Autism associated with another medical condition
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[
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 .
Molecularly defined
Syndromes recognized by genome-wide testing, not by hypothesis-driven testing (since clinical recognition is difficult).
Currently undefined
Currently undefined.[
clarification needed ]
Characteristics of syndromic ASD conditions
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]
See also
References
^
a
b
c
d
e
f 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 .
^
a
b 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 .
^
a
b
c
d
e
f
g
h
i
j
k
l 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 .
^
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s 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 .