U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Intellectual disability, X-linked 2(XLID2)

MedGen UID:
162922
Concept ID:
C0796207
Mental or Behavioral Dysfunction
Synonyms: MRX2; XLID2
 
Monarch Initiative: MONDO:0010322
OMIM®: 300428

Definition

Nonsyndromic mental retardation with a large head, relatively short stature, highly arched palate, square facies, short hands and feet, and macroorchidism. [from MCA/MR]

Clinical features

From HPO
Macroorchidism
MedGen UID:
224727
Concept ID:
C1263023
Finding
The presence of abnormally large testes.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Poor fine motor coordination
MedGen UID:
356863
Concept ID:
C1867864
Finding
An abnormality of the ability (skills) to perform a precise movement of small muscles with the intent to perform a specific act. Fine motor skills are required to mediate movements of the wrists, hands, fingers, feet, and toes.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Relative macrocephaly
MedGen UID:
338607
Concept ID:
C1849075
Congenital Abnormality
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Square face
MedGen UID:
371253
Concept ID:
C1832127
Finding
Facial contours, as viewed from the front, show a broad upper face/cranium and lower face/mandible, creating a square appearance.

Professional guidelines

PubMed

Hong KN, Eshraghian EA, Arad M, Argirò A, Brambatti M, Bui Q, Caspi O, de Frutos F, Greenberg B, Ho CY, Kaski JP, Olivotto I, Taylor MRG, Yesso A, Garcia-Pavia P, Adler ED
J Am Coll Cardiol 2023 Oct 17;82(16):1628-1647. doi: 10.1016/j.jacc.2023.08.014. PMID: 37821174
Ream MA, Lam WKK, Grosse SD, Ojodu J, Jones E, Prosser LA, Rosé AM, Comeau AM, Tanksley S, Powell CM, Kemper AR
Genet Med 2023 Feb;25(2):100330. Epub 2022 Nov 29 doi: 10.1016/j.gim.2022.10.012. PMID: 36445366Free 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

Recent clinical studies

Etiology

Lui JC, Baron J
J Clin Endocrinol Metab 2024 Jan 18;109(2):312-320. doi: 10.1210/clinem/dgad420. PMID: 37450557
Sinnett SE, Boyle E, Lyons C, Gray SJ
Brain 2021 Nov 29;144(10):3005-3019. doi: 10.1093/brain/awab182. PMID: 33950254Free 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
Hu H, Haas SA, Chelly J, Van Esch H, Raynaud M, de Brouwer AP, Weinert S, Froyen G, Frints SG, Laumonnier F, Zemojtel T, Love MI, Richard H, Emde AK, Bienek M, Jensen C, Hambrock M, Fischer U, Langnick C, Feldkamp M, Wissink-Lindhout W, Lebrun N, Castelnau L, Rucci J, Montjean R, Dorseuil O, Billuart P, Stuhlmann T, Shaw M, Corbett MA, Gardner A, Willis-Owen S, Tan C, Friend KL, Belet S, van Roozendaal KE, Jimenez-Pocquet M, Moizard MP, Ronce N, Sun R, O'Keeffe S, Chenna R, van Bömmel A, Göke J, Hackett A, Field M, Christie L, Boyle J, Haan E, Nelson J, Turner G, Baynam G, Gillessen-Kaesbach G, Müller U, Steinberger D, Budny B, Badura-Stronka M, Latos-Bieleńska A, Ousager LB, Wieacker P, Rodríguez Criado G, Bondeson ML, Annerén G, Dufke A, Cohen M, Van Maldergem L, Vincent-Delorme C, Echenne B, Simon-Bouy B, Kleefstra T, Willemsen M, Fryns JP, Devriendt K, Ullmann R, Vingron M, Wrogemann K, Wienker TF, Tzschach A, van Bokhoven H, Gecz J, Jentsch TJ, Chen W, Ropers HH, Kalscheuer VM
Mol Psychiatry 2016 Jan;21(1):133-48. Epub 2015 Feb 3 doi: 10.1038/mp.2014.193. PMID: 25644381Free PMC Article
Storey E
Semin Neurol 2014 Jul;34(3):280-92. Epub 2014 Sep 5 doi: 10.1055/s-0034-1386766. PMID: 25192506

