Intellectual disability / Mental retardation

Intellectual disorder was previously known as Mental retardation

1. INTELLECTUAL DISABILITY Presenter: Dr . Keerthana Moderator: Dr. Hrishikesh Sir

2. Overview I ntroduction Definition Types Etiology Clinical Features Psychiatric Comorbidities Medical Comorbidities Diagnosis Prevention Differential Diagnosis Treatment Course & Prognosis Certification Benefits Schemes

3. INTRODUCTION Intellectual disability is a developmental disorder with heterogeneous set of impairments and conditions that result in cognitive limitation. Significant limitations Intellectual Functioning Adaptive behaviors I n I ndia, the rights of persons with disabilities act (2016) - introduced the term “intellectual disability” in the place of “mental retardation.”

4. However in signatory to WHO , where the ICD -10 guidelines are adopted in the clinical practice, the term “mental retardation” is still in clinical use. The WHO working group on the classification of intellectual disabilities has recommended replacing the term “mental retardation” with “ IDD ” in ICD -11 Thus, both the terms , intellectual disability and mental retardation, are in use in I ndia. Mental Retardation IDD

5. Definition : According to Who - icd 10, Intellectual disability is a condition of arrested or incomplete development of mind , which is especially characterized by impairment of skills manifested during the developmental period , which contribute to overall intelligence, i.e. cognitive, language, motor and social abilities. The WHO - I nternational Classification of Functioning, Disability, and Health ( ICF ) is the newest schema for classifying disability--an individual’s disability may be characterized by marked and severe problems in Capacity to function (‘impairments in body functions and structures’) Ability to function (‘activity limitations’) Opportunity to function (‘participation restrictions’)

6. DSM -5 – ID in the broader category of neurodevelopmental disorders. DSM-5 defines intellectual disability as involving ‘impairments of general mental abilities that impact adaptive functioning in three domains. These domains determines coping with everyday life and include Communication and social skills Personal independence School/work functioning

7. The National Sample Survey Organisation (NSSO) under the Department of Statistics, Government of India(2019) Prevalence rate of mental retardation - 20 per 1000 Prevalence of developmental delays - 30 per 1000 Incidence of mental retardation – Rural(3.1%) Urban(0.9%) The NIMH mentions that 2% of the general population is MR . Three quarters - mild retardation One-fourth - severe retardation.

8. Classification Subdivided by severity levels according to adaptive functioning and placing some weight on standardized IQ testing into (based on ICD-10 ) Mild ( I Q 50–70) Moderate ( I Q 35–49) Severe ( I Q 20– 34) Profound ( I Q below 20)

9. ETIOLOGY Periconceptional Factors Intrauterine Factors Perinatal and Postnatal Factors

10. PERICONCEPTIONAL FACTORS Genetic-chromosomal – Down syndrome Telomeric rearrangements Sex linked-single gene – Fragile X syndrome Rett syndrome Autosomal dominant – Phenylketonuria Neurofibromatosis Tay sacks Metabolic - Hypothyroidism Segmental autosomal syndromes - Prader–Willi syndrome Angelman syndrome Genetic and nutritional - Neural tube defects

11. Down syndrome : Most common genetic and leading cause of ID. Cognitive impairment - majority in the moderate to profound range of ID. Infant stimulation programs suggest that the cognitive intellectual potential have been underestimated .

12. Diagnosis of Alzheimer’s disease - high risk for the development by the time they reach 40 years of age Dementia – At end of their 7 th decade of life. Important determinants of risk : Factors modifying the rate and degree of Aβ deposition > overexpression of APP.

13. Telomeric Rearrangements : Induced by a variety of exposures (workplace and environmental) including Ionizing radiation Viral infections Toxic substances Associated with birth defects and neurodevelopmental delay in the infant. Cause more than 30% of severe ID , with majority of DS(as risk of cytogenic abnormalities)

14. sex linked single gene DISORDERS : Fragile X syndrome A non syndrome- common form of inherited ID (transcription factor FMR2) Primarily affects males - 0.5 to 4.2% of patients have ID Cognitive and learning disabilities are prominent Behavioural abnormalities – Autistic-like features Repetitive speech patterns Social anxiety Perseveration Gaze aversion Neuroimaging - Small posterior cerebellar vermis enlarged Hippocampus, Caudate nucleus, Thalamus, Latera ventricles Correlation for low IQ

15. Segmental autosomal syndromes Early onset cognitive disability are within this class: Williams Prader–Willi Angelman Williams Syndrome : 1/10,000 live births Developmental and language delays Pixie-like facial features Problems in gross motor skills Mild MR with relatively good face-processing skills.

