NEURODEVELOPMENTAL DISORDERS
DEVELOPMENTAL DELAY
Definition
Developmental delay describes the delayed acquisition of milestones, and is a description not a diagnosis. It
may be a symptom of developmental disabilities.
Common conditions
Intellectual disability with or without autism spectrum disorder .
o More on ASD later
o Mild ID (IQ 55-70) with ASD – these children go to support units in mainstream schools
o Moderate ID (IQ 40-55) – these children go to a support unit IO class in a mainstream school.
At around halfway in the moderate ID category (~IQ 50), the benefits of mainstream
integration tend to be lost as the children are so far behind their peers. These children go to
a special school.
Single non-heritable gene conditions
o Down Syndrome most common
Other heritable conditions
o Fragile X (discussed later)
Point mutations
o Williams syndrome
o VCFS (chromosome 22)
o Angelmans (chromosome 15)
Rare syndromes
Undiagnosed syndromes
INTELLECTUAL DISABILITY
ID is a permanent disability of cognition
beginning in childhood. In preschool we
call it developmental delay. It causes
impaired cognition, i.e. perception,
memory and reasoning that promotes
understanding, planning and
problem solving. The onset is in the
developmental period, and the
severity is determined by the level
of functional impairment. 2-4%
population is affected, with more
males affected (M:F 2:1).
In children with ID, things take longer and more repetitions are needed. In childhood, learning does occur, but
the functional gap widens.
Note that no matter how severely handicapped you are, you have to go to school at the age of 5. Also note
that above graph and table are separate and do not correlate.
COMORBIDITIES
Autism spectrum disorders
Epilepsy
Cerebral palsy
Sensory impairments (often missed) – such as hearing/vision
General health (may be related to underlying condition) leads to shorter life expectancy
INVESTIGATIONS
Assessment should include:
o PCR for Fragile X, comparative genomic hybridisation (CGH) microarray
o FBC/UEC/LFTs/TFTs
o Urine metabolic screen
o Hearing and vision testing
MRI indicated if there are neurological signs
EEG only if seizures
EFFECT ON FAMILY
Chronic sorrow and joy
High care needs with activities of daily living and therapies
Family stress, relationship breakdown – note that some children are in out of home care
Financial – e.g. carer allowance, carer payment. Recently there is a transition to the NDIS – basically a
butt load more paperwork
AUTISM SPECTRUM DISORDER
Definition
ASD is characterised by deficits in social communication and social interaction. It involves repetitive behaviours
and restricted interests. Deficits must be
Maladaptive
Present in multiple contexts
Begin in early development
Not better explained by intellectual disability
The presentation is highly variable, and depends on the child’s age and co-morbidities. The child’s “adaptive
function” determines the level of ASD
Level I Requiring support
Level II Requiring substantial support
Level III Requiring very substantial support
Some statistics
40-70% have language impairment
45% have intellectual disability
8-30% have epilepsy
ADHD seen in 28-44%
Anxiety/depression in 70%
Medications have a limited role
Stimulants e.g. ritalin: reduce activity and increase attention
SSRIs e.g. fluoxetine: reduce anxiety, repetitive behaviours and alleviate depression
Anti-psychotics e.g. risperidone: reduce agitation, self-injury and aggression. Side effects of
risperidone include weight gain and dyskinesia (which may not be treatable)
CEREBRAL PALSY
CP is a non-progressive motor disability which results in abnormal posture movements and tone, due to brain
injury in early brain development. Prevalence is 2 per 1000. Signs may change as the child develops, including
motor delay/feeding difficulties/abnormal movements/hand preference. Types of CP include:
75% spasticity (hemiplegia, diplegia or quadriplegia)
20% dyskinetic (basal ganglia damage)
5% ataxic (cerebellar lesions, hypotonia)
Statistics
10% due to perinatal asphyxia
10% due to other brain malformations
80-90% have abnormal MRI
Comorbidities:
o 25-33% epilepsy
