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Hearing loss, X-linked 4(DFNX4)

MedGen UID:
376307
•Concept ID:
C1848204
•
Disease or Syndrome
Synonyms: DEAFNESS, NONSYNDROMIC SENSORINEURAL PROGRESSIVE 6; Deafness, X-linked 4; DEAFNESS, X-LINKED 6, PROGRESSIVE; DFNX4; DFNX4 (DFN6) Nonsyndromic Hearing Loss and Deafness
 
Gene (location): SMPX (Xp22.12)
 
Monarch Initiative: MONDO:0010238
OMIM®: 300066

Definition

X-linked deafness-4 is a nonsyndromic form of progressive hearing loss with postlingual onset. Affected males show earlier onset of hearing loss than affected females (summary by del Castillo et al., 1996). [from OMIM]

Clinical features

From HPO
High-frequency hearing impairment
MedGen UID:
42358
•Concept ID:
C0018780
•
Disease or Syndrome
A type of hearing impairment affecting primarily the higher frequencies of sound (3,000 to 6,000 Hz).
See: Feature record | Search on this feature
Sensorineural hearing loss disorder
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.
See: Feature record | Search on this feature

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHearing loss, X-linked 4

Professional guidelines

PubMed

Renal, auricular, and ocular outcomes of Alport syndrome and their current management.
Zhang Y, Ding J
Pediatr Nephrol 2018 Aug;33(8):1309-1316. Epub 2017 Sep 1 doi: 10.1007/s00467-017-3784-3. PMID: 28864840
X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.
Savige J, Storey H, Il Cheong H, Gyung Kang H, Park E, Hilbert P, Persikov A, Torres-Fernandez C, Ars E, Torra R, Hertz JM, Thomassen M, Shagam L, Wang D, Wang Y, Flinter F, Nagel M
PLoS One 2016;11(9):e0161802. Epub 2016 Sep 14 doi: 10.1371/journal.pone.0161802. PMID: 27627812Free PMC Article
PRPS1 mutations: four distinct syndromes and potential treatment.
de Brouwer AP, van Bokhoven H, Nabuurs SB, Arts WF, Christodoulou J, Duley J
Am J Hum Genet 2010 Apr 9;86(4):506-18. doi: 10.1016/j.ajhg.2010.02.024. PMID: 20380929Free PMC Article

Recent clinical studies

Etiology

Spectrum of Alport syndrome in an Indian cohort.
Yadav M, Jadon T, Singh G, Devi KG, Chandan M, Khandelwal P, Meena J, Geetha TS, Faruq M, Hari P, Sinha A, Bagga A
Pediatr Nephrol 2025 Feb;40(2):393-405. Epub 2024 Sep 16 doi: 10.1007/s00467-024-06507-1. PMID: 39278986
Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.
Bosman A, Appelman-Dijkstra NM, Boot AM, de Borst MH, van de Ven AC, de Jongh RT, Bökenkamp A, van den Bergh JP, van der Eerden BCJ, Zillikens MC
Calcif Tissue Int 2024 Mar;114(3):255-266. Epub 2024 Jan 16 doi: 10.1007/s00223-023-01172-2. PMID: 38226986Free PMC Article
X-linked deafness/incomplete partition type 3: Radiological evaluation of temporal bone and intracranial findings.
Parlak S, Gumeler E, Sennaroglu L, Ozgen B
Diagn Interv Radiol 2022 Jan;28(1):50-57. doi: 10.5152/dir.2021.20791. PMID: 34914607
Molecular Epidemiology in 591 Italian Probands With Nonsyndromic Retinitis Pigmentosa and Usher Syndrome.
Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
Ocular features in Alport syndrome: pathogenesis and clinical significance.
Savige J, Sheth S, Leys A, Nicholson A, Mack HG, Colville D
Clin J Am Soc Nephrol 2015 Apr 7;10(4):703-9. Epub 2015 Feb 3 doi: 10.2215/CJN.10581014. PMID: 25649157Free PMC Article

