Nonsyndromic deafness

Other names: Non-syndromic genetic deafness
Treatment| vancomycin

Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Genetic changes are related to the following types of nonsyndromic deafness.

* DFNA: nonsyndromic deafness, autosomal dominant
* DFNB: nonsyndromic deafness, autosomal recessive
* DFNX: nonsyndromic deafness, X-linked
* nonsyndromic deafness, mitochondrial

Each type is numbered in the order in which it was described. For example, DFNA1 was the first described autosomal dominant type of nonsyndromic deafness. Mitochondrial nonsyndromic deafness involves changes to the small amount of DNA found in mitochondria, the energy-producing centers within cells.[1]

Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear. The inner ear consists of three parts: a snail-shaped structure called the cochlea that helps process sound, nerves that send information from the cochlea to the brain, and structures involved with balance. Loss of hearing caused by changes in the inner ear is called sensorineural deafness. Hearing loss that results from changes in the middle ear is called conductive hearing loss. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic deafness involve changes in both the inner ear and the middle ear; this combination is called mixed hearing loss.

## Contents

* 1 Classification
* 2 Signs and symptoms
* 3 Genetics
* 3.1 Genes related to nonsyndromic deafness
* 4 Diagnosis
* 5 Treatment
* 6 Epidemiology
* 7 References
* 8 Further reading
* 9 External links

## Classification[edit | edit source]

Nonsyndromic deafness can occur at any age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.

## Signs and symptoms[edit | edit source]

The clinical presentation of this condition is not associated with other signs and symptoms, other than partial or complete loss of hearing.[2]The severity of hearing loss varies and can change over time. It can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The loss may be stable, or it may progress as a person gets older. Particular types of nonsyndromic deafness often show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.[citation needed]

## Genetics[edit | edit source]

Nonsyndromic deafness can have different patterns of inheritance. Between 75% and 80% of cases are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Usually, each parent of an individual with autosomal recessive deafness is a carrier of one copy of the altered gene. These carriers do not have hearing loss.

Another 20% to 25% of nonsyndromic deafness cases are autosomal dominant, which means one copy of the altered gene in each cell is sufficient to result in hearing loss. People with autosomal dominant deafness most often inherit an altered copy of the gene from a parent who has hearing loss.

Between 1% and 2% of cases show an X-linked pattern of inheritance, which means the mutated gene responsible for the condition is located on the X chromosome. Males with X-linked nonsyndromic deafness tend to develop more severe hearing loss earlier in life than females who inherit a copy of the same gene mutation. Fathers will not pass X-linked traits to their sons since they do not pass on the X chromosome to their male offspring.

Mitochondrial nonsyndromic deafness, which results from changes to the DNA in mitochondria, occurs in fewer than 1% of cases in the United States. The altered mitochondrial DNA is passed from a mother to her sons and daughters. This type of deafness is not inherited from fathers.

Late onset progressive deafness is the most common neurological disability of the elderly. Although hearing loss of greater than 25 decibels is present in only 1% of young adults between the ages of 18–24 years of age, this increases to 10% in persons between 55–64 years of age and approximately 50% in octogenarians.

The relative contribution of heredity to age-related hearing impairment is not known, however the majority of inherited late-onset deafness is autosomal dominant and non-syndromic (Van Camp et al., 1997). Over forty genes associated with autosomal dominant non-syndromic hearing loss have been localized and of these fifteen have been cloned.

### Genes related to nonsyndromic deafness[edit | edit source]

Condition due to dominant cis mutation R75Q with recessive mutation V37I of the GJB2-a) Biochemical coupling through Cx26-WT and (b–d) mutant gap junctions

Mutations in the ACTG1, CABP2, CDH23, CLDN14, COCH, COL11A2, DFNA5, ESPN, EYA4, GJB2, GJB6, KCNQ4, MYO15A, MYO6, MYO7A, OTOF, PCDH15, POU3F4, SLC26A4, STRC, TECTA, TMC1, TMIE, TMPRSS3, USH1C, and WFS1 genes cause nonsyndromic deafness, with weaker evidence currently implicating genes CCDC50, DIAPH1, DSPP, ESRRB, GJB3, GRHL2, GRXCR1, HGF, LHFPL5, LOXHD1, LRTOMT, MARVELD2, MIR96, MYH14, MYH9, MYO1A, MYO3A, OTOA, PJVK, POU4F3, PRPS1, PTPRQ, RDX, SERPINB6, SIX1, SLC17A8, TPRN, TRIOBP, SLC26A5, and WHRN.

