Pediatrics (System-Integrated)

Autism spectrum disorder: screening and referral

Clinical Overview and When to Suspect Autism Spectrum Disorder

— Prevalence ~1 in 36 children at age 8

— Male:female ratio ~4:1 (females underdiagnosed — more camouflaging)

— Strong genetic loading: ~80% heritability; recurrence risk in siblings ~10–20%

— Parent reports "he doesn't respond to his name" by 12 months

— No babbling or pointing/gesturing by 12 months, no single words by 16 months, no 2-word phrases by 24 months

— Loss of language or social skills at any age (regression — red flag, evaluate immediately)

— Lack of joint attention, lack of pretend play by 18 months

— Restricted interests, lining up toys, hand-flapping, toe-walking, insistence on sameness

— Sensory hyper-/hyporeactivity (covers ears, indifferent to pain, food selectivity by texture)

— Intellectual disability (~35%), ADHD (~30–50%), anxiety, epilepsy (~20%), GI complaints, sleep disturbance, feeding/PICA, genetic syndromes (Fragile X, tuberous sclerosis, Rett, 22q11)

Board pearl: AAP recommends universal ASD-specific screening at the 18- and 24-month well-child visits (in addition to general developmental screening at 9, 18, and 30 months). A "watch and wait" approach when screening is positive is the wrong answer — early referral drives outcomes.

Definition: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by persistent deficits in social communication/interaction plus restricted, repetitive patterns of behavior, interests, or activities (RRBs), with onset in early developmental period and functional impairment.

Epidemiology (US, CDC ADDM):

When to suspect ASD in primary care:

Comorbidities to anticipate:

Step 3 framing: ASD is a clinical diagnosis based on DSM-5-TR criteria — not a lab or imaging diagnosis. Primary care role is surveillance at every well visit, formal screening at 18 and 24 months, and prompt referral if positive.

Presentation Patterns and Key History

— A. Social communication/interaction deficits across multiple contexts:

— Deficits in social-emotional reciprocity (reduced back-and-forth conversation, failure to share interests/emotions)

— Deficits in nonverbal communicative behaviors (poor eye contact, reduced gestures, flat affect)

— Deficits in developing/maintaining relationships (difficulty with imaginative play, no peer interest)

— B. Restricted, repetitive behaviors (≥2 of 4):

— Stereotyped/repetitive motor movements, speech, or object use (echolalia, lining up toys)

— Insistence on sameness, rigid routines, ritualized behavior (distress at small changes)

— Highly restricted, fixated interests of abnormal intensity (memorizing train schedules)

— Hyper- or hyporeactivity to sensory input (textures, sounds, lights, pain)

— Level 1: "Requiring support"

— Level 2: "Requiring substantial support"

— Level 3: "Requiring very substantial support"

— Toddler: failure to respond to name, no joint attention, language delay, no pointing

— Preschool: odd play, echolalia, scripted speech, meltdowns with routine changes

— School-age: social awkwardness, "little professor" speech, bullying victim, narrow interests

— Adolescent (often the missed female): anxiety, depression, eating issues, social exhaustion from masking

— "Does your child point to show you things they find interesting?" (protodeclarative pointing — absent in ASD)

— "Does your child play pretend?" (absent or limited)

— "How does your child react to changes in routine?"

— Family history of ASD, ID, genetic syndromes; prenatal valproate exposure; advanced parental age

Key distinction: Pointing to request (give me that) may be preserved, but pointing to share (look at that!) is the discriminating absence in ASD. Joint attention deficit is the social-communication core feature on board stems.

Two DSM-5-TR symptom domains (both required):

Severity levels (specified separately for each domain):

Age-specific presentation:

High-yield history questions:

Physical Exam Findings and Developmental Assessment

— Poor eye contact, doesn't orient to name, doesn't engage examiner socially

— Repetitive motor behaviors: hand-flapping, rocking, spinning, toe-walking

— Unusual play: lining up toys, spinning wheels, no symbolic/pretend play

— Echolalia (immediate or delayed), scripted/pedantic speech, atypical prosody

— Sensory responses: covering ears at exam-room sounds, fascination with lights

— Macrocephaly in ~15–20% (accelerated head growth in first 2 years)

— Microcephaly → consider Rett syndrome, congenital infection, other syndromes

— Plot all parameters; deceleration of head growth + regression in a girl = Rett until proven otherwise

— Fragile X: long face, large ears, macroorchidism (post-pubertal), joint hyperlaxity

— Tuberous sclerosis: hypopigmented (ash-leaf) macules under Wood lamp, facial angiofibromas, shagreen patch, seizures

