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).
This article may be too technical for most readers to understand. (June 2023) |
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 medical condition, generally a syndrome.
Syndromic autism represents about 25% of the total ASD cases.[4][5] In most[quantify] cases, its etiology is known.[2][4]
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[which?] syndromic forms of ASD can also have different[compared to?] phenomenology.[clarification needed]
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[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.: 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).
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: 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, mild to moderate intellectual disability, 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 | Monogenic disorder: TSC1 TSC2 | 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 | Monogenic disorder: DHCR7 | 11 | 55% [in a single study composed by 33 participants] | [10] | ||
Neurofibromatosis type I | Monogenic disorder: 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 | Chromosomal disorder: trisomy 21 | 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 | Microdeletion 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] |