16. Prader Willi syndrome : Paternally inherited abnormality 1/15,000 live births. Developmental delay Hypotonia Feeding problems in infancy - severe obesity Mild MR Behavioral characteristics – Temper tantrums Ritualistic or obsessive-compulsive behavior Upturned nose Smooth philtrum

17. Angelman Syndrome Maternally inherited abnormality Characterized by – Severe MR Microcephaly, hypopigmented skin & eyes Hyper motoric behaviour : Hand-flapping Jerky movements with outbursts of laughter Short attention span Seizures with onset under 3 years of age Puffiness around eyes Blue eyes Epicanthal fold Long upper lip length Small and widely spaced teeth Wide mouth (ear to ear smile) Prominent lower lip Small chin

18. Combinations of genetic and nutritional factors Neural tube defects (NTD) – Spina bifida Anencephaly Meningomyelocele Majority of cases - nutritional deficit of folate Small proportion - genetic problem NTD is attributable to only a small proportion of ID Failure of neural tube closure during the third to eighth week of gestation

19. Phenylketonuria (PKU) deficiency : Rare defect - 1 per 15,000 Sequelae of MR can be prevented - adherence to a strict diet during infancy and early childhood. Severe ID and microcephaly - 75–90% of children of mothers with Classic PKU Less severe cognitive deficit - children of mothers with Atypical PKU Dietary restrictions during pregnancy Reduce maternal blood phenylalanine levels Prevent phenylalanine metabolite accumulation Improve the outcome in offspring if the diet is started prior to conception and maintained throughout pregnancy

20. Hypothyroidism : Hypothyroidism during pregnancy- Leading cause of id in offspring A genetic form of hypothyroidism (when untreated - cretinism ) Cretinism – ID Neurodevelopmental deficits in the newborn after 3 months of age Other sensory and motor impairments

21. INTRAUTERINE FACTORS Infection – Toxoplasmosis Rubella Cytomegalovirus Herpes Gonorrhea Group B streptococcus Chlamydia Trichomonas vaginalis Bacterial vaginosis, Herpes simplex virus, HIV Metals and chemicals - Lead, mercury Nutritional - Iodine

22. Intrauterine infections : The impact depends on the time of exposure during gestation. Cytomegalovirus : Approximately 10% of infants with asymptomatic infections at birth develop serious sequelae Optic atrophy Learning disabilities MR The mortality rate - 30% More than 90% of survivors have neurological impairments – Microcephaly Seizures MR Hearing and vision problems.

23. Toxoplasma : The outcomes associated with untreated prenatal exposure - Microcephaly, Hydrocephalus Cerebral palsy , Epilepsy ID Urinary tract infections : There is relative risk for ID or developmental delay among children of mothers with urinary tract infection. AIDS : Perinatally acquired HIV infection and pediatric AIDS - cause of ID The neurodevelopmental effects of pediatric AIDS – Microcephaly Delays in cognitive and motor development

24. Substances : Teratogenic and neurotoxic to human embryo and fetal development and possible links to ID Antimicrobials (e.g., sulphonamides, isoniazid, ribavirin) Anticonvulsants (e.g., phenytoin, carbamazepine) Psychotropic drugs Warfarin Aminopterin

25. PERINATAL AND POSTNATAL FACTORS Birth complications and effects – Prematurity Low birth weight Asphyxia Childhood Infections Environmental exposures – Lead Mercury Injury - Traumatic brain injuries from vehicle crashes Child abuse and neglect Deprivation - Insufficient stimulation

26. Prematurity and low birth weight: The risk is higher in very low birth weight and will usually manifest as severe ID Premature birth is associated with increased risk of ID at the age of 10 Fetal stroke : Identifiable pregnancy event like Ischemic injury Hemorrhagic disturbances of coagulation Fetal disorders - pyruvate carboxylase deficiency can result in ID Birth trauma and asphyxia : Reduces the formation of brain pathways – mainly adaptive behaviour – cognitive deficits and usually mild retardation

27. Post natal infections Most significant infectious causes of ID Meningitis Encephalitis Varicella Injuries Severe, traumatic brain injury (with loss of consciousness for> 24 h) during childhood - long-term cognitive deficits, ID Deprivation includes : Children living in extreme poverty Disordered parenting because of mental illness of a parent Children faced with family stress, crisis, or neglect for any reason