The causes of nonsyndromic deafness can be complex. Researchers have identified more than 30 genes that, when mutated, may cause nonsyndromic deafness; however, some of these genes have not been fully characterized. Many genes related to deafness are involved in the development and function of the inner ear. Gene mutations interfere with critical steps in processing sound, resulting in hearing loss. Different mutations in the same gene can cause different types of hearing loss, and some genes are associated with both syndromic and nonsyndromic deafness. In many families, the gene(s) involved have yet to be identified.

Deafness can also result from environmental factors or a combination of genetic and environmental factors, including certain medications, peri-natal infections (infections occurring before or after birth), and exposure to loud noise over an extended period.

Types include:

OMIM | Gene  | Type

|
|

124900 | DIAPH1 | DFNA1
600101 | KCNQ4 | DFNA2A
612644 | GJB3 | DFNA2B
601544 | GJB2 | DFNA3A
612643 | GJB6 | DFNA3B
600652 | MYH14 | DFNA4
600994 | DFNA5 | DFNA5
601543 | TECTA | DFNA8/12
601369 | COCH | DFNA9
601316 | EYA4 | DFNA10
601317 | MYO7A | DFNA11, neurosensory
601868 | COL11A2 | DFNA13
602459 | POU4F3 | DFNA15
603622 | MYH9 | DFNA17
604717 | ACTG1 | DFNA20/26
606346 | MYO6 | DFNA22
605192 | SIX1 | DFNA23
605583 | SLC17A8 | DFNA25
608641 | GRHL2 | DFNA28
606705 | TMC1 | DFNA36
605594 | DSPP | DFNA36, with dentinogenesis
607453 | CCDC50 | DFNA44
607841 | MYO1A | DFNA48
613074 | MIR96 | DFNA50
220290 | GJB2 | DFNB1A
612645 | GJB6 | DFNB1B
600060 | MYO7A | DFNB2, neurosensory (see also Usher syndrome)
600316 | MYO15A | DFNB3
600971 | TMIE | DFNB6
600974 | TMC1 | DFNB7
601072 | TMPRSS3 | DFNB8, childhood onset
601071 | OTOF | DFNB9
601386 | CDH23 | DFNB12
603720 | STRC | DFNB16
602092 | USH1C | DFNB18
603629 | TECTA | DFNB21
607039 | OTOA | DFNB22
609533 | PCDH15 | DFNB23
611022 | RDX | DFNB24
613285 | GRXCR1 | DFNB25
609823 | TRIOBP | DFNB28
607101 | MYO3A | DFNB30
607084 | WHRN | DFNB31
608565 | ESRRB | DFNB35
609006 | ESPN | DFNB36
607821 | MYO6 | DFNB37
608265 | HGF | DFNB39
610153 | MARVELD2 | DFNB49
609706 | COL11A2 | DFNB53
610220 | PJVK | DFNB59
611451 | LRTOMT | DFNB63
610265 | LHFPL5 | DFNB67
613079 | LOXHD1 | DFNB77
613307 | TPRN | DFNB79
613391 | PTPRQ | DFNB84
613453 | SERPINB6 | DFNB91
614899 | CABP2 | DFNB93
304500 | PRPS1 | DFNX1
304400 | POU3F4 | DFNX2
580000 | MT-RNR1, COX1[3] | deafness, aminoglycoside-induced
500008 | (several mtDNA)  | DFN, sensorineural, mt

## Diagnosis[edit | edit source]

In terms of the diagnosis of this condition can be evaluated by audiogram:[4]

* Mild loss 20 and 40 dB
* Moderate loss 41 and 70 db
* Severe loss 71 and 90 dB
* Profound loss 91 and 120 dB

## Treatment[edit | edit source]

Treatment is supportive and consists of management of manifestations. User of hearing aids and/or cochlear implant, suitable educational programs can be offered. Periodic surveillance is also important.[5]

## Epidemiology[edit | edit source]

About 1 in 1,000 children in the United States is born with profound deafness. By age 9, about 3 in 1,000 children have hearing loss that affects the activities of daily living. More than half of these cases are caused by genetic factors. Most cases of genetic deafness (70% to 80%) are nonsyndromic; the remaining cases are caused by specific genetic syndromes. In adults, the chance of developing hearing loss increases with age; hearing loss affects half of all people older than 80 years.

