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X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome

MedGen UID:
162925
•Concept ID:
C0796264
•
Disease or Syndrome
Synonyms: Sex-linked mental retardation, short stature, obesity and hypogonadism; Young Hughes syndrome
SNOMED CT: X-linked intellectual disability, hypogonadism, ichthyosis, obesity, short stature syndrome (765471005); Young Hughes syndrome (765471005)
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:0017614
Orphanet: ORPHA3055

Definition

A rare X-linked intellectual disability syndrome with characteristics of intellectual disability associated with short stature, obesity, primary hypogonadism and an ichthyosiform skin condition. There have been no further descriptions in the literature since 1982. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome

Professional guidelines

PubMed

Genotype-phenotype spectrum of 130 unrelated Indian families with Mucopolysaccharidosis type II.
Agrawal N, Verma G, Saxena D, Kabra M, Gupta N, Mandal K, Moirangthem A, Sheth J, Puri RD, Bijarnia-Mahay S, Kapoor S, Danda S, H SV, Datar CA, Ranganath P, Shukla A, Dalal A, Srivastava P, Devi RR, Phadke SR
Eur J Med Genet 2022 Mar;65(3):104447. Epub 2022 Feb 8 doi: 10.1016/j.ejmg.2022.104447. PMID: 35144014
Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.
Faundes V, Goh S, Akilapa R, Bezuidenhout H, Bjornsson HT, Bradley L, Brady AF, Brischoux-Boucher E, Brunner H, Bulk S, Canham N, Cody D, Dentici ML, Digilio MC, Elmslie F, Fry AE, Gill H, Hurst J, Johnson D, Julia S, Lachlan K, Lebel RR, Byler M, Gershon E, Lemire E, Gnazzo M, Lepri FR, Marchese A, McEntagart M, McGaughran J, Mizuno S, Okamoto N, Rieubland C, Rodgers J, Sasaki E, Scalais E, Scurr I, Suri M, van der Burgt I, Matsumoto N, Miyake N, Benoit V, Lederer D, Banka S
Genet Med 2021 Jul;23(7):1202-1210. Epub 2021 Mar 5 doi: 10.1038/s41436-021-01119-8. PMID: 33674768Free PMC Article
Prenatal findings and the genetic diagnosis of fetal overgrowth disorders: Simpson-Golabi-Behmel syndrome, Sotos syndrome, and Beckwith-Wiedemann syndrome.
Chen CP
Taiwan J Obstet Gynecol 2012 Jun;51(2):186-91. doi: 10.1016/j.tjog.2012.04.004. PMID: 22795092

Recent clinical studies

Etiology

Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.
Kavanaugh BC, Elacio J, Best CR, St Pierre DG, Pescosolido MF, Ouyang Q, Biedermann J, Bradley RS, Liu JS, Jones RN, Morrow EM
J Med Genet 2024 Oct 23;61(11):1031-1039. doi: 10.1136/jmg-2024-109973. PMID: 39237363Free 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
Female-restricted syndromic intellectual disability in a patient from Thailand.
Sinthuwiwat T, Ittiwut C, Porntaveetus T, Shotelersuk V
Am J Med Genet A 2019 May;179(5):758-761. Epub 2019 Mar 3 doi: 10.1002/ajmg.a.61106. PMID: 30828969
PIBIDS syndrome in two Brazilian siblings.
Abagge KT, Haupenthal F, Felber GY, Raskin S
BMJ Case Rep 2018 Dec 22;11(1) doi: 10.1136/bcr-2017-223744. PMID: 30580289Free PMC Article
Fragile X syndrome.
Laxova R
Adv Pediatr 1994;41:305-42. PMID: 7992687

Diagnosis

Renpenning syndrome in a female.
Cho RY, Peñaherrera MS, Du Souich C, Huang L, Mwenifumbo J, Nelson TN, Elliott AM, Adam S; CAUSES Study, Eydoux P, Yang GX, Chijiwa C, Van Allen MI, Friedman JM, Robinson WP, Lehman A
Am J Med Genet A 2020 Mar;182(3):498-503. Epub 2019 Dec 16 doi: 10.1002/ajmg.a.61451. PMID: 31840929
Baraitser-Winter cerebrofrontofacial syndrome.
Yates TM, Turner CL, Firth HV, Berg J, Pilz DT
Clin Genet 2017 Jul;92(1):3-9. Epub 2016 Nov 30 doi: 10.1111/cge.12864. PMID: 27625340
X-linked mental deficiency.
des Portes V
Handb Clin Neurol 2013;111:297-306. doi: 10.1016/B978-0-444-52891-9.00035-X. PMID: 23622180
Genetics of obesity and overgrowth syndromes.
Sabin MA, Werther GA, Kiess W
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):207-20. doi: 10.1016/j.beem.2010.09.010. PMID: 21396586
Fragile X syndrome.
Laxova R
Adv Pediatr 1994;41:305-42. PMID: 7992687

