Transcript Developmental Disabilities and Pervasive Developmental disorders

Developmental Disabilities and
Pervasive Developmental
disorders
Dr. Sophia Hrycko
April 22, 2008
Objectives
• To review Developmental Disabilities
• To review Pervasive Developmental
Disorders
• To discuss comorbidity and treatment
options
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, selfcare, independence, functional/academic skills,
work, health, leisure, safety
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
Mild Mental Retardation
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IQ between 50 and 70
85% of persons with MR
Often not identified before gr 1 or 2
Can learn academic skills up to about gr 6 by late
teens.
• Can achieve social and vocational skills with
minimal self-support but may require assistance
when under stress (social, financial)
• “Educable”
Moderate Mental Retardation
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IQ 35-40 to 50- 55
10 % of persons with MR
Can talk or learn to communicate
Unlikely to progress beyond gr2
May learn to travel alone to familiar places
May function under sheltered conditions in
unskilled or semiskilled work.
• “Trainable”
Severe Mental Retardation
• IQ 20-25 to 35-40
• 4 % of persons with MR
• Minimal speech, unable to profit from
training in self-help (age 0 to 5)
• Can learn to communicate or talk, be
trained in elemental health habits.
• Will require complete supervision.
Profound Mental Retardation
• IQ below 20 or 25
• 1 to 2% of persons with MR
• Most have an identifiable cause for their
condition.
• May be taught some self-care skills.
• Will need nursing care.
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.
Etiology
• Prenatal
– Genetic disorders
– Congenital malformations/infections
– Exposure: rubella, CMV, Syphilis, Toxoplasmosis,
Herpes, AIDS, FAS
– Maternal diseases: DM
• Perinatal causes
– Infections, delivery complications, trauma
– Complications of prematurity: ischemia, hypoxia, intra
cerebral hemorrhage
• Postnatal causes
– Environmental/Social (deprivation, malnutrition)
– Infections, toxins, trauma, inborn errors of metabolism
Genetic
• Genetic disorders account for 55% cases of moderate to
severe MR, 10-15% of cases of mild MR
• Mutation of single genes: Fra X and Rett syndrome with
absence of single protein FMRP and MECP2
• Microdeletion syndromes: result from the deletion of
multiple genes: Smith-Magenis syndrome, addition or
absence of entire chromosomes such as Down syndrome,
X and Y chromosome aneuploidies (47 XXY/Klinefelter
syndrome, 45,X/Turner syndrome) leading to
overexpression or imbalance of many genes and
subsequent neurodevelopmental abnormalies.
• About 25% more males have MR than females (males are
uniquely vulnerable to genetic mutations on the X
chromosome, they have only 1)
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.
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
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
Down Syndrome
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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
Down syndrome. Note
depressed nasal bridge,
epicanthal folds, mongoloid
slant of eyes, low-set ears,
and large tongue.
Down Syndrome
• A boy with Down
syndrome at age A. 2
• B. age 5
• C. age 11
• D. age 14
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
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
Fra X
• Carriers may show enhancement of verbal
comprehension skills, combined with drive for
learning can make them exceptional students.
• 45% of carrier males have advanced degrees (MS,
MD, PhD)
• Older carriers (M and F) have problems with
tremor and ataxia associated with cognitive
decline: Fragile X-associated tremor/ataxia
syndrome (seen in 40% of M with premutation)
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
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.
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
Turner Syndrome
• XO
• Incidence: 1/2500 live births
• Patient with Turner’s syndrome
exhibiting short stature, low-set
ears, webbed neck, shield chest,
and widely spaced, hypoplastic
nipples.
• Cubitus valgus,cardiac defects,
gonadal dysgenesis
• Mild developmental disability
is common
• 25% ADHD
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
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.
Neurofibromatosis type 1
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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
Velocardiofacial Syndrome
• 22q11.2 deletion syndrome
• Prevalence 1/ 5900-1/9700
live birth
• CATCH 22: Cardiac
Anomaly, T-cell deficits,
Clefting and Hypocalcemia
• LD, pharyngeal hypotonia,
slender hands/digits
• 25% develop schizophrenia
• ADHD 35-46%
• anxiety
Fetal Alcohol Syndrome
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
Mental disorders in Persons with
MR
• Increased risk (2 to 5)
• ADHD, 9 to 18%
• Impulse control disorders
– Self-injury
– Aggression
• Anxiety Disorders
• Psychosis NOS
• Mood Disorders
Treatment
• Multidisciplinary
• Multimodal
• Prioritize target symptoms and co-morbid
medical conditions
• Monitor multiple domains of functioning
• Pharmacological interventions target
specific symptoms
• Family Support Programs: financial, respite
Pervasive Developmental
disorders
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Autistic Disorder
Rett’s Disorder
Childhood Disintegrative Disorder
Asperger’s Disorder
Pervasive Developmental disorder NOS
Autistic Disorder
• Diagnostic Features
– 3 main sets of behavioral characteristics:’
- Social abnormality
- Language abnormality
- Stereotyped repetitive pattern of behavior
• Age of onset: prior to age 3
• Male/Female = 4/1
• Prevalence: 9.5 / 10 000 (range 2.3 to 30.8/
10 000)
Autistic Disorder
• Course: variable, strongest predictive
factors for adult outcome are IQ (below 70
is strongly indicative of poor social
adjustment) and the level of language
functioning at age 5
• Etiology: unknown, evidence of strong
genetic component; abnormal serotonergic
activity, hyperdopaminergic activity
Diagnostic Criteria
• Qualitative impairment in Social Interaction
• Impairment in the use of multiple nonverbal
behaviors: eye to eye gaze, facial expression, body
postures and gestures to regulate social interaction
• Failure to develop peer relationships appropriate to
developmental level
• Lack of spontaneous seeking to share enjoyment,
interests or achievements with other people (not
showing, bringing or pointing out objects of
interests)
• Absence of social or emotional reciprocity
Cont.
