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X-linked intellectual disability-macrocephaly-macroorchidism syndrome

MedGen UID:
930075
•Concept ID:
C4304406
•
Disease or Syndrome
Synonyms: Johnson syndrome; X-linked intellectual disability, macrocephaly, macroorchidism syndrome
SNOMED CT: Johnson syndrome (719825000); X-linked intellectual disability, macrocephaly, macroorchidism syndrome (719825000)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
•Concept ID:
C1845977
•
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
See: This record
X-linked recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0019419
Orphanet: ORPHA85320

Definition

This syndrome has characteristics of intellectual deficit affecting both sexes, macrocephaly, and macroorchidism in the majority of affected males. It has been described in 12 individuals from two generations of one family. Other males from this family did not display intellectual deficit but did present macroorchidism and macrocephaly. Transmission is X-linked and the causative gene has been located to the q12-q21 region of the X chromosome. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked intellectual disability-macrocephaly-macroorchidism syndrome

Professional guidelines

PubMed

ATR-X syndrome: genetics, clinical spectrum, and management.
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
Prenatal diagnosis of Simpson-Golabi-Behmel syndrome.
Magini P, Palombo F, Boito S, Lanzoni G, Mongelli P, Rizzuti T, Baccarin M, Pippucci T, Seri M, Lalatta F
Am J Med Genet A 2016 Dec;170(12):3258-3264. Epub 2016 Sep 9 doi: 10.1002/ajmg.a.37873. PMID: 27612164
Molecular basis for prospective pharmacological treatment strategies in intellectual disability syndromes.
Verpelli C, Galimberti I, Gomez-Mancilla B, Sala C
Dev Neurobiol 2014 Feb;74(2):197-206. Epub 2013 Jul 19 doi: 10.1002/dneu.22093. PMID: 23695997

Recent clinical studies

Etiology

X-Linked Epilepsies: A Narrative Review.
Bernardo P, Cuccurullo C, Rubino M, De Vita G, Terrone G, Bilo L, Coppola A
Int J Mol Sci 2024 Apr 8;25(7) doi: 10.3390/ijms25074110. PMID: 38612920Free PMC Article
Epigenetic Causes of Overgrowth Syndromes.
Lui JC, Baron J
J Clin Endocrinol Metab 2024 Jan 18;109(2):312-320. doi: 10.1210/clinem/dgad420. PMID: 37450557Free PMC Article
ATR-X syndrome: genetics, clinical spectrum, and management.
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
Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms.
Wang YR, Xu NX, Wang J, Wang XM
World J Pediatr 2019 Dec;15(6):528-535. Epub 2019 Oct 5 doi: 10.1007/s12519-019-00309-4. PMID: 31587141
The neurobiology of X-linked intellectual disability.
Bassani S, Zapata J, Gerosa L, Moretto E, Murru L, Passafaro M
Neuroscientist 2013 Oct;19(5):541-52. Epub 2013 Jul 2 doi: 10.1177/1073858413493972. PMID: 23820068

Diagnosis

MECP2-Related Disorders in Males.
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
Kabuki Syndrome-Clinical Review with Molecular Aspects.
Boniel S, Szymańska K, Śmigiel R, Szczałuba K
Genes (Basel) 2021 Mar 25;12(4) doi: 10.3390/genes12040468. PMID: 33805950Free PMC Article
Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms.
Wang YR, Xu NX, Wang J, Wang XM
World J Pediatr 2019 Dec;15(6):528-535. Epub 2019 Oct 5 doi: 10.1007/s12519-019-00309-4. PMID: 31587141
NAA10-related syndrome.
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
Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.
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

Therapy

X-chromosome inactivation: implications in human disease.
Pereira G, Dória S
J Genet 2021;100 PMID: 34553695
Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.
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
HDAC8: a multifaceted target for therapeutic interventions.
Chakrabarti A, Oehme I, Witt O, Oliveira G, Sippl W, Romier C, Pierce RJ, Jung M
Trends Pharmacol Sci 2015 Jul;36(7):481-92. Epub 2015 May 23 doi: 10.1016/j.tips.2015.04.013. PMID: 26013035
Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome.
Mégarbané H, Mégarbané A
Orphanet J Rare Dis 2011 May 21;6:29. doi: 10.1186/1750-1172-6-29. PMID: 21600032Free PMC Article
Fragile X syndrome.
Laxova R
Adv Pediatr 1994;41:305-42. PMID: 7992687

Prognosis

Semaphorin-Plexin Signaling: From Axonal Guidance to a New X-Linked Intellectual Disability Syndrome.
Steele JL, Morrow MM, Sarnat HB, Alkhunaizi E, Brandt T, Chitayat DA, DeFilippo CP, Douglas GV, Dubbs HA, Elloumi HZ, Glassford MR, Hannibal MC, Héron B, Kim LE, Marco EJ, Mignot C, Monaghan KG, Myers KA, Parikh S, Quinonez SC, Rajabi F, Shankar SP, Shinawi MS, van de Kamp JJP, Veerapandiyan A, Waldman AT, Graf WD
Pediatr Neurol 2022 Jan;126:65-73. Epub 2021 Oct 18 doi: 10.1016/j.pediatrneurol.2021.10.008. PMID: 34740135
Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination?
Vancamp P, Demeneix BA, Remaud S
Front Endocrinol (Lausanne) 2020;11:283. Epub 2020 May 13 doi: 10.3389/fendo.2020.00283. PMID: 32477268Free PMC Article
Challenges in molecular diagnosis of X-linked Intellectual disability.
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
Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.
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
Mitochondrial cytopathies.
El-Hattab AW, Scaglia F
Cell Calcium 2016 Sep;60(3):199-206. Epub 2016 Mar 4 doi: 10.1016/j.ceca.2016.03.003. PMID: 26996063

Clinical prediction guides

Bioinformatic prediction of putative conveyers of O-GlcNAc transferase intellectual disability.
Mitchell CW, Czajewski I, van Aalten DMF
J Biol Chem 2022 Sep;298(9):102276. Epub 2022 Jul 19 doi: 10.1016/j.jbc.2022.102276. PMID: 35863433Free PMC Article
Challenges in molecular diagnosis of X-linked Intellectual disability.
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
The expanding phenotypes of cohesinopathies: one ring to rule them all!
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
HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients.
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
Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.
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

CUL4B-associated epilepsy: Report of a novel truncating variant promoting drug-resistant seizures and systematic review of the literature.
Della Vecchia S, Lopergolo D, Trovato R, Pasquariello R, Ferrari AR, Bartolini E
Seizure 2023 Jan;104:32-37. Epub 2022 Nov 29 doi: 10.1016/j.seizure.2022.11.014. PMID: 36476360
Eye and ocular adnexa manifestations of MED12-related disorders.
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
ATR-X syndrome: genetics, clinical spectrum, and management.
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
MECP2-related conditions in males: A systematic literature review and 8 additional cases.
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
Oral Manifestations of Rett Syndrome-A Systematic Review.
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

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