Developmental Disabilities and Pervasive Developmental disorders

1. Developmental Disabilities and Pervasive Developmental disorders Dr. Sophia Hrycko April 4, 2012

2. Objectives • To review Developmental Disabilities • To review Pervasive Developmental Disorders (will only review questions, as topic was covered earlier today) • To discuss comorbidity and treatment options

3. Case • A 12 y old girl is brought to the Emergency by 2 police officers because of suicidal ideation. She is in handcuffs. • She is screaming, bit her mouth, blood is smeared all over her T-shirt, face and hands. • You are paged urgently. • Think about what you want to ask, we will come back to this……

4. Developmental Disability • Often diagnosed in infancy • Mental retardation is the result of a pathological process in the brain characterized by limitations in intellectual and adaptive function. • Areas of function affected: communication, self-care, independence, functional/academic skills, work, health, leisure, safety (helpful when you try to take a history, as it can guide some of your questions)

5. DSM-IV-TR • Mental retardation requires intellectual deficits (IQ measured by standardized test) and deficit in adaptive function (use of measure with deficits in at least two areas of deficits, Vineland Adaptive Behavior Scale: communications, daily living skills, socialization and motor skills) • Manifested before age of 18

6. TABLE 21–3. Clinical features of mental retardation Source.Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Used with permission.

7. #1 • DSM-IV-TR lists the prevalence of mental retardation in the US as • A. 1% • B. 3% • C. 5% • D. 6% • E. None of the above

8. #1A • DSM-IV-TR lists the prevalence of mental retardation in the US as • A. 1% • B. 3% • C. 5% • D. 6% • E. None of the above

9. #2 • When IQ is used as the sole criterion for mental retardation, the prevalence rate is estimated to be: • A. 0.5% • B. 1% • C. 2% • D. 3% • E. 10%

10. #2A • When IQ is used as the sole criterion for mental retardation, the prevalence rate is estimated to be: • A. 0.5% • B. 1% • C. 2% • D. 3% • E. 10%

11. #3 • The DSM-IV-Tr criteria for mental retardation include ALL of the following essential features EXCEPT: • A. Subnormal intellectual functioning • B. Commensurate deficits in adaptive functioning • C. Onset before 18 years of age • D.IQ less than 75

12. #3A • The DSM-IV-Tr criteria for mental retardation include ALL of the following essential features EXCEPT: • A. Subnormal intellectual functioning • B. Commensurate deficits in adaptive functioning • C. Onset before 18 years of age • D.IQ less than 75 (less than 70)

13. Epidemiology • About 1% of the population. • 1.5 time more common in men • High mortality rates with severe or profound MR because of complications associated with physical disorders.

14. Etiology • Genetic • Down syndrome • Fragile X • Prader-Willi syndrome • PKU • Neurofibromatosis • Tuberous sclerosis • Developmental/Acquired • Environmental/social • (organic cause about 50%, pre/peri/post natal insult)

15. #4 • Moderate Mental retardation • A. Reflects an IQ range of 25 to 40 • B. Is seen in approximately 3 to 4% of persons with mental retardation • C. Has an identifiable organic etiology in the vast majority of cases • D. Usually is associated with the ability to achieve academic skills at the second to 3rd grade level • E. All of the above

16. #4A • Moderate Mental retardation • A. Reflects an IQ range of 25 to 40 • B. Is seen in approximately 3 to 4% of persons with mental retardation • C. Has an identifiable organic etiology in the vast majority of cases • D. Usually is associated with the ability to achieve academic skills at the second to 3rd grade level • E. All of the above

17. Acquired/developmental • Prenatal: rubella, CMV, Syphilis, Toxoplasmosis, Herpes, AIDS, fetal alcohol syndrome • Complications of pregnancy • Perinatal • Infection, head trauma, etc.

18. Environmental/Social • Toxic exposure: lead • Severe Psychosocial deprivation • Failure to thrive • Abuse • Neglect • Attachment disorder

19. A. Adrenoleukodystrophy B. Rett’s disorder C. Acquired immune deficiency syndrome AIDS D. Rubella E. Cytomegalic virus CMV F. Toxoplasmosis Mental retardation with periventricular intracerebral calcifications, jaundice, microcephaly and hepatosplenomegaly Progressive encephalopathy and MR in 50% of children born to mother with this disorder An X-linked MR syndrome that is degenerative and affects only females Diffulse demyelination of cerebral cortex leading to visual and intellectual impairment, seizures, and spasticity, and adrenocortical insufficiency MR, microcephay, microphthalmia, congenital heart disease, deafness, cataracts #5

