U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Intellectual disability, X-linked, with or without seizures, arx-related(XLID29)

MedGen UID:
208681
Concept ID:
C0796244
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 29; MENTAL RETARDATION, X-LINKED 29; MENTAL RETARDATION, X-LINKED 32; MENTAL RETARDATION, X-LINKED 33; MENTAL RETARDATION, X-LINKED 38; MENTAL RETARDATION, X-LINKED 43; Mental retardation, X-linked 52; MENTAL RETARDATION, X-LINKED 76; MENTAL RETARDATION, X-LINKED 87; XLID29
 
Gene (location): ARX (Xp21.3)
 
Monarch Initiative: MONDO:0010317
OMIM®: 300419

Definition

Intellectual developmental disorder-29 (XLID29) is a nonspecific form of XLID. It is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (DEE1; 308350) to Partington syndrome (309510) (Kato et al., 2004; Wallerstein et al., 2008). [from OMIM]

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Testicular dysgenesis
MedGen UID:
86232
Concept ID:
C0302885
Finding
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Sensorineural hearing impairment
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Long palpebral fissure
MedGen UID:
340300
Concept ID:
C1849340
Finding
Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.
Periorbital fullness
MedGen UID:
1710990
Concept ID:
C4760994
Finding
Increase in periorbital soft tissue.

Professional guidelines

PubMed

D'Avanzo F, Rigon L, Zanetti A, Tomanin R
Int J Mol Sci 2020 Feb 13;21(4) doi: 10.3390/ijms21041258. PMID: 32070051Free PMC Article
Turk BR, Theda C, Fatemi A, Moser AB
Int J Dev Neurosci 2020 Feb;80(1):52-72. Epub 2020 Jan 26 doi: 10.1002/jdn.10003. PMID: 31909500Free PMC Article
Engelen M, Kemp S, Poll-The BT
Curr Neurol Neurosci Rep 2014 Oct;14(10):486. doi: 10.1007/s11910-014-0486-0. PMID: 25115486

Recent clinical studies

Etiology

Gupta AO, Raymond G, Pierpont EI, Kemp S, McIvor RS, Rayannavar A, Miller B, Lund TC, Orchard PJ
Expert Opin Biol Ther 2022 Sep;22(9):1151-1162. Epub 2022 Sep 19 doi: 10.1080/14712598.2022.2124857. PMID: 36107226
León NY, Harley VR
Hum Genet 2021 Dec;140(12):1625-1634. Epub 2021 Sep 15 doi: 10.1007/s00439-021-02361-5. PMID: 34524523
Mohamed S, He QQ, Singh AA, Ferro V
Adv Carbohydr Chem Biochem 2020;77:71-117. Epub 2019 Oct 26 doi: 10.1016/bs.accb.2019.09.001. PMID: 33004112
Zanni G, Bertini E
Handb Clin Neurol 2018;155:175-189. doi: 10.1016/B978-0-444-64189-2.00011-1. PMID: 29891057
Anazi S, Maddirevula S, Faqeih E, Alsedairy H, Alzahrani F, Shamseldin HE, Patel N, Hashem M, Ibrahim N, Abdulwahab F, Ewida N, Alsaif HS, Al Sharif H, Alamoudi W, Kentab A, Bashiri FA, Alnaser M, AlWadei AH, Alfadhel M, Eyaid W, Hashem A, Al Asmari A, Saleh MM, AlSaman A, Alhasan KA, Alsughayir M, Al Shammari M, Mahmoud A, Al-Hassnan ZN, Al-Husain M, Osama Khalil R, Abd El Meguid N, Masri A, Ali R, Ben-Omran T, El Fishway P, Hashish A, Ercan Sencicek A, State M, Alazami AM, Salih MA, Altassan N, Arold ST, Abouelhoda M, Wakil SM, Monies D, Shaheen R, Alkuraya FS
Mol Psychiatry 2017 Apr;22(4):615-624. Epub 2016 Jul 19 doi: 10.1038/mp.2016.113. PMID: 27431290

