Syndromic autism
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.[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 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 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.[4]
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.
| 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] |
References
- Benger, Matthew; Kinali, Maria; Mazarakis, Nicholas D. (December 2018). "Autism spectrum disorder: prospects for treatment using gene therapy". Molecular Autism. 9 (1): 39. doi:10.1186/s13229-018-0222-8. PMC 6011246. PMID 29951185.
- Sztainberg, Yehezkel; Zoghbi, Huda Y (November 2016). "Lessons learned from studying syndromic autism spectrum disorders". Nature Neuroscience. 19 (11): 1408–1417. doi:10.1038/nn.4420. PMID 27786181. S2CID 3332899. Retrieved 4 June 2023.
- Richards, Caroline; Jones, Christopher; Groves, Laura; Moss, Jo; Oliver, Chris (October 2015). "Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis". The Lancet Psychiatry. 2 (10): 909–916. doi:10.1016/S2215-0366(15)00376-4. PMID 26341300. Retrieved 27 May 2023.
- Fernandez, Bridget A.; Scherer, Stephen W. (31 December 2017). "Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach". Dialogues in Clinical Neuroscience. 19 (4): 353–371. doi:10.31887/DCNS.2017.19.4/sscherer. PMC 5789213. PMID 29398931.
- Bourgeron, Thomas (September 2015). "From the genetic architecture to synaptic plasticity in autism spectrum disorder". Nature Reviews Neuroscience. 16 (9): 551–563. doi:10.1038/nrn3992. PMID 26289574. S2CID 12742356. Retrieved 8 June 2023.
- Marlborough, M.; Welham, A.; Jones, C.; Reckless, S.; Moss, J. (December 2021). "Autism spectrum disorder in females with fragile X syndrome: a systematic review and meta-analysis of prevalence". Journal of Neurodevelopmental Disorders. 13 (1): 28. doi:10.1186/s11689-021-09362-5. PMC 8299695. PMID 34294028.
- Ramocki, Melissa B.; Peters, Sarika U.; Tavyev, Y. Jane; Zhang, Feng; Carvalho, Claudia M. B.; Schaaf, Christian P.; Richman, Ronald; Fang, Ping; Glaze, Daniel G.; Lupski, James R.; Zoghbi, Huda Y. (December 2009). "Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome". Annals of Neurology. 66 (6): 771–782. doi:10.1002/ana.21715. PMC 2801873. PMID 20035514.
- Soorya, Latha; Kolevzon, Alexander; Zweifach, Jessica; Lim, Teresa; Dobry, Yuriy; Schwartz, Lily; Frank, Yitzchak; Wang, A Ting; Cai, Guiqing; Parkhomenko, Elena; Halpern, Danielle; Grodberg, David; Angarita, Benjamin; Willner, Judith P; Yang, Amy; Canitano, Roberto; Chaplin, William; Betancur, Catalina; Buxbaum, Joseph D (December 2013). "Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency". Molecular Autism. 4 (1): 16. doi:10.1186/2040-2392-4-18. PMC 3707861. PMID 23758760.
- Splawski, Igor; Timothy, Katherine W.; Sharpe, Leah M.; Decher, Niels; Kumar, Pradeep; Bloise, Raffaella; Napolitano, Carlo; Schwartz, Peter J.; Joseph, Robert M.; Condouris, Karen; Tager-Flusberg, Helen; Priori, Silvia G.; Sanguinetti, Michael C.; Keating, Mark T. (October 2004). "CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism". Cell. 119 (1): 19–31. doi:10.1016/j.cell.2004.09.011. PMID 15454078. S2CID 15325633.
- Thurm, Audrey; Tierney, Elaine; Farmer, Cristan; Albert, Phebe; Joseph, Lisa; Swedo, Susan; Bianconi, Simona; Bukelis, Irena; Wheeler, Courtney; Sarphare, Geeta; Lanham, Diane; Wassif, Christopher A.; Porter, Forbes D. (December 2016). "Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update". Journal of Neurodevelopmental Disorders. 8 (1): 12. doi:10.1186/s11689-016-9145-x. PMC 4822234. PMID 27053961.
- Cummings, Katherine; Watkins, Alice; Jones, Chris; Dias, Renuka; Welham, Alice (December 2022). "Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics". Journal of Neurodevelopmental Disorders. 14 (1): 1. doi:10.1186/s11689-021-09406-w. PMC 8903687. PMID 34983360.
- Thomas, Andrea T.; Waite, Jane; Williams, Caitlin A.; Kirk, Jeremy; Oliver, Chris; Richards, Caroline (December 2022). "Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis". Journal of Neurodevelopmental Disorders. 14 (1): 49. doi:10.1186/s11689-022-09459-5. PMC 9429597. PMID 36045324.
- Norina, Usman; Moushumi, Sur (2023-03-06). "CHARGE Syndrome". ncbi.nlm.nih.gov. StatPearls Publishing. PMID 32644625. Bookshelf ID: NBK559199. Archived from the original on 2023-06-06. Retrieved 2023-06-07.
- Colleen A, Morris (2023-04-13) [9 april 1999]. "Williams Syndrome". ncbi.nlm.nih.gov. GeneReviews. PMID 20301427. Bookshelf ID: NBK1249. Archived from the original on 2023-06-06. Retrieved 2023-06-07.
- Bromley, Rebecca; Weston, Jennifer; Adab, Naghme; Greenhalgh, Janette; Sanniti, Anna; McKay, Andrew J; Tudur Smith, Catrin; Marson, Anthony G (30 October 2014). "Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child". Cochrane Database of Systematic Reviews. 2020 (6): CD010236. doi:10.1002/14651858.CD010236.pub2. PMC 7390020. PMID 25354543.
- Clayton-Smith, Jill; Bromley, Rebecca; Dean, John; Journel, Hubert; Odent, Sylvie; Wood, Amanda; Williams, Janet; Cuthbert, Verna; Hackett, Latha; Aslam, Neelo; Malm, Heli; James, Gregory; Westbom, Lena; Day, Ruth; Ladusans, Edmund; Jackson, Adam; Bruce, Iain; Walker, Robert; Sidhu, Sangeet; Dyer, Catrina; Ashworth, Jane; Hindley, Daniel; Diaz, Gemma Arca; Rawson, Myfanwy; Turnpenny, Peter (December 2019). "Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability". Orphanet Journal of Rare Diseases. 14 (1): 180. doi:10.1186/s13023-019-1064-y. PMC 6642533. PMID 31324220.
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