- Nonsyndromic deafness
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.
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.
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 GJB3, and MYO1A.
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.
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
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.
- GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, Mitochondrial
- GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, DFNA3
- GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, DFNB1
- GeneReviews/NCBI/NIH/UW entry on DFNX1 Nonsyndromic Hearing Loss and Deafness
- GeneReviews/NCBI/NIH/UW entry on OTOF-Related Deafness
Diseases of the ear and mastoid process (H60–H99, 380–389) Outer ear Middle ear and mastoid Inner ear and
central pathwaysCommon pathwayExcessive responseOtherAcquired auditory processing disorder · Spatial hearing loss
Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies (1) Basic domains (2) Zinc finger
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 22.5: Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (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 3, Fuchs' dystrophy 3) · ZEB2 (Mowat-Wilson syndrome)
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 syndromeCleidocranial dysostosis
(0) Other transcription factors0.6: Kabuki syndrome Ungrouped Transcription coregulators Genetic disorder, extracellular: scleroprotein disease (excluding laminin and keratin) Collagen disease
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
COL7: Epidermolysis bullosa dystrophica · Recessive dystrophic epidermolysis bullosa · Bart syndrome · Transient bullous dermolysis of the newborn
COL8: Fuchs' dystrophy 1
COL10: Schmid metaphyseal chondrodysplasiaBullous pemphigoid
LamininJunctional epidermolysis bullosa · Laryngoonychocutaneous syndrome Other Genetic disorder, membrane: Solute carrier disorders 1-10SLC1A3 (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 21-40
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