Diagnosis

Pascual-Alonso A, Martínez-Monseny AF, Xiol C, Armstrong J
Int J Mol Sci 2021 Sep 4;22(17) doi: 10.3390/ijms22179610. PMID: 34502518Free 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
Neri G, Schwartz CE, Lubs HA, Stevenson RE
Am J Med Genet A 2018 Jun;176(6):1375-1388. Epub 2018 Apr 25 doi: 10.1002/ajmg.a.38710. PMID: 29696803Free PMC Article
Cappa M, Bizzarri C, Vollono C, Petroni A, Banni S
Endocr Dev 2011;20:149-160. Epub 2010 Dec 16 doi: 10.1159/000321236. PMID: 21164268
Torres RJ, Puig JG
Orphanet J Rare Dis 2007 Dec 8;2:48. doi: 10.1186/1750-1172-2-48. PMID: 18067674Free PMC Article

Therapy

Qian J, Guan X, Xie B, Xu C, Niu J, Tang X, Li CH, Colecraft HM, Jaenisch R, Liu XS
Sci Transl Med 2023 Jan 18;15(679):eadd4666. doi: 10.1126/scitranslmed.add4666. PMID: 36652535
Sinnett SE, Boyle E, Lyons C, Gray SJ
Brain 2021 Nov 29;144(10):3005-3019. doi: 10.1093/brain/awab182. PMID: 33950254Free PMC Article
Sonoda H, Morimoto H, Yoden E, Koshimura Y, Kinoshita M, Golovina G, Takagi H, Yamamoto R, Minami K, Mizoguchi A, Tachibana K, Hirato T, Takahashi K
Mol Ther 2018 May 2;26(5):1366-1374. Epub 2018 Mar 6 doi: 10.1016/j.ymthe.2018.02.032. PMID: 29606503Free PMC Article
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

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
Hiatt SM, Trajkova S, Sebastiano MR, Partridge EC, Abidi FE, Anderson A, Ansar M, Antonarakis SE, Azadi A, Bachmann-Gagescu R, Bartuli A, Benech C, Berkowitz JL, Betti MJ, Brusco A, Cannon A, Caron G, Chen Y, Cochran ME, Coleman TF, Crenshaw MM, Cuisset L, Curry CJ, Darvish H, Demirdas S, Descartes M, Douglas J, Dyment DA, Elloumi HZ, Ermondi G, Faoucher M, Farrow EG, Felker SA, Fisher H, Hurst ACE, Joset P, Kelly MA, Kmoch S, Leadem BR, Lyons MJ, Macchiaiolo M, Magner M, Mandrile G, Mattioli F, McEown M, Meadows SK, Medne L, Meeks NJL, Montgomery S, Napier MP, Natowicz M, Newberry KM, Niceta M, Noskova L, Nowak CB, Noyes AG, Osmond M, Prijoles EJ, Pugh J, Pullano V, Quélin C, Rahimi-Aliabadi S, Rauch A, Redon S, Reymond A, Schwager CR, Sellars EA, Scheuerle AE, Shukarova-Angelovska E, Skraban C, Stolerman E, Sullivan BR, Tartaglia M, Thiffault I, Uguen K, Umaña LA, van Bever Y, van der Crabben SN, van Slegtenhorst MA, Waisfisz Q, Washington C, Rodan LH, Myers RM, Cooper GM
Am J Hum Genet 2023 Feb 2;110(2):215-227. Epub 2022 Dec 30 doi: 10.1016/j.ajhg.2022.12.007. PMID: 36586412Free PMC Article
Tian MQ, Liu XR, Lin SM, Wang J, Luo S, Gao LD, Chen XB, Liang XY, Liu ZG, He N, Yi YH, Liao WP; China Epilepsy Gene 1.0 Project
CNS Neurosci Ther 2023 Feb;29(2):727-735. Epub 2022 Dec 13 doi: 10.1111/cns.14057. PMID: 36514184Free PMC Article
LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC
PLoS One 2017;12(2):e0170843. Epub 2017 Feb 2 doi: 10.1371/journal.pone.0170843. PMID: 28152038Free PMC Article
Lisik MZ, Sieron AL
Med Sci Monit 2008 Nov;14(11):RA221-9. PMID: 18971887

