Syndromic autism

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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).

Contents

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 ]

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] [ clarification needed ]

Following the proposal, ASD would be divided into genetic categories, including: [4]

Clinically defined

Syndromes recognized by clinicians (depending on their experience), typically confirmed by a targeted genetic testing.

Molecularly defined

Syndromes recognized by genome-wide testing, not by hypothesis-driven testing (since clinical recognition is difficult).

Characteristics of syndromic ASD conditions
ConditionCause Chromosome(s) involved (if a mutation)ASD prevalence (95% CI)Clinically/Molecularly definedOther characteristicsRef.
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]

See also

References

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  8. 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.
  9. 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.
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