alport syndrome hearing loss

RATIONALE: Alport Syndrome (AS) is a progressive genetic condition characterized by chronic kidney disease (CKD), hearing loss, and eye abnormalities. It is caused by mutations in the genes COL4A3, COL4A4 , and COL4A5 . Heterozygous mutations in COL4A4 and COL4A3 cause autosomal dominant Alport Syndrome (ADAS), and a spectrum of phenotypes ranging from asymptomatic hematuria to CKD, with variable extra-renal features. In the past, heterozygous mutations in these genes were thought to be benign, however recent studies show that about 30% of patients can progress to CKD, and 15% can progress to end stage kidney disease (ESKD)...

Alport syndrome (AS) is a hereditary kidney disorder of type IV collagen caused by pathogenic variants in the COL4A3, COL4A4 and COL4A5 genes. Previously several cases of digenic AS, caused by two pathogenic variants in two of the three COL4A genes, have been reported. Patients with digenic AS may present with a more severe phenotype compared to patients with single variants, depending on the percentage affected type IV trimeric collagen chain. We report a newly discovered case of trigenic AS. A 52-year-old female presented with hematuria at the age of 24 years and developed hypertension by the age of 30...

PURPOSE: To describe a patient with a rare co-occurrence of Usher syndrome type 1C (USH1C) and renal disease, suspected to be secondary to Alport syndrome. METHOD: Case report and literature review of cases with Usher syndrome and renal failure. Clinical examination, color fundus photography, visual field tests, electroretinography and whole exome sequencing were used to diagnose and document the patient's clinical presentation. RESULTS: An 18-year-old female with known history of congenital hearing loss and chronic renal failure, presents with progressive night and peripheral visual impairment suspicious for an inherited retinal disease...

BACKGROUND AND OBJECTIVE: Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis...

Objective: To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods: Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results: This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27...

BACKGROUND: We report a three-generation family with isolated Alport-like retinal abnormalities in the absence of lenticonus, hearing loss, kidney disease, and detectable molecular genetic defects in known Alport-related genes. METHODS: Clinical examination includes ocular biomicroscopy, fundus photography, optical coherence tomography, dipstick urinalysis, serum creatinine assessment, and molecular genetic analysis. RESULTS: The proband, her mother, and her maternal grandmother had normal best-corrected visual acuity and normal visual fields in both eyes...

We report two cases of Alport syndrome and compare the clinical presentations and imaging findings in these cases. The clinical examination consisted of best-corrected visual acuity (BCVA), direct ophthalmoscopy, and slit-lamp examination. Macular optical coherence tomography (OCT) and anterior segment OCT (AS-OCT) and were utilized to document the details of the anterior and posterior segment pathologies. In order to evaluate systemic presentations of Alport syndrome, nephrology, and otolaryngology were consulted for each patient...

Alport syndrome is an genetic disorder that distresses the basement membrane of the kidneys and can also impact other organs, such as the cochlea of the inner ear and eyes. It is characterized by mutation causing abnormalities in the collagen within the basement membrane, which has a crucial role in the filtration process of the kidneys. These abnormalities lead to progressive kidney damage and often result in chronic kidney disease. In some cases of Alport syndrome, the abnormal collagen can also affect the cochlea in the inner ear, leading to sensorineural hearing loss...

Most male X-linked Alport syndrome patients with COL4A5 nonsense mutations experience end-stage kidney failure by 30 years old. Although there is no definition of high-flow arteriovenous fistula, access blood flows greater than 2000 mL/min might predict the occurrence of high-output heart failure. A 50-year-old Japanese man had suffered from proteinuria at 4 years old and sensorineural hearing loss and a lenticular lens at 20 years old. He had started to receive hemodialysis treatment due to end-stage kidney disease at 22 years old...

Alport syndrome (AS) is a rare genetic disorder categorized by the progressive loss of kidney function, sensorineural hearing loss and eye abnormalities. It occurs due to mutations in three genes that encode for the alpha chains of type IV collagen. Globally, the disease is classified based on the pattern of inheritance into X-linked AS (XLAS), which is caused by pathogenic variants in COL4A5, representing 80% of AS. Autosomal recessive AS (ARAS), caused by mutations in either COL4A3 or COL4A4, represents 15% of AS...