• Qualitative impairment in Communication
– Delay in or total lack of, development of spoken
language (no attempt to compensate with
gestures or mime)
– If speech present, marked impairment in the
ability to initial or sustain conversation with
others
– Stereotyped and repetitive use of language or
idiosyncratic language
– Lack of varied, spontaneous make-believe play
or social imitative play appropriate to develop.
level
Cont.
• Restricted repetitive and stereotyped
patterns of behavior, interest and activities
– Encompassing preoccupation with one or more
stereotyped and restricted patterns of interest
that is abnormal either in intensity or in focus
– Inflexible adherence to specific, nonfunctional
routines or rituals
– Stereotyped and repetitive motor mannerisms:
hand or finger flapping or twisting, complex
whole-body movements
– Persistent preoccupation with parts of objects
Consider Evaluation if by:
• 12 months: No babbling or gesturing
(pointing, waving bye-bye)
• 16 months: No single words
• 24 months: No spontaneous 2 word phrases
(i.e. not just echolalia or repeating someone
else’s words)
• Any age: any loss of any language or social
skills
Consider Evaluation if
• Especially when combined with language
delays:
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Abnormal eye contact
Aloofness
Not responding to one’s name
Not using gestures to point or show
Lack of interactive play
Lack of interest in other children
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
Autistic Disorder Associated
Findings
• Abnormal Imaging Studies: underactivation of
fusiform gyrus, abnormality in the medial
temporal lobe, increase in brain size in some
• EEG abnormalities: varied, non-specific
• Non-specific neurological symptoms: primitive
reflexes, delayed hand dominance
• Medical conditions associated with Autism:
encephalitis, neurofibromatosis, PKU untreated,
tuberous sclerosis, fragile X, anoxia, maternal
rubella
• Epilepsy in 10 – 35%
Rett’s Disorder (Andreas Rett
1966)
• All of the following are required:
– 1. Apparently normal prenatal and perinatal
development
– 2. Apparently normal psychomotor
development through the first 5 months after
birth
– 3. Normal head circumference at birth
Rett’s Disorder cont.
• Onset of all of the following after the period of
normal development:
– 1. Deceleration of head growth between ages 5 and 48
months
– 2. Loss of previously acquired purposeful hand skills
between ages 5 and 30 months with the subsequent
development of stereotyped hand movements (e.g. handwringing or hand washing)
– 3. Loss of social engagement early in the course
– 4. Appearance of poorly coordinated gait or trunk
movements
– 5. Severely impaired expressive and receptive language
development with severe psychomotor retardation
Rett’s Disorder cont
• Prevalence rate: 1/ 15000 – 22 000 females
• 26% incidence of sudden and unexpected death
• X-linked dominant mutation with lethality in
hemizygous males
• Mutation in the transcription regulatory gene
MECP2
• Stages:
– Normal prenatal/perinatal development
– Period of developmental stagnation
– Gradual, insidious delay in development, decelerated
head and body growth, lack of interest in the
environment, loss of previously acquired skills
(purposeful hand movements)
Rett’s Disorder cont
• Developmental plateau (school age)
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Severe MR
Seizures
Motor problems
Breathing difficulties (breath-holding spells, air
swallowing)
– Bruxism
– Scoliosis
• Final phase
– Nonambulatory secondary to motor problems, scoliosis
Childhood Disintegrative
Disorder (Heller 1908)
• Apparently normal development for at least the
first 2 years after birth as manifested by the
presence of age-appropriate verbal and nonverbal
communication, social relationships, play and
adaptive behavior
• Clinically signif. loss of previously acquired skills
(before age 10) in > areas:
– Expressive or receptive language
– Social skills or adaptive behavior
Childhood Disintegrative
Disorder cont.
