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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
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.
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

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
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
Lee S, Clinard K, Young SP, Rehder CW, Fan Z, Calikoglu AS, Bali DS, Bailey DB Jr, Gehtland LM, Millington DS, Patel HS, Beckloff SE, Zimmerman SJ, Powell CM, Taylor JL
JAMA Netw Open 2020 Jan 3;3(1):e1920356. doi: 10.1001/jamanetworkopen.2019.20356. PMID: 32003821Free PMC Article

Recent clinical studies

Etiology

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
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
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
Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, Scherer SW
Am J Hum Genet 2014 May 1;94(5):677-94. Epub 2014 Apr 24 doi: 10.1016/j.ajhg.2014.03.018. PMID: 24768552Free PMC Article

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
Bökenkamp A, Ludwig M
Pediatr Nephrol 2016 Dec;31(12):2201-2212. Epub 2016 Mar 24 doi: 10.1007/s00467-016-3343-3. PMID: 27011217Free PMC Article
Tylki-Szymańska A
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:107-13. PMID: 25345092
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

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
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
Tylki-Szymańska A
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:107-13. PMID: 25345092

Prognosis

van Geest FS, Groeneweg S, van den Akker ELT, Bacos I, Barca D, van den Berg SAA, Bertini E, Brunner D, Brunetti-Pierri N, Cappa M, Cappuccio G, Chatterjee K, Chesover AD, Christian P, Coutant R, Craiu D, Crock P, Dewey C, Dica A, Dimitri P, Dubey R, Enderli A, Fairchild J, Gallichan J, Garibaldi LR, George B, Hackenberg A, Heinrich B, Huynh T, Kłosowska A, Lawson-Yuen A, Linder-Lucht M, Lyons G, Monti Lora F, Moran C, Müller KE, Paone L, Paul PG, Polak M, Porta F, Reinauer C, de Rijke YB, Seckold R, Menevşe TS, Simm P, Simon A, Spada M, Stoupa A, Szeifert L, Tonduti D, van Toor H, Turan S, Vanderniet J, de Waart M, van der Wal R, van der Walt A, van Wermeskerken AM, Wierzba J, Zibordi F, Zung A, Peeters RP, Visser WE
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1136-e1147. doi: 10.1210/clinem/dgab750. PMID: 34679181Free PMC Article
Hackeng WM, Brosens LAA, Kim JY, O'Sullivan R, Sung YN, Liu TC, Cao D, Heayn M, Brosnan-Cashman J, An S, Morsink FHM, Heidsma CM, Valk GD, Vriens MR, Nieveen van Dijkum E, Offerhaus GJA, Dreijerink KMA, Zeh H, Zureikat AH, Hogg M, Lee K, Geller D, Marsh JW, Paniccia A, Ongchin M, Pingpank JF, Bahary N, Aijazi M, Brand R, Chennat J, Das R, Fasanella KE, Khalid A, McGrath K, Sarkaria S, Singh H, Slivka A, Nalesnik M, Han X, Nikiforova MN, Lawlor RT, Mafficini A, Rusev B, Corbo V, Luchini C, Bersani S, Pea A, Cingarlini S, Landoni L, Salvia R, Milione M, Milella M, Scarpa A, Hong SM, Heaphy CM, Singhi AD
Gut 2022 May;71(5):961-973. Epub 2021 Apr 13 doi: 10.1136/gutjnl-2020-322595. PMID: 33849943Free PMC Article
Cenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C
Neuropathol Appl Neurobiol 2020 Jun;46(4):303-322. Epub 2019 Nov 25 doi: 10.1111/nan.12587. PMID: 31698507
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
Tylki-Szymańska A
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:107-13. PMID: 25345092

Clinical prediction guides

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
Tylki-Szymańska A
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:107-13. PMID: 25345092

Recent systematic reviews

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
da Silva EM, Strufaldi MW, Andriolo RB, Silva LA
Cochrane Database Syst Rev 2014 Jan 8;(1):CD008185. doi: 10.1002/14651858.CD008185.pub3. PMID: 24399699

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