28. Environmental chemicals Toluene Nitrous oxide Carbon monoxide Organochlorines Organophosphates Methanol Perchloroethylene Carbon disulphide Lead Mercury Arsenic Manganese Aluminium Carbon tetrachloride Methylene chloride Ethylene glycol Associated with some neurobehavioural dysfunctions

29. CLINICAL FEATURES

30. AGE degree OF INTELLECTUAL DISABILITY Mild moderate severe profound Preschool Age (0 to 5 yrs) Maturation and Development Develop social & communication skills Minimal retardation in sensorimotor area May not be diagnosed until school challenges child's social and communication skills. Learn to communicate slowly Poor social awareness Fair motor development Profits from training in self-help Can be managed with moderate Supervision. Typically obvious in the preschool years Poor motor development Speech minimal Unable to profit from training in self-help Little or no communication skills Gross disability Minimal capacity for functioning in sensorimotor areas Needs nursing care

31. AGE TYPE OF INTELLECTUAL DISABILITY Mild moderate severe profound School Age (6 to 20 yrs) Training and Education Cognitive deficits like Poor ability to abstract, Egocentric thinking Can learn academic skills up to approximately sixth-grade level Can be guided toward social conformity Social isolation Aware of their deficits and feel alienated from peers Profit from training in social and occupational skills Unlikely to Progress beyond second-grade level May learn to travel alone in familiar places Some language development may occur Learn to communicate Can be trained in elemental health habits Profits from systematic habit training but not from vocational training Some motor development present Respond to limited training in self-help .

32. AGE TYPE OF INTELLECTUAL DISABILITY Mild Moderate severe profound Adult (21 yrs and Above) Social and Vocational Adequacy Achieve social and vocational skills Poor self-esteem and Dependence leads to lack of social spontaneity Can live independently in ordinary surroundings Need help in Parenting, Coping with family responsibilities, housing, unusual stress, employment Achieve self-maintenance in unskilled or semiskilled work Dressing, feeding, and attention to hygiene can be acquired Require support in Use of money, Road sense Supported employment and residential provision Contribute partially to self maintenance under complete supervision Develop self protection skills to a useful level Look after themselves under close supervision Communicate in a simple way—by using objects of reference. Simple tasks and engage in limited social activities Some speech development present Simple self-help skills may be acquired. Require constant support and supervision, even for simple activities of daily living

33. 3–5 times at higher risk compared to the general population C umulative prevalence - 40%. Adults – 16 to 45%. Children – 50% Relation Shared genetic factors Medical adversities that affect the brain (e.g. epilepsy, cerebral palsy) Environments of increased family psychosocial adversity Intellectual disability itself might impact PSYCHIATRIC COMORBIDITIES

34. W ritten off as spectrum manifestations of ID - mostly underreported, misdiagnosed, and undertreated . Therefore, special efforts are required to identify behavioural and psychiatric disorders. Disorders with higher rates in individuals with intellectual disability include Schizophrenia Bipolar disorder Dementia ASD & ADHD. Behavioural problems are particularly common, especially hyperactivity, stereotypies, and self-injury

35. Psychotic disorders : 3–4% of people with intellectual disability, compared with less than 1% in the general population. Delusions - less elaborate Hallucinations - simpler content Thought disorder - difficult to identify. Diagnosis made when intellectual functioning worsens without organic cause If in doubt, a trial of antipsychotic drugs is sometimes appropriate. Treatment is same - Often lower doses needed and titration should be slower. Stereotyped movements and social withdrawal, may wrongly suggest schizophrenia, so a comparison with previous behavior is always valuable.

36. Mood disorders : Prevalence is slightly higher than that of the general population. Less likely to complain, hence diagnosis is based on: Appearance of sadness, changes in appetite and sleep(depression) Behavioural signs of excitement, irritability, or hyperactivity(mania) Patients with adequate verbal abilities may describe hallucinations or delusions. Commonly in association with Down’s syndrome Differential – Thyroid dysfunction, especially prevalent in people with Down’s syndrome. The rate of suicide is lower. The rate of deliberate self-harm is less certain, because it is difficult to decide patients’ intentions

37. Anxiety disorders and related conditions : Anxiety disorders - especially at times of stress, and social anxiety is often seen in individuals with fragile X syndrome. Adjustment disorders – common in intellectual disability Obsessive–compulsive disorders are also found. Conversion and dissociative symptoms - florid, taking forms that can be interpreted in terms of the patient’s understanding of illness. Treatment - adjustments in the patient’s environment, and reassurance.