— Neurofibromatosis-1: café-au-lait macules (≥6, >5 mm), axillary freckling

— Angelman/Prader-Willi: dysmorphism, hypotonia, distinctive behavior

— PKU: musty odor, fair complexion (if newborn screen missed)

— Smith-Lemli-Opitz: 2-3 toe syndactyly, ptosis

— Hypotonia, motor clumsiness, toe-walking

— Look for focal deficits (atypical → imaging warranted)

— Hearing screen — always rule out hearing loss as a cause of language delay

— M-CHAT-R/F at 18 and 24 months (screening, not diagnostic)

— Ages & Stages Questionnaire (ASQ) or PEDS for general developmental surveillance

Step 3 management: Before attributing language delay to ASD, order audiology evaluation (formal audiometry or ABR if uncooperative) and confirm normal vision — these are corrected causes and a frequent distractor on exams.

General observation (often the most informative):

Growth and head circumference:

Targeted exam for syndromic causes:

Neurologic exam:

Standardized developmental assessment in office:

Screening Tools and Initial Workup

— General developmental screening: 9, 18, and 30 months (validated tool — ASQ, PEDS)

— ASD-specific screening: 18 months and 24 months with M-CHAT-R/F

— Surveillance (informal) at every well-child visit

— 20-item parent questionnaire, ages 16–30 months

— Score 0–2 = low risk; 3–7 = medium risk → administer follow-up interview; ≥8 = high risk → refer immediately, skip follow-up

— Sensitivity ~85%, specificity ~99% after follow-up step

— A positive M-CHAT-R/F is not a diagnosis — it triggers referral

— Audiology evaluation — mandatory for any language delay

— Vision screen

— Lead level if risk factors (pica, old housing) — required in many state Medicaid programs

— Newborn screen review (PKU, congenital hypothyroidism)

— Chromosomal microarray (CMA) — first-line, yield ~10–20%

— Fragile X (FMR1) testing — particularly in males, family history of ID

— Karyotype only if clinical suspicion of aneuploidy

— MECP2 (girls with regression — Rett)

— PTEN if macrocephaly >2.5 SD

— Whole-exome sequencing increasingly first-line in many centers

— EEG if suspected seizures or regression; not routine

— Metabolic studies if regression, hypotonia, dysmorphism, consanguinity

Board pearl: A 24-month-old with positive M-CHAT-R/F is referred to (1) developmental-behavioral pediatrics/child psychiatry/psychology for diagnostic evaluation AND (2) Early Intervention (Part C, IDEA) AND (3) audiology — all three simultaneously, without waiting for the diagnosis to be confirmed.

AAP screening schedule (memorize):

M-CHAT-R/F (Modified Checklist for Autism in Toddlers, Revised with Follow-up):

Initial laboratory and ancillary evaluation (after positive screen or clinical suspicion):

First-tier genetic testing (per ACMG):

Second-tier (consider, often via specialist):

Diagnostic Confirmation — Specialist Evaluation

— Developmental-behavioral pediatrician, child psychiatrist, child neurologist, or licensed clinical psychologist with autism expertise

— Diagnosis is clinical, based on DSM-5-TR criteria, supported by standardized instruments

— ADOS-2 (Autism Diagnostic Observation Schedule, 2nd ed.): semi-structured, play-based observation; modules tailored to age/language level

— ADI-R (Autism Diagnostic Interview-Revised): structured caregiver interview, ~2 hours

— Combined ADOS-2 + ADI-R is the research/clinical reference standard

— Mullen Scales of Early Learning, Bayley-4 (young children)

— WISC-V, Stanford-Binet (older)

— Vineland-3 Adaptive Behavior Scales — essential for severity level and service eligibility

— Quantify expressive/receptive language gap

— Assess sensory processing, fine/gross motor, feeding

— CMA + Fragile X for all

— MECP2 in females, PTEN if macrocephaly, WES per local protocol

— Brain MRI only if focal neuro signs, microcephaly, regression, or seizures

— EEG only if clinical seizures or epileptiform regression (Landau-Kleffner mimicker)

— Level 1 (high-functioning, formerly Asperger): support social skills, often mainstream classroom

— Level 2/3: substantial supports, may need self-contained classroom, ABA-intensive

Key distinction: The CMA + Fragile X combination identifies a genetic etiology in ~25% of ASD cases and changes counseling (recurrence risk, associated medical surveillance for syndromes like 22q11, tuberous sclerosis, PTEN-hamartoma tumor syndrome). Routine brain MRI and EEG are not indicated in uncomplicated ASD evaluation.

