Autism Flashcards
What is the prevalence of autism?
1 in 59 in children ages 8 years
Boys 4x more likely
What percentage of children with autism have ID (IQ < 70)?
31% of children
What maternal medications are associated with autism?
Valproate, thalidomide, misoprostol
Antidepressants
Anti-convulsant medications
What maternal medications are associated with autism?
Valproate, thalidomide, misoprostol
Antidepressants
Anti-convulsant medications
What infections are associated with autism?
Rubella and TORCH
What are perinatal factors in autism?
Extreme Prematurity (<26 weeks gestation)
Gestational diabetes
Maternal hemorrhage
Viral infections – trigger immune response, increased IL-6
Umbilical cord complications
Fetal presentation
Fetal distress
Birth injury/trauma
Summer birth
Low birth weight
Low 5 minute Apgar
Meconium aspiration
Neonatal anemia and hyperbilirubinemia
The concordance for strict autism in monozygotic males/females is?
males 58%/females 60%
The concordance for strict autism in dizygotic males/females is?
21%/females 27%
What percentage of autism is caused by CNVs?
7-20%
What percentage of autism is caused by single-gene disorders?
5-7%
What percentage of autism is unknown cause?
> 70%
What percentage of autism is “essential” or lack of physical abnormalities?
70%
What is the incidence of autism in Down syndrome?
16.5%
What is the incidence of autism in 22q11.2 deletion syndrome?
20%
What percentage of autism cases are caused by Fragile X?
1-5%
What are the features of Fragile X in males?
Slightly increased birth weight
Average height in childhood
Macrocephaly
Long face; large ears – not all cases
Macro-orchidism – post pubertal
Lax joints; velvety skin
MVP/Aortic dilatation – post pubertal
Developmental delay/Autism (50-70%) or autistic behaviors
Periventricular heterotopia and other neuroradiologic abnormalities
What are the features of Fragile X in females?
Heterozygous for full mutation
Milder Physical Features
Prominent ears
Long, narrow face
High arched palate
Hyperextensible joints
Double-jointed thumbs
Single palmar crease
Flat feet
Murmur or systolic click
Milder developmental issues
Carriers may have mild symptoms, depression, POI
What are the features of Phelan-McDermid syndrome?
Neonatal hypotonia
Normal to accelerated growth
Absent or severely delayed speech
Global developmental delay
Normal head circumference
Minor dysmorphic facial features
Full brow, flat midface , ptosis, puffy eyelids, long eyelashes, wide nasal bridge, bulbous nose, puffy cheeks,
pointed chin, large/prominent ears
Autistic behaviors
Mouthing or chewing non-food items decreased pain perception
What is the genetic cause of Phelan-McDermid syndrome?
Microdeletion chr 22q13.3 (80%)
Intragenic deletion of SHANK3
What is the most common del/dup that causes autism?
16p11.2 del/dup most common - accounts for 1.1-1.2% of cases
How is autism thought to affect the brain?
Analysis supports the hypothesis that autism is primarily a disease of synaptic and neuronal connectivity malfunction.
What are first-tier genetic tests in non-dysmorphic autism?
CMA and Fragile X
What is second tier genetic testing in autism?
MeCP2 sequencing in females
MeCP2 duplication in males
PTEN testing if HC >2.5 SD
Autism/ID gene panel
What is recurrence risk of having a second child with autism?
10-15%
What is recurrence risk of having a third child with autism (if subsequent child is boy/girl)?
50% if the subsequent child is boy and 12% if the child is a girl