Clinical prediction guides

Hiatt SM, Trajkova S, Sebastiano MR, Partridge EC, Abidi FE, Anderson A, Ansar M, Antonarakis SE, Azadi A, Bachmann-Gagescu R, Bartuli A, Benech C, Berkowitz JL, Betti MJ, Brusco A, Cannon A, Caron G, Chen Y, Cochran ME, Coleman TF, Crenshaw MM, Cuisset L, Curry CJ, Darvish H, Demirdas S, Descartes M, Douglas J, Dyment DA, Elloumi HZ, Ermondi G, Faoucher M, Farrow EG, Felker SA, Fisher H, Hurst ACE, Joset P, Kelly MA, Kmoch S, Leadem BR, Lyons MJ, Macchiaiolo M, Magner M, Mandrile G, Mattioli F, McEown M, Meadows SK, Medne L, Meeks NJL, Montgomery S, Napier MP, Natowicz M, Newberry KM, Niceta M, Noskova L, Nowak CB, Noyes AG, Osmond M, Prijoles EJ, Pugh J, Pullano V, Quélin C, Rahimi-Aliabadi S, Rauch A, Redon S, Reymond A, Schwager CR, Sellars EA, Scheuerle AE, Shukarova-Angelovska E, Skraban C, Stolerman E, Sullivan BR, Tartaglia M, Thiffault I, Uguen K, Umaña LA, van Bever Y, van der Crabben SN, van Slegtenhorst MA, Waisfisz Q, Washington C, Rodan LH, Myers RM, Cooper GM
Am J Hum Genet 2023 Feb 2;110(2):215-227. Epub 2022 Dec 30 doi: 10.1016/j.ajhg.2022.12.007. PMID: 36586412Free 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
Piché J, Van Vliet PP, Pucéat M, Andelfinger G
Cell Cycle 2019 Nov;18(21):2828-2848. Epub 2019 Sep 13 doi: 10.1080/15384101.2019.1658476. PMID: 31516082Free 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
LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC
PLoS One 2017;12(2):e0170843. Epub 2017 Feb 2 doi: 10.1371/journal.pone.0170843. PMID: 28152038Free PMC Article

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
Shah A, Bapna M, Al-Saif H, Li R, Couser NL
Ophthalmic Genet 2022 Feb;43(1):126-129. Epub 2021 Oct 20 doi: 10.1080/13816810.2021.1989601. PMID: 34670449
Inuzuka LM, Guerra-Peixe M, Macedo-Souza LI, Pedreira CC, Gurgel-Giannetti J, Monteiro FP, Ramos L, Costa LA, Crippa ACS, Lourenco CM, Pachito DV, Sukys-Claudino L, Gaspar LS, Antoniuk SA, Dutra LPS, Diniz SSL, Pires RB, Garzon E, Kok F
Eur J Paediatr Neurol 2021 Sep;34:7-13. Epub 2021 Jun 21 doi: 10.1016/j.ejpn.2021.05.013. PMID: 34271245
da Silva EM, Strufaldi MW, Andriolo RB, Silva LA
Cochrane Database Syst Rev 2016 Feb 5;2(2):CD008185. doi: 10.1002/14651858.CD008185.pub4. PMID: 26845288Free PMC Article
Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Mol Genet Metab 2014 Aug;112(4):259-74. Epub 2014 May 29 doi: 10.1016/j.ymgme.2014.05.011. PMID: 24953403

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...