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Syndromic autism (or syndromic autism spectrum disorders) denotes cases of autism spectrum disorder 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 (or non-syndromic autism spectrum disorders).
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
Autism spectrum disorder (ASD) is referred to as syndromic when it is one of the many characteristics associated with a broader medical condition, generally a syndrome.
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.
Certain syndromic forms of ASD can also have different phenomenology.
Non-syndromic autism
Non-syndromic autism, also called classic autism or idiopathic autism (as in most cases, the etiology is unknown), represents the majority of total autism cases.
In most cases, its cause is polygenic.
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 three genetic categories:
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.: NF1, TSC, PTEN-associated macrocephaly syndrome, some males with FXS)
- Syndromes caused by CNVs (e.g.: microdeletion 22q11.2 syndrome)
- Teratogens (e.g.: valproate aembryopathy)
Molecularly defined
Syndromes recognized by genome-wide testing, not by hypothesis-driven testing (since clinical recognition is difficult).
- Chromosomal (e.g.: isodicentric 15q)
- ASD-risk genes (e.g.: ADNP, ARIDB1B, ANK2, SCN2A)
- ASD-associated CNVs (e.g.: 16p11.2 deletion/duplication, exonic NRXN1 deletions)
Currently undefined
Currently undefined.
| Condition | Cause | Chromosome(s) involved (if a mutation) | ASD prevalence (95% CI) | Clinically/Molecularly defined | Other characteristics | Ref. |
|---|---|---|---|---|---|---|
| Fragile X syndrome | Monogenic disorder: FMR1 (encodes FMRP) |
X | 30% (20.0–31.0) 22% (15.0–30.0) 14% (13–18) |
Clinically defined | 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) | 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% (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, epilepsy, speech deficits, sleep disturbance, epilepsy, ID | ||
| Phelan-McDermid syndrome | Monogenic disorder: SHANK3 |
22 | 84% | Molecularly defined | ||
| 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% (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% | Clinically defined |
See also
References
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