic imprinting, leading to revolutionary changes in the field of molecular genetics and the understanding of uniparental disomy.
Negative FISH results in PWS may be due to maternal uniparental disomy (UPD) of chromosome 15 (2 number 15 chromosomes from the mother) and can be confirmed by methylation studies.

Angelman syndrome

The Angelman syndrome (AS) also involves deletion at 15q11-q13 (deletion of the maternal copy of the gene region).
ID, absent speech, microcephaly, seizures, puppetlike ataxic movements, inappropriate laughter, and facial dysmorphisms characterize AS.
The candidate genes within the AS critical region include UBE3A, whose protein product is important in the posttranslational modification of proteins by ubiquitination, and GABRA3, a subunit of the GABAa receptor.
Negative FISH results in AS may be due to paternal UPD of chromosome 15 (2 number 15 chromosomes from the father) and can be confirmed with methylation studies.
Point mutations occasionally are found in AS with negative results on FISH and UPD studies.

Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) involves deletion at 17p11.2.
ID, short stature, brachydactyly, minor skeletal and facial anomalies, sleep disturbance, self-injurious behaviors, and other organ system malformations characterize this contiguous gene deletion syndrome.^[15]
Although as many as 100 genes may be deleted in SMS, the physical characteristics are subtle.

CATCH 22 syndrome

The CATCH 22 syndrome, which comprises DiGeorge Syndrome (DGS) and velocardiofacial syndrome (VCF), involves deletion at 22q11.
Infants with classic DGS are identified readily by aplasia or hypoplasia of the thymus, T cell lymphopenia, conotruncal cardiac defects, oral-motor dysfunction, and facial dysmorphisms (eg, low-set malformed ears, small jaw, palatal defects, hypertelorism, antimongoloid palpebral slant).
Minor variants may meet clinical criteria for the VCF syndrome. With a prevalence of 1 in 4,000 people, it is the most common known microdeletion disorder.
The majority of individuals with CATCH 22 have learning disabilities or mild ID and comorbid psychiatric disorders including schizophrenia and mood disorders with psychosis.

Williams syndrome

The Williams syndrome involves deletion at 7q11.^[16]
Characteristic facial features are described as "elfin." In the majority, valvular stenosis, poor growth, hypotonia, late-onset contractures, dental anomalies, infantile colic, oral-motor discoordination, and hyperacusis (ie, hypersensitivity to sound) are reported. Infantile hypercalcemia may be transient and is often subclinical.
Mild to moderate ID, relative preservation of language, and associated weakness in visual-spatial development are typical.
Elastin is the candidate gene presumed responsible for some of Williams syndrome features, including supravalvular aortic stenosis.

Wolf-Hirschhorn syndrome

The Wolf-Hirschhorn syndrome, also known as 4p- syndrome, involves deletion at 4p16.3.
Severe growth retardation, microcephaly, "Greek helmet" facies and orofacial clefts, and other midline fusion defects characterize this syndrome.
The region of deletion is gene dense, and an undefined number of genes may contribute to this phenotype.

Langer-Giedion syndrome

This syndrome, also known as trichorhinophalangeal syndrome type II, involves deletion at 8q24.1.
Learning disabilities and the presence of ID vary.
Facial dysmorphisms include microcephaly, large ears, bulbous nose, broad nasal bridge, elongated philtrum, and sparse scalp hair. Multiple nevi and skeletal anomalies may be present.

Miller-Dieker syndrome

The Miller-Dieker syndrome (MDS) involves deletion at 17p13.3.
Infants present with severe neurologic impairment, seizures, and hypotonia secondary to lissencephaly. The smooth cerebral cortex with absent or decreased gyral formation results from abnormal neuronal migration.
The identified gene LIS1 may function as a G protein subunit in cellular signal transduction that is important in telencephalon development.
Many contiguous gene deletion syndromes for which a FISH probe is not available have been recognized in association with ID. A comprehensive survey is beyond the scope of this article.

