Pervasive developmental disorders: childhood autism, Asperger syndrome, and Rett syndrome. Epidemiology, etiology, clinical features, course, and treatment

At a glance

1. ICD-10's pervasive developmental disorders (F84) include childhood autism, atypical autism, Rett syndrome, childhood disintegrative disorder and Asperger syndrome. ICD-11 and DSM-5 merge autism and Asperger syndrome into one autism spectrum disorder, and treat Rett syndrome as a genetic neurological disorder.
2. Autism is a lifelong difference in social communication and interaction, with restricted, repetitive behaviours and interests and unusual sensory responses, present from early childhood. It affects about 1 in 100 people, boys three to four times more often.
3. Red flags in a toddler are no babbling or pointing by 12 months, no words by 16 months, no two-word phrases by 2 years, poor response to name and little shared attention; any loss of language or social skills at any age needs prompt assessment.
4. Diagnosis is clinical, by a multidisciplinary team, supported by ADOS-2 and ADI-R; hearing is tested, and genetic tests are done when there is intellectual disability or dysmorphism.
5. Autism is about 80 per cent heritable. Vaccines do not cause autism: the MMR claim was fraudulent and retracted, and large studies show no link.
6. Support comes first: early parent-mediated communication interventions, education and adaptations. No drug treats the core features; risperidone or aripiprazole are for severe irritability, melatonin for sleep, and comorbid ADHD, anxiety and epilepsy are treated.
7. Rett syndrome affects girls, from de novo MECP2 variants: normal development, then regression from 6 to 18 months, with loss of hand use and speech, hand-wringing and slowing head growth. Trofinetide, approved in the US in 2023, was authorised in the EU in 2026.

01Definition and overview

Autism is a neurodevelopmental condition, a lifelong difference in how a person communicates, relates to others and experiences the world. ICD-10 groups it with related conditions as the pervasive developmental disorders, defined by a triad of impaired reciprocal social interaction, impaired communication, and restricted, stereotyped, repetitive interests and activities.

ICD-11 (6A02) and DSM-5 have one autism spectrum disorder, defined by two domains: persistent difficulties in social communication and interaction, and restricted, repetitive and inflexible patterns of behaviour, interests or activities, including sensory differences, present from early development (though they may only become clear when social demands exceed capacity) and impairing. ICD-11 specifies whether there is a disorder of intellectual development and how much functional language there is; DSM-5 adds levels of support (1, requiring support; 2, substantial; 3, very substantial) and specifiers such as a known genetic condition.

02Etiology and pathophysiology

Autism

Autism is among the most heritable of psychiatric conditions, at about 80 per cent in twin and family studies. A sibling of an autistic child has a risk of roughly 1 in 5 to 1 in 10. The genetics combine:

• many common variants of small effect, shared in part with ADHD, depression and schizophrenia;
• rare de novo variants and copy number variants of large effect (16p11.2, 15q11–13 duplication, SHANK3, CHD8), mostly in genes for synapses and the regulation of gene expression, and commoner when there is intellectual disability;
• single-gene syndromes: fragile X, tuberous sclerosis, PTEN variants with a large head, Rett syndrome.

Environmental risks are smaller: prematurity, older parents, maternal diabetes, congenital rubella, and prenatal valproate, which roughly triples the risk. The brain develops differently from before birth: some children show early brain overgrowth, and connectivity between regions is altered. Autism is not caused by parenting, the "refrigerator mother" idea of the 1950s, which was wrong and caused much harm.

The rise in recorded autism comes mostly from wider criteria, the merger of Asperger syndrome and better recognition in girls, adults and people without intellectual disability; no new cause has been found.

Rett syndrome

Rett syndrome is caused in most classic cases by a variant in MECP2 on the X chromosome (Xq28), almost always de novo and usually on the father's X. Its protein, MeCP2, binds methylated DNA and regulates the expression of many genes in mature neurons, so neurons that formed normally fail to mature and keep their connections. Girls survive because about half their cells use the healthy X; boys with the same variant usually have a severe neonatal encephalopathy and die young. Related conditions once called Rett variants, from CDKL5 (seizures from the first months) and FOXG1 (a congenital form), are now separate disorders.

