Intellectual Disability

Outline
z

Definition
z Medical investigation
z Common
C
syndromes
d
z Associated comorbidity and
management
z Educational issues
z Medication
z Transition to adulthood

Definition
z

Terminology differs across Western

world
z Australia intellectual disability
z UK
learning disabilities
z USA
mental retardation

Cognitive Functioning
WHO 1968
z

mild ID
z moderate ID
z severe ID
z profound ID

IQ
IQ
IQ
IQ

50-55
50 55 to 70
35-40 to 50-55
20
20-25
25 tto 35
35-40
40
below 20-25

Old terminology
gy
z

idiot profound
idiotz imbecile -moderate/severe
z moron or feeble
f bl mindedi d d mild
ild

Definition
z

A significant impairment of cognitive and

adaptive functions, with age of onset
before 18 years
years.
z Usual presentation is with impairments in
adaptive functioning
functioning.

DSM-IV and ICD-10

zDSM
z

IV

dysfunction or impairment in >2

areas:communication, self-care, home
living, social/interpersonal skills, use of
community resources, self direction,
functional academic skills, work, leisure ,
health and safety
z onset before age
g 18

DSM-1V and ICD-10

zICD-10
ICD 10
z

mental retardation is a condition of

arrested
t d or incomplete
i
l t d
development
l
t off
the mind, which is especially
characterised by impairment of skills
manifested during the developmental
period contributing to the overall level of
period,
intelligence- cognitive, language, motor
and social abilities

Classification
z DSM IV
z Published 1995 text revision 2000
z
z

vs

z DSM
S V
z 10 years of revision due May 2013

DSM IV
z

Mental Retardation
z A. Significantly subaverage intellectual
functioning: an IQ of approximately 70 or
below on an individually administered IQ
test (for infants
infants, a clinical judgment of
significantly subaverage intellectual
functioning).
functioning)

DSM IV
z

B. Concurrent deficits or impairments in

present adaptive functioning (i.e., the person's
effectiveness in meeting the standards
expected for his or her age by his or her
cultural group) in at least two of the following
areas: communication,
i ti
selfcare,
lf
h
home liliving,
i
social/interpersonal skills, use of community
resources self-direction
resources,
self-direction, functional academic
skills, work, leisure, health, and safety.

DSM IV
z
z
z
z
z
z

C. The onset is before age

g 18 yyears.
Code based on degree of severity reflecting level of
intellectual impairment:
317 Mild Mental Retardation: IQ level 50
5055
55 to
approximately 70
318.0 Moderate Mental Retardation: IQ level 3540
t 5055
to
50 55
318.1 Severe Mental Retardation: IQ level 2025 to
3540
318.2 Profound Mental Retardation: IQ level below
20 or 25

DSM V
z
z

Intellectual Disability
A. Current intellectual deficits of two or more
standard deviations below the population
p p
mean, which generally translates into
performance in the lowest 3% of a persons
age and cultural group, or an IQ of 70 or
below. This should be measured with an
individualized standardized
individualized,
standardized, culturally
appropriate, psychometrically sound measure.

DSM V
z

B. And concurrent deficits in at least two

domains of adaptive functioning of at least two
or more standard deviations, which generally
translates into performance in the lowest 3 %
of a persons age and cultural group, or
standard
t d d scores off 70 or b
below.
l
Thi
This should
h ld b
be
measured with individualized, standardized,
culturally appropriate
appropriate, psychometrically sound
measures. Adaptive behavior domains
typically
yp
y include:

DSM V
z

Conceptual skills (communication

(communication,
language, time, money, academic)
z Social skills (interpersonal skills
skills, social
responsibility, recreation, friendships)
z Practical
P ti l skills
kill (d
(daily
il liliving
i skills,
kill work,
k
travel)
.

DSM V
z

C. With onset during the developmental

C
period.

z
z

Code no longer based on IQ level

Adaptive
p
Functioning
g
z

Refers to how effectively individuals

cope with everyday life demands, and
how well they meet standards of
personal independence expected of
someone of that age and socioeconomic
and cultural background.