38. Eating disorders : Overeating and unusual dietary preferences are frequent in intellectual disability. Abnormal eating behaviors, including PICA are common Classical eating disorders - less common than in the general population. Personality disorder : Difficult to diagnose among people with intellectual disability. Sometimes the personality disorder leads to greater problems in management than those caused by the intellectual disability itself. Environment to match the patient’s temperament, and less on attempts to bring about change through self-understanding.

39. Delirium : Occur as a response to infection, medication, and other precipitating factors. More common in childhood and in old age than at other ages. Disturbed behavior is sometimes the first indication of physical illness. Dementia : Prevalence of 18.3% > 65 years, making it 2–3 times more common May initially present with seizures, progressive decline in intellectual & social functioning

40. Autism spectrum disorder and attention deficit hyperactivity disorder : Hyperactive behavior and autistic-like behavior are frequent symptoms of intellectual disability More common than general population Reflects an overlap with regard to genetic factors Abnormal movements : Stereotypes Mannerisms Rhythmic movement disorders (including head banging and rocking) Sleep disorders : Impaired sleep is common with prevalence - 9% to 34% Associated with challenging behaviors and worsening of cognitive impairment. Interventions such as improving sleep hygiene, melatonin if indicated 40% of children and 20% of adults with severe intellectual disability

41. Behavior that challenges : Problematic behavior that is relatively specific to intellectual disability Behavior sufficient to impair the physical safety of a person with intellectual disability, to pose a danger to others, or to make participation in the community difficult . 20% - children and adolescents, and 15% - adults have some form of ‘behavior that challenges’ More likely to be encountered in Small-scale community settings Environments that are poorly organized When unable to respond well to the needs of the person

42. Causes of behaviour that challenges : Physical:  Pain Discomfort Malaise Neuropsychiatric causes Mood disorders Psychosis Anxiety ADHD Dementia Psychological trauma: Reaction to abuse or loss Wish to escape an unpleasant situation

43. Communication difficulties: Hearing loss Unclear communication Insufficient vocabulary Phenotype-related behaviours:  Prader–Willi syndrome – skin picking and OCD Lesch–Nyhan syndrome – self injurious behaviour, Fragile X syndrome – autistic and hyperactive behaviour Smith–Magenis syndrome – self hugging stereotypy, trichotillomania Under stimulation or overstimulation Desire for attention or other reward Side effects of medication

44. Assessment might require Underlying medical and organic factors Psychological/ psychiatric factors Communication, and social/environmental factors. Intervention must address the person, environment, and the interaction between the two as they might be expressing unhappiness in their current environment. Intervention includes : Proactive and reactive strategies Psychotherapy Communication Positive programming

45. MEDICAL COMORBIDITIES Various medical comorbidities are often associated with ID Some are a consequence of ID itself S ignificant barriers for training and developmental learning Few of the common medical comorbidities are the following: Epilepsy Spasticity Dystonia Ataxia Visual & hearing impairment C ongenital heart disease Short stature C left lip and cleft palate C ongenital talipes equinovarus C ongenital dislocation of hip joint R enal malformations Vitamin and mineral deficiencies Feeding disorder

46. The diagnostic process involves: H istory taking Medical examination Intellectual and adaptive behavioral assessment Identification of comorbid psychiatric disorders Laboratory investigations. DIAGNOSIS

47. History taking : C hief complaints in chronological order with mode of onset, duration, and precipitating event H istory of presenting illness D etails of potential stressors, coping, and adaptation by the family Detailed prenatal and perinatal history Medical comorbidities and its treatments Psychiatric history - D etails of onset, evolution, treatment history and current status of behavioral or psychopathological disturbances F amily history: Consanguinity; family history of intellectual disability, hereditary disorders Developmental history in greater detail: M otor, language, and communication Self-help skills Socioemotional skills Cognition Occupational skills/leisure-time activities

48. Physical examination : Routine systemic examination A nthropometric assessment O bservation of atypical morphological features Detailed physical examination helps to identify the etiology in a majority of cases, detect comorbid medical conditions, and also order appropriate investigations

49. Behavioral observation : Observation of general appearance O ddities in behavior A ttention span R eceptive and expressive speech abilities S ocial and interpersonal abilities Socioculturally appropriate stimuli could be presented to understand: L evel of general fund of knowledge G eneric concepts A bstract thinking R easoning Problem-solving abilities G eneral mental status examination for children to complement the behavioral observation

