![]() | This article may be too technical for most readers to understand.(June 2023) |
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 (or non-syndromic autism spectrum disorder).
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 represents about 25% of the total ASD cases. [4] [5] In most 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.[ citation needed ]
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. [4] [ clarification needed ]
Following the proposal, ASD would be divided into genetic categories, including: [4]
Syndromes recognized by clinicians (depending on their experience), typically confirmed by a targeted genetic testing.
Syndromes recognized by genome-wide testing, not by hypothesis-driven testing (since clinical recognition is difficult).
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, hyperactivity, mild to moderate 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, 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] | |||
Williams 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] |