Single gene mutation syndromes

Tuberous sclerosis

Hypopigmented cutaneous macules (ie, ash-leaf spots), calcified intracranial cortical tubers with or without heterotopias, seizures, retinal hamartomas, and renal angiomyolipomas characterize this hamartomatous condition.
ID may or may not be seen in affected individuals; the presence of seizures is the factor most associated with poor cognitive outcome. Autism is a rather common finding in children with tuberous sclerosis associated with ID.
This is an autosomal-dominant inherited condition with about half of affected individuals resulting from a new mutation. Two genes have been identified, one at 9q34 (TSC1) and the other at 16p13 (TSC2). A variety of deletions, rearrangements, and point mutations have been implicated in tuberous sclerosis.

Rubinstein-Taybi syndrome

Broad terminal phalanges, beaked nose, down-slanting palpebral fissures, epicanthal folds, and microcephaly characterize this syndrome.
Behavioral aspects include variable degrees of impulsivity, distractibility, instability of mood, and stereotypies.^[17]
This is an autosomal-dominant inherited condition, with the majority of cases representing new deletions or point mutations of the CREB-binding protein gene (16p13.3).

Coffin-Lowry syndrome

This syndrome is characterized by hypertelorism, down-slanting palpebral fissures, frontal prominence, thickened lips and nasal septum, as well as dental and skeletal anomalies.
It is an X-linked condition, with females having mild manifestations. The syndrome results from mutations in the RSK2 gene, which encodes a CREB kinase (Xp22.2-p22.1).^[18]

Rett syndrome

Developmental stagnation then regression, progressive microcephaly, seizures, ataxia, and autisticlike behaviors are seen in affected females.
This X-linked dominant condition with presumed lethality for affected males is caused by mutations in MeCP2, a transcriptional repressor (Xq28).^[19]

Smith-Lemli-Opitz syndrome

Malformations consistent with holoprosencephaly sequence, syndactyly of toes 2 and 3, micrognathia, cleft palate, and moderate to severe ID are seen.
This autosomal-recessive inherited condition results from increases in 7-dehydrocholesterol (7-DHC) due to mutations in the 7-DHC reductase gene (11q12-q13).
Treatment with an oral cholesterol "cocktail" has shown some promise in this syndrome.

Costello syndrome

Characteristic clinical features include polyhydramnios, failure to thrive, cardiac anomalies, and tumor predisposition.
Mean IQ is in the mild ID range, but the spectrum extends from severe ID to average intelligence. Affected males are lower functioning than females and have significantly more behavioral problems.^[20]
Mutation in HRAS is identified, resulting in a gain of function of the encoded protein and increased activation of the cellular signaling pathway Ras-MAPK.^[21]

Many other single-gene disorders are associated with ID with additional phenotypic and behavioral features including such problems as microcephaly, seizures, or short stature, with or without dysmorphic facies.

Recent advances in genetic linkage analysis techniques in families with multiple affected members have revealed more than 50 candidate genes along the X chromosome. In some kindreds with a pattern of X-linked nonsyndromic mild MR (XLMR), linkage analysis has identified candidate genes that code for interleukin receptors, G protein signaling factors, transcription factors, and transcriptional repressors.

Environmental causes

Fetal alcohol syndrome and fetal alcohol effect

Alcohol results in a wide range of teratogenic effects.^[22]The most severely affected individuals meet criteria for fetal alcohol syndrome (FAS) by demonstrating short palpebral fissures, dental crowding, camptodactyly flattened philtrum, thin vermillion border, flattening of the maxillary area, microphthalmia, prenatal and postnatal growth deficiency, microcephaly, and developmental delay.

Fetal alcohol effect (FAE) can be diagnosed only in the context of (1) maternal history of alcohol use and (2) a child with developmental and behavioral abnormalities that also manifests growth deficiency or the characteristic facial dysmorphisms.

