Introduction to Intellectual Disability Flashcards
What are Intellectual Disabilities?
-Significant impairment in intellectual functioning (IQ <70)
-Significant impairment in adaptive behaviour (> 2 SDs below mean on tests of adaptive behaviour)
-Evidence of 1 and 2 in the developmental period (i.e. under 18 years old)
What is mild ID? (ICD-11)
IQ: 2-3 SDs below mean
-Over 80% of ID population
-independence in self care, practical domestic skills
-basic reading/writing
-most people never diagnosed
-may need help with housing and employment or when under unusual stress
What is moderate ID?
IQ/ adaptive behaviour: 3-4 SDs below mean
-limited language skills
-need help with self-care
-about 10-12% of the ID population
-Majority have identifiable organic aetiology
What is severe ID?
IQ/ adaptive behaviour: > 4 SDs below mean
-Use of words/gestures for basic needs
-motor impairment & others are common
about 4-7%
-can undertake simple tasks and engage in limited social activities
What is profound ID?
IQ/ adaptive behaviour: > 4 SDsbelow mean
-1-2% of the ID population
-some eventually acquire some simple speech and social behaviour
-no self care skills
-Organic aetiology is clear in most
What proportion of people have intellectual disabilities?
Intellectual impairment ~2.5%, ID 1%, Severe ID 0.35%
What conditions are excluded from ID by definition?
-Educationally disadvantaged people
-Brain injury in adulthood
-Progressive neurological conditions in adulthood such as dementia
-Cognitive decline due to severe mental illness/substance misuse
What is the aetiology of ID? can name a few
-Down syndrome
-Neural tube defects
-Perinatal factors
congenital hypothyroidism (neonatal screening)
-Foetal alcohol syndrome
-Iodine deficiency
-Fragile-X syndrome
-Other genetic disorders (PWS / Angelman, Rett syndrome & tuberous sclerosis)
Phenylketonuria, inborn errors of metabolism
Most cases-unknown aetiology
What are copy number variants (CNVs)?
-Submicroscopic chromosomal deletions or duplications
-Typically >1000 bp
-De novo or inherited
-Common vs rare
-CNV in neurodevelopmental genes = more adverse functional consequences
-Associated with ID, Autism and -
-Schizophrenia
CNVs in autism spectrum disorders (ASD)
-Risk for autism first described at the 16p11.2 locus
-Many more CNVs found e.g. exonic NRXN1 deletions (affects neurotransmission)
-CNVs now thought to be the cause of 10-20% of autism cases
copy number variants in schizophrenia
-CNV deletions at chromosomes 1, 15, 22 implicated in Sz
-VCFS/22q11.2 deletion – one of the strongest risk factors for psychosis (~40% of VCFS del carriers)
-Robust contribution of CNV to schizophrenia, loci involved in neurological functions (e.g. postsynaptic density)
Down syndrome (trisomy 21)
-1 in 700 live births
increased risk of early onset dementia (AD), depression
-40% above 50 & 80% lifetime risk in DS for AD
-APP gene triplicated on Chr 21
-Note trisomy, translocations & mosaicism
-Epilepsy 10% in childhood, biphasic prevalence because seizures common in those with AD
What is Prader-Willi syndrome?
-loss of paternal chromosome 15 material
-insatiable appetite, obesity, pica, skin picking
-depression, psychosis behavioural disorders, OCD symptoms
physical characteristics:
-overweight, narrow temple distance and almond shaped eyes, thin upper lip, downturned mouth
What is Angelman Syndrome?
-loss of maternal chromosome 15 material
-Happy presentation with laughter with hand flapping, clapping
-Epilepsy 90%
-Severe/profound ID
-Fair hair, blue eyes (above 60%) microcephaly and long face wide spread teeth
What is Lesch-Nyhan Syndrome?
-X-linked recessive disorder of purine metabolism
-1:380,000 births
microcephaly, ID, choreoathetosis,
-seizures 50%, hyperuricaemia
severe compulsive self-injurious behaviour, biting of fingers and lips
What is 22q11.2 deletion Syndrome?
-microdeletion in 22q11.2 region
-Incidence 1 in 4000-6000 live births.
=Most cases are spontaneous (90%) or autosomal dominant (10%)
-Di George/VCFS/deletion 22 syndrome: overlapping phenotypic variations
Hypocalcaemia 60% seizures
What are the clinical manifestations of 22q11.2 deletion?
-Mean IQ is 70 - 50% will have ID
-Typically Verbal IQ > Performance IQ
-Borderline – mild ID
Elaborate on o22q11.2 deletion & psychosis
-Increased prevalence of OCD, ADHD
-30 % of VCFS sample had psychotic illness (24% schizophrenia) (Murphy et al. 1999)
-Commonest known genetic cause of schizophrenia
-2% of sample with schizophrenia had VCFS (Bassett et al. 1998)