ASD is accepted to be a neurodevelopmental condition with a biological basis. The heterogeneity of affected individuals and genetic complexity has undoubtedly contributed to the daunting task of identifying the cause(s) of ASD. Continuing research has not identified a clear aetiology, but evidence suggests that it has a complex genetic basis with strong heritability (60% concordance reported in twin studies). Recurrence rates for siblings have been reported between 3 and 10% with up to 18.7% when the broader autism spectrum is considered.
Advances in molecular genetics have identified genetic variations e.g. ‘rare causal’ copy number variants and single gene polymorphisms which are significant or ‘causal’ in approximately 10% of people diagnosed with ASD. De novo events may be implicated in simplex families, whereas multiplex families (when more than one family member is affected by ASD) may pass a specific genetic variation through the generations which increases the risk of ASD. It is possible that several genes of small effect may act through an epigenetic mechanism and environmental factors influence phenotypic expression. In 10-15% of cases ASD is associated with a known medical condition.
Consistently recognized genetic conditions include tuberous sclerosis (TS) and fragile X. Studies have shown that between 1% and 3% of children with autism have TS and similar percentages have fragile X. Other associations and a list of additional medical risk factors are shown in below.
– Risk factors for autism spectrum disorder
Sibling with ASD
Parental schizophrenia-like-psychosis or affective disorder
Maternal sodium valproate use during pregnancy
Gestational age less than 35 weeks
Birth defects associated with central nervous system including cerebral palsy
– Other medical conditions associated with ASD
Fetal alcohol syndrome
Duchenne muscular dystrophy
Clinical research has demonstrated differences in trajectories of head growth in children with ASD. Macrocephaly is a recognized feature of ASD in 20-30% of cases though must be interpreted in the context of parental head circumferences.
Studies have shown that as a group, head circumference accelerates during the first 2 years of life, with deceleration possibly occurring in later childhood since average head circumference has been reported in adolescence and adulthood. Although there have been conflicting views around the relevance and cause of these changes, they are reported to happen prior to the onset of clinical symptoms and may be a useful clinical indicator. Gene mutations in PTEN (Phosphatase and Tensin Homolog) have been found in children with ASD and macrocephaly with case series reporting a yield of 5% in those with head circumferences greater than 98th percentile.
Research continues to study neurobiological differences in ASD considering variation in neurotransmitters, volumetric and functioning differences of various regions within the brain, but the relevance to clinical practice of most identified abnormalities has not been established.
Various environmental factors have been reported in the literature. Risk factors are shown in this article and include prematurity less than 35 weeks gestation, prenatal maternal valproate use and congenital rubella. The controversy of links between the MMR vaccine and ASD are unfounded.