Syndromic autism

Studying the differences and similarities (e.g., common pathways) between syndromic and non-syndromic cases can provide insights about the pathophysiology of autism and pave the way to new autism therapies.

Syndromic autism represents about 25% of the total ASD cases. In most cases, its etiology is known. Monogenic disorders are one of the causes of syndromic autism, which in this case are also known as monogenic autism spectrum disorders. They account for about 5% of the total ASD cases. SCN2A is the leading monogenic cause of autism.

Classification

A 2017 study proposed to replace the classification syndromic/non-syndromic ASD into one based on the genetic etiology of the condition, specifying if the syndromic condition occurs in the context of a "phenotype first" clinically defined syndrome or from a "genotype first" molecularly defined syndrome.

Following the proposal, ASD would be divided into genetic categories, including:

Clinically defined

Syndromes recognized by clinicians (depending on their experience), typically confirmed by a targeted genetic testing.

• Chromosomal (e.g., Down syndrome)
• Syndromes caused by mutations in single genes (e.g., SCN2A-related autism, NF1 mutation, tuberous sclerosis, PTEN-associated macrocephaly syndrome, some males with fragile X syndrome)
• Syndromes caused by CNVs (e.g., DiGeorge syndrome)
• Teratogens (e.g., fetal valproate spectrum disorder)

Molecularly defined

Syndromes recognized by genome-wide testing, not by hypothesis-driven testing (since clinical recognition is difficult).

• Chromosomal (e.g., isodicentric 15q)
• Autism-associated genes (e.g., ADNP, ARIDB1B, ANK2, SCN2A, KCNH1)
• Autism-associated CNVs (e.g., 16p11.2 deletion/duplication, exonic NRXN1 deletions)