INTRODUCTION: The penetrance and phenotypic spectrum of autosomal dominant Alport Syndrome (ADAS), affecting 1 in 106, remains understudied. METHODS: Using data from 174,418 participants in the Geisinger MyCode/DiscovEHR study, an unselected health system-based cohort with whole exome sequencing, we identified 403 participants who were heterozygous for likely pathogenic COL4A3 variants. Phenotypic data was evaluated using International Classification of Diseases (ICD) codes, laboratory data, and chart review...

OBJECTIVE: To investigate the clinical features and genetic variant of a child with X-linked dominant Alport syndrome (XLAS). METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data of the child was collected. Next generation sequencing (NGS) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members. RESULTS: The child, a 12-year-old boy, had mainly manifested gross hematuria, proteinuria, nephrotic syndrome, and progressive renal impairment in conjunct with hearing loss...

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome. METHODS: A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family...

BACKGROUND: Alport syndrome (AS; OMIM#308,940) is a hereditary kidney disease that progresses over time and is distinguished by hearing loss and ocular irregularities. The syndrome has three subtypes, namely X-linked (XL; OMIM#301,050), autosomal recessive (AR; OMIM#203,780), and autosomal dominant (AD; OMIM#104,200), which are categorized based on their respective modes of inheritance. XLAS is attributed to a pathogenic variant in the COL4A5 (OMIM*303,630) gene, which encodes the α5(IV) chain of type IV collagen (Col-IV)...

Alport syndrome (AS) is a hereditary progressive glomerular disease associated with sensorineural hearing loss and ocular abnormalities. It is attributed to the altered structure and the subsequent dysfunction of the glomerular basement membrane (GBM) due to the mutated type IV collagen a3/a4/a5 chains. It may emerge either as an X-linked disease, the most common, or as an autosomal disease, both recessive and dominant. A female patient, 26 years old, came in 2023 to the Department of Oral Medicine/ Pathology, Dental School, Aristotle University of Thessaloniki, complaining about pain and a burning sensation in her right cheek...

PURPOSE: This article presents a review of the main causes of inherited dual sensory impairment (DSI) with an emphasis on the multidisciplinary approach. METHODS: A narrative review of English literature published before January 2023 was conducted using PubMed, Medline, and Scopus databases. The different causes of inherited DSI are discussed from a multidisciplinary perspective. RESULTS: There are a wide range of dual sensory impairment (DSI), commonly referred to as blindness and deafness...

Alport syndrome (AS), a type IV collagen disorder, leads to glomerular disease and, in some patients, hearing loss. AS is treated with inhibitors of the renin-angiotensin system; however, a need exists for novel therapies, especially those addressing both major pathologies. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist (DEARA) under clinical development for focal segmental glomerulosclerosis and IgA nephropathy. We report the ability of sparsentan to ameliorate both renal and inner ear pathologies in an autosomal-recessive Alport mouse model...

UNLABELLED: Most data on Alport Syndrome (AS) due to COL4A3 are limited to families with autosomal recessive AS or severe manifestations such as focal segmental glomerulosclerosis (FSGS). Using data from 174,418 participants in the Geisinger MyCode/DiscovEHR study, an unselected health system-based cohort with whole exome sequencing, we identified 403 participants (0.2%) who were heterozygous for likely pathogenic COL4A3 variants. Phenotypic data was evaluated using International Classification of Diseases (ICD) codes, laboratory data, and chart review...

Alport syndrome is a hereditary disorder characterized by kidney disease, ocular abnormalities, and sensorineural hearing loss. Work in understanding the cause of Alport syndrome and the molecular composition of the glomerular basement membrane ultimately led to the identification of COL4A3 , COL4A4 (both on chromosome 2q36), and COL4A5 (chromosome Xq22), encoding the α3, α4, and α5 chains of type IV collagen, as the responsible genes. Subsequent studies suggested that autosomal recessive Alport syndrome and males with X-linked Alport syndrome have more severe disease, whereas autosomal dominant Alport syndrome and females with X-linked Alport syndrome have more variability...

The genotype-phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype-phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25...