Developmental regression — the loss of previously acquired skills — is never a normal variant and always requires urgent investigation. The causes range from treatable metabolic conditions to neurodegenerative disease to abuse and neglect. West syndrome (infantile spasms) is a particularly critical diagnosis: characteristic salaam spasms (brief clusters of head-dropping, arm-extending movements) beginning at 3–12 months are accompanied by hypsarrhythmia on EEG and are associated with severe intellectual disability if not treated within days. Any parent who describes their infant having episodes of head drops or arm jerks must be referred same-day. Duchenne muscular dystrophy is an X-linked condition — calf hypertrophy and Gower's sign (using hands to climb up legs from floor) are the classic examination findings, typically presenting at 3–5 years. Early diagnosis enables genetic counselling and access to disease-modifying therapy (ataluren, exon-skipping). Hand preference before 18 months of age indicates asymmetric motor development and suggests unilateral cerebral pathology until proven otherwise.

The four developmental domains are semi-independent — a child can have isolated speech delay with normal motor development (hearing loss, ASD, familial language delay), or isolated gross motor delay with normal cognition (cerebral palsy, muscular dystrophy). The domain pattern guides investigation and referral. Corrected age is essential for premature infants: a 6-month-old baby born at 28 weeks gestation has a corrected age of only 3 months and should be assessed against 3-month milestones, not 6-month. Failure to use corrected age leads to massive over-referral of premature infants. The limit age is the age by which 97.5% of children achieve a milestone — failure to reach it requires prompt referral regardless of "wait and see" reassurance. Protodeclarative pointing (pointing to share interest — "look at that!") at 12 months is a key ASD screening marker — its absence, combined with no joint attention, is one of the strongest early predictors of autism. This is distinct from protoimperative pointing (pointing to request something) which is preserved in ASD.

Foetal alcohol spectrum disorder (FASD) is the most common preventable cause of developmental delay in the UK — it affects approximately 2–3% of the population and is consistently underdiagnosed. Key features include: flat philtrum, thin upper lip, small palpebral fissures, short stature, microcephaly, intellectual disability, and executive function difficulties. Any maternal alcohol use during pregnancy warrants FASD consideration. Bilingualism is a critical consideration in speech assessment — bilingual children exposed to two languages at home have larger total vocabulary across both languages than monolingual children, but may appear to have expressive language delay in English. Assessment should ideally be conducted in the child's dominant language, and parents should be asked what language is spoken at home. Adverse childhood experiences (ACEs) — documented in the Felitti et al ACE study — have dose-dependent effects on neurodevelopment; a child with 4+ ACEs has dramatically increased risk of developmental, cognitive, and behavioural difficulties. The social history is not separate from the medical history.

Tuberous sclerosis (TSC) is an autosomal dominant neurocutaneous condition — ash-leaf macules are present from birth and may only be visible under a Wood's lamp in fair-skinned children. TSC causes epilepsy (infantile spasms are a common presentation), autism, and intellectual disability. Early diagnosis allows mTOR inhibitor therapy (everolimus) for subependymal giant cell astrocytomas and seizure control. Neurofibromatosis type 1 (NF1) affects 1 in 3,000 — six or more café-au-lait patches >5mm in a pre-pubertal child is diagnostic. NF1 causes learning difficulties in ~50%, speech and language problems, and attention difficulties. Serum creatine kinase (CK) must be checked in any boy with motor delay — Duchenne MD causes CK levels 50–100× normal (often >10,000 IU/L) even before clinical weakness is apparent. The diagnosis window for disease-modifying therapy (exon-skipping, gene therapy) in Duchenne is closing rapidly — early diagnosis by age 3 is a treatment target. Head circumference must be measured and plotted at every developmental assessment — microcephaly is often subtle and its significance is underappreciated.

Chromosomal microarray has replaced standard karyotype as the first-line genetic test for unexplained GDD — it has ~10× higher resolution and detects submicroscopic copy number variants that a standard karyotype misses. The diagnostic yield for unexplained GDD/intellectual disability is 15–20%, making it the single highest-yield investigation in this context. Fragile X syndrome is the most common inherited (vs chromosomal) cause of intellectual disability — it is X-linked, so boys are more severely affected, and there is a premutation carrier state in females associated with premature ovarian insufficiency and fragile X-associated tremor/ataxia syndrome (FXTAS). Testing family members of an affected child has significant reproductive counselling implications. Hearing loss is the most common and most treatable cause of speech and language delay — it affects 1–2 per 1,000 newborns for significant bilateral loss, and glue ear (otitis media with effusion) affects up to 80% of children at some point. Formal audiology is mandatory in all children with speech and language delay and should be the first investigation requested, not the last.

