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Deafness, X-linked 5(DFNX5)

MedGen UID:
335096
•Concept ID:
C1845095
•
Disease or Syndrome
Synonyms: AUDITORY NEUROPATHY, X-LINKED, 1, WITH PERIPHERAL SENSORY NEUROPATHY; DEAFNESS, X-LINKED 5, WITH PERIPHERAL NEUROPATHY; DFNX5
 
Gene (location): AIFM1 (Xq26.1)
 
OMIM®: 300614

Definition

X-linked deafness-5 is a neurologic disorder characterized by childhood onset of auditory neuropathy and later onset of distal sensory impairment affecting the peripheral nervous system (summary by Zong et al., 2015). [from OMIM]

Clinical features

From HPO
Tinnitus
MedGen UID:
52760
•Concept ID:
C0040264
•
Disease or Syndrome
Tinnitus is an auditory perception that can be described as the experience of sound, in the ear or in the head, in the absence of external acoustic stimulation.
See: Feature record | Search on this feature
Hearing impairment
MedGen UID:
235586
•Concept ID:
C1384666
•
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
See: Feature record | Search on this feature
Abnormal speech discrimination
MedGen UID:
322986
•Concept ID:
C1836752
•
Finding
A type of hearing impairment prominently characterized by a difficulty in understanding speech, rather than an inability to hear speech. Poor speech discrimination is a very common symptom of high frequency hearing loss.
See: Feature record | Search on this feature
Abnormal middle ear reflexes
MedGen UID:
410175
•Concept ID:
C1970887
•
Finding
See: Feature record | Search on this feature
Unsteady gait
MedGen UID:
68544
•Concept ID:
C0231686
•
Finding
A shaky or wobbly manner of walking.
See: Feature record | Search on this feature
Areflexia
MedGen UID:
115943
•Concept ID:
C0234146
•
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
See: Feature record | Search on this feature
Sensory axonal neuropathy
MedGen UID:
334116
•Concept ID:
C1842587
•
Finding
An axonal neuropathy of peripheral sensory nerves.
See: Feature record | Search on this feature
Distal sensory impairment
MedGen UID:
335722
•Concept ID:
C1847584
•
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeafness, X-linked 5
Follow this link to review classifications for Deafness, X-linked 5 in Orphanet.

Professional guidelines

PubMed

Genotype/phenotype correlations of childhood-onset congenital sideroblastic anaemia in a European cohort.
Fouquet C, Le Rouzic MA, Leblanc T, Fouyssac F, Leverger G, Hessissen L, Marlin S, Bourrat E, Fahd M, Raffoux E, Vannier JP, Jäkel N, Knoefler R, Triolo V, Pasquet M, Bayart S, Thuret I, Lutz P, Vermylen C, Touati M, Rose C, Matthes T, Isidor B, Kannengiesser C, Ducassou S
Br J Haematol 2019 Nov;187(4):530-542. Epub 2019 Jul 23 doi: 10.1111/bjh.16100. PMID: 31338833
X-linked Alport syndrome: pathogenic variant features and further auditory genotype-phenotype correlations in males.
Zhang X, Zhang Y, Zhang Y, Gu H, Chen Z, Ren L, Lu X, Chen L, Wang F, Liu Y, Ding J
Orphanet J Rare Dis 2018 Dec 22;13(1):229. doi: 10.1186/s13023-018-0974-4. PMID: 30577881Free 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

Genetic findings of Sanger and nanopore single-molecule sequencing in patients with X-linked hearing loss and incomplete partition type III.
Chen Y, Qiu J, Wu Y, Jia H, Jiang Y, Jiang M, Wang Z, Sheng HB, Hu L, Zhang Z, Wang Z, Li Y, Huang Z, Wu H
Orphanet J Rare Dis 2022 Feb 21;17(1):65. doi: 10.1186/s13023-022-02235-7. PMID: 35189936Free PMC Article
X-linked Malformation Deafness: Neurodevelopmental Symptoms Are Common in Children With IP3 Malformation and Mutation in POU3F4.
Smeds H, Wales J, Karltorp E, Anderlid BM, Henricson C, Asp F, Anmyr L, Lagerstedt-Robinson K, Löfkvist U
Ear Hear 2022 Jan/Feb;43(1):53-69. doi: 10.1097/AUD.0000000000001073. PMID: 34133399Free 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
Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis.
Bush RA, Wei LL, Sieving PA
Cold Spring Harb Perspect Med 2015 Jun 22;5(8):a017368. doi: 10.1101/cshperspect.a017368. PMID: 26101206Free PMC Article
Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.
Finsterer J, Löscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G
J Neurol Sci 2012 Jul 15;318(1-2):1-18. Epub 2012 May 1 doi: 10.1016/j.jns.2012.03.025. PMID: 22554690

