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Image from GeneReviews
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Autosomal dominant nonsyndromic hearing loss 6(LFSNHL)

MedGen UID:
331419
•Concept ID:
C1833021
•
Disease or Syndrome
Synonyms: Autosomal dominant nonsyndromic deafness 6; DEAFNESS, AUTOSOMAL DOMINANT 14; DEAFNESS, AUTOSOMAL DOMINANT 38; DEAFNESS, AUTOSOMAL DOMINANT 6; DFNA6/14/38 Nonsyndromic Low-Frequency Sensorineural Hearing Loss; LFSNHL; WFS1-Related Low-Frequency Sensory Hearing Loss
 
Gene (location): WFS1 (4p16.1)
Related gene: CISD2
 
Monarch Initiative: MONDO:0010963
OMIM®: 600965

Definition

WFS1 spectrum disorder (WFS1-SD) comprises classic WFS1 spectrum disorder and nonclassic WFS1 spectrum disorder. Classic WFS1-SD, a progressive neurodegenerative disorder, is characterized by onset of diabetes mellitus and optic atrophy before age 16 years. Additional complications may include one or more of the following: variable hearing impairment / deafness, diabetes insipidus, neurologic abnormalities, neurogenic bladder, and psychiatric abnormalities. Nonclassic WFS1-SD is less common than classic WFS1-SD. Phenotypes that appear to be milder than classic WFS1-SD include: optic atrophy and hearing impairment; neonatal diabetes, profound congenital deafness, and cataracts; isolated diabetes mellitus; isolated congenital cataracts; and isolated congenital, slowly progressive, and low-frequency (<2000 Hz) sensorineural hearing loss. [from GeneReviews]

Additional description

From OMIM
Low frequency sensorineural hearing loss is an unusual type of hearing loss in which frequencies of 2,000 Hz and below are predominantly affected. Many patients have tinnitus, but there are otherwise no associated features such as vertigo. Because high frequency hearing is generally preserved, LFSNHL patients retain excellent understanding of speech, although presbycusis or noise exposure may cause high frequency loss later in life. LFSNHL worsens over time without progressing to profound deafness; in contrast, low frequency hearing loss linked to DFNA1 (124900), caused by mutations in the DIAPH1 gene (602121), is associated with progression to profound deafness by the fourth decade of life (summary by Bespalova et al., 2001).  http://www.omim.org/entry/600965

Clinical features

From HPO
Progressive sensorineural hearing impairment
MedGen UID:
335894
•Concept ID:
C1843156
•
Disease or Syndrome
A progressive form of sensorineural hearing impairment.
See: Feature record | Search on this feature
Low-frequency sensorineural hearing impairment
MedGen UID:
816775
•Concept ID:
C3810445
•
Finding
A form of sensorineural hearing impairment that affects primarily the lower frequencies.
See: Feature record | Search on this feature

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

COCH-related autosomal dominant nonsyndromic hearing loss: a phenotype-genotype study.
Oh KS, Walls D, Joo SY, Kim JA, Yoo JE, Koh YI, Kim DH, Rim JH, Choi HJ, Kim HY, Yu S, Smith RJ, Choi JY, Gee HY, Jung J
Hum Genet 2022 Apr;141(3-4):889-901. Epub 2021 Sep 16 doi: 10.1007/s00439-021-02368-y. PMID: 34529116Free PMC Article
Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.
Naito T, Nishio SY, Iwasa Y, Yano T, Kumakawa K, Abe S, Ishikawa K, Kojima H, Namba A, Oshikawa C, Usami S
PLoS One 2013;8(5):e63231. Epub 2013 May 23 doi: 10.1371/journal.pone.0063231. PMID: 23717403Free PMC Article