Who makes the diagnosis:

Gold-standard diagnostic instruments:

Cognitive and adaptive testing:

Speech-language and OT evaluations:

Genetic and medical workup (confirmatory, beyond initial tier):

Differentiate severity for service planning:

Referral Pathway and Early Intervention Logic

— Refer at first positive screen or clinical suspicion, not after diagnostic confirmation

— Early intensive intervention before age 3 produces the largest gains in cognition, language, and adaptive function

— 1. Diagnostic evaluation: developmental-behavioral pediatrics, child psychiatry, psychology, or neurology

— 2. Early Intervention (IDEA Part C): for children <3 years old — free, federally mandated; family contacts state EI program directly or PCP refers

— 3. Public school district (IDEA Part B, Section 619): for children ≥3 years old — Individualized Education Program (IEP), evaluation required within state-mandated timeline (often 60 days)

— Audiology (always)

— Speech-language pathology

— Occupational therapy (sensory, feeding, fine motor)

— Genetics consultation after first-tier testing or for syndromic features

— Applied Behavior Analysis (ABA) — most evidence; 20–40 hr/week ideal in early years

— Early Start Denver Model (ESDM) — naturalistic developmental-behavioral, ages 12–48 months

— Pivotal Response Treatment, JASPER, DIR/Floortime

— Speech therapy + AAC (augmentative/alternative communication) for nonverbal children (PECS, speech-generating devices)

— Social skills training for school-age

— Chelation, hyperbaric O2, secretin, "leaky gut" diets, stem cells, MMS — counsel families against

Step 3 management: For a 22-month-old with positive M-CHAT-R/F, the correct order set is: (1) refer to state Early Intervention program today, (2) refer to developmental-behavioral pediatrics for ADOS-2, (3) audiology, (4) initiate CMA + Fragile X testing. Do not delay EI referral pending formal diagnosis.

The "do not wait" principle:

Three parallel referrals from primary care:

Ancillary referrals:

Evidence-based interventions:

What does NOT work / harmful:

Pharmacotherapy — Targeting Comorbid Symptoms

— Risperidone — ages 5–16, atypical antipsychotic; start low (0.25 mg qhs <20 kg; 0.5 mg ≥20 kg)

— Aripiprazole — ages 6–17; start 2 mg/day, titrate

— Indications: severe aggression, self-injury, tantrums interfering with function — not for core ASD symptoms

— Monitor: weight, BMI, fasting glucose, lipids, prolactin, AIMS (tardive dyskinesia) baseline and periodically; sedation, EPS

— Methylphenidate — first-line; ASD children more sensitive, start lower (e.g., 2.5–5 mg) and titrate slowly; higher rate of irritability/appetite loss than neurotypical ADHD

— Atomoxetine or guanfacine ER/clonidine ER — useful when stimulants poorly tolerated; guanfacine helpful for hyperactivity + sleep

— SSRIs (fluoxetine, sertraline) — modest evidence; start at low doses, watch for activation/disinhibition (more common in ASD)

— Black box warning: suicidality in <25 y/o — monitor weekly initially

— Sleep hygiene first

— Melatonin 1–3 mg 30 min before bedtime — best-studied pharmacologic option

— Standard antiepileptic management; avoid valproate in females of childbearing potential when alternatives exist

Board pearl: In a 7-year-old with ASD and severe self-injurious head-banging unresponsive to behavioral therapy, risperidone or aripiprazole is the FDA-approved choice. Baseline metabolic panel, weight/height, and AIMS exam must precede initiation, with metabolic monitoring at 3 months then yearly.

Core principle: No medication treats core ASD social-communication deficits. Pharmacotherapy targets comorbid symptoms or dangerous behaviors that impair function or interfere with behavioral therapy.

FDA-approved agents for irritability/aggression/self-injury in ASD:

ADHD symptoms (co-occur in 30–50%):

Anxiety/depression (older children, adolescents):

Sleep disturbance (very common):

Seizures (~20% lifetime):

Procedures and Non-Pharmacologic Therapeutic Bundle

— Applied Behavior Analysis (ABA): evidence-based, 20–40 hours/week in early years; insurance coverage mandated in most US states

— Early Start Denver Model (ESDM): naturalistic, parent + therapist delivered, ages 12–48 months — proven gains in IQ, language, adaptive behavior

— Pivotal Response Treatment (PRT), JASPER (Joint Attention, Symbolic Play, Engagement, Regulation)

— TEACCH: structured teaching, visual supports — useful in school environments

— Speech-language therapy

— Picture Exchange Communication System (PECS) and speech-generating devices (AAC) for minimally verbal children — do NOT delay AAC for fear of impeding speech (myth); AAC supports, not replaces, expressive language development

— Sensory integration, fine motor, ADLs, feeding

— IFSP (Individualized Family Service Plan) <3 years — Part C

— IEP (Individualized Education Program) ≥3 years — Part B

— 504 Plan for accommodations when IEP not required (higher-functioning students)

— Parent-mediated interventions (e.g., PACT, RUBI for disruptive behavior) — improve generalization and reduce caregiver stress

— Begin by age 14–16 for vocational training, independent living skills, guardianship/supported decision-making decisions before age 18

— Chelation, hyperbaric oxygen, secretin, IVIG, stem cell therapy, "miracle mineral solution" (MMS — actually bleach; report if used)

CCS pearl: Order set for newly diagnosed ASD includes: ABA referral, speech therapy, OT, audiology (if not done), genetics consult (if not done), Early Intervention or school IEP referral, parent education, and metabolic baseline only if starting antipsychotic.