Adaptive
p
functioning
g
z

influenced by a number of factors

z motivation
z personality
lit style
t l
z education, social and vocational
opportunities
zg
general medical conditions and mental
disorders that co-exist with ID

Measures of adaptive
p
functioning
g
z

Is the instrument suitable to the ethnic

and cultural background?
z Vineland -uses
uses a number of different
sources to gauge adaptive functioning

Frequency
q
y
z

occurs in 1-10
1 10 % of the population and is
most accurately diagnosed in the school
years.
years
z Developmental delay often used in
preschool years
z sex ratio 1.5 :1 M:F
z biological inequity related to the sex
chromosomes with the well established
X- linked single gene mutations

Frequency
q
y
z

If we use the IQ construct then we

assume it is a normally distributed trait in
the general population and therefore 2 %
of individuals would have an IQ less than
70.
70
z Most studies report rates of 1-2.5%
z In
I those
th
with
ith IQ
IQs lless th
than 50 th
the
frequency is 0.3-0.5%

Demography
g p y
z

mild intellectual disability is associated

with low social class
z a much weaker association exists in
people with more severe ID

Aetiology
gy
z

WHY INVESTIGATE?
z 1. Diagnosis provides prediction
z 2.
2 Oft
Often vigorously
i
l sought
ht b
by th
the ffamily
il
z 3. Helps establish accurate recurrence
risk

Whyy Investigate?
g
z

4. Prevents expensive unnecessary and

4
invasive investigations
z 5.
5 Helps guide treatment and
management

Diagnostic
g
yyield
z

significant improvement in yield over last

2 decades
z high frequency of the involvement of
genes
z mostt important
i
t t studies
t di include
i l d th
thorough
h
physical examination
z cytogenetics, neuroimaging and accurate
EEG recording

Aetiology
gy
z

no longer true that the greatest yield is in

those with more severe ID
z due to newer diagnostic techniques in
dysmorphology, cytogenetics and
molecular genetics
genetics, neuroimaging and
clinical neurophysiology yield is not
dependent on degree of ID any longer

How to investigate
g
z

Most patients lack specific findings on

history or examination
z GG banded chromosomes and single
gene disorders such as fragile X

Microarrayy testing
g
z

Microarray based genomic copy number

Microarrayanalysis
z Other names are
z Chromosomal Microarray (CMA)
z Molecular Karyotyping

CMA
z
z

Includes

array based
b
d comparative
ti genomic
i
hybridization (aCGH)
z Single nucleotide polymorphism
(SNP)arrays

CMA
z

G-banded
G
banded karyotype

Cytogeneticist
C
t
ti i t visualizes
i
li
and
d analyzes
l
for chromosomal rearrangements
i l di gains
including
i and
d llosses

CMA
z

Not standard in all clinical settings

z International Standard Cytogenomic
Array Consortium (ISCA)
z 10 clinicians, 17 clinical laboratory
geneticists,
ti i t 9 genome scientists
i ti t and
d
bioinformatiticians
z Focused on clinical application of CMA

At present CMA is not recommended for

prenatal testing although multicentre
studies are underway to look at this
z (Queensland
(Q
l d RH status
t t can b
be d
detected
t t d
by this technology)

PAthogenicity
g
y of
z

Assessment of the pathogenicity of CNV

Parents
P
t mustt be
b counselled
ll d about
b t th
the
implications of detection of copy number
variants
i t off uncertain
t i significance
i ifi
and
d
unrelated to childs problems

What CMA does not detect

z

Array CGH does not detect change in

FMR gene in fragile X so first line should
still ask for fragile
fragile X DNA testing
testing

If a child has a phenotype suggesting a

specific microdeletion syndrome (VCFS
Smith Magenis or Williams )
z Discuss with lab probably best to do
single specific locus test 22q11FISH or
22 11MLPA

How to investigate
g
z

NO doubt for non specific ID

ID, congenital
abnormalities, or autism microarray is
the first line test.
test

N
Now
h
has a M
Medicare
di
ititem.