Therapy

(R,R)-1,12-Dimethylspermine can mitigate abnormal spermidine accumulation in Snyder-Robinson syndrome.
Murray Stewart T, Khomutov M, Foley JR, Guo X, Holbert CE, Dunston TT, Schwartz CE, Gabrielson K, Khomutov A, Casero RA Jr
J Biol Chem 2020 Mar 6;295(10):3247-3256. Epub 2020 Jan 29 doi: 10.1074/jbc.RA119.011572. PMID: 31996374Free PMC Article
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
Genetics of obesity and overgrowth syndromes.
Sabin MA, Werther GA, Kiess W
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):207-20. doi: 10.1016/j.beem.2010.09.010. PMID: 21396586
Neurological findings in Hunter disease: pathology and possible therapeutic effects reviewed.
Al Sawaf S, Mayatepek E, Hoffmann B
J Inherit Metab Dis 2008 Aug;31(4):473-80. Epub 2008 Jul 13 doi: 10.1007/s10545-008-0878-x. PMID: 18618289
Fragile X syndrome.
Laxova R
Adv Pediatr 1994;41:305-42. PMID: 7992687

Prognosis

Genotype-phenotype spectrum of 130 unrelated Indian families with Mucopolysaccharidosis type II.
Agrawal N, Verma G, Saxena D, Kabra M, Gupta N, Mandal K, Moirangthem A, Sheth J, Puri RD, Bijarnia-Mahay S, Kapoor S, Danda S, H SV, Datar CA, Ranganath P, Shukla A, Dalal A, Srivastava P, Devi RR, Phadke SR
Eur J Med Genet 2022 Mar;65(3):104447. Epub 2022 Feb 8 doi: 10.1016/j.ejmg.2022.104447. PMID: 35144014
Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.
Muthusamy B, Nguyen TT, Bandari AK, Basheer S, Selvan LDN, Chandel D, Manoj J, Gayen S, Seshagiri S, Chandra Girimaji S, Pandey A
Eur J Med Genet 2020 Jan;63(1):103635. Epub 2019 Feb 21 doi: 10.1016/j.ejmg.2019.02.007. PMID: 30797980Free PMC Article
A new CUL4B variant associated with a mild phenotype and an exceptional pattern of leukoencephalopathy.
Weissbach S, Reinert MC, Altmüller J, Krätzner R, Thiele H, Rosenbaum T, Nürnberg P, Gärtner J
Am J Med Genet A 2017 Oct;173(10):2803-2807. Epub 2017 Aug 17 doi: 10.1002/ajmg.a.38390. PMID: 28817236
X-linked elliptocytosis with impaired growth is related to mutated AMMECR1.
Basel-Vanagaite L, Pillar N, Isakov O, Smirin-Yosef P, Lagovsky I, Orenstein N, Salmon-Divon M, Tamary H, Zaft T, Bazak L, Meyerovitch J, Pelli T, Botchan S, Farberov L, Weissglas-Volkov D, Shomron N
Gene 2017 Mar 30;606:47-52. Epub 2017 Jan 9 doi: 10.1016/j.gene.2017.01.001. PMID: 28089922
Donor splice-site mutation in CUL4B is likely cause of X-linked intellectual disability.
Londin ER, Adijanto J, Philp N, Novelli A, Vitale E, Perria C, Serra G, Alesi V, Surrey S, Fortina P
Am J Med Genet A 2014 Sep;164A(9):2294-9. Epub 2014 Jun 4 doi: 10.1002/ajmg.a.36629. PMID: 24898194Free PMC Article

Clinical prediction guides

Renpenning syndrome in a female.
Cho RY, Peñaherrera MS, Du Souich C, Huang L, Mwenifumbo J, Nelson TN, Elliott AM, Adam S; CAUSES Study, Eydoux P, Yang GX, Chijiwa C, Van Allen MI, Friedman JM, Robinson WP, Lehman A
Am J Med Genet A 2020 Mar;182(3):498-503. Epub 2019 Dec 16 doi: 10.1002/ajmg.a.61451. PMID: 31840929
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
X-linked elliptocytosis with impaired growth is related to mutated AMMECR1.
Basel-Vanagaite L, Pillar N, Isakov O, Smirin-Yosef P, Lagovsky I, Orenstein N, Salmon-Divon M, Tamary H, Zaft T, Bazak L, Meyerovitch J, Pelli T, Botchan S, Farberov L, Weissglas-Volkov D, Shomron N
Gene 2017 Mar 30;606:47-52. Epub 2017 Jan 9 doi: 10.1016/j.gene.2017.01.001. PMID: 28089922
Donor splice-site mutation in CUL4B is likely cause of X-linked intellectual disability.
Londin ER, Adijanto J, Philp N, Novelli A, Vitale E, Perria C, Serra G, Alesi V, Surrey S, Fortina P
Am J Med Genet A 2014 Sep;164A(9):2294-9. Epub 2014 Jun 4 doi: 10.1002/ajmg.a.36629. PMID: 24898194Free PMC Article

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