Abstract
Neurodevelopmental disorders include a wide range of phenotypes caused by defects in the development and functioning of the central nervous system. Genetic factors play an important role in their aetiology.
The view of the mode of genetic determination of neurodevelopmental disorders has changed several times during the last few decades. Today, a combined model prevails, according to which both common genetic variants with small effect and rare variants with strong effect participate in the development of these disorders, and both these mechanisms operate in parallel in each patient.
Deciphering of polygenic networks of common variants is difficult, and the first associated loci have been reported only recently. Identification of variants with strong effect is easier, and they have been found in several hundred genes.
Interestingly, these genes often support basic cellular processes, and their mutations appear to be tolerated in most systems, with the exception of the central nervous system. Progress in the identification of causal genes allows the definition of new syndromes involving neurodevelopmental disorders based on genetics.
Today, however, this success is limited only to highly penetrant mutations in genes causing more frequent and more severe monogenic syndromes with lower phenotypic variability, and therefore many participating genes and the clinical entities linked to them remain unknown. Better understanding of the genetic mechanisms is already reflected in a more efficient genetic diagnostics, and will hopefully enable targeted therapy of some syndromes associated with neurodevelopmental disorders in the future. neurovývojová porucha, poruchy autistického spektra, vzácná varianta.