## References[edit | edit source]

1. ↑ Reference, Genetics Home. "nonsyndromic hearing loss". Genetics Home Reference. Archived from the original on 15 April 2017. Retrieved 14 April 2017.
2. ↑ "Nonsyndromic hearing loss: MedlinePlus Genetics". medlineplus.gov. Archived from the original on 19 January 2022. Retrieved 23 January 2022.
3. ↑ Usami, S; Nishio, S; Adam, MP; Ardinger, HH; Pagon, RA; Wallace, SE; Bean, LJH; Stephens, K; Amemiya, A (1993). "Nonsyndromic Hearing Loss and Deafness, Mitochondrial". PMID 20301595. `{{cite journal}}`: Cite journal requires `|journal=` (help)
4. ↑ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Non syndromic genetic deafness". www.orpha.net. Archived from the original on 26 February 2021. Retrieved 23 January 2022.
5. ↑ Smith, Richard JH; Jones, Mary-Kayt N. (1993). "Nonsyndromic Hearing Loss and Deafness, DFNB1". GeneReviews. University of Washington, Seattle. Archived from the original on 2017-01-18. Retrieved 2021-09-29.

## Further reading[edit | edit source]

* Pandya, Arti (21 April 2011). Nonsyndromic Hearing Loss and Deafness, Mitochondrial. University of Washington, Seattle. PMID 20301595. NBK1422. Archived from the original on 9 September 2021. Retrieved 29 September 2021. In Pagon RA, Bird TD, Dolan CR, et al., eds. (1993). GeneReviews. Seattle WA: University of Washington, Seattle. Archived from the original on 2019-09-10. Retrieved 2021-09-29.
* Smith, Richard JH; Sheffield, Abraham M; Camp, Guy Van (19 April 2012). Nonsyndromic Hearing Loss and Deafness, DFNA3. University of Washington, Seattle. PMID 20301708. NBK1536. Archived from the original on 23 September 2020. Retrieved 29 September 2021. In GeneReviews
* Smith, Richard JH; Camp, Guy Van (2 January 2014). Nonsyndromic Hearing Loss and Deafness, DFNB1. University of Washington, Seattle. PMID 20301449. NBK1272. Archived from the original on 18 January 2017. Retrieved 29 September 2021. In GeneReviews
* Huijun Yuan; Xue Z Liu (4 August 2011). DFNX1 Nonsyndromic Hearing Loss and Deafness. University of Washington, Seattle. PMID 21834172. NBK57098. Archived from the original on 1 December 2020. Retrieved 29 September 2021. In GeneReviews
* Smith, Richard JH; Gurrola, II, Jose G; Kelley, Philip M (14 June 2011). "OTOF-Related Deafness". OTOF-Related Deafness. University of Washington, Seattle. PMID 20301429. NBK1251. Archived from the original on 13 August 2020. Retrieved 29 September 2021. In GeneReviews

## External links[edit | edit source]

Classification|

* ICD-10: H90.5

|

External resources|

* Orphanet: 87884

* v
* t
* e

Symptoms, signs, and medical tests relating to hearing and balance

Hearing|

| Symptoms|

* Hearing loss

|

Tests|

* Hearing test
* Rinne test
* Tone decay test
* Weber test
* Audiometry
* pure tone
* visual reinforcement

Balance|

| Symptoms|

* Vertigo
* nystagmus

|

Tests|

* Dix–Hallpike test
* Unterberger test
* Romberg's test
* Vestibulo–ocular reflex