Causes of ID
z
z
z
z

Chromosomal
abnormalities
Syndromes
y
Monogenic
conditions known
Structural CNS

4-28%
4
28%

z
z

3-7%
%
3-9%

7-17%

Causes of ID
z
z
z
z
z

Complications of
prematurity
Endocrine/metabolic
causes
Cultural-FamilialID
Unique monogenic
Unknown
U
o

2-10%
2
10%

1-5 %

3-12%
1-5%
30-50%
30
50%

z
z

Evolving
g Phenotype
yp over Time
z

Rett syndrome
z Prader Willi syndrome
z Angelman
A
l
syndrome
d
z Velocadiofacial syndrome
z Williams syndrome
z Noonan syndrome
z Fragile X syndrome

Historyy and physical

p y
examination
z

detailed birth and and prenatal history

z hereditary and family history
z three
th
generation
ti pedigree
di
z consanguinity
z Foetal loss
z FH of learning difficulites

Physical
y
examination
z

skin changes
z documentation of minor anomalies or
abnormal findings by detailed description
and measurement
z video
id monitoring
it i off posture
t
and
d gaitit or
behaviour characteristics.
z serial evaluations over several years
z hearing
g and vision

Diagnosis-Genetics
g
z

Imprinting may be cause of differential

expression in conditions affecting same
portion of genome eg Prader Willi and
Angelman
z Trinucleotide repeat expansion is
another mechanism
z rearrangementt off subtelomeric
bt l
i regions
i
recently implicated

Diagnosis-Genetics
g
z

high resolution banding

z FISH( fluorescence in situ hybridisation)
z subtelomeric
bt l
i analysis
l i iis iimportant
t t iin
moderate to severe ID
z these subtelomeric chromosome defects
have been found in 6.5-7.4% of children
with mod-severe ID

Diagnosis-Metabolic
g
z

metabolic testing should be focused

z neonatal hypotonia, progressive
coarsening of features
features, loss of skills
skills,
recurrent coma etc
z acid
id b
base
z plasma and urine amino acids
z organic acids
z thyroid screen

Diagnosis-Metabolic
g
z

lysosomal enzyme analysis

z plasma and urine carnitine analysis,
z plasma
l
VLCFA
z extremely low yield for unselected
metabolic screening

Neuroimaging
g g
z

consider especially in patients with

z microcephaly
z macrocephaly
h l
z neurologic signs (spasticity, ataxia,
dystonia, seizures, loss of psychomotor
skills, abnormal reflexes)
z abnormal cranial contour

Neuroimaging
g g
z

CT for cranial synostosis or where

intracranial calcification is likely (TS,
intrauterine infection)
z MRI study of choice
z PET scanning
i
z may help date onset of problem
(prenatal, perinatal, postnatal).

Environmental
factors
z

lead and methlylmercury poisoning

z alcohol
z thalidomide
th lid id
z valproic acid
z polychlorinated biphenyls, dioxins,
pesticides and tobacco smoke may
p
y be
potential neurotoxins

Behavioural Phenotypes
yp
z

conditions with a known cause and a

characteristic behavioural presentation
z Down , fragile X
X, 22q 11 deletion
deletion, Prader
-Willi, Angelmans, Retts, SmithMagenis foetal alcohol syndromes
Magenis,
z individually rare but together 0.5% of
child
hild population
l ti

Down syndrome
y
z
z

1/600 live births figure always quoted

2004 Victorian
Vi t i study
t d
z 1 in 350 pregnancies affected
z 1/1150 live births

1/3 of all cases of severe and profound

ID
z smaller proportion of those with mild to
moderate ID
z 1/3 psychiatric
hi t i di
disorder
d
z 1/4 develop epilepsy in adulthood
z many develop Alzheimers in 40s

22q11
q deletion syndrome
y
z

1/3000 or even 1/2000 children

z IQ can be normal and severe ID rare
z Attention
Att ti d
deficits,
fi it nonverbal
b l llearning
i
disability, lack of energy
z Autistic type features
z Abnormal brain changes
g on MRI

22q11
q deletion syndrome
y
z

85% cases have submicroscopic

deletion at 22q11.2.
z Wide phenotypic expression
z 180 associated anomalies
z facial dysmorphism
z congenital
g
heart disease
z hypotonia and immune disorders

