Key Facts

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a wide range of presentations, from individuals with significant intellectual disability and limited language to those with average or above-average intelligence. It is a lifelong condition, and management focuses on support, skill development, and addressing comorbidities.

Epidemiology

Prevalence is approximately 1-2% in the UK (estimated 700,000 autistic people). Male:female ratio approximately 3-4:1 in clinic samples, though increasing recognition of autism in girls/women suggests true ratio may be closer to 2:1. Prevalence appears to have increased significantly, largely due to broader diagnostic criteria, increased awareness, and better identification.

Aetiology

ASD is a highly heritable condition (heritability ~80-90%):

• Genetic: Polygenic in most cases; monogenic causes in ~10-20% (Fragile X, tuberous sclerosis, Rett syndrome, PTEN mutations, 22q11.2 deletion, chromosomal abnormalities)
• De novo mutations: Copy number variants (CNVs) found in ~10-20% of cases
• Environmental: Advanced parental age, extreme prematurity, prenatal valproate exposure, prenatal infections (weak associations)
• No association with MMR vaccine — extensively disproven (Wakefield's fraudulent 1998 paper was retracted)

Pathophysiology

ASD involves atypical neural connectivity — both local over-connectivity and long-range under-connectivity. Affected brain regions include the prefrontal cortex, amygdala, fusiform face area, and mirror neuron system. There is altered synaptic development and pruning, with differences in neurotransmitter systems including glutamate, GABA, serotonin, and oxytocin pathways.

Social Communication and Interaction Difficulties

• Reduced or absent eye contact
• Delayed or absent spoken language (or regression of language)
• Difficulty understanding and using non-verbal communication (gestures, facial expressions)
• Lack of social reciprocity — difficulty with back-and-forth conversation
• Reduced social interest or social motivation
• Difficulty understanding others' perspectives (theory of mind)
• Challenges in forming and maintaining peer relationships

Restricted and Repetitive Behaviours

• Stereotyped motor movements (hand flapping, spinning, rocking)
• Insistence on sameness, inflexible adherence to routines
• Highly restricted, fixated interests (e.g., trains, numbers, specific topics)
• Sensory hyper- or hypo-reactivity (distress at certain sounds/textures; or seeking sensory input)
• Echolalia (repeating words/phrases)
• Lining up objects

Presentation by Age

• Infants: Reduced social smiling, poor eye contact, lack of pointing/shared attention, no babbling by 12 months
• Toddlers: Language delay, no single words by 16 months, no two-word phrases by 24 months, regression of skills
• School-age: Social difficulties, struggling with friendships, inflexibility, meltdowns with changes in routine
• Adolescents: Anxiety, depression, isolation, difficulty with social demands of secondary school

Red Flags

• No babbling by 12 months, no pointing by 12 months, no single words by 16 months, no two-word phrases by 24 months
• Loss of previously acquired language or social skills at any age
• Lack of response to name by 12 months
• Absence of joint attention (shared interest in objects/events)
• Marked sensory sensitivities interfering with daily function

Bedside

• Developmental history: Detailed history from parents covering social development, communication, play, behaviour, sensory profile
• Observation: Direct observation in structured and unstructured settings
• Developmental milestones: Assess gross motor, fine motor, language, social, adaptive skills
• Validated screening tools: M-CHAT (Modified Checklist for Autism in Toddlers) — screening; not diagnostic

Specialist Assessment

• ADOS-2 (Autism Diagnostic Observation Schedule): Semi-structured, standardised observation — gold standard
• ADI-R (Autism Diagnostic Interview-Revised): Structured parent interview — gold standard
• Cognitive assessment: Developmental quotient or IQ testing (e.g., WISC-V for school-age, Bayley for infants)
• Speech and language assessment: Receptive and expressive language, pragmatic skills

Bloods

• Not required for ASD diagnosis
• Consider if syndromic cause suspected:
  • Fragile X testing: If intellectual disability + family history
  • Chromosomal microarray: If dysmorphic features, intellectual disability, or epilepsy
  • Lead level: If pica behaviour
  • Metabolic screen: If regression or clinical concern

Imaging

• MRI brain: Only if neurological abnormality (e.g., macrocephaly, regression, seizures, focal signs)
• EEG: If epilepsy suspected (~20-30% comorbidity)

Special Tests

• Genetic testing: Chromosomal microarray and/or Fragile X as first-line genetic investigations where indicated (co-existing intellectual disability, dysmorphic features, family history)

Non-pharmacological

• Speech and language therapy: Core intervention — pragmatic language skills, social communication, augmentative and alternative communication (AAC) if needed
• Educational support: EHCP (Education, Health and Care Plan), specialist or mainstream placement with support, structured teaching environment (e.g., TEACCH approach)
• Behavioural strategies: Visual supports, social stories, visual timetables, clear routines, sensory adaptations
• Parent/carer training: Understanding autism, managing behaviour, communication strategies
• Occupational therapy: Sensory integration, daily living skills, motor skills
• Social skills groups: Structured programmes for school-age children
• Transition planning: Preparing for key transitions (school changes, adulthood)

Pharmacological

• No medication treats core ASD features
• Comorbidity-specific treatment:
  • ADHD: Methylphenidate (start lower dose than typical ADHD — increased sensitivity to side effects) or atomoxetine
  • Anxiety: Sertraline 25mg OD titrated (off-licence in children), CBT
  • Irritability/aggression: Risperidone 0.25mg OD titrated (max 1mg OD in <50kg) — short-term use only; aripiprazole also used
  • Sleep: Melatonin 2-5mg nocte (licensed as Slenyto/Circadin for ASD-related sleep difficulties in children)
  • Epilepsy: Standard anti-seizure medications as indicated

Surgical/Interventional

• Not applicable for ASD

Referral Criteria

• Suspected ASD — refer to local autism assessment pathway (paediatrician, CAMHS, or specialist autism service)
• NICE CG128 recommends assessment within 3 months of referral
• Multi-disciplinary assessment team should include paediatrician/psychiatrist, SALT, and psychologist

• Lifelong condition: ASD is not 'cured' but outcomes vary enormously
• Intellectual disability: Present in ~30%; remaining 70% have average or above-average intelligence
• Independence: Approximately 50-60% of autistic adults live independently or semi-independently
• Employment: Only ~22% of autistic adults in the UK are in any form of employment (significantly below general population)
• Mental health: ~70% have at least one comorbid mental health condition; suicide risk is elevated (~7× in autistic adults without intellectual disability)
• Life expectancy: Reduced by an average of 16-30 years (driven by epilepsy, accidents, and suicide)
• Early intervention (before age 3) is associated with significantly better long-term outcomes in language and adaptive behaviour

DSM-5 Diagnostic Criteria for ASD

Genetic Syndromes Associated with ASD