Syndromic autism
Syndromic autism 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.
Studying the differences and similarities 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, typically confirmed by a targeted genetic testing.- Chromosomal
- Syndromes caused by mutations in single genes
- Syndromes caused by CNVs
- Teratogens
Molecularly defined
- Chromosomal
- Autism-associated genes
- Autism-associated CNVs
| Condition | Cause | Chromosome involved | ASD prevalence | Clinically/Molecularly defined | Other characteristics | |
| Fragile X syndrome | Monogenic disorder: FMR1 | X | 30% 22% 14% | Clinically defined | Long/narrow face, macroorchidism, long ears and philtrum, hyperactivity, mild to moderate intellectual disability, seizures | |
| Rett syndrome | Monogenic disorder: MECP2 | X | 61.0% | Clinically defined | Microcephaly, breathing irregularities, language deficits, repetitive/stereotyped hand movements, epilepsy, ID | |
| MECP2 duplication syndrome | Monogenic disorder: MECP2 | X | 100% | Clinically defined | Brachycephaly, spasticity, recurrent respiratory infections, gastrointestinal hypermotility, genitourinary abnormalities, epilepsy, ID | |
| Tuberous sclerosis complex | Monogenic disorder: TSC1 TSC2 | 9 16 | 36.0% | Clinically defined | Benign tumours in multiple organs, epilepsy | |
| Angelman's syndrome | Monogenic disorder: UBE3A | 15 | 34.0% | Cheerful demeanour, microcephaly, speech deficits, sleep disturbance, epilepsy, ID | ||
| Phelan-McDermid syndrome | Monogenic disorder: SHANK3 | 22 | 84% | Molecularly defined | ||
| KCNH1-related disorders | Monogenic disorder: KCNH1 | 1 | Molecularly defined, formerly clinically defined as Temple–Baraitser Syndrome or Zimmermann–Laband Syndrome | Mild to severe developmental delay, profound intellectual disability, neonatal hypotonia, myopathic facial appearance, and infantile-onset seizures | ||
| Timothy syndrome | Monogenic disorder: CACNA1C | 12 | 80% | Clinically defined | ||
| Smith-Lemli-Opitz syndrome | Monogenic disorder: DHCR7 | 11 | 55% | |||
| Neurofibromatosis type I | Monogenic disorder: NF1 | 17 | 18% | Clinically defined | ||
| PTEN hamartoma tumor syndrome | Monogenic disorder: PTEN | 10 | 17% | Clinically defined | ||
| Down syndrome | Chromosomal disorder: trisomy 21 | 21 | 16% | Clinically defined | ||
| Cohen's syndrome | Monogenic disorder: VPS13B | 8 | 54% | Clinically defined | ||
| Cornelia de Lange syndrome | Polygenic disorder | 43% | Clinically defined | |||
| CHARGE syndrome | Monogenic disorder: CHD7 | 8 | 28% | Clinically defined | ||
| Noonan's syndrome | Polygenic disorder | 15% | ||||
| Williams syndrome | Microdeletion syndrome: 7q11.23 | 7 | 12% | |||
| 22q11.2 deletion syndrome | Microdeletion syndrome: 22q11.2 | 22 | 11% | Clinically defined | ||
| Fetal valproate spectrum disorder | Teratogen: valproate | 8–15% | Clinically defined |