Disease relevance of DFN4

• OBJECTIVE: Locus DFN4 is an X-linked nonsyndromic hearing loss locus originally mapped to Xp21 [1].
• Radiological findings for patients with congenital sensorineural hearing loss and mixed hearing loss include, single cavity anomaly (one patient), dilated vestibule and superior semicircular canal (one patient), and absent internal auditory canal (IAC) (two patients) [2].
• Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa [3].
• We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction [3].
• The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes [4].

Psychiatry related information on DFN4

• In addition the boy had postnatal growth failure, apparent severe mental retardation, congenital scalp defects and scalp hair patterning abnormalities, aplasia of the nasal alae, nasolacrimo-cutaneous fistulae, hypotonia, severe congenital sensorineural deafness, and small conical and widely spaced teeth [5].

High impact information on DFN4

• Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss, vestibular dysfunction and visual impairment due to early onset retinitis pigmentosa (RP) [6].
• RESULTS: Of 52 sequential probands referred for congenital sensorineural hearing loss, 22 (42%) were found to have GJB2 mutations [7].
• Pendred's syndrome, an autosomal-recessive condition characterized by congenital sensorineural hearing loss and goiter, is caused by mutations in the PDS gene [8].
• Pendred's syndrome is a combination of congenital sensorineural hearing loss and iodine organification defect leading to a positive perchlorate test and goiter [9].
• There is no specific biochemical marker of this disease, and the diagnosis depends upon the demonstration of the triad of congenital sensorineural hearing loss, goiter, and abnormal perchlorate discharge test [10].

Chemical compound and disease context of DFN4

• Pendred's syndrome is an autosomal recessive disease characterized by goiter, impaired iodide organification, and congenital sensorineural deafness [11].

Biological context of DFN4

• Clinical phenotype of DFN2, DFN4 and DFN6 [12].
• In a South African girl of Xhosa stock with severe piebaldism and profound congenital sensorineural deafness we identified a novel missense substitution at a highly conserved residue in the intracellular kinase domain of the KIT proto-oncogene, R796G [13].
• In conclusion, there are no major abnormalities for repolarization parameters in children with congenital sensorineural deafness, when compared to hearing counterparts, if heart rates are similar [14].
• Congenital sensorineural deafness in dogs: a molecular genetic approach toward unravelling the responsible genes [15].
• Congenital sensorineural hearing loss was documented by auditory brain-stem responses in four infected infants (two had mild bilateral loss, one had mild unilateral loss, and one had extreme unilateral loss) but in no controls [16].

Anatomical context of DFN4

• The gene recently cloned that is responsible for the Pendred syndrome (PDS), an autosomal recessive disease characterized by goiter and congenital sensorineural deafness, is mainly expressed in the thyroid gland [17].
• Hypoplasia of the bony canal for the cochlear nerve in patients with congenital sensorineural hearing loss: initial observations [18].
• Linkage analysis has been carried out in a family with severe congenital sensorineural deafness with a structural abnormality of the inner ear [19].
• This comprises Klippel Feil's (KF) anomaly (congenitally fused cervical vertebrae), congenital sensorineural deafness and Duane's retraction syndrome (deficient abduction with retraction on adduction) [20].
• This is the first report of a combination of congenital sensorineural hearing loss, partial agenesis of the corpus callosum, and an arachnoid cyst [21].

Other interactions of DFN4

• The restriction of the DFN4 locus to DMD suggests that dystrophin may play an important role in hearing [22].
• A second family with nonsyndromic sensorineural hearing loss linked to Xp21.2: refinement of the DFN4 locus within DMD [22].
• Congenital sensorineural deafness associated with EEG abnormalities, epilepsy and high familial incidence [23].

Analytical, diagnostic and therapeutic context of DFN4

• There was no statistical difference between patients with and without GJB2-related congenital sensorineural hearing loss with regard to open-set and closed-set speech recognition performance at 12, 24, and 36 months after cochlear implantation [24].
• EEG studies showed a high rate of abnormal tracings associated with congenital sensorineural deafness [23].
• CONCLUSION: Pediatric patients with congenital sensorineural hearing loss without other comorbid conditions (eg, developmental delay, inner ear malformations) perform well when they receive cochlear implantation and auditory habilitation [24].
• Four of our 19 pediatric cochlear implant recipients with congenital sensorineural hearing loss were identified with US and implanted prior to the onset of signs or symptoms of visual loss [25].
• There is also a strong case for including a 12 lead ECG as part of the investigative work up of all children with congenital sensorineural deafness in whom a firm aetiology has not been established [26].

References