Recent clinical studies

Etiology

Identification of homozygous missense variant in SIX5 gene underlying recessive nonsyndromic hearing impairment.
Kakar MU, Akram M, Zubair Mehboob M, Younus M, Bilal M, Waqas A, Nazir A, Shafi M, Umair M, Ahmad S, Rafeeq MM
PLoS One 2022;17(6):e0268078. Epub 2022 Jun 16 doi: 10.1371/journal.pone.0268078. PMID: 35709191Free PMC Article
WFS1 and GJB2 mutations in patients with bilateral low-frequency sensorineural hearing loss.
Kasakura-Kimura N, Masuda M, Mutai H, Masuda S, Morimoto N, Ogahara N, Misawa H, Sakamoto H, Saito K, Matsunaga T
Laryngoscope 2017 Sep;127(9):E324-E329. Epub 2017 Mar 8 doi: 10.1002/lary.26528. PMID: 28271504
Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.
Naito T, Nishio SY, Iwasa Y, Yano T, Kumakawa K, Abe S, Ishikawa K, Kojima H, Namba A, Oshikawa C, Usami S
PLoS One 2013;8(5):e63231. Epub 2013 May 23 doi: 10.1371/journal.pone.0063231. PMID: 23717403Free PMC Article
Presymptomatic diagnosis of nonsyndromic hearing loss by genotyping.
Chen AH, Mueller RF, Prasad SD, Greinwald JH Jr, Manaligod J, Muilenburg AC, Verhoeven K, Van Camp G, Smith RJ
Arch Otolaryngol Head Neck Surg 1998 Jan;124(1):20-4. doi: 10.1001/archotol.124.1.20. PMID: 9440775
Nonsyndromic hearing loss: an analysis of audiograms.
Liu X, Xu L
Ann Otol Rhinol Laryngol 1994 Jun;103(6):428-33. doi: 10.1177/000348949410300602. PMID: 8203808

Diagnosis

COCH-related autosomal dominant nonsyndromic hearing loss: a phenotype-genotype study.
Oh KS, Walls D, Joo SY, Kim JA, Yoo JE, Koh YI, Kim DH, Rim JH, Choi HJ, Kim HY, Yu S, Smith RJ, Choi JY, Gee HY, Jung J
Hum Genet 2022 Apr;141(3-4):889-901. Epub 2021 Sep 16 doi: 10.1007/s00439-021-02368-y. PMID: 34529116Free PMC Article
Genetics of Hearing Loss--Nonsyndromic.
Chang KW
Otolaryngol Clin North Am 2015 Dec;48(6):1063-72. Epub 2015 Aug 11 doi: 10.1016/j.otc.2015.06.005. PMID: 26275501
Genetic causes of nonsyndromic hearing loss.
Skvorak Giersch AB, Morton CC
Curr Opin Pediatr 1999 Dec;11(6):551-7. doi: 10.1097/00008480-199912000-00014. PMID: 10590915
Presymptomatic diagnosis of nonsyndromic hearing loss by genotyping.
Chen AH, Mueller RF, Prasad SD, Greinwald JH Jr, Manaligod J, Muilenburg AC, Verhoeven K, Van Camp G, Smith RJ
Arch Otolaryngol Head Neck Surg 1998 Jan;124(1):20-4. doi: 10.1001/archotol.124.1.20. PMID: 9440775
Nonsyndromic hearing loss: an analysis of audiograms.
Liu X, Xu L
Ann Otol Rhinol Laryngol 1994 Jun;103(6):428-33. doi: 10.1177/000348949410300602. PMID: 8203808

Therapy

SNP linkage analysis and whole exome sequencing identify a novel POU4F3 mutation in autosomal dominant late-onset nonsyndromic hearing loss (DFNA15).
Kim HJ, Won HH, Park KJ, Hong SH, Ki CS, Cho SS, Venselaar H, Vriend G, Kim JW
PLoS One 2013;8(11):e79063. Epub 2013 Nov 18 doi: 10.1371/journal.pone.0079063. PMID: 24260153Free PMC Article