20. A. Adrenoleukodystrophy B. Rett’s disorder C. Acquired immune deficiency syndrome AIDS D. Rubella E. Cytomegalic virus CMV F. Toxoplasmosis (MR, diffuse intracerebral calcifications, hydrocephalus, seizures and chorioretinitis Mental retardation with periventricular intracerebral calcifications, jaundice, microcephaly and hepatosplenomegaly E Progressive encephalopathy and MR in 50% of children born to mother with this disorder C An X-linked MR syndrome that is degenerative and affects only females B Diffulse demyelination of cerebral cortex leading to visual and intellectual impairment, seizures, and spasticity, and adrenocortical insufficiency A MR, microcephaly, microphthalmia, congenital heart disease, deafness, cataracts D #5A

21. Comorbidity • Up to 2/3 of individuals with MR have comorbid mental disorders. • The more severe the MR, the higher the risk for other mental disorders. • Disruptive and conduct-disorder behaviors are more frequent in Mild MR • Autistic disorder more common with severely retarded individuals.

22. #6 • Common manifestations of anxiety in persons with mental retardation include • A. Aggression • B. Agitation • C. Repetitive behaviors • D. Self-injury • E. All of the above

23. #6A • Common manifestations of anxiety in persons with mental retardation include • A. Aggression • B. Agitation • C. Repetitive behaviors • D. Self-injury • E. All of the above

24. Evaluation • Complete history and physical exam • Will need to evaluate Intellectual function (WISC or WPPSI) and Adaptive function (Vineland Adaptive Behavior Scale) • Sensory screening ( speech, hearing) • Laboratory studies: • Genetic testing, metabolic testing, thyroid/lead screening, imaging

25. Practice Parameters: Evaluation of child with Global Develop. Delay • Metabolic screening NOT indicated in initial evaluation (yield 1%) • Routine cytogenetic studies and molecular testing for FRA X mutation recommended (yield 3.5-10%) • Consider Rett syndrome in girls with unexplained moderate to severe delay • Serum lead when identifiable risk • EEG NOT recommended initially unless features of epilepsy • Imaging with MRI > CT if physical findings • Shevell et al Neurology 2003 60:367-380

26. Down Syndrome • Trisomy 21, 95% nondisjunction • 1 in 1000 live births • 1 in 80 at 40 yrs • Hypotonia, upward slanted palpebral fissures, midface depression, flat wide nasal bridge, simian crease, short stature, increased incidence of thyroid anomaly and congenital heart disease. • Passive, affable • 25% ADHD • Verbal processing > auditory processing • Increased risk of depression and dementia as adult

27. Fragile X • Mutation of the FMRI gene at Xq27.3. Full mutation: CGG trinucleotide repeat > 200 to 230 repeats • Prevalence 1/1000 male births and 1/3000 female birth • Second most known cause of MR of genetic origin (10-12% MR in men) • long face, large ears, midface hypoplasia, arched palate

28. Men and boys with fragile-X syndrome, showing classical facial features

29. Fragile X • Macroorchidism • Short stature, strabismus, joint laxity • ADHD, anxiety, speech/language delays, shyness, irritability, stereotypies. LD in some female • Male: moderate to severe MR • Female: mild MR

30. #7 • Fragile X syndrome • A. Has a phenotype that includes postpubertal microorchidism • B. Affects only males • C. Usually causes severe to profound MR • D. Has a phenotype that includes large head and large ears • E. All of the above

31. #7A • Fragile X syndrome • A. Has a phenotype that includes postpubertal microorchidism • B. Affects only males • C. Usually causes severe to profound MR • D. Has a phenotype that includes large head and large ears • E. All of the above

32. #8 • Which of the following disorders is least often associated with Fragile X syndrome: • A. Autistic disorder • B. Schizotypal personality disorder • C. Attention deficit/hyperactivity disorder • D. Bipolar disorder • E. Social anxiety disorder

33. #8A • Which of the following disorders is least often associated with Fragile X syndrome: • A. Autistic disorder • B. Schizotypal personality disorder • C. Attention deficit/hyperactivity disorder • D. Bipolar disorder • E. Social anxiety disorder

34. Praeder-Willi Syndrome • Deletion on long arm of chr. 15q11-15q13 (70% paternal, rest maternal uniparental disomy) • 1 in 15 000 birth • Hyperphagia • Obesity • Small hands/feet • Short stature • Microorchidism • Fair hair/light skin • Almond shaped eyes

35. Praeder-Willi Syndrome • Obsessions and compulsions • High rates of behavior problems: aggression, temper tantrums, emotional lability, daytime sleepiness • Increased risk for OCD, affective and impulse control disorders.