The prevalence of FAS may be as high as 1.9 in 1000 live births and is the leading cause of ID in the Western world. The impact of the milder FAE remains unknown. The teratogenic effects of alcohol may be responsible for as many as 8% of cases of mild ID. Alcohol's deleterious effects on cortical plasticity contribute to cognitive impairment.

Congenital hypothyroidism

Congenital hypothyroidism (known as cretinism in the past) is a neurologic syndrome that results from severe thyroid hormone deficiency during the fetal period. In the infant, the syndrome comprises deaf mutism, moderate to severe ID, spasticity, and strabismus.

Normal fetal brain development requires sufficient production of both maternal and fetal thyroid hormones. Normal glandular production of T4 and T3 requires sufficient dietary intake of iodine.

Iodine deficiency may affect an estimated 800 million people worldwide. It can result in endemic goiter, fetal wastage, milder degrees of developmental delay, and endemic congenital hypothyroidism.

Perinatal/postnatal conditions: These conditions are responsible for fewer than 10% of all ID cases.

Congenital cytomegalovirus (CMV)

Congenital rubella - No longer an important etiology in countries with high vaccination rates

Intraventricular hemorrhage related to extreme prematurity - An important cause only in societies with advanced neonatal care and survival of the premature

Hypoxic-ischemic encephalopathy - Always results in combined CP/MR

Traumatic brain injury - Shaken baby syndrome, closed head injury sustained in motor vehicle accidents

Meningitis - Decreasing in importance as the incidence of Haemophilus influenzae type B decreases in vaccinated populations

Trichomoniasis during pregnancy^[23]