Prognosis

WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome.
Lim HD, Lee SM, Yun YJ, Lee DH, Lee JH, Oh SH, Lee SY
BMC Med Genomics 2023 Apr 11;16(1):79. doi: 10.1186/s12920-023-01506-x. PMID: 37041640Free PMC Article
A novel KCNQ4 gene variant (c.857A>G; p.Tyr286Cys) in an extended family with non‑syndromic deafness 2A.
Li Q, Liang P, Wang S, Li W, Wang J, Yang Y, An X, Chen J, Zha D
Mol Med Rep 2021 Jun;23(6) Epub 2021 Apr 13 doi: 10.3892/mmr.2021.12059. PMID: 33846771Free PMC Article
A novel missense mutation in the ACTG1 gene in a family with congenital autosomal dominant deafness: A case report.
Lee CG, Jang J, Jin HS
Mol Med Rep 2018 Jun;17(6):7611-7617. Epub 2018 Mar 29 doi: 10.3892/mmr.2018.8837. PMID: 29620237Free PMC Article
A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.
Sanggaard KM, Kjaer KW, Eiberg H, Nürnberg G, Nürnberg P, Hoffman K, Jensen H, Sørum C, Rendtorff ND, Tranebjaerg L
Am J Med Genet A 2008 Apr 15;146A(8):1017-25. doi: 10.1002/ajmg.a.32174. PMID: 18348273
A gene for autosomal dominant nonsyndromic hearing loss (DFNA12) maps to chromosome 11q22-24.
Verhoeven K, Van Camp G, Govaerts PJ, Balemans W, Schatteman I, Verstreken M, Van Laer L, Smith RJ, Brown MR, Van de Heyning PH, Somers T, Offeciers FE, Willems PJ
Am J Hum Genet 1997 May;60(5):1168-73. PMID: 9150164Free PMC Article

Clinical prediction guides

WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome.
Lim HD, Lee SM, Yun YJ, Lee DH, Lee JH, Oh SH, Lee SY
BMC Med Genomics 2023 Apr 11;16(1):79. doi: 10.1186/s12920-023-01506-x. PMID: 37041640Free PMC Article
COCH-related autosomal dominant nonsyndromic hearing loss: a phenotype-genotype study.
Oh KS, Walls D, Joo SY, Kim JA, Yoo JE, Koh YI, Kim DH, Rim JH, Choi HJ, Kim HY, Yu S, Smith RJ, Choi JY, Gee HY, Jung J
Hum Genet 2022 Apr;141(3-4):889-901. Epub 2021 Sep 16 doi: 10.1007/s00439-021-02368-y. PMID: 34529116Free PMC Article
A novel KCNQ4 gene variant (c.857A>G; p.Tyr286Cys) in an extended family with non‑syndromic deafness 2A.
Li Q, Liang P, Wang S, Li W, Wang J, Yang Y, An X, Chen J, Zha D
Mol Med Rep 2021 Jun;23(6) Epub 2021 Apr 13 doi: 10.3892/mmr.2021.12059. PMID: 33846771Free PMC Article
Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.
Naito T, Nishio SY, Iwasa Y, Yano T, Kumakawa K, Abe S, Ishikawa K, Kojima H, Namba A, Oshikawa C, Usami S
PLoS One 2013;8(5):e63231. Epub 2013 May 23 doi: 10.1371/journal.pone.0063231. PMID: 23717403Free PMC Article
A novel locus for autosomal dominant nonsyndromic hearing loss identified at 5q31.1-32 in a Chinese pedigree.
Xia J, Deng H, Feng Y, Zhang H, Pan Q, Dai H, Long Z, Tang B, Deng H, Chen Y, Zhang R, Zheng D, He Y, Xia K
J Hum Genet 2002;47(12):635-40. doi: 10.1007/s100380200098. PMID: 12522684

Recent systematic reviews

WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome.
Lim HD, Lee SM, Yun YJ, Lee DH, Lee JH, Oh SH, Lee SY
BMC Med Genomics 2023 Apr 11;16(1):79. doi: 10.1186/s12920-023-01506-x. PMID: 37041640Free PMC Article

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