Syndromic autism
This article may be too technical for most readers to understand.(June 2023) |
Syndromic autism (or syndromic autism spectrum disorders) denotes cases of
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.[1][2][3][4]
Syndromic autism
Autism spectrum disorder (ASD) is referred to as syndromic when it is one of the many characteristics associated with a broader
Syndromic autism represents about 25% of the total ASD cases.[4][5] In most[quantify] cases, its etiology is known.[2][4]
Certain[
Non-syndromic autism
Non-syndromic autism, also called classic autism or
In most[quantify] cases, its cause is polygenic.[citation needed]
Classification
A 2017 study[relevant?] 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.[4][clarification needed]
Following the proposal, ASD would be divided into three genetic categories:[4]
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.: )
- 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.: ANK2, SCN2A)
- ASD-associated CNVs (e.g.: 16p11.2 deletion/duplication, exonic NRXN1 deletions)
Currently undefined
Currently undefined.[clarification needed]
Condition | Cause | Chromosome(s) involved (if a mutation) | ASD prevalence ( 95% CI ) |
Clinically/Molecularly defined | Other characteristics | Ref. |
---|---|---|---|---|---|---|
Fragile X syndrome | Monogenic disorder: (encodes FMRP)FMR1 |
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, hyperactivity, intellectual disability (ID), seizures |
[1][3][4][6] |
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 | [1][3][4] |
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 | [1][4][7] |
Tuberous sclerosis complex |
9 16 |
36.0% (33.0–40.0) | Clinically defined | Benign tumours in multiple organs, epilepsy | [1][3][4] | |
Angelman's syndrome |
Monogenic disorder: UBE3A |
15 | 34.0% (24.0–37.0) | Cheerful demeanour, microcephaly, epilepsy, speech deficits, sleep disturbance, epilepsy, ID | [1][3] | |
Phelan-McDermid syndrome |
Monogenic disorder: SHANK3 |
22 | 84% [in a single study composed by 32 participants] | Molecularly defined | [4][8] | |
Timothy syndrome | Monogenic disorder: CACNA1C |
12 | 80% [in a single study composed by 17 participants] | Clinically defined | [4][9] | |
Smith-Lemli-Opitz syndrome |
DHCR7 |
11 | 55% [in a single study composed by 33 participants] | [10] | ||
Neurofibromatosis type I | NF1 |
17 | 18% (9.0–29.0) | Clinically defined | [3][4] | |
PTEN hamartoma tumor syndrome |
Monogenic disorder: PTEN |
10 | 17% (8–27) | Clinically defined | [4][11] | |
Down syndrome | 21 | 16% (8.0–24.0) | Clinically defined | [3][4] | ||
Cohen's syndrome |
Monogenic disorder: VPS13B |
8 | 54% (44.0–64.0) | Clinically defined | [3][4] | |
Cornelia de Lange syndrome | Polygenic disorder |
43% (32.0–53.0) | Clinically defined | [3][4] | ||
CHARGE syndrome | Monogenic disorder: CHD7 |
8 | 28% (16–41) | Clinically defined | [4][12][13] | |
Noonan's syndrome |
Polygenic disorder |
15% (7.0–26.0) | [3] | |||
William's syndrome |
Microdeletion syndrome: 7q11.23 |
7 | 12% (6.0–20.0) | [3][14] | ||
22q11.2 deletion syndrome |
22q11.2 |
22 | 11% (5.0–19.0) | Clinically defined | [3][4] | |
Fetal valproate spectrum disorder |
Teratogen: valproate |
8–15% [in VPA exposed children] | Clinically defined | [4][15][16] |
See also
References
- ^ PMID 29951185.
- ^ S2CID 3332899. Retrieved 4 June 2023.
- ^ PMID 26341300. Retrieved 27 May 2023.
- ^ PMID 29398931.
- S2CID 12742356. Retrieved 8 June 2023.
- PMID 34294028.
- PMID 20035514.
- PMID 23758760.
- S2CID 15325633.
- PMID 27053961.
- PMID 34983360.
- PMID 36045324.
- from the original on 2023-06-06. Retrieved 2023-06-07.
- from the original on 2023-06-06. Retrieved 2023-06-07.
- PMID 25354543.
- PMID 31324220.