50. TEST AGE CONTENT Seguin form board Reliable for 3-11 yrs Valid for all age groups Eye hand coordination, Shape concept, Visual perception, Cognitive ability Stanford-Binet Intelligence Scale 3 yrs – adulthood Knowledge, Quantitative reasoning, Visual-spatial processing, Working memory, fluid reasoning Malin’s Intelligence Scale 6 – 16 yrs Information,Comprehension,Arithmetic,Similarities,Vocabulary,Picture completion, Performance IQ,.Full scale IQ Developmental Screening Test 0 – 15 yrs Developmental delay, Behavioural problems Vineland Social Maturity Scale 0 – 15 yrs Adaptive behavioural skills Progressive matrices Standard 11 yrs – adults Abstract reasoning, Fluid intelligence b. Colored Gessel’s Drawing Test 15 months – 11 yrs Motor and language development, personal-social-adaptive behaviour Bhatia’s Battery of Performance Test of Intelligence 11 yrs and above Attention level, Adaptive behaviour Wechsler Intelligence Scale for Children and Adults 6 – 16 yrs and 11 months Sustained effort, Attention and Concentration Intellectual Assessment Below standardized instruments evaluate cognitive abilities across multiple domains including verbal, performance, memory, and problem solving .

51. Neurological Examination I ncidence and severity is direct proportion to the degree of intellectual disability. Sensory impairments occur frequently among persons with intellectual disabilities. Disturbances in motor areas are abnormalities of Muscle tone(spasticity or hypotonia) Reflexes (hyperreflexia) Involuntary movements(choreoathetosis)

52. Laboratory examination

53. Hearing and Speech Evaluations Hearing and speech should be evaluated routinely as hearing impairments can simulate intellectual disability The commonly used methods of hearing and speech evaluation, however, require the patient's cooperation Thus are often unreliable in severely disabled persons. DIFFERENTIAL DIAGNOSIS Neglect or abuse of child may contributing to delays in development Sensory disabilities, especially deafness can be mistaken Expressive and receptive speech Cerebral palsy Chronic, debilitating medical diseases Seizure disorders Alexia, Agraphia, Aphasia Learning disorders Autism spectrum disorder (ASD) Dementia Cognitive impairment

54. PREVENTION Primary Prevention : Actions taken to eliminate or reduce the conditions that lead to development of intellectual disability Screening babies for PKU Amniocentesis – 15 week of gestation Chorionic villi sampling – 8 week of gestation A non-invasive blood test - materniT21 is a proprietary prenatal test that detects abnormalities of chromosomes 21,18,13, X and Y. It is highly specific for Down syndrome Education about strategies to prevent intellectual disability, such as Abstinence from alcohol during pregnancy Optimal maternal and child health care Family and genetic counseling Secondary and Tertiary Prevention : Prompt attention to medical and psychiatric complications of intellectual disability can diminish their course (secondary prevention) Minimize the sequelae or consequent disabilities (tertiary prevention).

55. Educational Interventions : A comprehensive program that addresses academics and training in Adaptive skills Social skills Vocational skills Particular attention should focus on communication and efforts to improve the quality of life Behavioral and Cognitive-Behavioral Interventions : Behavior therapy - Minimize aggressive and destructive behaviors. Positive reinforcement - desired behaviors Benign punishment -objectionable behaviors Cognitive therapy- dispelling false beliefs, relaxation exercises with self-instruction Psychodynamic therapy - To decrease conflicts about expectations that result in persistent anxiety, rage, and depression. NON PHARMACOLOGICAL MANAGEMENT

56. Family Education Educating about ways to enhance competence and self-esteem while maintaining realistic expectations for the patient. Should be allowed opportunities to express their feelings Psychiatrist should give the parents all the basic and current medical information regarding causes, treatment, and other pertinent areas Social Intervention Improving the quantity and quality of social competence is a critical part of their care. Special Olympics International is the largest recreational sports program geared for this population. A recent study confirmed positive effects of the Special Olympics on the social competence

57. PHARMACOLOGICAL MANAGEMENT Aggression, Irritability, and Self-injurious Behavior, Psychosis Explosive rages Risperidone Propranolol Attention-Deficit/Hyperactivity Disorder Methylphenidate Risperidone Amphetamine based preparations Clonidine Atomoxetine Depressive Disorders Fluoxetine Paroxetine Sertraline Stereotypical Motor Movements Haloperidol Chlorpromazine Obsessive-compulsive Disorder Fluoxetine Fluvoxamine Paroxetine Sertraline