Diagnosis

León NY, Harley VR
Hum Genet 2021 Dec;140(12):1625-1634. Epub 2021 Sep 15 doi: 10.1007/s00439-021-02361-5. PMID: 34524523
Chiurazzi P, Kiani AK, Miertus J, Paolacci S, Barati S, Manara E, Stuppia L, Gurrieri F, Bertelli M
Acta Biomed 2020 Nov 9;91(13-S):e2020003. doi: 10.23750/abm.v91i13-S.10684. PMID: 33170170Free PMC Article
D'Avanzo F, Rigon L, Zanetti A, Tomanin R
Int J Mol Sci 2020 Feb 13;21(4) doi: 10.3390/ijms21041258. PMID: 32070051Free PMC Article
Wu Y, Lyon GJ
Exp Mol Med 2018 Jul 27;50(7):1-10. doi: 10.1038/s12276-018-0098-x. PMID: 30054457Free PMC Article
Anazi S, Maddirevula S, Faqeih E, Alsedairy H, Alzahrani F, Shamseldin HE, Patel N, Hashem M, Ibrahim N, Abdulwahab F, Ewida N, Alsaif HS, Al Sharif H, Alamoudi W, Kentab A, Bashiri FA, Alnaser M, AlWadei AH, Alfadhel M, Eyaid W, Hashem A, Al Asmari A, Saleh MM, AlSaman A, Alhasan KA, Alsughayir M, Al Shammari M, Mahmoud A, Al-Hassnan ZN, Al-Husain M, Osama Khalil R, Abd El Meguid N, Masri A, Ali R, Ben-Omran T, El Fishway P, Hashish A, Ercan Sencicek A, State M, Alazami AM, Salih MA, Altassan N, Arold ST, Abouelhoda M, Wakil SM, Monies D, Shaheen R, Alkuraya FS
Mol Psychiatry 2017 Apr;22(4):615-624. Epub 2016 Jul 19 doi: 10.1038/mp.2016.113. PMID: 27431290

Therapy

Pereira G, Dória S
J Genet 2021;100 PMID: 34553695
Zhu J, Eichler F, Biffi A, Duncan CN, Williams DA, Majzoub JA
Endocr Rev 2020 Aug 1;41(4):577-93. doi: 10.1210/endrev/bnaa013. PMID: 32364223Free PMC Article
Groeneweg S, van Geest FS, Peeters RP, Heuer H, Visser WE
Endocr Rev 2020 Apr 1;41(2) doi: 10.1210/endrev/bnz008. PMID: 31754699
Kyle SM, Vashi N, Justice MJ
Open Biol 2018 Feb;8(2) doi: 10.1098/rsob.170216. PMID: 29445033Free PMC Article
Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, Armant M, Dansereau C, Lund TC, Miller WP, Raymond GV, Sankar R, Shah AJ, Sevin C, Gaspar HB, Gissen P, Amartino H, Bratkovic D, Smith NJC, Paker AM, Shamir E, O'Meara T, Davidson D, Aubourg P, Williams DA
N Engl J Med 2017 Oct 26;377(17):1630-1638. Epub 2017 Oct 4 doi: 10.1056/NEJMoa1700554. PMID: 28976817Free PMC Article

Prognosis

Ma CY, Li C, Zhou X, Zhang Z, Jiang H, Liu H, Chen HJ, Tse HF, Liao C, Lian Q
Biomed Pharmacother 2021 Nov;143:112214. Epub 2021 Sep 21 doi: 10.1016/j.biopha.2021.112214. PMID: 34560537
van de Stadt SIW, Huffnagel IC, Turk BR, van der Knaap MS, Engelen M
Neuropediatrics 2021 Aug;52(4):252-260. Epub 2021 Jun 30 doi: 10.1055/s-0041-1730937. PMID: 34192790
Zhu J, Eichler F, Biffi A, Duncan CN, Williams DA, Majzoub JA
Endocr Rev 2020 Aug 1;41(4):577-93. doi: 10.1210/endrev/bnaa013. PMID: 32364223Free PMC Article
Tylki-Szymańska A
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:107-13. PMID: 25345092
Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, Poll-The BT
Orphanet J Rare Dis 2012 Aug 13;7:51. doi: 10.1186/1750-1172-7-51. PMID: 22889154Free PMC Article