Behavioral interventions (the foundation of treatment):

Communication interventions:

Occupational therapy:

School-based services (IDEA):

Parent training programs:

Social skills groups for school-age and adolescents

Transition planning:

Treatments that lack evidence / are harmful (counsel against):

Special Populations — Genetic Syndromes and Medical Comorbidities

— Fragile X syndrome (FMR1): most common inherited cause of ID/ASD; long face, large ears, macroorchidism (post-pubertal), hand-flapping. Test all children with ASD regardless of phenotype. Cascade testing for family.

— Tuberous sclerosis complex (TSC1/TSC2): ASH-leaf macules (Wood lamp), facial angiofibromas, infantile spasms, cortical tubers. Up to 50% of TSC patients have ASD. ECG (rhabdomyomas), renal US (AMLs), brain MRI.

— Rett syndrome (MECP2): girls; normal development then regression at 6–18 mo, hand-wringing stereotypies, deceleration of head growth, breath-holding/hyperventilation, seizures. Test MECP2 in any girl with regression.

— PTEN-hamartoma: macrocephaly >2.5 SD; cancer surveillance required

— 22q11.2 deletion, Angelman, Smith-Magenis, Williams, Down syndrome, neurofibromatosis-1

— Epilepsy (~20% lifetime, peaks in early childhood and adolescence) — EEG if clinical seizures

— GI symptoms — constipation, GERD, food selectivity; treat conventionally; don't attribute to "leaky gut"

— Sleep disorders (50–80%) — behavioral first, melatonin second

— Feeding/nutrition — selective eating → vitamin D, iron, calcium, zinc deficiencies; consider scurvy in extreme cases

— Obesity (especially with antipsychotics) — monitor BMI

— Pica — recheck lead

— Mental health: anxiety, depression, OCD, ADHD

Board pearl: A girl with normal first-year milestones who loses purposeful hand use and develops midline hand-wringing with deceleration of head circumference → Rett syndrome; order MECP2 testing, not just routine ASD workup. Brain MRI is unrevealing.

Syndromic ASD — recognize and pursue:

Medical comorbidities to actively screen for:

Renal/hepatic adjustments: rare in pediatric ASD pharmacotherapy; antipsychotics largely hepatic metabolism — caution with hepatic dysfunction; check ALT before/during risperidone if indicated

Special Populations — Females, Adolescents, and Adults

— Diagnostic gap: M:F ratio narrows from 4:1 to ~3:1 when ascertainment is rigorous

— Camouflaging/masking: imitating peers, scripting social interactions, intense effort with social exhaustion → present later with anxiety, depression, eating disorders

— Often diagnosed in adolescence/adulthood after years of misdiagnosis (social anxiety, BPD, OCD)

— Special interests may be socially typical (animals, celebrities) and miss criteria-based suspicion

— Increased anxiety, depression, suicidality — screen at every visit (PHQ-9, GAD-7, Ask Suicide-Screening Questions/ASQ)

— Sexuality and consent education — adapted, concrete, repeated

— Higher risk of sexual victimization → safety education

— Driving evaluation may be needed (slower processing, executive function)

— Substance use rates lower overall but higher in those with co-occurring ADHD

— Vocational training, supported employment, post-secondary supports

— Health care transition plan, transfer to adult PCP/psychiatrist

— Guardianship vs. supported decision-making vs. power of attorney — discuss before age 18; default is full legal autonomy at 18 unless court orders otherwise

— Lifetime persistence of core features; outcomes vary widely

— Higher rates of unemployment, social isolation, comorbid depression

— Mortality: elevated, especially from epilepsy, accidents, suicide (in higher-functioning); discuss safety

— Recurrence risk ~10–20% in siblings; counsel on avoiding valproate in pregnancy (known teratogen → ↑ASD risk)

— Maternal SSRI use has small/uncertain effect; do not stop SSRI for prevention

Key distinction: A 15-year-old girl with anxiety, depression, "intense friendships," eating issues, and exhaustion from "trying to fit in" — consider late-diagnosed ASD before settling on primary anxiety or borderline traits. Refer for diagnostic evaluation.