Diagnosis

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
Role of skeletal muscle in ear development.
Rot I, Baguma-Nibasheka M, Costain WJ, Hong P, Tafra R, Mardesic-Brakus S, Mrduljas-Djujic N, Saraga-Babic M, Kablar B
Histol Histopathol 2017 Oct;32(10):987-1000. Epub 2017 Mar 8 doi: 10.14670/HH-11-886. PMID: 28271491
Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy.
Liu XZ, Xie D, Yuan HJ, de Brouwer AP, Christodoulou J, Yan D
Int J Audiol 2013 Jan;52(1):23-8. Epub 2012 Nov 28 doi: 10.3109/14992027.2012.736032. PMID: 23190330Free PMC Article
Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.
Finsterer J, Löscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G
J Neurol Sci 2012 Jul 15;318(1-2):1-18. Epub 2012 May 1 doi: 10.1016/j.jns.2012.03.025. PMID: 22554690
Alport syndrome. A review of the ocular manifestations.
Colville DJ, Savige J
Ophthalmic Genet 1997 Dec;18(4):161-73. doi: 10.3109/13816819709041431. PMID: 9457747

Therapy

Retinoschisis associated with Kearns-Sayre syndrome.
Chertkof J, Hufnagel RB, Blain D, Gropman AL, Brooks BP
Ophthalmic Genet 2020 Oct;41(5):497-500. Epub 2020 Aug 13 doi: 10.1080/13816810.2020.1799416. PMID: 32787478Free PMC Article
Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy.
Liu XZ, Xie D, Yuan HJ, de Brouwer AP, Christodoulou J, Yan D
Int J Audiol 2013 Jan;52(1):23-8. Epub 2012 Nov 28 doi: 10.3109/14992027.2012.736032. PMID: 23190330Free PMC Article
Cochlear implantation in children with congenital X-linked deafness due to novel mutations in POU3F4 gene.
Stankovic KM, Hennessey AM, Herrmann B, Mankarious LA
Ann Otol Rhinol Laryngol 2010 Dec;119(12):815-22. doi: 10.1177/000348941011901205. PMID: 21250553
Evidence that mutations in the X-linked DDP gene cause incompletely penetrant and variable skewed X inactivation.
Plenge RM, Tranebjaerg L, Jensen PK, Schwartz C, Willard HF
Am J Hum Genet 1999 Mar;64(3):759-67. doi: 10.1086/302286. PMID: 10053010Free PMC Article
Inheritance of skewed X chromosome inactivation in a large family with an X-linked recessive deafness syndrome.
Orstavik KH, Orstavik RE, Eiklid K, Tranebjaerg L
Am J Med Genet 1996 Jul 12;64(1):31-4. doi: 10.1002/(SICI)1096-8628(19960712)64:1<31::AID-AJMG4>3.0.CO;2-U. PMID: 8826445

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
Retinoschisis associated with Kearns-Sayre syndrome.
Chertkof J, Hufnagel RB, Blain D, Gropman AL, Brooks BP
Ophthalmic Genet 2020 Oct;41(5):497-500. Epub 2020 Aug 13 doi: 10.1080/13816810.2020.1799416. PMID: 32787478Free 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
Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis.
Bush RA, Wei LL, Sieving PA
Cold Spring Harb Perspect Med 2015 Jun 22;5(8):a017368. doi: 10.1101/cshperspect.a017368. PMID: 26101206Free PMC Article
X-linked Alport syndrome in Hellenic families: phenotypic heterogeneity and mutations near interruptions of the collagen domain in COL4A5.
Demosthenous P, Voskarides K, Stylianou K, Hadjigavriel M, Arsali M, Patsias C, Georgaki E, Zirogiannis P, Stavrou C, Daphnis E, Pierides A, Deltas C; Hellenic Nephrogenetics Research Consortium
Clin Genet 2012 Mar;81(3):240-8. Epub 2011 Mar 13 doi: 10.1111/j.1399-0004.2011.01647.x. PMID: 21332469

Clinical prediction guides

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
Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families.
Su Y, Gao X, Huang SS, Mao JN, Huang BQ, Zhao JD, Kang DY, Zhang X, Dai P
BMC Med Genet 2018 Sep 4;19(1):157. doi: 10.1186/s12881-018-0630-9. PMID: 30176854Free PMC Article
Uveal coloboma: clinical and basic science update.
Chang L, Blain D, Bertuzzi S, Brooks BP
Curr Opin Ophthalmol 2006 Oct;17(5):447-70. doi: 10.1097/01.icu.0000243020.82380.f6. PMID: 16932062
Mutations of RPGR in X-linked retinitis pigmentosa (RP3).
Vervoort R, Wright AF
Hum Mutat 2002 May;19(5):486-500. doi: 10.1002/humu.10057. PMID: 11968081
Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q).
Stojkovic T, Latour P, Vandenberghe A, Hurtevent JF, Vermersch P
Neurology 1999 Mar 23;52(5):1010-4. doi: 10.1212/wnl.52.5.1010. PMID: 10102421

Recent systematic reviews

Surgical Outcomes With Cochlear Implantation in Patients With Enlarged Cochlear Aperture: A Systematic Review.
Wong K, Bahethi RR, Weitzman RE, Schwam ZG, Wanna GB
Otol Neurotol 2021 Jun 1;42(5):638-645. doi: 10.1097/MAO.0000000000003021. PMID: 33492060

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