36. Phenylketonuria • Autosomal Recessive defect in phenylalanine hydroxylase 12q.24.1 or cofactor 11q22.3-q23.3 • Cause accumulation of phenylalanine if untreated and will result in MR (mild to profound), microcephaly, delayed speech, seizures and behavior problems (self-injury, hyperactivity) • Prevalence 1/12 000 • Fair skin, blue eyes, blond hair

37. Tuberous Sclerosis • Autosomal Dominant • Mutation in TSC1 gene (hamartin) 9q34 or the TSC2 tumor suppressor gene (tuberin) 16p13 • Prevalence 1/6 000 • Spectrum of MR, none (30%) to profound • Epilepsy, autism, hyperactivity, impulsivity, aggression, self-injurious behaviors, sleep problems

38. Tuberous Sclerosis Figure 589-2 Tuberous sclerosis. A, CT scan with subependymal calcifications characteristic of tuberous sclerosis. B, The MRI demonstrates multiple subependymal nodules in the same patient (black arrow). Parenchymal tubers are also visible on both the CT and the MRI scan as low-density areas in the brain parenchyma.

39. Neurofibromatosis type 1 • Autosomal dominant • 17q11.2 • Prevalence 1/3 000 • (NF2 1/33 000, 22q) • Café au lait spots • Neurofibromas • Short stature and macrocephaly in 30- 45% • 10% with moderate to profound MR • ADHD, anxiety, mood problems

40. #9 • True or False: Relative to the general population, people with MR are more likely to show autism, behavior disorders, substance abuse, and affective disorders.

41. #9A True or False: Relative to the general population, people with MR are more likely to show autism, behavior disorders, substance abuse, and affective disorders. MR: more likely to show psychosis, autism, behavior disorders and less likely to be diagnosed with substance abuse and affective disorder.

42. Fetal Alcohol Syndrome

43. Fetal Alcohol Syndrome • Most common preventable cause of MR • 1/3 000 live birth • Microcephaly, short stature, midface hypoplasia, short palpebral fissure • Thin upper lip, micrognatia, hypoplastic long/smooth philtrum • Mild to moderate MR, irritability, memory impairment, LD, behavior problems

44. A. Prader-Willi syndrome B. Down’s syndrome C. Fragile X syndrome D. Phenylketonuria Attributed to a deletion in chromosome 15 Most commonly occurs via autosomal recessive transmission Abnormalities involving chromosome 21 Occurs via a chromosomal mutation at Xq27.3 Example of a genomic imprinting #10

45. A. Prader-Willi syndrome B. Down’s syndrome C. Fragile X syndrome D. Phenylketonuria Attributed to a deletion in chromosome 15 A Most commonly occurs via autosomal recessive transmission D Abnormalities involving chromosome 21 B Occurs via a chromosomal mutation at Xq27.3 C Example of a genomic imprinting A #10A

46. #11 • Which of the following features does not distinguish autistic disorder from mixed receptive-expressive language disorder? • A. Echolalia • B. Stereotypies • C. Imaginative play • D. Associated deafness • E. Family history of speech delay

47. #11A • Which of the following features does not distinguish autistic disorder from mixed receptive-expressive language disorder? • A. Echolalia • B. Stereotypies • C. Imaginative play • D. Associated deafness • E. Family history of speech delay (25% for both autistic and language disorders)

48. Autistic Disorder Associated Features • IQ below 70 for 75% of autistics • Uneven cognitive skills • Level of receptive language below expressive language • Behavioral symptoms: hyperactivity, impulsivity, aggressiveness, self-injurious behavior (head banging, finger/hand/wrist biting), temper tantrums • Abnormal mood (giggling or weeping) • Lack of fear

49. Evaluation ( PDD and MR) • History • Pregnancy, neonatal and developmental hx, medical hx, family and psychosocial factors, intervention hx. • Psychiatric examination of the child • Medical evaluation • Physical exam, including neurological exam • Audiological/visual exam • Psychological evaluation • Speech/language/communication assessment • OT evaluation

50. Differential Diagnosis - PDD • Various PDDs • MR not associated with PDD • Specific developmental disorder, e.g. language • Early onset psychosis