Speech and Language Therapy (SALT) referral should not be delayed pending paediatric assessment — SALT is the most evidence-based intervention for speech and language delay and early intervention is critical. The critical period for language acquisition extends to approximately 7 years — the brain's neuroplasticity for language is highest in early childhood, and delayed intervention has lasting consequences. For autism, NICE NG142 recommends that the ASD diagnostic pathway begins with a multi-agency assessment team — in the UK, referral is typically to a community paediatrics team or Child Development Centre (CDC). The Education, Health and Care Plan (EHCP) — under the Children and Families Act 2014 — replaces the old Statement of Special Educational Needs. A child with significant developmental needs can request an EHCP assessment from the local authority — GP letters supporting the application are important. GPs should be familiar with the EHCP process and able to write supporting letters. The average waiting time for ASD assessment in the UK is now 2–3 years in many areas — early referral is essential, and GPs should signpost to support organisations (National Autistic Society) while families wait.

The principle of "treatable causes first" is critical in developmental delay — hypothyroidism, hearing loss, PKU, and seizure disorders are all modifiable conditions where delay in treatment causes preventable developmental harm. Congenital hypothyroidism treated within the first 2 weeks of life has an excellent neurodevelopmental prognosis — untreated, it causes cretinism (severe intellectual disability). This is why the newborn bloodspot screen is so important. The Hanen programme ("It Takes Two to Talk") is a parent-training intervention for language delay — evidence shows parental responsiveness to child communication attempts is a key driver of language development, and teaching parents to respond contingently, wait expectantly, and use child-directed speech produces measurable language gains. Early intensive behavioural intervention (EIBI/ABA — Applied Behaviour Analysis) for young children with ASD has the strongest evidence base of any ASD-specific intervention — the NICE guideline NG142 supports its use in early childhood. Sleep disorders affect 50–80% of children with ASD and GDD — they have a significant impact on the whole family. Melatonin is the most evidence-based pharmacological intervention for ASD-related sleep problems and is commonly prescribed via paediatrics with GP continuation.

The "30 million word gap" study (Hart and Risley, 1995) demonstrated that children from lower socioeconomic backgrounds hear 30 million fewer words by age 3 than their more advantaged peers — this gap strongly predicts school attainment and life outcomes. Language exposure from birth is a critical developmental intervention, not a parenting nicety. The "serve and return" model of responsive interaction (coined by the Harvard Centre on the Developing Child) is one of the most robust concepts in early child development — infants who experience consistent responses to their vocalisations and gestures develop stronger neural architecture for language, emotional regulation, and executive function. GPs should actively signpost parents to the Hanen programme, which translates this science into practical parenting techniques. Disability Living Allowance (DLA) for children under 16 is a non-means-tested benefit for children with developmental disability or chronic health conditions — GP support letters significantly increase successful applications. Many families are unaware of their entitlements — proactively asking "Do you know what financial and practical support is available?" is a meaningful clinical intervention.

The Annual Health Check for people with learning disabilities is one of the most important primary care quality indicators — it is an NHS England Directed Enhanced Service (DES) and enables systematic health surveillance for a population at high risk of preventable health conditions (hypothyroidism, epilepsy, mental health problems, constipation, obesity). Learning disability is associated with 20-year shorter life expectancy — largely due to preventable conditions identified and treated too late. The STOMP programme (Stopping Over-Medication of People with Learning Disability, Autism or Both) was launched in 2016 after data showed that up to 30% of people with learning disabilities were prescribed antipsychotic medication without a diagnosed mental health condition — often to manage behaviours that challenge. GPs should review all psychotropic prescriptions in patients with learning disabilities at each annual health check, considering deprescribing where appropriate. Transition from paediatric to adult services is consistently identified as the highest-risk period for young people with developmental disabilities — service discontinuity, loss of coordinated care, and social isolation increase rates of mental health crisis, self-harm, and carer breakdown at this time. Active GP monitoring from age 14 with explicit transition planning is a clinical priority.