Females with ASD — the missed population:

Adolescents:

Transition to adult care (start by age 14):

Adults:

Pregnancy considerations (adult patient or sibling planning):

Complications and Adverse Outcomes

— Elopement/wandering in ~50% of children with ASD; major drowning risk → swim training, door alarms, ID bracelets, GPS devices, water safety counseling at every visit

— Self-injurious behavior (head-banging, hand-biting) — assess for pain (otitis, dental, constipation) before assuming behavioral

— Aggression toward caregivers/siblings

— Suicidality — elevated risk, particularly in adolescents with higher cognitive function and depression

— Epilepsy — bimodal peaks (early childhood, adolescence), ~20% lifetime

— Constipation, GERD, dental caries (sensory aversion to brushing)

— Obesity and metabolic syndrome (diet selectivity + antipsychotics)

— Sleep deprivation → behavioral deterioration

— Nutritional deficiencies from food selectivity (vitamin D, iron, vitamin C/scurvy in extremes)

— Anxiety disorders (~40%), depression, OCD, ADHD, oppositional defiant, tics

— Antipsychotic weight gain, metabolic syndrome, prolactin elevation, EPS, sedation, tardive dyskinesia

— Stimulant-induced irritability (more common than in neurotypical ADHD)

— SSRI activation/disinhibition

— Polypharmacy creep — review and deprescribe regularly

— Caregiver burnout, depression, financial strain → screen caregivers and offer respite resources

— Sibling stress and mental health

— 2–3× general population; drowning, seizures, suicide major contributors

Step 3 management: At every ASD well visit, document water safety counseling and elopement risk assessment — wandering accounts for the largest preventable mortality in young children with ASD. Provide families with the AAP "Big Red Safety Toolkit" equivalent resources.

Behavioral and safety:

Medical complications:

Mental health comorbidities (drive much of disability):

Iatrogenic / treatment-related:

Family/social:

Mortality:

When to Escalate — Urgent Referral and Crisis Management

— Developmental regression at any age (especially loss of language or social skills)

— Suspected seizures — staring spells, focal motor, post-ictal confusion → urgent neurology + EEG

— Suicidal ideation or plan — emergency psychiatric evaluation

— Severe self-injurious behavior causing tissue damage

— Aggression with safety risk to child, caregivers, siblings

— Catatonia (rare but real in ASD adolescents) — mutism, posturing, rigidity → emergency psych

— Acute behavioral crisis with safety concerns → ED for psychiatric evaluation

— Status epilepticus, new-onset seizures → ED

— Severe dehydration/malnutrition from food refusal → admit

— Avoid sensory overload in ED: quiet room, dim lights, minimize staff turnover, caregiver at bedside, advance preparation when possible

— Failure to make progress in early intervention after 6 months → re-evaluate diagnosis and intensify

— New regression in an established ASD child → re-image, EEG, metabolic, MECP2 if not done

— Genetics: dysmorphism, family history, after initial first-tier testing for counseling

— Neurology: seizures, regression, focal exam, abnormal head circumference trajectory

— Child psychiatry: medication management, severe aggression, comorbid mood/anxiety

— GI: refractory constipation, suspected EoE/celiac in food refusal

— Provide families with crisis hotlines (988), mobile crisis teams, safety plan, behavior emergency plan from ABA team

CCS pearl: For an ASD adolescent in the ED with acute agitation, de-escalation and environmental modification come first (quiet room, familiar caregiver, predictable communication). If pharmacologic, oral risperidone or olanzapine preferred over IM where feasible; avoid restraints unless safety requires.

Same-day urgent referral indicators (do not wait for routine):

ED/inpatient triage:

Outpatient escalation:

Specialist referral indications:

Crisis planning:

Key Differentials — Same-Category (Neurodevelopmental/Psychiatric)

— Delays across domains but social reciprocity and joint attention are preserved relative to mental age

— Many ASD children also have ID (~35%) — both diagnoses can co-exist

— Language delay without social-communication deficits or RRBs

— Child still points to share, shows joint attention, engages socially

— Social-communication deficits without RRBs — DSM-5-TR distinct category

— Diagnose only after ASD ruled out

— Inattention/hyperactivity without core social-communication or RRB features

— Frequently co-occurs with ASD (~30–50%)

— Selective mutism: speaks at home, silent at school — preserved social interest with familiar people

— Social anxiety: desires social interaction but fears it; ASD lacks the desire/skill

— Ego-dystonic obsessions with anxiety relief from compulsions

— ASD restricted interests are ego-syntonic, pleasurable

— History of profound neglect (e.g., institutional care); improves with stable caregiving

— May mimic ASD socially but RRBs less prominent and history is diagnostic

— Repetitive movements without core social-communication deficits

— Positive symptoms (hallucinations, delusions) absent in ASD

— Onset typically late adolescence/young adult

Key distinction: Language disorder vs. ASD — both have delayed speech, but the ASD child also has deficits in joint attention, social reciprocity, and pretend play, plus RRBs. A child with isolated language delay who points, shares, and plays imaginatively does not have ASD.

