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.
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.
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.
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.
Contents
- 1 Epidemiology
- 2 Genes related to nonsyndromic deafness
- 3 Genetics
- 4 External links
Epidemiology
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.
Genes related to nonsyndromic deafness
Mutations in the ACTG1, 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, 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 |
| 605316 |
TMPRSS3 |
DFNB10, congenital |
| 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 |
| 304500 |
PRPS1 |
DFNX1 |
| 304400 |
POU3F4 |
DFNX2 |
Genetics
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-snydromic hearing loss have been localized and of these fifteen have been cloned.
External links
- Pandya, Arti (21 April 2011). Nonsyndromic Hearing Loss and Deafness, Mitochondrial. PMID 20301595. NBK1422. In Pagon RA, Bird TD, Dolan CR, et al., ed. (1993–). GeneReviews™ [Internet]. Seattle WA: University of Washington, Seattle.
- Smith, Richard JH; Sheffield, Abraham M; Camp, Guy Van (19 April 2012). Nonsyndromic Hearing Loss and Deafness, DFNA3. PMID 20301708. NBK1536. In GeneReviews
- Smith, Richard JH; Camp, Guy Van (2 January 2014). Nonsyndromic Hearing Loss and Deafness, DFNB1. PMID 20301449. NBK1272. In GeneReviews
- Huijun Yuan; Xue Z Liu (4 August 2011). DFNX1 Nonsyndromic Hearing Loss and Deafness. PMID 21834172. NBK57098. In GeneReviews
- Smith, Richard JH; Gurrola, II, Jose G; Kelley, Philip M (14 June 2011). OTOF-Related Deafness. PMID 20301429. NBK1251. In GeneReviews
|
Diseases of the ear and mastoid process (H60–H99, 380–389)
|
|
| Outer ear |
- Otitis externa
- Otomycosis
|
|
Middle ear
and mastoid |
- Otitis media
- Mastoiditis
- Bezold's abscess
- Gradenigo's syndrome
- Tympanosclerosis
- Cholesteatoma
- Perforated eardrum
|
|
Inner ear and
central pathways |
| Common pathway |
- Labyrinthitis/Otitis interna
|
|
| Equilibrioception |
- Vertigo/Balance disorder: peripheral
- Ménière's disease
- BPPV
- Vestibular neuronitis
- Perilymph fistula
- central (Central positional nystagmus)
|
|
| Hearing |
| Hearing impairment |
- Conductive hearing loss
- Otosclerosis
- Superior canal dehiscence
- Sensorineural hearing loss
- Presbycusis
- Cortical deafness
|
|
| Excessive response |
- Tinnitus
- Hyperacusis/Phonophobia
|
|
| Deafblindness |
- Wolfram syndrome
- Usher syndrome
|
|
| Other |
- Auditory processing disorder
- Spatial hearing loss
|
|
|
|
|
|
|
|
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
|
|
| 3 |
- Desmin: Desmin-related myofibrillar myopathy
- Dilated cardiomyopathy 1I
- Peripherin: Amyotrophic lateral sclerosis
|
|
| 4 |
- Neurofilament: Parkinson's disease
- Charcot–Marie–Tooth disease 1F, 2E
- Amyotrophic lateral sclerosis
|
|
| 5 |
- 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)
|
|
See also: cytoskeletal proteins
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies
|
|
| (1) Basic domains |
| 1.2 |
- Feingold syndrome
- Saethre–Chotzen syndrome
|
|
| 1.3 |
|
|
|
(2) Zinc finger
DNA-binding domains |
| 2.1 |
- (Intracellular receptor): Thyroid hormone resistance
- Androgen insensitivity syndrome
- 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
- HOXD13
- PDX1
- LMX1B
- MSX1
- Tooth and nail syndrome
- OFC5
- PITX2
- POU4F3
- POU3F4
- ZEB1
- Posterior polymorphous corneal dystrophy
- Fuchs' dystrophy 3
- ZEB2
|
|
| 3.2 |
- PAX2
- PAX3
- PAX4
- PAX6
- Gillespie syndrome
- Coloboma of optic nerve
- PAX8
- Congenital hypothyroidism 2
- PAX9
|
|
| 3.3 |
- FOXC1
- Axenfeld syndrome 3
- Iridogoniodysgenesis, dominant type
- FOXC2
- Lymphedema–distichiasis syndrome
- FOXE1
- Bamforth–Lazarus syndrome
- FOXE3
- Anterior segment mesenchymal dysgenesis
- FOXF1
- FOXI1
- Enlarged vestibular aqueduct
- FOXL2
- Premature ovarian failure 3
- FOXP3
|
|
| 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 |
|
|
|
| (0) Other transcription factors |
|
|
| Ungrouped |
- TCF4
- ZFP57
- 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)
|
|
|
See also transcription factors and intracellular receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, extracellular: scleroprotein disease (excluding laminin and keratin)
|
|
| 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
|
|
| COL4: |
|
|
| 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: |
|
|
| COL9: |
- Multiple epiphyseal dysplasia 2, 3, 6
|
|
| COL10: |
- Schmid metaphyseal chondrodysplasia
|
|
| COL11: |
- Weissenbacher–Zweymüller syndrome
- Otospondylomegaepiphyseal dysplasia (see also C2/11)
|
|
| COL17: |
|
|
|
| Laminin |
- Junctional epidermolysis bullosa
- Laryngoonychocutaneous syndrome
|
|
| Other |
- Congenital stromal corneal dystrophy
- Raine syndrome
- Urbach–Wiethe disease
- TECTA
|
|
see also fibrous proteins
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
|
Genetic disorder, membrane: Solute carrier disorders
|
|
| 1-10 |
- SLC1A3
- SLC2A1
- SLC2A5
- SLC2A10
- Arterial tortuosity syndrome
- SLC3A1
- SLC4A1
- Hereditary spherocytosis 4/Hereditary elliptocytosis 4
- SLC4A11
- Congenital endothelial dystrophy type 2
- Fuchs' dystrophy 4
- SLC5A1
- Glucose-galactose malabsorption
- SLC5A2
- SLC5A5
- Thyroid dyshormonogenesis type 1
- SLC6A19
- SLC7A7
- Lysinuric protein intolerance
- SLC7A9
|
|
| 11-20 |
- SLC11A1
- SLC12A3
- SLC16A1
- SLC16A2
- Allan–Herndon–Dudley syndrome
- SLC17A5
- SLC17A8
|
|
| 21-40 |
- SLC26A2
- Multiple epiphyseal dysplasia 4
- Achondrogenesis type 1B
- Recessive multiple epiphyseal dysplasia
- Atelosteogenesis, type II
- Diastrophic dysplasia
- SLC26A4
- SLC35C1
- SLC39A4
- Acrodermatitis enteropathica
- SLC40A1
|
|
see also solute carrier family
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