Other|

| Symptoms|

* Ear pain

|

Tests|

* Otoscope
* pneumatic
* tympanometry

* v
* t
* e

Cytoskeletal defects

Microfilaments|

| Myofilament|

| Actin|

* Hypertrophic cardiomyopathy 11
* Dilated cardiomyopathy 1AA
* DFNA20
* Nemaline myopathy 3

|

Myosin|

* Elejalde syndrome
* Hypertrophic cardiomyopathy 1, 8, 10
* Usher syndrome 1B
* Freeman–Sheldon syndrome
* DFN A3, 4, 11, 17, 22; B2, 30, 37, 48
* May–Hegglin anomaly

Troponin|

* Hypertrophic cardiomyopathy 7, 2
* Nemaline myopathy 4, 5

Tropomyosin|

* Hypertrophic cardiomyopathy 3
* Nemaline myopathy 1

Titin|

* Hypertrophic cardiomyopathy 9

Other|

* Fibrillin
* Marfan syndrome
* Weill–Marchesani syndrome
* Filamin
* FG syndrome 2
* Boomerang dysplasia
* Larsen syndrome
* Terminal osseous dysplasia with pigmentary defects

IF|

| 1/2|

* Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1
* Striate palmoplantar keratoderma 3
* Epidermolytic hyperkeratosis
* IHCM
* KRT2E (Ichthyosis bullosa of Siemens)
* KRT3 (Meesmann juvenile epithelial corneal dystrophy)
* KRT4 (White sponge nevus)
* KRT5 (Epidermolysis bullosa simplex)
* KRT8 (Familial cirrhosis)
* KRT10 (Epidermolytic hyperkeratosis)
* KRT12 (Meesmann juvenile epithelial corneal dystrophy)
* KRT13 (White sponge nevus)
* KRT14 (Epidermolysis bullosa simplex)
* KRT17 (Steatocystoma multiplex)
* KRT18 (Familial cirrhosis)
* KRT81/KRT83/KRT86 (Monilethrix)
* Naegeli–Franceschetti–Jadassohn syndrome
* Reticular pigmented anomaly of the flexures

|

* Desmin: Desmin-related myofibrillar myopathy
* Dilated cardiomyopathy 1I

* GFAP: Alexander disease

* Peripherin: Amyotrophic lateral sclerosis

* Neurofilament: Parkinson's disease
* Charcot–Marie–Tooth disease 1F, 2E
* Amyotrophic lateral sclerosis

* Laminopathy: LMNA
* Mandibuloacral dysplasia
* Dunnigan Familial partial lipodystrophy
* Emery–Dreifuss muscular dystrophy 2
* Limb-girdle muscular dystrophy 1B
* Charcot–Marie–Tooth disease 2B1
* LMNB
* Barraquer–Simons syndrome
* LEMD3
* Buschke–Ollendorff syndrome
* Osteopoikilosis
* LBR
* Pelger–Huet anomaly
* Hydrops-ectopic calcification-moth-eaten skeletal dysplasia

Microtubules|

| Kinesin|

* Charcot–Marie–Tooth disease 2A
* Hereditary spastic paraplegia 10

|

Dynein|

* Primary ciliary dyskinesia
* Short rib-polydactyly syndrome 3
* Asphyxiating thoracic dysplasia 3

Other|

* Tauopathy
* Cavernous venous malformation

Membrane|

* Spectrin: Spinocerebellar ataxia 5
* Hereditary spherocytosis 2, 3
* Hereditary elliptocytosis 2, 3

Ankyrin: Long QT syndrome 4

* Hereditary spherocytosis 1

Catenin|

* APC
* Gardner's syndrome
* Familial adenomatous polyposis
* plakoglobin (Naxos syndrome)
* GAN (Giant axonal neuropathy)

Other|

* desmoplakin: Striate palmoplantar keratoderma 2
* Carvajal syndrome
* Arrhythmogenic right ventricular dysplasia 8

* plectin: Epidermolysis bullosa simplex with muscular dystrophy
* Epidermolysis bullosa simplex of Ogna

* plakophilin: Skin fragility syndrome
* Arrhythmogenic right ventricular dysplasia 9

* centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II)

Related topics: Cytoskeletal proteins

* v
* t
* e

Genetic disorders relating to deficiencies of transcription factor or coregulators

