AUTISM SPECTRUM DISORDERS

Autism Spectrum Disorders (ASD) represent a heterogeneous group of neurodevelopmental conditions characterized by altered maturation and connectivity of brain networks. From a clinical perspective, ASD is typically characterized by:

• Persistent impairment in communication and social interaction, which may manifest as difficulties in verbal and non-verbal language, understanding others’ emotions, and social reciprocity.
• The presence of restricted, repetitive, and stereotyped behaviors and interests, which may include rituals, insistence on sameness, repetitive movements, or an intense focus on specific objects or topics.

Comorbidità frequenti:

• Intellectual disability (≈30–40% of cases);
• Language disorders;;
• Epilepsy (affecting up to 20–30% of individuals);
• Sleep and behavioral disorders.

INCIDENCE OF CONDITIONS ASSOCIATED WITH AUTISM SPECTRUM DISORDERS

The prevalence of ASD has increased over the past decades, partly due to the broadening of diagnostic criteria and greater clinical and social awareness. It is estimated that more than1 in 100 children are affected by an autism spectrum disorder. In Italy, according to data from the Istituto Superiore di Sanità, approximately 1 in 77 children aged 7 to 9 receive an ASD diagnosis, with a markedly higher prevalence in males, who are about 4.4 times more likely to be affected compared to females^¹.

1. Istituto Superiore di Sanità. Disturbi dello spettro autistico nei bambini e negli adolescenti. Linea guida 2023.

GENETIC BASIS OF AUTISM SPECTRUM DISORDERS

Scientific evidence indicates that genetic factors play a predominant role in the development of autism, accounting for approximately 70–90% of cases.^²⁻³

Genetic abnormalities may include:

• Point mutations or pathogenic variants in key genes involved in neuronal development, synaptogenesis, and synaptic transmission (e.g., CHD8, SCN2A, SHANK3, SYNGAP1). ^⁴⁻⁵
• Copy Number Variants (CNVs), i.e., microdeletions or microduplications of chromosomal regions, such as those located on 16p11.2 or 15q13.3.
• Genetic syndromes associated with autism,, including tuberous sclerosis, Rett syndrome, and Phelan- McDermid syndrome, which account for a significant proportion of syndromic ASD cases.^⁶⁻⁷

2. Tick B et al. Heritability of autism spectrum disorders: a meta-analysis of twin studies. JAMA Psychiatry. 2016;73(3): 258-268.
3. Sandin S et al. The familial risk of autism. JAMA. 2014;311(17):1770-1777.
4. Satterstrom FK et al. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism. Cell. 2020;180(3):568-584.e23.
5. Iossifov I et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014;515:216-221.
6. Rolland T, et al. Phenotypic effects of genetic variants associated with autism Nat Med. 2023 Jul;29(7):1671-1680.
7. Grove J et al. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019;51:431-444.