Clinical prediction guides

Mahdi SS, Jafri HA, Allana R, Amenta F, Khawaja M, Qasim SSB
Int J Environ Res Public Health 2021 Jan 28;18(3) doi: 10.3390/ijerph18031162. PMID: 33525609Free PMC Article
Sandweiss AJ, Brandt VL, Zoghbi HY
Lancet Neurol 2020 Aug;19(8):689-698. doi: 10.1016/S1474-4422(20)30217-9. PMID: 32702338
De Luca C, Race V, Keldermans L, Bauters M, Van Esch H
Br Med Bull 2020 May 15;133(1):36-48. doi: 10.1093/bmb/ldz039. PMID: 32043524
Moortgat S, Berland S, Aukrust I, Maystadt I, Baker L, Benoit V, Caro-Llopis A, Cooper NS, Debray FG, Faivre L, Gardeitchik T, Haukanes BI, Houge G, Kivuva E, Martinez F, Mehta SG, Nassogne MC, Powell-Hamilton N, Pfundt R, Rosello M, Prescott T, Vasudevan P, van Loon B, Verellen-Dumoulin C, Verloes A, Lippe CV, Wakeling E, Wilkie AOM, Wilson L, Yuen A, Study D, Low KJ, Newbury-Ecob RA
Eur J Hum Genet 2018 Jan;26(1):64-74. Epub 2017 Nov 27 doi: 10.1038/s41431-017-0038-6. PMID: 29180823Free PMC Article
de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, Vulto-van Silfhout AT, Koolen DA, de Vries P, Gilissen C, del Rosario M, Hoischen A, Scheffer H, de Vries BB, Brunner HG, Veltman JA, Vissers LE
N Engl J Med 2012 Nov 15;367(20):1921-9. Epub 2012 Oct 3 doi: 10.1056/NEJMoa1206524. PMID: 23033978

Recent systematic reviews

De Feyter S, Beyens A, Callewaert B
J Inherit Metab Dis 2023 Mar;46(2):163-173. Epub 2023 Feb 3 doi: 10.1002/jimd.12590. PMID: 36692329
León NY, Harley VR
Hum Genet 2021 Dec;140(12):1625-1634. Epub 2021 Sep 15 doi: 10.1007/s00439-021-02361-5. PMID: 34524523
Mahdi SS, Jafri HA, Allana R, Amenta F, Khawaja M, Qasim SSB
Int J Environ Res Public Health 2021 Jan 28;18(3) doi: 10.3390/ijerph18031162. PMID: 33525609Free PMC Article
Mallack EJ, Turk BR, Yan H, Price C, Demetres M, Moser AB, Becker C, Hollandsworth K, Adang L, Vanderver A, Van Haren K, Ruzhnikov M, Kurtzberg J, Maegawa G, Orchard PJ, Lund TC, Raymond GV, Regelmann M, Orsini JJ, Seeger E, Kemp S, Eichler F, Fatemi A
J Inherit Metab Dis 2021 May;44(3):728-739. Epub 2021 Jan 9 doi: 10.1002/jimd.12356. PMID: 33373467Free PMC Article
Vairo FPE, Chwal BC, Perini S, Ferreira MAP, de Freitas Lopes AC, Saute JAM
Mol Genet Metab 2019 Jan;126(1):6-13. Epub 2018 Dec 11 doi: 10.1016/j.ymgme.2018.12.005. PMID: 30594472

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...