(1) Basic domains|

| 1.2|

* Feingold syndrome
* Saethre–Chotzen syndrome

|

1.3|

* Tietz syndrome

(2) Zinc finger
DNA-binding domains|

| 2.1|

* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis

|

2.2|

* Barakat syndrome
* Tricho–rhino–phalangeal syndrome

2.3|

* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2

2.5|

* Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains|

| 3.1|

* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome

|

3.2|

* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3

3.3|

* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX

3.5|

* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts|

| 4.2|

* Hyperimmunoglobulin E syndrome

|

4.3|

* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome

4.7|

* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome

4.11|

* Cleidocranial dysostosis

(0) Other transcription factors|

| 0.6|

* Kabuki syndrome

|

Ungrouped|

* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8

Transcription coregulators|

| Coactivator:|

* CREBBP
* Rubinstein–Taybi syndrome

|

Corepressor:|

* HR (Atrichia with papular lesions)

* v
* t
* e

Diseases of collagen, laminin and other scleroproteins

Collagen disease|

| COL1:|

* Osteogenesis imperfecta
* Ehlers–Danlos syndrome, types 1, 2, 7

|

COL2:|

* Hypochondrogenesis
* Achondrogenesis type 2
* Stickler syndrome
* Marshall syndrome
* Spondyloepiphyseal dysplasia congenita
* Spondyloepimetaphyseal dysplasia, Strudwick type
* Kniest dysplasia (see also C2/11)

COL3:|

* Ehlers–Danlos syndrome, types 3 & 4
* Sack–Barabas syndrome

COL4:|

* Alport syndrome

COL5:|

* Ehlers–Danlos syndrome, types 1 & 2

COL6:|

* Bethlem myopathy
* Ullrich congenital muscular dystrophy

COL7:|

* Epidermolysis bullosa dystrophica
* Recessive dystrophic epidermolysis bullosa
* Bart syndrome
* Transient bullous dermolysis of the newborn

COL8:|

* Fuchs' dystrophy 1

COL9:|

* Multiple epiphyseal dysplasia 2, 3, 6

COL10:|

* Schmid metaphyseal chondrodysplasia

COL11:|

* Weissenbacher–Zweymüller syndrome
* Otospondylomegaepiphyseal dysplasia (see also C2/11)

COL17:|

* Bullous pemphigoid

COL18:|

* Knobloch syndrome

Laminin|

* Junctional epidermolysis bullosa
* Laryngoonychocutaneous syndrome

Other|

* Congenital stromal corneal dystrophy
* Raine syndrome
* Urbach–Wiethe disease
* TECTA
* DFNA8/12, DFNB21

see also fibrous proteins

* v
* t
* e

Genetic disorder, membrane: Solute carrier disorders

1-10|

* SLC1A3
* Episodic ataxia 6
* SLC2A1
* De Vivo disease
* SLC2A5
* Fructose malabsorption
* SLC2A10
* Arterial tortuosity syndrome
* SLC3A1
* Cystinuria
* SLC4A1
* Hereditary spherocytosis 4/Hereditary elliptocytosis 4
* SLC4A11
* Congenital endothelial dystrophy type 2
* Fuchs' dystrophy 4
* SLC5A1
* Glucose-galactose malabsorption
* SLC5A2
* Renal glycosuria
* SLC5A5
* Thyroid dyshormonogenesis type 1
* SLC6A19
* Hartnup disease
* SLC7A7
* Lysinuric protein intolerance
* SLC7A9
* Cystinuria

11-20|

* SLC11A1
* Crohn's disease
* SLC12A3
* Gitelman syndrome
* SLC16A1
* HHF7
* SLC16A2
* Allan–Herndon–Dudley syndrome
* SLC17A5
* Salla disease
* SLC17A8
* DFNA25

21-40|

* SLC26A2
* Multiple epiphyseal dysplasia 4
* Achondrogenesis type 1B
* Recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
* SLC26A4
* Pendred syndrome
* SLC35C1
* CDOG 2C
* SLC39A4
* Acrodermatitis enteropathica
* SLC40A1
* African iron overload

see also solute carrier family
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