o 50% cognitive impairment
o 10% vision, 4% hearing impairment
Management
Management depends on the degree of handicap. Naturally, the worse the disease, the more aggressive the
treatment is. It can involve:
Speech/physiotherapy/OT/Educational
Rehab teams may use PEG feeds/Botox/Surgery
Treatment options
Strengthening
Stretching
Splinting
Botulinum toxin A
(Selective Dorsal Rhizotomy) level 2 or 3
Serial casting Level 1-3. Usually to get feet into a good position for walking
Orthopaedic surgery
Oral medications (Level 3-5)
Intrathecal baclofen pump treatment (level 3- 5)
Pain management (level 3-5). More tone = more pain
Scoliosis surgery
Adaptive equipment
Palliative care
Opposite shows GMFCS – the gross motor function classification score, displaying the physical
abilities and needs of different grades of severity – as we see it ranges from normal to requiring
a walker or a wheelchair
DOWN SYNDROME
Down syndrome occurs in 1:1000 live births, and 95% are due to complete trisomy 21,
3-4% from unbalanced translocation and 1% from mosaicism. Complications include:
Intellectual disability
Cardiac
Thyroid
Respiratory
Vision/hearing
Management
Triple screen (AFP/HCG/oestriol) + US = 85% detection, with 5% false positive rate
Early issue is feeding and growth
Cardiac – 40-50%
o Atrioventricular canal
Development – delayed gross motor and speech, mild to moderate ID, IQ decreases from 60 to 40 on
average with increasing age
10% have autism
Alzheimers – 75% by 60 yo
FRAGILE X
Fragile X affects boys mainly. The degree of ID is related to the
number of repeats, and can range from mild to severe. These
children are tall with long face with prominent ears, and often
have autistic features.
It is caused by mutation of the FMR1 gene on X chromosome (so
the mother may be mildly affected). There is a trinucleotide
repeat sequence. Carriers have 50-150 repeats, while >200
repeats is generally found in affected individuals
Frequency
1/1250 males
1/5000 females
Medical concerns
Large ears, long face, large testes
20% can have epilepsy
Ligamentatous laxity
Fragile X learning
0-4: developmental delay, speech delay, perseveration, cluttering, hyperactivity, gaze aversion,
flapping, sensory defensiveness
5-18+: Mild – moderate (+) intellectual disability, females 1/3 – ½ have ID, social aversion/anxiety,
poor coordination
VELOCARDIOFACIAL SYNDROME
Velocardiofacial syndrome occurs due to an interstitial deletion at
22q11.2 (del 22q).
There is autosomal dominant transmission, and prevalence is 1 in
4000.
Abnormalities
Mild – moderate intellectual disability
Behavioural problems
Learning difficulties
Palatal abnormalities, VPI (50%) CSOM
Congenital heart disease (75%)
Characteristic facies (beaked nose, narrow palpebral fissures, small chin)
Thymic aplasia, hypocalcaemia (rare)
WILLIAMS SYNDROME
Williams syndrome is caused by micro-deletion elastin (ELN) gene chr (de novo). Prevalence is 1/8,000.
Features include:
Infantile hypercalcaemia
Supravalvular aortic stenosis (75%)
Elfin-like facies
Growth deficiency
Microcephaly
Mild to moderate intellectual disability
Verbal > performance skills
Hyperactivity
Emotional lability
ANGELMAN SYNDROME
80% of angelman syndrome cases is due to 15q11-q13 (UBE3) maternal deletion, but other
causes can include paternal uniparental disomy. A healthy individual receives two copies of
chromosome 15, but due to epigenetic imprinting, one is silenced. The maternal allele is
almost exclusively the active one, so if the maternal allele of UBE3A is lost or mutated, the
result is Angelman Syndrome.
Features
Laughing paroxysms, excitable
Hand flapping
Seizures
Large mouth, jaw, fair/blonde
Severe intellectual disability
Hyperactive
Jerky “puppet” gait
Emotionally labile
Management
Multi-disciplinary management, including:
Skills development
Family support
Community engagement
Challenges
Self-care – daily life harder for families
Behaviour – ‘terrible twos’ persist
Safety – kitchens, roads, public places
Personal hygiene – toileting, menstruation
Sexuality – masturbation, interests, vulnerability, fertility
Mental health - boredom, sadness, anxiety
Natural history