22q11
q deletion syndrome
y
z

hypernasal speech is due to submucous

cleft palate
z velopharyngeal insufficiency or cleft
palate
z infections
i f ti
off respiratory
i t
tract
t t and
d ear due
d
to partial or total absence of the thymus
gland
l d
z Fits - check calcium levels because of
aberrant functioning if the parathyroid
glands

Fragile
g X syndrome
y
z

third most common 1/3000

z distal part of the long arm of X
chromosome
z trinucleotide repeat expansion
z apart from ID, boys have more deficits in
motors skills, autistic features, social
anxiety, tangential language,
hyperactivity, attentional difficulties

Fragile
g X syndrome
y
z

hypersensitivity to sensory stimuli and

social stimuli
z inhibitory control deficits
z macroorchidism (100 mls) only past
puberty
b t
z girls with fragile X have fewer problems

Fragile
g X syndrome
y
z

Scoring system of 6 historical/clinical

characteristics
z ID,
ID family history
history, elongated face
face, large
or prominent ears, attention deficit
hyperactivity and autistic
autistic-like
like behaviour
z if we only test those with 5 out of 6 then
60 % off ttesting
ti could
ld b
be eliminated
li i t d
without missing positive cases

Fragile
g X syndrome
y
z

laboratory confirmation is relatively

inexpensive
z molecular analysis of the FMR1 gene
z normal CGG repeat segments <50
z premutations 50-230 repeats
z full mutations >230 repeats
p

Fragile
g X syndrome
y
z

deletions and point mutations of the

FMR1 are rare but should be looked for
in persons with characteristic
phenotypes and normal CGG repeat
analysis
z Other fragile sites FRAXE may be found
using cytogenetic and molecular studies
z Test anyone with unexplained ID
especially
i ll with
ith ffamily
il hi
history
t

Prader-Willi syndrome
y
z

loss of the paternal contribution of the

proximal portion of the long arm of
chromosome 15 (deletion or maternal
disomy or imprinting of 15q11-13)
z high incidence of ID
z obsessive, repetitive activities
z mood instability, self mutilation

Prader- Willi syndrome

y
z

1/10,000
1/10
000
z hypotonia, failure to thrive, delayed
sexual development
development, scoliosis
scoliosis,
acromicria, small stature and persistent
skin picking
z Flat face prominent forehead with
bit
bitemporal
l narrowing
i and
d almond
l
d
shaped eyes with triangular mouth

Prader-Willi
z

first 6 months
z hypotonia, feeding difficulties, sleepiness
z 1-4
1 4 years h
hyperphagia
h i d
develops
l
d
due tto
hypothalamic abnormalities
z hypotonia improves
z most important
p
issue is dietary
y
management
z medication,
medication GH
GH, behavioural approach

Angelman
g
syndrome
y
z

caused by loss of maternal contribution

to proximal portion of long arm of
chromosome 15
z no speech
z obsessions,
b
i
compulsions,
l i
overactivity,
ti it
eating and sleeping difficulties
z 50% have episodes of inappropriate
laughter

Rett syndrome
y
z

1/10,000
1/10
000 females
z rarely occurs in males
z Distal
Di t l arm off X
Xq28
28 75% d
due tto mutation
t ti
of MECP2 gene
z normal development until 6-18 months
z deceleration of head growth
g

Rett Syndrome
y
z

inability to walk
z ataxic movements of torso and limbs
z rate
t off regression
i is
i variable
i bl months
th
z regression is followed by a period of
stabilisation then re-emergence of skills
z hyperventilation
yp
and breath holding
g
z facial grimacing and hand ringing

Rett syndrome
y
z

Loss of purposeful hand movements with

stereotypic movements
z loss of verbal skills
z All lead to loss of function, physical
(
(scoliosis
li i and
d lleg d
deformities),
f
iti ) social,
i l
linguistic and adaptive behaviours

Foetal alcohol syndrome

y
z

neuronal apoptosis may be triggered in

the last trimester and this may be
sensitive time for the effects of ethyl
alcohol (intrauterine synaptogenic
phase)
z Studies of 10 -12 year old boys, show
those whose parents with alcohol and
drug abuse have a higher rate of ID than
a control group