03Clinical features

Autism

About a third to two-fifths of autistic children have intellectual disability; others have average or high intelligence, often with an uneven profile of strengths and difficulties, and a few have exceptional isolated skills. Girls and women more often camouflage their difficulties by imitating others, have interests that seem typical in kind if not in intensity, and are diagnosed later or misdiagnosed, for example with anxiety or a personality disorder. Adults often present with secondary anxiety or depression, burnout or difficulties at work.

Red flags for referral:

• no babbling, pointing or other gestures by 12 months;
• no single words by 16 months, and no spontaneous two-word phrases by 24 months;
• little response to name, eye contact or shared enjoyment, and no pretend play;
• repetitive movements, lining up objects, unusual sensory interests;
• any loss of language or social skills at any age, which also raises the question of epilepsy, Rett syndrome or a neurodegenerative disorder.

Comorbidity is the rule: ADHD in about 3 in 10, anxiety in up to 40 per cent, sleep problems in half or more, depression in adolescents and adults, epilepsy in about 1 in 10 (and up to a third with intellectual disability), gastrointestinal problems, feeding difficulties, tics and dyspraxia. Behaviour that challenges is often driven by distress, pain, sensory overload or change.

Asperger syndrome

ICD-10 requires that language (single words by 2, phrases by 3) and cognitive development were not delayed. Speech is fluent but may be pedantic, formal or one-sided; interests are intense and narrow; motor clumsiness is common. Difficulties often become clearer in adolescence, as relationships grow more complex, and anxiety and depression are frequent.

Rett syndrome

Development seems normal for the first 6 months or longer, then stalls and regresses:

The diagnosis needs a period of regression followed by recovery or stabilisation, with partial or complete loss of purposeful hand skills and of spoken language, an impaired or absent gait, and stereotyped hand movements, without brain injury, metabolic disease or severe infection as a cause. Supportive features include breathing disturbances when awake (over-breathing, breath-holding), bruxism, disturbed sleep, cold small hands and feet, scoliosis and bouts of laughing or screaming. Acquired microcephaly, a slowing of head growth, is common. Epilepsy affects most patients, and a long QT interval can cause sudden death. Intellectual disability is usually severe.

04Diagnosis and management

Recognition and assessment

In the US, the American Academy of Pediatrics recommends universal autism screening at 18 and 24 months, most often with the M-CHAT-R/F, a 20-question parent checklist for 16 to 30 months with a follow-up interview for intermediate scores. UK practice, and much of Europe, does not screen the whole population, but acts on concerns from parents, nurseries and health checks. A child with red flags is referred, without waiting, to a multidisciplinary team (paediatrician or psychiatrist, psychologist, speech and language therapist), which:

• takes a developmental history from the parents, with a structured interview such as the ADI-R, DISCO or 3di;
• observes the child, with the ADOS-2, a standardised play- and conversation-based assessment in modules by age and language, and gathers reports from nursery or school;
• assesses cognitive and language ability, and adaptive functioning;
• examines for dysmorphic features, skin signs of tuberous sclerosis and neurological signs, measures head size, and tests hearing and vision.

The instruments support but never replace clinical judgement. Investigations are not routine, but genetic tests (chromosomal microarray and fragile X) are done when there is intellectual disability, dysmorphic features or congenital anomalies, and US guidance advises them for every autistic child; an EEG is done for suspected seizures or regression. Adults are assessed with an informant's account of their childhood; the AQ-10 can screen.

Support and treatment of autism

The aim is not to cure autism but to help the person communicate, learn and live well, and to treat what comes with it.

• Early intervention: parent-mediated social communication programmes, in which parents learn to follow the child's lead and respond to their communication, improve parent-child interaction and some autism features, with effects lasting years.
• Education: adjustments in mainstream school or specialist provision; visual timetables and structure, predictable routines, warnings of change.
• Speech and language therapy and communication aids; occupational therapy for sensory needs and daily skills.
• Psychological support: adapted CBT for anxiety; positive behaviour support for behaviour that challenges.
• Family and adults: information, parent training and respite; help with work, housing and adapted mental health care.

No drug treats the core features of autism. Drugs are used for what comes with it:

Chelation, secretin, hyperbaric oxygen, exclusion diets and "miracle mineral solution" (chlorine dioxide) do not work, and some have killed or harmed children; families are told so, kindly, because they are widely promoted.