Global developmental delay / intellectual disability (ID):

Language disorder (expressive/mixed receptive-expressive):

Social (pragmatic) communication disorder:

ADHD:

Anxiety disorders / selective mutism:

OCD:

Reactive attachment disorder / severe deprivation:

Stereotypic movement disorder:

Schizophrenia (older adolescents):

Key Differentials — Other Categories (Medical and Sensory)

— Mandatory rule-out for any language delay

— Sensorineural loss → poor response to name, delayed language, but social engagement and joint attention preserved

— Order audiogram or ABR; review newborn hearing screen

— Severe visual impairment can produce ASD-like behaviors (lack of eye contact, stereotypies — "blindisms")

— Distinguish via ophthalmology evaluation

— Pica + developmental concerns → check lead level

— Treat with chelation only for elevated lead, not for "autism treatment"

— PKU (if newborn screen missed), creatine deficiency, mitochondrial disorders, Smith-Lemli-Opitz, mucopolysaccharidoses

— Regression, hypotonia, dysmorphism, hepatosplenomegaly, consanguinity → metabolic workup

— Especially congenital CMV — leading nongenetic cause of sensorineural hearing loss and developmental delay; consider CMV PCR (urine or saved newborn dried blood spot) in unexplained hearing loss + developmental concerns

— Prenatal alcohol exposure, characteristic facies (smooth philtrum, thin vermilion, short palpebral fissures), growth restriction, cognitive/behavioral phenotype overlapping ASD

— Regression of language with EEG abnormalities (CSWS) — order EEG including sleep

— Institutionalization → quasi-autism that improves with caregiving

— Untreated congenital hypothyroidism — review newborn screen

Board pearl: Any child presenting with language regression deserves an audiology evaluation, EEG (especially overnight to capture sleep — Landau-Kleffner), and MECP2 testing in girls before settling on ASD as the regression etiology.

Hearing loss:

Vision impairment:

Lead toxicity / heavy metal exposure:

Inborn errors of metabolism:

Congenital infections (TORCH):

Fetal alcohol spectrum disorder (FASD):

Landau-Kleffner syndrome (acquired epileptic aphasia):

Severe neglect/trauma:

Thyroid disease:

Long-Term Plan, Secondary Prevention, and Care Coordination

— Coordinated, family-centered, longitudinal care

— Maintain master problem list, medication list, allergy list, care team contacts

— Reconcile after every specialist visit

— Vaccines on standard schedule — there is no link between vaccines and autism; address parental hesitancy with evidence and motivational interviewing

— Lead screening per state guidelines, dental visits q6mo (high caries risk), vision/hearing

— BMI tracking; metabolic labs if on antipsychotic (fasting glucose, lipids, prolactin)

— Continue evidence-based behavioral therapies; reassess intensity annually

— Medication review at every visit — deprescribe when behavior stable

— Sleep, GI, nutrition reviewed at every well visit

— IEP reviewed annually; full re-evaluation every 3 years

— Track progress on measurable goals

— Advocate for least restrictive environment with appropriate supports

— Respite care, parent support groups, sibling support

— Caregiver depression screening (PHQ-2/9) at child's visits

— Connect with Autism Society, state autism councils, Family Voices

— Most US states mandate ABA coverage; assist with appeals

— Supplemental Security Income (SSI) for qualifying families

— Medicaid waivers (HCBS) for home/community-based services

— Vocational, post-secondary, independent living, guardianship/supported decision-making, transfer to adult medical/psychiatric care

Step 3 management: When parents express vaccine hesitancy citing ASD concerns, acknowledge their concern, share the strength of evidence (multiple large studies, no link), continue to recommend the schedule, and document the discussion. Do not dismiss the family from the practice for refusal; offer alternative schedules only after standard recommendation.

