Revision about hearing loss in the Alport's syndrome, analyzing the clinical, genetic and bio-molecular aspects

Abstract

Alport Syndrome is a genetic disorder characterized by hematuria, which often leads to renal failure. It may also be accompanied by extra-renal alterations, such as: sensorineural hearing loss, and ocular abnormalities. Dominant forms related to the X chromosome and caused by mutations in the locus COL4A5 have been described, as well as an autossomic recessive form resulting from mutations in the locus COL4A3 or COL4A4. An autossomic dominant type of AS has also been reported. The disease is caused by changes in the collagen type IV chains, where symptoms reflect the damage to the basal membrane of several organs. The alpha3.alpha4.alpha5(IV) networks are found in the kidneys, cochlea and eyes. The objective was to characterize AS in this group of patients. In the current literature review it was found that: 1. AS is characterized by hematuria that may develop into renal failure and can also be accompanied by extra-renal manifestations. Hearing loss is a frequent extra-renal finding and one of the first symptoms of AS, therefore representing a relevant factor in the prognosis of the renal disease; 2. It is a genetic disorder resulting from abnormalities in the chains of collagen type IV in the basal membranes; 3. The hearing loss in AS is typically sensorineural with variable intensities, progressive and symmetrical, affecting middle and high frequencies; 4. Otolaryngologists should include a urine test in the SNHL work-up. It is essential to have an otologist involved in the treatment of these patients.

Audiometric characteristics of a Dutch family with Muckle-Wells syndrome

“…Furthermore, pathology at the level of the basilar membrane could be responsible for the good speech recognition scores seen in the present family, which is also found in Alport syndrome. (Moon et al, 2008;Alves and De Quintanilha Ribeiro, 2005) Results of the audiometric evaluation also indirectly support the hypothesis of improper motion of the basilar membrane in patients with MWS. Suprathreshold measures such as DL f and gap detection were within the normal range or at least close to data obtained in two groups of patients with known abnormalities of the tectorial membrane (Plantinga et al, 2007;De Leenheer et al, 2004).…”

“…Since ossification did not occur in other parts of the temporal bone, an otosclerotic pathogenesis was excluded (Muckle and Wells, 1962). The cause of hearing impairment in MWS is still unknown, but the basilar membrane could be involved in the pathogenesis of hearing impairment, as is the case in the pathogenesis of Alport syndrome (Moon et al, 2008;Alves and De Quintanilha Ribeiro, 2005;Merchant et al, 2004). The structurally defective basement membrane in Alport syndrome probably provides inadequate adhesion between the organ of Corti and the underlying basilar membrane.…”

Inner ear defects and hearing loss in mice lacking the collagen receptor DDR1

“…42 Furthermore, mutations in the COL4A3-5 genes cause Alport syndrome, an inherited disorder showing progressive nephropathy, ocular abnormalities, and sensorineural hearing loss. 43 In contrast, COL4A3-knockout mice did not present with an uniformly elevated hearing threshold, since only three out of 12 animals studied showed a significantly altered ABR. 44 In a parallel study, thickening of the strial BM was observed in COL4A3-null mice at the ultrastructural level; however, a slight shift in auditory threshold shift was reported only in some older animals.…”

Childhood Hearing Australasian Medical Professionals network: Consensus guidelines on investigation and clinical management of childhood hearing loss

“…Disease in both organ systems can be related to mutations in these pathways, including glomerulopathies, tubulopathies, ciliopathies and congenital anomalies of the kidney and urinary tract . Examples are listed in Table . Urinalysis is recommended where there is delayed onset of SNHL, progressive SNHL or if there is a family history of renal disease as listed above.…”