Syndromic autism (or syndromic autism spectrum disorder) denotes cases of autism that are associated with a broader medical condition, generally a syndrome. Cases without such association, which account for the majority of total autism cases, are known as non-syndromic autism, non-syndromic autism spectrum disorder, or idiopathic 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)
+ Characteristics of syndromic ASD conditions Condition Cause Chromosome(s) involved (if a mutation) ASD prevalence (95% CI) Clinically/Molecularly defined Other characteristics Fragile X syndrome Monogenic disorder:FMR1 (encodes FMRP) X 30% (20.0–31.0) [male individuals only] 22% (15.0–30.0) [mixed sex] 14% (13–18) [female individuals only] Clinically defined [in some males] Long/narrow face, macroorchidism, long ears and philtrum, hyperactivity, mild to moderate intellectual disability (ID), seizures Rett syndrome Monogenic disorder:MECP2 X 61.0% (46.0–74.0) [female individuals only] Clinically defined Microcephaly, breathing irregularities, language deficits, repetitive/stereotyped hand movements, epilepsy, ID MECP2 duplication syndrome Monogenic disorder:MECP2 X 100% [in a single study composed by 9 male participants] Clinically defined Brachycephaly, spasticity, recurrent respiratory infections, gastrointestinal hypermotility, genitourinary abnormalities, epilepsy, ID Tuberous sclerosis complex Monogenic disorder:TSC1 TSC2 916 36.0% (33.0–40.0) Clinically defined Benign tumours in multiple organs, epilepsy Angelman's syndrome Monogenic disorder:UBE3A 15 34.0% (24.0–37.0) Cheerful demeanour, microcephaly, speech deficits, sleep disturbance, epilepsy, ID Phelan-McDermid syndrome Monogenic disorder:SHANK3 22 84% [in a single study composed by 32 participants] Molecularly defined KCNH1-related disordersMonogenic disorder: KCNH11Molecularly defined, formerly clinically defined as Temple–Baraitser Syndrome or Zimmermann–Laband SyndromeMild to severe developmental delay, profound intellectual disability, neonatal hypotonia, myopathic facial appearance, and infantile-onset seizures Timothy syndrome Monogenic disorder:CACNA1C 12 80% [in a single study composed by 17 participants] Clinically defined Smith-Lemli-Opitz syndrome Monogenic disorder:DHCR7 11 55% [in a single study composed by 33 participants] Neurofibromatosis type I Monogenic disorder:NF1 17 18% (9.0–29.0) Clinically defined PTEN hamartoma tumor syndrome Monogenic disorder:PTEN 10 17% (8–27) Clinically defined Down syndrome Chromosomal disorder:trisomy 21 21 16% (8.0–24.0) Clinically defined Cohen's syndrome Monogenic disorder:VPS13B 8 54% (44.0–64.0) Clinically defined Cornelia de Lange syndrome Polygenic disorder 43% (32.0–53.0) Clinically defined CHARGE syndrome Monogenic disorder:CHD7 8 28% (16–41) Clinically defined Noonan's syndrome Polygenic disorder 15% (7.0–26.0) Williams syndrome Microdeletion syndrome:7q11.23 7 12% (6.0–20.0) 22q11.2 deletion syndrome Microdeletion syndrome:22q11.2 22 11% (5.0–19.0) Clinically defined Fetal valproate spectrum disorder Teratogen:valproate 8–15% [in VPA exposed children] Clinically defined
See also
Causes of autism Conditions comorbid to autism
References