58. COURSE AND PROGNOSIS : Although the underlying intellectual impairment does not improve, in most cases of intellectual disability, level of adaptation increases with age Can be influenced positively by an enriched and supportive environment Persons with mild and moderate mental intellectual disabilities have the most flexibility in adapting to various environmental conditions Comorbid psychiatric disorders negatively impact overall prognosis and increased vulnerability to side effects of psychopharmacologic agents are often the case

59. CERTIFICATION : According to Rights of Persons with Disabilities Act 2016,assessment is done through 3 stages Screening Diagnosis D isability calculation The minimum age for certification - one completed year. 1-5yrs - certificate with a diagnosis of GDD . 5yrs - certificate as ID . The authority shall comprise the following: (a) the medical superintendent or chief medical officer or civil surgeon or any other equivalent authority as notified by the state government; (b) pediatrician or pediatric neurologist (where available)/psychiatrist or physician (if age >18 years); (c) clinical or rehabilitation psychologist; and (d) psychiatrist. Temporary certificate - <5 years,valid for a maximum of 3 or 5 years of age, whichever is earlier. As per the act, the certificate will have to be renewed at the age of 5, 10, and 18 years. The certificate issued at 18 years of age will be valid lifelong.

60. Maintenance Allowance of Rs.1,500/- per month with a disability percentage of 45% and above are eligible for this benefit. Special schools provide 4 sets of uniform for free of cost. Shelter home for the adult mentally challenged(14 yrs ): Non Governmental Organisations are identified and given grants to run homes. The State Resource Cum Training Centre- Disability certificate Railway Concession Concessions for Government Examinations Concession of 75% for bus travel with escort etc are issued Early Intervention Centres have been established at this centre – nutritious meal,68 centres are benefitted under this scheme 0-5 years are admitted in these centres -Various training programmes organized Education Tour to Govt Special School Students – 300 per person Therapeutical Services - Chennai, Tiruvallur and Kanchipuram Districts BENEFITS :

61. DISHA Early Intervention and School Readiness Scheme ( upto 10 yrs ) GHARAUNDA H ousing and care services throughout the life VIKAAS - Day Care > 10 years for enhancing interpersonal and vocational skills SAMARTH - Respite Care Abandoned PwDs , Families in crisis-Family respite time GYAN PRABHA T o encourage people for pursuing educational/ vocational courses SCHEMES NIRAMAYA P rovide affordable Health Insurance to persons PRERNA A marketing scheme to create viable & wide spread channels for sale of products and services produced SAMBHAV   To setup additional resource centres in each city, to collect the Aids, software and other form of assistive devices

62. REFERENCES - Kaplan HI, Sadock BJ. Comprehensive textbook of psychiatry, Vols. 1-2. Williams & Wilkins Co; 1989. McDermott, S., Durkin, M. S., Schupf , N., & Stein, Z. A. (n.d.). Epidemiology and Etiology of Mental Retardation. Handbook of Intellectual and Developmental Disabilities, 3–40. Kishore M T, Udipi GA, Seshadri SP. Clinical practice guidelines for assessment and management of intellectual disability. Indian J Psychiatry 2019;61, Suppl S2:194-210 Salvador- Carulla L, Reed GM, Vaez -Azizi LM, et al. Intellectual developmental disorders: towards a new name, definition and framework for "mental retardation/intellectual disability" in ICD-11.  World Psychiatry . 2011;10(3):175-180. Gilissen C, Hehir-Kwa JY, Thung DT, van de Vorst M, van Bon BW, Willemsen MH,  et al.  Genome sequencing identifies major causes of severe intellectual disability. Nature 2014;511:344-7 Girimaji SC. Clinical practice guidelines for the diagnosis and management of children with mental retardation. Indian Psychiatric Society Clinical Practice Guidelines, 2008;43-67 Handen BL, Gilchrist R. Practitioner review: Psychopharmacology in children and adolescents with mental retardation. J Child Psychol Psychiatry 2006;47:871-82. Kishore MT, Nizamie SH, Nizamie A. The behavioural profile of psychiatric disorders in persons with intellectual disability. J Intellect Disabil Res 2005; 49; 852-7 Michelson DJ, Shevell MI, Sherr EH, Moeschler JB, Gropman AL, Ashwal S,  et al.  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;77:1629-35.   Moeschler JB. Medical genetics diagnostic evaluation of the child with global developmental delay or intellectual disability. Curr Opin Neurol 2008

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