Neurodegenerative disorders

Differential Diagnoses

Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003 Jul 16. 290(3):337-44. [QxMD MEDLINE Link].
Dawson G, Munson J, Webb SJ, Nalty T, Abbott R, Toth K. Rate of head growth decelerates and symptoms worsen in the second year of life in autism. Biol Psychiatry. 2007 Feb 15. 61(4):458-64. [QxMD MEDLINE Link].
Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology. 2003 Feb 11. 60(3):367-80. [QxMD MEDLINE Link].
Rueda JR, Ballesteros J, Tejada MI. Systematic review of pharmacological treatments in fragile X syndrome. BMC Neurol. 2009 Oct 13. 9:53. [QxMD MEDLINE Link]. [Full Text].
Wigal T, Greenhill L, Chuang S, McGough J, Vitiello B, Skrobala A. Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry. 2006 Nov. 45(11):1294-303. [QxMD MEDLINE Link].
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th Edition. Washington, DC: APA Press; 2013.
Birch HG, Richardson SA, Baird D, Horobin G, Illsley R. Mental Subnormality in the Community: A Clinical and Epidemiologic Study. Baltimore: Williams & Wilkins; 1970.
Strauss D, Eyman RK. Mortality of people with mental retardation in California with and without Down syndrome, 1986-1991. Am J Ment Retard. 1996 May. 100(6):643-53. [QxMD MEDLINE Link].
Patja K, Mölsä P, Iivanainen M. Cause-specific mortality of people with intellectual disability in a population-based, 35-year follow-up study. J Intellect Disabil Res. 2001 Feb. 45:30-40. [QxMD MEDLINE Link].
Rutter M, Graham P. Epidemiology of psychiatric disorder. Rutter M, Tizard J, Whitemore P. Education, Health and Behavior. London, England: Longman Group; 1970. 178-201.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision. Washington DC: American Psychiatric Association; 2000.
Shattuck PT. The contribution of diagnostic substitution to the growing administrative prevalence of autism in US special education. Pediatrics. 2006 Apr. 117(4):1028-37. [QxMD MEDLINE Link].
Kenneth Lyons Jones. Smith's Recognizable Patterns of Human Malformations. 6. Elsevier Saunders; 2006. 160-161.
Kaufmann WE, Abrams MT, Chen W. Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X syndrome. Am J Med Genet. 1999 Apr 2. 83(4):286-95. [QxMD MEDLINE Link].
Greenberg F, Lewis RA, Potocki L. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2). Am J Med Genet. 1996 Mar 29. 62(3):247-54. [QxMD MEDLINE Link].
Tassabehji M, Metcalfe K, Fergusson WD. LIM-kinase deleted in Williams syndrome [letter]. Nat Genet. 1996 Jul. 13(3):272-3. [QxMD MEDLINE Link].
Verhoeven WM, Tuinier S, Kuijpers HJ, Egger JI, Brunner HG. Psychiatric Profile in Rubinstein-Taybi Syndrome. A Review and Case Report. Psychopathology. 2009 Nov 20. 43(1):63-68. [QxMD MEDLINE Link].
Marques Pereira P, Schneider A, Pannetier S, Heron D, Hanauer A. Coffin-Lowry syndrome. Eur J Hum Genet. 2009 Nov 4. [QxMD MEDLINE Link].
Amir RE, Van den Veyver IB, Wan M. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpG-binding protein 2. Nat Genet. 1999 Oct. 23(2):185-8. [QxMD MEDLINE Link].
Axelrad ME, Schwartz DD, Fehlis JE, Hopkins E, Stabley DL, Sol-Church K, et al. Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome. Am J Med Genet A. 2009 Dec. 149A(12):2666-72. [QxMD MEDLINE Link]. [Full Text].
Gripp KW, Lin AE, Stabley DL. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am J Med Genet A. 2006 Jan 1. 140(1):1-7. [QxMD MEDLINE Link].
Autti-Ramo I, Fagerlund A, Ervalahti N. Fetal alcohol spectrum disorders in Finland: Clinical delineation of 77 older children and adolescents. Am J Med Genet A. 2006 Jan 15. 140(2):137-43. [QxMD MEDLINE Link].
Mann JR, McDermott S, Barnes TL, Hardin J, Bao H, Zhou L. Trichomoniasis in pregnancy and mental retardation in children. Ann Epidemiol. 2009 Dec. 19(12):891-9. [QxMD MEDLINE Link].
Moeschler JB, Shevell M,. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. 2006 Jun. 117(6):2304-16. [QxMD MEDLINE Link].
Mefford HC, Batshaw ML, Hoffman EP. Genomics, intellectual disability, and autism. N Engl J Med. 2012 Feb 23. 366(8):733-43. [QxMD MEDLINE Link].
Liang JS, Shimojima K, Yamamoto T. Application of array-based comparative genome hybridization in children with developmental delay or mental retardation. Pediatr Neonatol. 2008 Dec. 49(6):213-7. [QxMD MEDLINE Link].
Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JP, Burton H. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. 2009 Mar. 11(3):139-46. [QxMD MEDLINE Link].