Diagnosis

An unusual case of nephrotic syndrome.
Wildes DM, Fitzsimons A, Doyle B, Green A, Sweeney C, Awan A
Pediatr Nephrol 2024 Nov;39(11):3205-3208. Epub 2024 May 23 doi: 10.1007/s00467-024-06408-3. PMID: 38780768Free PMC Article
Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.
Bosman A, Appelman-Dijkstra NM, Boot AM, de Borst MH, van de Ven AC, de Jongh RT, Bökenkamp A, van den Bergh JP, van der Eerden BCJ, Zillikens MC
Calcif Tissue Int 2024 Mar;114(3):255-266. Epub 2024 Jan 16 doi: 10.1007/s00223-023-01172-2. PMID: 38226986Free PMC Article
Molecular Epidemiology in 591 Italian Probands With Nonsyndromic Retinitis Pigmentosa and Usher Syndrome.
Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.
Savige J, Storey H, Il Cheong H, Gyung Kang H, Park E, Hilbert P, Persikov A, Torres-Fernandez C, Ars E, Torra R, Hertz JM, Thomassen M, Shagam L, Wang D, Wang Y, Flinter F, Nagel M
PLoS One 2016;11(9):e0161802. Epub 2016 Sep 14 doi: 10.1371/journal.pone.0161802. PMID: 27627812Free PMC Article
Ocular features in Alport syndrome: pathogenesis and clinical significance.
Savige J, Sheth S, Leys A, Nicholson A, Mack HG, Colville D
Clin J Am Soc Nephrol 2015 Apr 7;10(4):703-9. Epub 2015 Feb 3 doi: 10.2215/CJN.10581014. PMID: 25649157Free PMC Article

Therapy

Endpoints and Design for Clinical Trials in USH2A-Related Retinal Degeneration: Results and Recommendations From the RUSH2A Natural History Study.
Maguire MG, Birch DG, Duncan JL, Ayala AR, Ayton LN, Cheetham JK, Cheng P, Durham TA, Ferris FL 3rd, Hoyng CB, Huckfeldt RM, Jaffe GJ, Kay C, Lad EM, Leroy BP, Liang W, McDaniel LS, Melia M, Michaelides M, Pennesi ME, Sahel JA, Samarakoon L; REDI Working Group and the Foundation Fighting Blindness Clinical Consortium Investigator Group
Transl Vis Sci Technol 2024 Oct 1;13(10):15. doi: 10.1167/tvst.13.10.15. PMID: 39382872Free PMC Article
Renal, auricular, and ocular outcomes of Alport syndrome and their current management.
Zhang Y, Ding J
Pediatr Nephrol 2018 Aug;33(8):1309-1316. Epub 2017 Sep 1 doi: 10.1007/s00467-017-3784-3. PMID: 28864840
X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.
Savige J, Storey H, Il Cheong H, Gyung Kang H, Park E, Hilbert P, Persikov A, Torres-Fernandez C, Ars E, Torra R, Hertz JM, Thomassen M, Shagam L, Wang D, Wang Y, Flinter F, Nagel M
PLoS One 2016;11(9):e0161802. Epub 2016 Sep 14 doi: 10.1371/journal.pone.0161802. PMID: 27627812Free PMC Article
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
Norrie disease and MAO genes: nearest neighbors.
Chen ZY, Denney RM, Breakefield XO
Hum Mol Genet 1995;4 Spec No:1729-37. doi: 10.1093/hmg/4.suppl_1.1729. PMID: 8541872