Medical home model — the PCP role:

Routine preventive care (do not skip because of ASD):

Symptom-targeted maintenance:

Education plan:

Family supports:

Insurance and benefits:

Transition planning (age ≥14):

Follow-Up, Monitoring, and Counseling Cadence

— Standard schedule (2 wk, 2/4/6/9/12/15/18/24/30 mo, then yearly)

— Developmental screening at 9, 18, 30 mo; ASD-specific at 18 and 24 mo

— More frequent visits for medication titration or behavioral crises

— Every 3–6 months for first 1–2 years to assess therapy progress and family adjustment

— Annual re-evaluation of intervention intensity, comorbidities, school placement

— Antipsychotics: weight/BMI/BP each visit; fasting glucose, lipids, prolactin at baseline, 3 months, then yearly; AIMS exam q6mo for tardive dyskinesia

— Stimulants: HR, BP, weight, height, appetite, sleep, mood at each visit

— SSRIs: weekly contact x 4 wk after start in <25 y/o (FDA black box), then monthly to stable

— Water safety and elopement prevention — door alarms, fencing, ID, swim lessons

— Dental hygiene (sensory adaptations, sedation dentistry if needed)

— Nutrition and feeding

— Sleep hygiene

— Sexuality/safety education in adolescence

— Caregiver well-being (PHQ-2 for primary caregiver)

— Annual IEP meeting; PCP letters of medical necessity for therapies

— 504 Plan for higher-functioning students requiring accommodations

— Recurrence risk for siblings (~10–20% empirical, higher if syndromic etiology identified)

— Cascade testing if a familial variant is found

Board pearl: A 6-year-old with ASD started on risperidone 6 months ago presents for follow-up. Required monitoring includes weight/BMI, fasting glucose, fasting lipid panel, prolactin (if symptomatic), and AIMS exam. Failure to monitor metabolic parameters is a board-favored patient-safety vignette.

Well-child visit cadence (AAP Bright Futures):

Monitoring after diagnosis:

Medication monitoring:

Counseling at every visit:

School communication:

Genetic counseling:

Ethical, Legal, and Patient Safety Considerations

— Parents/guardians provide consent for minors; child assent should be sought developmentally appropriately

— At age 18, legal autonomy defaults to the patient — even with significant ID

— Options for adult decision-making support:

— Supported decision-making (least restrictive, preferred when possible)

— Power of attorney, health care proxy

— Guardianship — court-ordered, most restrictive; pursue only when necessary

— Discuss with families starting at age 14–16 so legal arrangements are in place before 18th birthday

— Suspected child abuse/neglect → mandatory report to CPS (children with ASD have elevated abuse risk)

— Use of harmful "treatments" (e.g., MMS/chlorine dioxide, unsupervised chelation) constitutes medical neglect — report

— Counsel, document, maintain relationship; respect autonomy while continuing to recommend

— In outbreak scenarios, communicate community/herd risk

— Transfer to adult PCP/psychiatrist at age 18–21 — prepare summary, medication list, behavior plan, warm handoff

— Communication barriers in adult ED → carry a one-page medical/communication summary

— Consent process must accommodate cognitive level; IRB-approved adapted consent for participants with ID

— School records, genetic results, psychiatric diagnoses — protect under HIPAA/FERPA

— Discuss who has access before initiating testing (e.g., genetic discrimination protections under GINA)

— Avoid in school and clinical settings except for imminent safety; document and debrief

— ADA accommodations; Section 504; Olmstead (community integration)

Step 3 management: A 17-year-old with ASD and moderate ID will turn 18 in 4 months. The most appropriate next step is to discuss decision-making options (supported decision-making, health care proxy, guardianship) with the family and refer to a disability attorney or community legal aid so arrangements are in place before legal majority transfers automatically.

Informed consent and assent:

Mandatory reporting:

Vaccine refusal:

Transition-of-care safety:

Research participation:

Confidentiality:

Restraint and seclusion:

Disability rights:

High-Yield Associations and Rapid-Fire Facts

Board pearl: Among rapid-fire associations, the highest-yield combos: (1) macrocephaly → PTEN; (2) ash-leaf macules → TSC; (3) girl + regression → Rett; (4) male + large testes/long face → Fragile X. Each implies a different test beyond the standard CMA + FMR1.

Screening: M-CHAT-R/F at 18 and 24 months (AAP universal)

First-tier genetics: Chromosomal microarray + Fragile X (FMR1) for all

Macrocephaly + ASD: think PTEN-hamartoma — order PTEN testing

Girl + regression + hand-wringing + decel head circumference: Rett (MECP2)

Ash-leaf spots + infantile spasms + ASD: Tuberous sclerosis

Long face, large ears, macroorchidism, ID: Fragile X

Valproate in pregnancy: ↑ASD risk — avoid when alternatives exist

MMR vaccine and autism: no causal link (large studies; Wakefield retracted)

Universal genetic testing yield: ~10–20% with CMA, additional ~2–5% with FMR1, higher with WES

Joint attention + protodeclarative pointing: deficient in ASD — most discriminating early sign

Echolalia + scripted speech: classic

Toe-walking + sensory issues: common but nonspecific

FDA-approved meds for ASD irritability: risperidone (≥5 y), aripiprazole (≥6 y) — for behavior, not core ASD

