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Autism, susceptibility to, X-linked 2(AUTSX2)

MedGen UID:
336964
Concept ID:
C1845539
Finding
Synonyms: AUTSX2; NLGN4-Related X-Linked Mental Retardation
 
Gene (location): NLGN4X (Xp22.32-22.31)
 
Monarch Initiative: MONDO:0010341
OMIM®: 300495

Definition

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Impaired intellectual development coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which intellectual disability is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850. [from OMIM]

Clinical features

From HPO
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Lack of spontaneous play
MedGen UID:
373380
Concept ID:
C1837650
Finding
Lack of peer relationships
MedGen UID:
335162
Concept ID:
C1845337
Finding
The state of not having relationships with peers outside of school or organized activity appropriate to developmental level. This may be caused by behavioral or physical barriers.
Abnormal nonverbal communicative behavior
MedGen UID:
867425
Concept ID:
C4021798
Mental or Behavioral Dysfunction
Abnormalities in eye contact, communicative facial expressions, gesture use, or the use of others' bodies to communicate convey shared meanings within a culture that replace or supplement verbal communication.
Restrictive behavior
MedGen UID:
892681
Concept ID:
C4021799
Mental or Behavioral Dysfunction
Behavior characterized by an abnormal limitation to a few interests and activities.
Inflexible adherence to routines
MedGen UID:
1853268
Concept ID:
C5826341
Finding
A need to strictly adhere to repetitive routines or patterns of behavior which are created by the environment. One becomes upset or distressed when their routines are disrupted or altered.
Plagiocephaly
MedGen UID:
78562
Concept ID:
C0265529
Congenital Abnormality
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Increased serum serotonin
MedGen UID:
488950
Concept ID:
C0877243
Finding
A increased concentration of serotonin in the blood.

Professional guidelines

PubMed

Zahorakova D, Lelkova P, Gregor V, Magner M, Zeman J, Martasek P
J Hum Genet 2016 Jul;61(7):617-25. Epub 2016 Mar 17 doi: 10.1038/jhg.2016.19. PMID: 26984561

Recent clinical studies

Etiology

Mpoulimari I, Zintzaras E
Psychiatr Genet 2022 Jun 1;32(3):91-104. Epub 2022 Mar 31 doi: 10.1097/YPG.0000000000000316. PMID: 35353796
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
Cristino AS, Williams SM, Hawi Z, An JY, Bellgrove MA, Schwartz CE, Costa Lda F, Claudianos C
Mol Psychiatry 2014 Mar;19(3):294-301. Epub 2013 Feb 26 doi: 10.1038/mp.2013.16. PMID: 23439483
Caglayan AO
Dev Med Child Neurol 2010 Feb;52(2):130-8. Epub 2010 Jan 5 doi: 10.1111/j.1469-8749.2009.03523.x. PMID: 20059518

Diagnosis

Kahanovitch U, Patterson KC, Hernandez R, Olsen ML
Int J Mol Sci 2019 Aug 5;20(15) doi: 10.3390/ijms20153813. PMID: 31387202Free PMC Article
Ramírez-Cheyne JA, Duque GA, Ayala-Zapata S, Saldarriaga-Gil W, Hagerman P, Hagerman R, Payán-Gómez C
Clin Genet 2019 Feb;95(2):262-267. Epub 2018 Nov 27 doi: 10.1111/cge.13469. PMID: 30414172
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
Marco EJ, Skuse DH
Soc Cogn Affect Neurosci 2006 Dec;1(3):183-93. doi: 10.1093/scan/nsl028. PMID: 18985105Free PMC Article

Therapy

Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622

Prognosis

Mpoulimari I, Zintzaras E
Psychiatr Genet 2022 Jun 1;32(3):91-104. Epub 2022 Mar 31 doi: 10.1097/YPG.0000000000000316. PMID: 35353796
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622
Jiang YH, Yuen RK, Jin X, Wang M, Chen N, Wu X, Ju J, Mei J, Shi Y, He M, Wang G, Liang J, Wang Z, Cao D, Carter MT, Chrysler C, Drmic IE, Howe JL, Lau L, Marshall CR, Merico D, Nalpathamkalam T, Thiruvahindrapuram B, Thompson A, Uddin M, Walker S, Luo J, Anagnostou E, Zwaigenbaum L, Ring RH, Wang J, Lajonchere C, Wang J, Shih A, Szatmari P, Yang H, Dawson G, Li Y, Scherer SW
Am J Hum Genet 2013 Aug 8;93(2):249-63. Epub 2013 Jul 11 doi: 10.1016/j.ajhg.2013.06.012. PMID: 23849776Free PMC Article
Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, Lupski JR, Ramocki MB
Autism Res 2013 Feb;6(1):42-50. Epub 2012 Nov 20 doi: 10.1002/aur.1262. PMID: 23169761Free PMC Article
Puusepp H, Kall K, Salomons GS, Talvik I, Männamaa M, Rein R, Jakobs C, Õunap K
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S5-11. doi: 10.1007/s10545-008-1063-y. PMID: 24137762

Clinical prediction guides

Mpoulimari I, Zintzaras E
Psychiatr Genet 2022 Jun 1;32(3):91-104. Epub 2022 Mar 31 doi: 10.1097/YPG.0000000000000316. PMID: 35353796
Saldarriaga W, Payán-Gómez C, González-Teshima LY, Rosa L, Tassone F, Hagerman RJ
J Dev Behav Pediatr 2020 Dec;41(9):724-728. doi: 10.1097/DBP.0000000000000850. PMID: 32947579
Jiang YH, Yuen RK, Jin X, Wang M, Chen N, Wu X, Ju J, Mei J, Shi Y, He M, Wang G, Liang J, Wang Z, Cao D, Carter MT, Chrysler C, Drmic IE, Howe JL, Lau L, Marshall CR, Merico D, Nalpathamkalam T, Thiruvahindrapuram B, Thompson A, Uddin M, Walker S, Luo J, Anagnostou E, Zwaigenbaum L, Ring RH, Wang J, Lajonchere C, Wang J, Shih A, Szatmari P, Yang H, Dawson G, Li Y, Scherer SW
Am J Hum Genet 2013 Aug 8;93(2):249-63. Epub 2013 Jul 11 doi: 10.1016/j.ajhg.2013.06.012. PMID: 23849776Free PMC Article
Bruneau N, Szepetowski P
Curr Pharm Des 2011;17(19):1914-23. doi: 10.2174/138161211796718198. PMID: 21711233
Mulle JG, Dodd AF, McGrath JA, Wolyniec PS, Mitchell AA, Shetty AC, Sobreira NL, Valle D, Rudd MK, Satten G, Cutler DJ, Pulver AE, Warren ST
Am J Hum Genet 2010 Aug 13;87(2):229-36. doi: 10.1016/j.ajhg.2010.07.013. PMID: 20691406Free PMC Article

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