What is not Autism

Dr Alpana Kondekar
Pediatric Neurologist
Associate professor and signatory Autism certification
Topiwala National Medical College &B.Y.L.Nair Hospital
A comprehensive study in JAMA psychiatry strongly suggests that autism is being
significantly over diagnosed ………
Rødgaard, E.M., et al. “Temporal changes in effect sizes of studies comparing individuals with and without autism: a meta-analysis.” JAMA Psychiatry
76.11 (2019): 1124-1132.

When to suspect condition other than Autism ?

• Consanguinity
• Global regression
• Refractory epilepsy
• Movement disorder
• Focal neurological deficits, hypotonia,dystonia
• Abnormal head size
• Cyclical vomiting, Skin rashes, Lethargy, Abnormal odour of body fluids,
Multiorgan dysfunction
• Dysmorphism
• Neurocutaneous stigmata
Mimics of Autism
Other Developmental and Behavioral disorders which may have
similar symptoms…..
• Hearing deficit
• Visual Deficit
• Intellectual Deficit
• Schizophrenia
• Sensory processing disorder
• Developmental language disorders
• Epileptic Aphasia
• Autoimmune encephalopathies/ PANDAS
 Case 1
• 6yrs/Male, 3rd child of NC
Parents.
• Symptomatic since 7 mts age
• Speech delay
• Self absorbed
• Hand flapping movements
• Screaming
• Refractory seizures WEST S
• Hyperactivity and aggression
• Global developmental delay
• Hypopigmented macules
over the medial aspect of
thigh & lumbar region
• Papular lesions over face &
AD -1/3rd ; Non famililal - 2/3rd
Mutation in 2 tumour suppressor genes
TSCI - 9q34 hamartin
TSC2 -16p13 tuberin .
Clinical Manifestations:
CNS: infantile spasms, Epilepsy, Cognitive impairment,
autism (25-60% ).
MRI- Cortical tubers,
Subependymal nodules,
Subependymal giant cell astrocytoma.
Skin : Ash leaf Macules (90%), Shagreen patch, facial
angiofibroma, periungual fibroma.
Other Manifestations:
Lymphangiomyomatosis
Renal angiomyolipoma
Cardiac rhabdomyoma
Multiple retinal nodular hamartomas
Bone Cysts, Dental pits.
CASE 2 9 yr old
Poor scholastic performance
Speech delay
Restricted interest in cars
Obscession with hand washing
Repeated rocking movements
Poor socialisation
Fleeting eye contact
Monotonus speech
o/e
HC- 49 CM
Prominent ears
Hypotonia
Macroorchidism
Fragile X syndrome (FXS) is a genetic disorder characterized by
mild-to-moderate intellectual disability. The average IQ in
males is under 55, while about two thirds of affected females Molecular DNA analysis is done to
are intellectually disabled. Physical features may include a long detect the increased number of
and narrow face, large ears, flexible fingers, and large testicles. CGG repeats.
Case 3
• 30 month old boy
• Speeh Delay (only cooing)
• Excessive laughing
• Fleeting eye contact
• Excess hand flapping movements
• Light complexion
• hypotonia
The commonest genetic mechanism (70-75% )-interstitial deletion of
chromosome
A class II - uniparental disomy (UPD) for chromosome 15 and
thereby fail to inherit a maternal copy of UBE3A.
Clin. Features:
Hypotonia, GERD, seizures, tremors, Ataxia, Prognathism.
Feeding & sleep disturbances
Inappropriate Laughter,
Poor speech, severe MR
Angelman Syndrome
Diagnosis- FISH
Case 4:
• 7 yr old boy, 2nd by BO / NCM
• developmental delay,
• abnormal hand flapping & leg stretching
movements,
• light colored skin.
• nocturnal enuresis
• late response to name
• Autistic features : arranging toys in row,
obsessed with papers, poor eye contact.
• O/E: AR/ Chr-15 (OCA gene)
• Oculocutaneous Albinism + OCA 1: Most severe form.Defect in Tyrosinase
activity.
• poor eye contact
OCA 2 : MC,Defect in ‘P’ Protein. associated with
• refractory error + AUTISTIC FEATURE
• Diagnosis: OCA 3 (Rufous Albinism )African Descendants.Red
Oculocutaneous albinism with hair, reddish brown skin, freckles.
OCA 4Rare, Similar to OCA 2
• Some inherited hypomelanotic skin dis. that
present with multiple systemic manifestations
are associated with autism.
• Hyperhomocystinemia, PKU
• Hypomelanosis of Ito
• Genes of these hypomelanotic skin disorders
have chr. loci that lie near the loci for genes of
autism.
• A major gene for most of them is on chr 15.
• Cytogenetics has shown that variation in Chr
15q24, 11p12-p13 are associated with Autism.
Contiguous to this is a cluster of genes-GABRA5,
GABRB3 and GABRG3→ code for receptors of GABA
.
Allelic variants of these GABA receptor genes →
risk of autism .
Case 5
• Developmental delay
• Speech – 5-10 words at 3
yrs…….regression
• seizure
• No eye contact , social ineraction
• Self mutilating behavior, restless
• Severe dystonia (neck, trunk, UL),
• Microcephaly (HC=49 cm)
• severe muscle wasting.
• Not able to sit without support,
almost bedridden
• Tone: hypertonia in all 4 limbs,
4/28/2021 Dr Alpana Kondekar TNMC Mumbai 12
• Oral creatine supplementation aim of correcting cerebral creatine
deficiency
• Strategies to reduce accumulation of GAA, such as high dose L-ornithine
and an arginine/protein restricted diet
• Creatine is given as creatine-monohydrate -of 400–800 mg/kg/d orally/enterally.
• L-Ornithine -400–800 mg/kg/d (molecular weight = 132.16) orally/enterally.
• If given as L-orni-thine–L-aspartate (molecular weight 265.26), the dosage should be
adjusted to provide amounts of L-ornithine corresponding to the amounts given as the
free form.
• L-Ornithine–HCl should not be given in high dosages because it can cause metabolic
acidosis
• An arginine-restricted diet, given as 0.3–0.4 g/kg/d of natural protein (containing
approximately 250 mg/kg/d ofL-arginine) to-gether with an arginine-free essential amino
acid supplement to achieve the age related DRI effectively reduces GAA levels.