Management of Rett syndrome

Care is lifelong and multidisciplinary: treatment of epilepsy; an ECG at diagnosis and periodically, avoiding drugs that prolong the QT interval; nutrition, often by gastrostomy, and treatment of reflux and constipation; bone health; physiotherapy and monitoring of scoliosis, which may need surgery; communication through eye-gaze technology; and support for the family.

Trofinetide, a synthetic analogue of a fragment of insulin-like growth factor 1, is the first drug for Rett syndrome. In the 12-week phase 3 trial it modestly improved caregiver-rated behaviour and clinician-rated global impression. Diarrhoea is very common, and vomiting and weight loss are frequent. It was approved in the US in March 2023 for patients aged 2 and over. In the EU, the CHMP first recommended refusal in early 2026, judging the effect too small, then recommended approval on re-examination; the European Commission authorised it in August 2026 for neurobehavioural symptoms in patients aged 5 and over, and its availability depends on each country's pricing and reimbursement. Gene therapies are in clinical trials.

05Epidemiology

of children and adults worldwide are autistic

about 1per centof children and adults worldwide are autistic

among diagnosed children

3–4 : 1boys to girlsamong diagnosed children

have Rett syndrome

1 in 10,000girlshave Rett syndrome

The WHO estimates that about 1 in 127 people worldwide were autistic in 2021, and European studies find around 1 per cent or more. In the US, the CDC's surveillance found 1 in 31 eight-year-olds identified in 2022, with boys 3.4 times more often, reflecting broad criteria and active identification. The male excess is partly real and partly underdiagnosis in girls. Childhood disintegrative disorder was always rare, at a few per 100,000.

Rett syndrome affects about 1 in 10,000 to 15,000 girls; it is one of the commonest genetic causes of severe intellectual disability in girls.

06Prognosis

Autism is lifelong, but its course varies widely. The best predictors of adult outcome are intellectual ability and useful spoken language by about the age of 5 or 6. Social communication often improves through childhood, while anxiety and difficulties with independence can grow in adolescence. Many autistic adults without intellectual disability study, work and have relationships, often with support; others need lifelong care. Unemployment, loneliness and mental illness are common.

Mortality is raised, roughly two to two and a half times in Swedish data, from epilepsy and accidents such as drowning in those with intellectual disability, and from suicide, especially in autistic women without intellectual disability. Suicidal thoughts in autistic adolescents and adults are common and are asked about directly, in plain, concrete language.

In Rett syndrome, the regression stops and some communication and eye contact return, but motor function declines slowly in adult life. Many women live into middle age and beyond. Death comes from respiratory infection, seizures, malnutrition and, suddenly, from breathing or heart rhythm disturbances.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1A mother brings her 22-month-old son because he has no words, does not point to show her things, rarely looks at her when she calls his name and spends long periods lining up cars. His hearing has not been tested. What should happen?

Reassure her that boys talk late and review at 3 yearsArrange a hearing test and refer him to the local multidisciplinary autism assessment teamDiagnose autism on the history and start risperidoneAdvise a gluten-free and casein-free diet

2A 2-year-old girl developed normally until about 12 months. Since then she has lost the few words she had and the use of her hands for play, and she makes constant hand-wringing movements. Her head growth has slowed and she has episodes of over-breathing. Which gene is most likely affected?

FMR1TSC2MECP2SHANK3

3The parents of a 12-month-old with an autistic older brother ask whether the MMR vaccine could cause autism in their baby. What is the accurate answer?

The 1998 paper that claimed a link was retracted as fraudulent, and large studies, including one of over 650,000 Danish children, found no link, even in siblings of autistic childrenThe vaccine should be split into three separate injections to be safeThe vaccine should be delayed until the child is 3A link exists only in children with a family history of autism

4A 9-year-old autistic boy has frequent severe aggression and self-injury despite a well-delivered behaviour support plan, speech and language input and treatment of his constipation and poor sleep. The family is at breaking point. What is the most appropriate next step?

An SSRI to treat his core autistic featuresChelation therapyLong-term high-dose haloperidolA trial of risperidone or aripiprazole, with baseline and follow-up weight, metabolic and prolactin monitoring, stopped if there is no clear benefit by 6 weeks

5In ICD-10, what separates Asperger syndrome from childhood autism?

Asperger syndrome has no restricted or repetitive behavioursAsperger syndrome begins after the age of 3In Asperger syndrome there is no general delay in spoken language or cognitive developmentAsperger syndrome affects only girls