Autism spectrum disorders (ASD) are among the neuropsychiatric diseases with the greatest heritability, as shown by high concordance rates of about 70% in monozygotic twins in earlier twin studies. Based on this, the empirical risk of recurrence for siblings of children with ASD is between 5 and 20%, i.e., significantly higher than for other multifactorial diseases. ASD are both clinically and genetically heterogeneous; the most common comorbidities are developmental disorders or reduced intelligence (about 70%), speech disorders (about 30%) or epilepsy.
It is now believed that modern genetic testing methods can find a genetic cause for about 20 to 25% of autism spectrum disorders (Baker et al, 2015). Approximately 20% carry de novo generated CNV (copy number variation), which are detected by chromosomal microarrays (CMA). Monogenic causes are found in 3-5%, mostly for syndromes caused by pathogenic variants in single genes that show ASD as a partial symptom.
The American College of Medical Genetics (ACMG) (Schaefer et al, 2013) recommends the use of a chromosomal microarray for the genetic diagnosis of patients with ASD in whom clinical examination does not give rise to suspicion of a specific genetic syndrome. If the chromosomal microarray analysis is not conclusive, the MECP2 gene (Rett syndrome) should be examined in girls, the FMR1 gene (fragile X syndrome) in boys, or the PTEN gene (Bannayan-Riley-Ruvalcaba syndrome) if macrocephaly is present .
It is now assumed that numerous genes, probably more than 1000, may be involved in the development of ASD, although it is not yet clear to what extent individual variants influence the expression in individual cases. Nevertheless, advanced diagnostics using NGS (gene panel diagnostics) can also lead to a diagnosis in individual cases and thus to more precise statements on the prognosis and the risk of recurrence.
Grove et al. 2019, Nat Genet 51:431 / Yuen et al. 2017, Nat Neurosci 20:602 / Baker et al. 2015, Pediatr Clin N Am 62:607 / Schaefer et al. 2013, Gen Med 15(5):399