Michelson DJ, Shevell MI, Sherr EH, Moeschler JB, Gropman AL, Ashwal S. Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2011 Oct 25. 77(17):1629-35. [QxMD MEDLINE Link].
Bazzano AT, Zeldin AS, Diab IR, Garro NM, Allevato NA, Lehrer D. The Healthy Lifestyle Change Program: a pilot of a community-based health promotion intervention for adults with developmental disabilities. Am J Prev Med. 2009 Dec. 37(6 Suppl 1):S201-8. [QxMD MEDLINE Link].
Kishnani PS, Sommer BR, Handen BL, Seltzer B, Capone GT, Spiridigliozzi GA, et al. The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am J Med Genet A. 2009 Aug. 149A(8):1641-54. [QxMD MEDLINE Link].
ACOG Committee Opinion. Number 371. July 2007. Sterilization of women, including those with mental disabilities. Obstet Gynecol. 2007 Jul. 110(1):217-20. [QxMD MEDLINE Link].
Bartlo P, Klein PJ. Physical activity benefits and needs in adults with intellectual disabilities: systematic review of the literature. Am J Intellect Dev Disabil. 2011 May. 116(3):220-32. [QxMD MEDLINE Link].
MASSACHUSETTS DEPARTMENT OF DEVELOPMENTAL SERVICES. Massachusetts Department of Developmental Services Annual Health Screening Recommendations. Available at http://www.mass.gov/Eeohhs2/docs/dmr/health_screening_checklist.pdf. Accessed: April 1, 2010.
Bull MJ. Health supervision for children with Down syndrome. Pediatrics. 2011 Aug. 128(2):393-406. [QxMD MEDLINE Link].
[Guideline] McCandless SE, Committee on Genetics. Clinical report—health supervision for children with Prader-Willi syndrome. Pediatrics. 2011 Jan. 127(1):195-204. [QxMD MEDLINE Link].
Ellis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R, et al. Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial. BMJ. 2008 Mar 15. 336(7644):594-7. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Moeschler JB, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. 2006 Jun. 117(6):2304-16. [QxMD MEDLINE Link]. [Full Text].
Ahn KJ, Jeong HK, Choi HS. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis. 2006 Jan 30. [QxMD MEDLINE Link].
American Psychiatric Association. APA DSM-5 Development: Proposed Revision: Mental Retardation. American Psychiatric Association DSM-5 Development. Available at http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=384. Accessed: March 20, 2010.
Capute AJ, Accardo PJ. Developmental Disabilities in Infancy and Childhood. Vol 1 and 2. Baltimore: Paul H Brookes. 1996: 1-619 and 1-521.
Developmental surveillance and screening of infants and young children. Pediatrics. 2001 Jul. 108(1):192-6. [QxMD MEDLINE Link].
Doheny KF, McDermid HE, Harum K. Cryptic terminal rearrangement of chromosome 22q13.32 detected by FISH in two unrelated patients. J Med Genet. 1997 Aug. 34(8):640-4. [QxMD MEDLINE Link].
Flint J, Wilkie AO, Buckle VJ. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995 Feb. 9(2):132-40. [QxMD MEDLINE Link].
Kirchhoff M, Gerdes T, Brunebjerg S. Investigation of patients with mental retardation and dysmorphic features using comparative genomic hybridization and subtelomeric multiplex ligation dependent probe amplification. Am J Med Genet A. 2005 Dec 15. 139(3):231-3. [QxMD MEDLINE Link].
Mao R, Wang X, Spitznagel EL. Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart. Genome Biol. 2005. 6(13):R107. [QxMD MEDLINE Link]. [Full Text].
Maulik PK, Mascarenhas MN, Mathers CD, Dua T, Saxena S. Prevalence of intellectual disability: a meta-analysis of population-based studies. Res Dev Disabil. 2011 Mar-Apr. 32(2):419-36. [QxMD MEDLINE Link].
Rubin IL, Crocker AC. Medical care for children and adults with developmental disabilities. Second edition. Baltimore, MD: Paul H Brookes Publishing Co, Inc; 2006.
Medina AE, Krahe TE, Ramoa AS. Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci. 2006 Jan 18. 26(3):1057-60. [QxMD MEDLINE Link].
Miyake N, Shimokawa O, Harada N. BAC array CGH reveals genomic aberrations in idiopathic mental retardation. Am J Med Genet A. 2006 Feb 1. 140(3):205-11. [QxMD MEDLINE Link].
Reiss S, Aman MG. Psychotropic Medications and Developmental Disabilities: The International Consensus Handbook. The Ohio State University Nisonger Center. 1998. 1-355.
Richardson SA, Koller H. Twenty-Two Years. Cambridge, MA: Harvard University Press. 1996. 1-328.
Schroeder S, Gerry M, Gertz G, Velasquez F. Final Project Report: Usage of the Term "Mental Retardation:" Language, Image and Public Education. June 2002.
Volkmar FR, Lewis M. Mental Retardation: Child and Adolescent Psychiatric Clinics of North America. Philadelphia: WB Saunders Company; 1996. 5: 769-993.