Foetal alcohol syndrome

y
z

Longitudinal studies of mothers with a

history of alcohol abuse in pregnancy
show a trend towards a dose response
relationship between level and length of
exposure to alcohol and intellectual
disability and behaviour problems
z smoking and alcohol in pregnancy
associated with ADHD

Prematurity
y
z

birthweight < 1000g risk factor for ID

z most survivors of 22-26 weeks will be
free of a major disability although 20%
will have ID diagnosed later
z 40-50%
40 50% will
ill d
develop
l neurodevelopmental
d
l
t l
and neuropsychiatric problems in
childhood
hildh d and
d tteenage years

Infections
z

meningitis and encephalitis in early

infancy and childhood still cause ID
although the outcomes are much better
now
z intrauterine CMV,
CMV toxoplasmosis and
rubella continue to cause ID
z measles
l and
d SSPE

Traumatic brain injury

j y
z

increases the risk of intellectual disability

z American study showed that exposure to
violence and trauma related
psychological distress showed a
decrease in IQ of 7
7.5
5 points and a
reduction in reading achievement by 10
points

Chemicals
z

Radiotherapy, chemotherapy and

Radiotherapy
intrathecal corticosteroids all implicated
in ID
z Prenatally exposed survivors of
Hiroshima and Nagasaki showed the
critical time was 8th-15th week of
gestation and the increase in prevalence
of ID was linearly dose related

Medical Problems
z

increased rate of medical problems

z epilepsy14-44% higher in more severe
ID
z combination of ID and epilepsy is a
strong
t
predictor
di t off psychiatric
hi t i and
d
behavioural problems
z Hypothyroidism is common in Down
syndrome

Medical problems
p
z

Stomach cancer
cancer, and cancer of gall
bladder, oesophagus, testis, thyroid and
connective tissue all occur with greater
frequency
z visual problems 10 times more common
cataract and keratoconus also common
z Hearing
H i problems
bl
40 titimes more
common
z In one study of institutionalised people
with IQ<50 69% had constipation

Psychiatric
y
disorders
z

Over represented in ID population

z As IQ decreases, these increase
z psychotic
h ti conditions,
diti
pica,
i
selflf injurious
i j i
behaviours, stereotypies and ADHD
symptoms
t
common

Psychiatric
y
disorders
z

Schizophrenia over-represented
over represented
z 4.4% vs 0.4% in general population
z similar
i il rates
t iin autism
ti
z other psychiatric disorders are at least as
common in an adult population of people
with ID as general community sample

Forensic issues
z

Low verbal IQ associated with increased

risk of conviction for violent crimes not
accounted for by socioeconomic or
educational status
z most common crimes are child sexual
abuse and arson
z also
l th
those with
ith ID are att greater
t risk
i k off
violence and sexual abuse

Treatment and intervention

z

Psychosocial, psychological and

Psychosocial
educational treatment help with overall
adjustment and behaviour in deprived
children with low IQ
z possibly may increase IQ as well
z Behavioural methods for self injury
appear to
t be
b best
b t if used
d systematically
t
ti ll
by well trained people

Psychotropic
y
p Medication
z

Recent Cochrane review

z 8 randomised controlled trials showed no
evidence of whether antipsychotics
helped or harmed adults with ID and
challenging behaviours

Risperidone
p
z

American study 2002

z double blind randomised controlled
z using
i risperidone
i
id
ffor di
disruptive
ti
behaviours in 118 children with ID aged
5 12 years
5-12
z good benefit and few side effects (slight
weight gain)
z another small study
y showed sedation
and weight gain were greater problems

Psychotropic
y
p Medication
z

Other drugs include naltrexone

naltrexone, mood
stabilisers, serotenergics
z Antiepileptics sometimes helpful
although one study using valproic acid in
a group with ID and epileptiform
discharges on EEG, showed a
deterioration in memory and increased
internalising behaviours

Societal attitudes
z

200 years ago these children were often

left to die
z Early 20th century eugenics movement
suggested sterilisation to prevent
spreading of genes to future generations
z Last 25 years more respect given to
rights
i ht off people
l with
ith ID