Hearing impairment, and Hematuria

Benign familial hematuria is an autosomal dominant condition manifest as nonprogressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane (GBM), and can be considered the mildest end of the spectrum of renal diseases due to type IV collagen defects of the basement membrane. The most severe end of the spectrum is represented by Alport syndrome ({301050}; {203780}, {104200}), which results in end-stage renal failure and may be associated with hearing loss and ocular anomalies (review by Lemmink et al. (1996)).

HEMATURIA, BENIGN FAMILIAL; BFH Is also known as tmn|thin membrane nephropathy|thin-basement-membrane nephropathy

• Hearing impairment
• Hypertension
• Renal insufficiency
• Proteinuria
• Stage 5 chronic kidney disease

SOURCES: OMIM MESH MENDELIAN

High myopia-sensorineural deafness syndrome is a rare genetic disease characterized by high myopia, typically ranging from -6.0 to -11.0 diopters, and moderate to profound, bilateral, progressive sensorineural hearing loss with prelingual-onset. Affected individuals do not present other systemic, ocular or connective tissue manifestations.

• Intellectual disability
• Hearing impairment
• Nystagmus
• Sensorineural hearing impairment
• Cognitive impairment

SOURCES: OMIM ORPHANET MENDELIAN

Alport syndrome is a hereditary disorder of the basement membrane, resulting in a glomerulonephropathy causing renal failure. Progressive deafness and ocular anomalies may also occur (Mochizuki et al., 1994; Colville et al. (1997)). For a general phenotypic description of Alport syndrome, see the X-linked dominant form (OMIM ). Approximately 85% of cases of Alport syndrome are X-linked and about 15% are autosomal recessive; autosomal dominant inheritance (OMIM ) is rare (van der Loop et al., 2000).See also benign familial hematuria (BFH ), a similar but milder disorder.

• Hearing impairment
• Failure to thrive
• Sensorineural hearing impairment
• Cataract
• Hypertension

SOURCES: OMIM ORPHANET MENDELIAN

Alport syndrome classically comprises nephritis, often progressing to renal failure, and sensorineural hearing loss (Alport, 1927). For a general phenotypic description of Alport syndrome, see the X-linked dominant form (OMIM ). Approximately 85% of cases of Alport syndrome are X-linked and about 15% are autosomal recessive (OMIM ); autosomal dominant inheritance is rare (van der Loop et al., 2000).Also see benign familial hematuria (BFH ), a similar but milder disorder also caused by mutation in the COL4A3 gene.An autosomal dominant disorder sharing the clinical features of Alport syndrome but with the addition of macrothrombocytopenia, known as Fechtner syndrome (OMIM ), is caused by mutation in the MYH9 gene (OMIM ) on chromosome 22q11.

• Hearing impairment
• Sensorineural hearing impairment
• Hypertension
• Myopia
• Renal insufficiency

SOURCES: OMIM MENDELIAN

Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop the clinical entity called 'nephrotic syndrome' (see NPHS1; {256300}), which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004; Mathis et al., 1998).D'Agati et al. (2011) provided a detailed review of FSGS, emphasizing that the disorder results from defects of the podocyte.Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Focal Segmental Glomerulosclerosis and Nephrotic SyndromeFocal segmental glomerulosclerosis and nephrotic syndrome are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also FSGS2 (OMIM ), caused by mutation in the TRPC6 gene (OMIM ); FSGS3 (OMIM ), associated with variation in the CD2AP gene (OMIM ); FSGS4 (OMIM ), mapped to chromosome 22q12; FSGS5 (OMIM ), caused by mutation in the INF2 gene (OMIM ); FSGS6 (OMIM ), caused by mutation in the MYO1E gene (OMIM ); FSGS7 (OMIM ), caused by mutation in the PAX2 gene (OMIM ); FSGS8 (OMIM ), caused by mutation in the ANLN gene (OMIM ); and FSGS9 (OMIM ), caused by mutation in the CRB2 gene (OMIM ).See also NPHS1 (OMIM ), caused by mutation in the NPHS1 gene (OMIM ); NPHS2 (OMIM ), caused by mutation in the podocin gene (OMIM ); NPHS3 (OMIM ), caused by mutation in the PLCE1 gene (OMIM ); and NPHS4 (OMIM ), caused by mutation in the WT1 gene (OMIM ).

FOCAL SEGMENTAL GLOMERULOSCLEROSIS 1; FSGS1 Is also known as glomerulosclerosis, focal segmental, 1

• Hearing impairment
• Pain
• Anemia
• Hypertension
• Edema

SOURCES: OMIM MESH MENDELIAN

Uveal coloboma-cleft lip and palate-intellectual disability is characterised by coloboma of the iris, bilateral cleft lip and palate, and intellectual deficiency of varying degree. A wide variability in clinical expression is observed. Some patients also present with microphthalmia, cataract, glaucoma, ptosis, sensorineural hearing loss and haematuria. To date, 12 cases have been described from three generations of a single family. Transmission is autosomal dominant.

• Intellectual disability
• Hearing impairment
• Nystagmus
• Strabismus
• Sensorineural hearing impairment

SOURCES: MESH OMIM ORPHANET MENDELIAN

The association of X-linked Alport syndrome with leiomyomatosis of the esophagus, tracheobronchial tree or female genitals has been reported in more than 30 families.

X-LINKED DIFFUSE LEIOMYOMATOSIS-ALPORT SYNDROME Is also known as xq22.3 microdeletion syndrome|chromosome xq22.3 centromeric deletion syndrome|alport syndrome and diffuse leiomyomatosis|leiomyomatosis, esophageal and vulval, with nephropathy|ats-dl

• Hearing impairment
• Failure to thrive
• Sensorineural hearing impairment
• Cataract
• Dysphagia

SOURCES: OMIM ORPHANET MENDELIAN

Hypertrophic cardiomyopathy and renal tubular disease due to mitochondrial DNA mutation is a mitochondrial oxidative phosphorylation disorder characterized by hypertrophic and dilated cardiomyopathy, failure to thrive, myopathy with generalized hypotonia and increased creatine kinase, developmental delay and/or regression with cerebral atrophy on brain MRI, renal manifestations including chronic renal failure, renal tubular acidosis and lactic acidosis. Additional clinical features include seizures and respiratory failure.

HYPERTROPHIC CARDIOMYOPATHY AND RENAL TUBULAR DISEASE DUE TO MITOCHONDRIAL DNA MUTATION Is also known as hypertrophic cardiomyopathy and renal tubular disease due to mtdna mutation

• Short stature
• Hearing impairment
• Sensorineural hearing impairment
• Anemia
• Hepatomegaly

SOURCES: ORPHANET MENDELIAN

Nail-patella syndrome (NPS) is a rare hereditary patellar dysostosis characterized by nail hypoplasia or aplasia, aplastic or hypoplastic patellae, elbow dysplasia, and the presence of iliac horns as well as renal and ocular anomalies.

NAIL-PATELLA SYNDROME Is also known as turner-kieser syndrome|onychoosteodysplasia

• Hearing impairment
• Cataract
• Hypertension
• Renal insufficiency
• Glaucoma

SOURCES: ORPHANET MENDELIAN

AMYLOIDOSIS, FAMILIAL VISCERAL Is also known as german type amyloidosis|amyloidosis, systemic nonneuropathic|amyloidosis viii|amyloidosis, familial renal|ostertag type amyloidosis

• Hearing impairment
• Neoplasm
• Pain
• Hypertension
• Peripheral neuropathy

SOURCES: ORPHANET OMIM MENDELIAN