4/28/2021 Dr Alpana Kondekar TNMC Mumbai 13

 Case -6
✓ 6 yrs old
✓ Developmental delay
✓ Self absorbed
✓ Poor eye contact
✓ No socialisation, no joint attention
✓ Repeated hand and neck movements
✓ Seizures
✓ No focal deficit.
✓ EEG- EPILEPTIFORM ACTIVITY

Focal epilepsy with speech

disorder and with or without
mental retardation
(OMIM#245570) is caused
by heterozygous mutations in
the GRIN2A gene
(OMIM*138253). BECT-----CSWS------LKS
 CASE 7
✓ 3 yr/girl
✓ Normal development till 18
month
✓ Regression of speech
✓ Hand movements
✓ No eye contact
✓ Bruxism
✓ microcephaly
Main Criteria
1.Partial or complete loss of acquired purposeful hand skills. • Supportive Criteria for atypical RTT
2.Partial or complete loss of acquired spoken language • Breathing disturbances when awake
3.Gait abnormalities: Impaired (dyspraxic) or absence of ability. • Bruxism when awake
4.Stereotypic hand movements such as hand wringing/squeezing,
• Impaired sleep pattern
clapping/tapping, mouthing and washing/rubbing automatisms
Required for typical or classic RTT • Abnormal muscle tone
Exclusion Criteria for typical RTT • Peripheral vasomotor disturbances
1.Brain injury secondary to trauma (peri- or postnatally), • Scoliosis/kyphosis
neurometabolic disease, or severe infection that causes • Growth retardation
neurological problems
2.Grossly abnormal psychomotor development in first 6 months
• Small cold hands and feet
of life • Inappropriate laughing/screaming spells
Required for typical or classic RTT • Diminished response to pain
*
1.A period of regression followed by recovery or stabilization • Intense eye communication - “eye
2.All main criteria and all exclusion criteria pointing”
3.Supportive criteria are not required, although often present in
typical RTT
Required for Atypical or NONclassic RTT
1.A period of regression followed by recovery or stabilization*
2.At least 2 out of the 4 main criteria
3.5 out of 11 supportive criteria
Case -7 CASE 8

4 yr old 6 yr old
Developmental delay Developmental delay
Symptomatic epilepsy Symptomatic epilepsy
Neonatal hypoglycemia Visual hearing Deficit
Visual hearing Deficit Congenital CMV
 What is not autism? Summary…..
Age Clinical feature Probable other diagnosis
Before birth Genetic report of non autism diagnosis
Around birth Significant Birth Asphyxia, Neonatal Seizures HIE
Obvious dys-morphism/anomalies, Other systems affected
6 months Abnormal BERA, proven deafness, vision deficits-cataract ROP, CP
onwards refractory seizures Malformations
Hypertonia, spasticity, delayed roll over, frequent convulsions, Developmental
neurocutaneous markers, abnormal MRI Brain suggesting specific encephalopathy
diagnosis, Cerebral palsy
1 year-3 year Delayed motor milestones, difficulty in standing sitting running, ASD NOS
Peak of repeated falls, relevant and coherent speech, child able to play
controversies hide and seek like normal kids
3 year onwards Only Social communication disorder, SPD, DCD-apraxia, Solitary SPD,DCD, OCD, ADHD
Sensory issues, hyperactivity without communication deficit,
severe MR with drooling/incontinence
5 years onwards Antisocial behavior with good speech, hyperacitivity with good IQ ADHD and neuropsychiatric
comorbidities
A diagnosis without knowing the cause is merely a label that
creates the illusion of understanding……

Thank you