Prognosis

Molecular Epidemiology in 591 Italian Probands With Nonsyndromic Retinitis Pigmentosa and Usher Syndrome.
Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
Pathogenic Variants in GPC4 Cause Keipert Syndrome.
Amor DJ, Stephenson SEM, Mustapha M, Mensah MA, Ockeloen CW, Lee WS, Tankard RM, Phelan DG, Shinawi M, de Brouwer APM, Pfundt R, Dowling C, Toler TL, Sutton VR, Agolini E, Rinelli M, Capolino R, Martinelli D, Zampino G, Dumić M, Reardon W, Shaw-Smith C, Leventer RJ, Delatycki MB, Kleefstra T, Mundlos S, Mortier G, Bahlo M, Allen NJ, Lockhart PJ
Am J Hum Genet 2019 May 2;104(5):914-924. Epub 2019 Apr 11 doi: 10.1016/j.ajhg.2019.02.026. PMID: 30982611Free PMC Article
Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.
Cabanillas R, Diñeiro M, Cifuentes GA, Castillo D, Pruneda PC, Álvarez R, Sánchez-Durán N, Capín R, Plasencia A, Viejo-Díaz M, García-González N, Hernando I, Llorente JL, Repáraz-Andrade A, Torreira-Banzas C, Rosell J, Govea N, Gómez-Martínez JR, Núñez-Batalla F, Garrote JA, Mazón-Gutiérrez Á, Costales M, Isidoro-García M, García-Berrocal B, Ordóñez GR, Cadiñanos J
BMC Med Genomics 2018 Jul 9;11(1):58. doi: 10.1186/s12920-018-0375-5. PMID: 29986705Free PMC Article
X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.
Savige J, Storey H, Il Cheong H, Gyung Kang H, Park E, Hilbert P, Persikov A, Torres-Fernandez C, Ars E, Torra R, Hertz JM, Thomassen M, Shagam L, Wang D, Wang Y, Flinter F, Nagel M
PLoS One 2016;11(9):e0161802. Epub 2016 Sep 14 doi: 10.1371/journal.pone.0161802. PMID: 27627812Free PMC Article
Ocular features in Alport syndrome: pathogenesis and clinical significance.
Savige J, Sheth S, Leys A, Nicholson A, Mack HG, Colville D
Clin J Am Soc Nephrol 2015 Apr 7;10(4):703-9. Epub 2015 Feb 3 doi: 10.2215/CJN.10581014. PMID: 25649157Free PMC Article

Clinical prediction guides

Clinical and genetic characterization of patients with eye diseases included in the Spanish Rare Diseases Patient Registry.
Lopez-de la Rosa A, Telleria JJ, Posada de la Paz M, Hermosilla-Gimeno IM, Rivas MA, Gilabert R, Coco-Martín RM
Orphanet J Rare Dis 2024 Jun 13;19(1):234. doi: 10.1186/s13023-024-03242-6. PMID: 38872169Free PMC Article
Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.
Bosman A, Appelman-Dijkstra NM, Boot AM, de Borst MH, van de Ven AC, de Jongh RT, Bökenkamp A, van den Bergh JP, van der Eerden BCJ, Zillikens MC
Calcif Tissue Int 2024 Mar;114(3):255-266. Epub 2024 Jan 16 doi: 10.1007/s00223-023-01172-2. PMID: 38226986Free PMC Article
Pathogenic Variants in GPC4 Cause Keipert Syndrome.
Amor DJ, Stephenson SEM, Mustapha M, Mensah MA, Ockeloen CW, Lee WS, Tankard RM, Phelan DG, Shinawi M, de Brouwer APM, Pfundt R, Dowling C, Toler TL, Sutton VR, Agolini E, Rinelli M, Capolino R, Martinelli D, Zampino G, Dumić M, Reardon W, Shaw-Smith C, Leventer RJ, Delatycki MB, Kleefstra T, Mundlos S, Mortier G, Bahlo M, Allen NJ, Lockhart PJ
Am J Hum Genet 2019 May 2;104(5):914-924. Epub 2019 Apr 11 doi: 10.1016/j.ajhg.2019.02.026. PMID: 30982611Free PMC Article
X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.
Savige J, Storey H, Il Cheong H, Gyung Kang H, Park E, Hilbert P, Persikov A, Torres-Fernandez C, Ars E, Torra R, Hertz JM, Thomassen M, Shagam L, Wang D, Wang Y, Flinter F, Nagel M
PLoS One 2016;11(9):e0161802. Epub 2016 Sep 14 doi: 10.1371/journal.pone.0161802. PMID: 27627812Free PMC Article
Ocular features in Alport syndrome: pathogenesis and clinical significance.
Savige J, Sheth S, Leys A, Nicholson A, Mack HG, Colville D
Clin J Am Soc Nephrol 2015 Apr 7;10(4):703-9. Epub 2015 Feb 3 doi: 10.2215/CJN.10581014. PMID: 25649157Free PMC Article

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