Melatonin: best-studied agent for ASD sleep

Most preventable cause of death in young ASD child: drowning/elopement

Epilepsy prevalence in ASD: ~20% lifetime; bimodal peaks

ADHD comorbidity: 30–50% — DSM-5-TR allows co-diagnosis (changed from DSM-IV)

ID comorbidity: ~35%

Sex ratio: ~4:1 M:F (narrows with better ascertainment)

IDEA Part C: ages 0–3, IFSP, free Early Intervention

IDEA Part B: ages 3–21, IEP through school district

Section 504: accommodations without IEP

Best evidence behavioral therapy: ABA, ESDM — early, intensive

Sibling recurrence risk: ~10–20%

Camouflaging: female phenotype, late diagnosis with anxiety/depression

Catatonia in ASD adolescent: real entity, emergency

Board Question Stem Patterns

— Toddler with limited eye contact, doesn't respond to name, no pointing, lines up toys

— Question: next step? → Administer M-CHAT-R/F (if not already done), or if positive → refer to developmental-behavioral pediatrics, Early Intervention, and audiology in parallel

— Wrong answers: "reassure and recheck at 30 months," "order MRI"

— Asks about next step → Multiple simultaneous referrals, not waiting for diagnosis

— Confirmed ASD, what labs? → CMA + Fragile X, audiology if not done; not routine MRI/EEG

— Girl with normal early development, loss of hand use at 12–18 mo, hand-wringing, decel HC → Rett, MECP2 testing

— Boy with language regression at 3–5 y, normal exam → EEG (sleep) for Landau-Kleffner

— Order PTEN testing

— FDA-approved options: risperidone or aripiprazole, with baseline metabolic and AIMS monitoring

— Acknowledge, educate using evidence (no MMR-autism link), continue to recommend schedule, document

— Young child with ASD and history of running off → water safety, fencing, door alarms, ID bracelet, GPS, swim lessons

— 17-year-old with ASD and ID approaching 18 → discuss decision-making supports (supported decision-making, POA, guardianship) before legal majority

— Consider missed ASD; refer for diagnostic evaluation

— Weight/BMI, fasting glucose, lipids, prolactin, AIMS

Key distinction: When the stem describes a positive screen, the right answer always includes Early Intervention referral, not "wait for the specialist." When the stem describes regression, the right answer always includes a workup beyond standard ASD (EEG, MECP2, possibly MRI/metabolic).

Pattern 1 — The 18- or 24-month well visit:

Pattern 2 — Positive M-CHAT-R/F:

Pattern 3 — Diagnostic workup:

Pattern 4 — The regression vignette:

Pattern 5 — Macrocephaly + ASD:

Pattern 6 — Severe aggression/self-injury unresponsive to behavioral therapy:

Pattern 7 — Vaccine hesitancy:

Pattern 8 — Safety vignette:

Pattern 9 — Transition vignette:

Pattern 10 — Adolescent female with anxiety/depression and social exhaustion:

Pattern 11 — Medication monitoring on risperidone:

One-Line Recap

ASD is a clinical, DSM-5-TR diagnosis defined by social-communication deficits plus restricted/repetitive behaviors, universally screened with M-CHAT-R/F at 18 and 24 months, with positive screens triggering simultaneous referral to diagnostic specialists, Early Intervention/IEP, and audiology — because early, intensive behavioral intervention, not pharmacotherapy, drives outcomes.

Board pearl: The recurring Step 3 theme is parallel action: at a positive screen, the right answer simultaneously initiates diagnostic referral, Early Intervention/IEP, audiology, and family education — because outcomes are time-sensitive and waiting for formal diagnosis costs irreplaceable developmental windows. Every well visit thereafter integrates safety counseling (water/elopement), comorbidity screening (sleep, GI, seizures, mental health), medication monitoring when applicable, and care coordination across the medical home, school IEP team, behavioral therapists, and family supports — the longitudinal, ambulatory, system-integrated pediatric care Step 3 rewards.

Screen: M-CHAT-R/F at 18 and 24 months; surveillance every well visit; refer immediately on positive — do not "watch and wait"

Workup: Audiology + CMA + Fragile X first-tier; MECP2 in girls with regression, PTEN if macrocephaly; routine MRI/EEG not indicated

Treat: Behavioral therapies (ABA, ESDM) are foundation; pharmacotherapy (risperidone, aripiprazole) only for comorbid irritability/aggression — no medication treats core ASD

Safety + lifespan: Water safety/elopement prevention save lives; monitor for epilepsy, mental health comorbidities, metabolic effects of antipsychotics; plan transition (guardianship/supported decision-making) before age 18; vaccines on standard schedule — no link to autism