– Bowel or bladder control
– Play
– Motor skills
• Abnormalities of functioning in at least 2 areas:
– Qualitative impairment in social interactions
– Qualitative impairment in communication
– Restricted, repetitive and stereotyped patterns of
behavior, interests and activities, including motor
stereotypies and mannerisms
Childhood Disintegrative
Disorder
• Prevalence: 1.7 per 100 000
• Presence of a period of normal development
before the onset of the deterioration and loss of
skills
• Typical age of onset 3 to 4 y old
• Very rare, strong male predominance
• Deterioration in self-help and motor skills is often
marked
• Apparently normal fife expectancy
• Has been associated with metachromatic
leukodystrophy, Schilder’s leukoencephalopathy
Asperger’s Disorder
• Impairment in social interactions
– Marked impairment in the use of multiple nonverbal
behaviors such as eye-to-eye gaze, facial expression,
body postures, and gestures to regulate social
interaction
– Failure to develop peer relationships appropriate to
developmental level
– A lack of spontaneous seeking to share enjoyment,
interests or achievements with other people
– Lac of social or emotional reciprocity
Asperger’s Disorder
• Restricted repetitive and stereotyped
patterns of behavior, interests and activities
– Encompassing preoccupation with one or more
stereotyped and restricted patterns of interest
that is abnormal either in intensity or focus
– Apparently inflexible adherence to specific,
nonfunctional routines or rituals
– Stereotyped and repetitive motor mannerisms
– Persistent preoccupation with parts of objects
Asperger’s Disorder
• There is no clinically significant general
delay in language
• There is no clinically significant delay in
cognitive development or in the
development of age-appropriate self-help
skills, adaptive behavior (other than in
social interactions) and curiosity about the
environment in childhood
Asperger’s Disorder cont.
• Prevalence estimated to 1 in 10 000
• More prevalent in males than females, ratio of 9 to
1
• Normal language development but their facial
expression, prosody and social gestures are often
deficient.
• Lack “intuitive knowledge” of how to approach
others.
• Delayed motor milestones, motor clumsiness
• Have to learn social skills through their intellect
Evaluation
• 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
Differential Diagnosis
• Various PDDs
• MR not associated with PDD
• Specific developmental disorder, e.g.
language
• Early onset psychosis
• Schizoid personality
Treatment Plan
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Multimodal
Establish goals for educational interventions
Establish target symptoms for intervention
Prioritize target symptoms and/or co-morbid
conditions
• Monitor multiple domains of functioning
(behavioral adjustment, adaptive skills, academic
skills, social/communicative skills, social
interactions)
• Monitor pharmacological interventions for efficacy
and side-effects.
Potential Targets for
Pharmacotherapy
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Motor hyperactivity
Inattention
Repetitive behavior
Motor and/or vocal tics
Aggression
Self-injury
Question
• The prognosis of autistic disorder is most
accurately described by which of the following
statements?
– A. The prognosis is good if the onset of the illness is at
birth
– B. The prognosis is good if the child has normal
auditory evoked potentials
– C. The prognosis is determined by language
development
– D. The prognosis is bad if either of the child’s parents
has manic-depressive illness
– E. None of the above
Question
• All of the following statements concerning autistic
disorder are true EXCEPT
– A. Incidence appears to be highest in upper
socioeconomic strata
– B. It occurs more commonly in boys than in girls
– C. It appears to be a neurologically based syndrome
– D. Mental retardation may or may not occur
– E. Grand mal seizures frequently occur
Question
• The hallmark feature of autistic spectrum
disorder is:
– A. Delayed expressive language
– B. Echolalia
– C. Functional intelligence quotient in the
superior range.
– D. Inability to relate socially.
– E. Stereotypy
References
• Volkmar F, Cook et al 1999. Practice
parameters for the assessment and treatment
of adolescents and adults with autism and
other PDD. J. Am. Acad. Child & Adol.
Psych. 38 (12 suppl): 32S- 54 S (erratum
2000 39 (7): 938 and 38: 12: 1611- 1615
• Mental Retardation: A Review of the Past
10 Years. Part 1. B.H. King et al 1997. J.
Am. Acad. Child Adole. Psych. 36:12,
1656- 1663 (1664 – 1671 for part II)
References
• http://www.mic.ki.se/Diseases/C16.html
• http://medgen.genetics.utah.edu/thumbnails.
htm
• http://ca.dir.yahoo.com/Health/diseases
• Fra X: http://www.fraxa.org
• Cornelia de lange: http://www.cdlsusa.org
• Handbook of Developmental Disabilities SL
Odom, RH Horner, ME Snell, J Blacher eds.
2007 The Guilford Press
References
• Child Adol Psych Clin NA 16 (2007)
– Fragile X syndrome 663-675
– VCFS 677-693
– Praeder-Willi 695-708
• Fetal alcohol spectrum disorder: Canadian
guidelines for diagnosis AE Chudley, J
Conry, JL Cook, C Loock, T. Rosales, N
LeBlanc CMAJ Mar 1, 2005 172 (5 suppl)
S1-S21