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Alport syndrome, autosomal dominant

MedGen UID:
339210
Concept ID:
C1567743
Disease or Syndrome
Synonyms: Alport syndrome dominant type; COL4A3 Alport Syndrome and Thin Basement Membrane Nephropathy; Renal failure and sensorineural hearing loss
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
 
Gene: COL4A3
Cytogenetic location: 2q36.3
OMIM: 104200

Disease characteristics

Alport syndrome (AS) is characterized by renal, cochlear, and ocular involvement. Renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with X-linked (XL) AS, and in all males and females with autosomal recessive (AR) AS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. Thin basement membrane nephropathy (TBMN) is characterized by persistent microscopic hematuria often first observed in childhood; progressive renal involvement and extrarenal abnormalities are rare. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Clifford E Kashtan   view full author information

Additional descriptions

From OMIM
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 (301050). Approximately 85% of cases of Alport syndrome are X-linked and about 15% are autosomal recessive (203780); autosomal dominant inheritance is rare (van der Loop et al., 2000). Also see benign familial hematuria (BFH; 141200), 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 (153640), is caused by mutation in the MYH9 gene (160775) on chromosome 22q11.  http://www.omim.org/entry/104200
From GHR
Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD). People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue at the back of the eye (retina). These eye abnormalities seldom lead to vision loss. Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females.  http://ghr.nlm.nih.gov/condition/alport-syndrome

Clinical features

Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Finding
A disorder characterized by laboratory test results that indicate blood in the urine.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
abnormal presence of protein in urine
Glomerulonephritis
MedGen UID:
504340
Concept ID:
CN000099
Finding
Inflammation of the renal glomeruli.
Nephrotic syndrome
MedGen UID:
504341
Concept ID:
CN000100
Finding
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Nephrocalcinosis
MedGen UID:
504348
Concept ID:
CN000117
Finding
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Stage 5 chronic kidney disease
MedGen UID:
505594
Concept ID:
CN003407
Finding
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Thickening of the glomerular basement membrane
MedGen UID:
505670
Concept ID:
CN004176
Finding
Increase in thickness of the basal lamina of the glomerulus of the kidney.
Myopia
MedGen UID:
504487
Concept ID:
CN000511
Finding
An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry.
Anterior polar cataract
MedGen UID:
504740
Concept ID:
CN001066
Finding
A `polar cataract` (HP:0010696) that affects the `anterior pole of the lens` (FMA:58897).
Lenticonus
MedGen UID:
504745
Concept ID:
CN001074
Finding
A conical projection of the anterior or posterior surface of the lens, occurring as a developmental anomaly.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of `hearing impairment` (HP:0000365) in one or both ears related to an `abnormal` (PATO:0000460) `functionality` (PATO:0001509) of the `cochlear nerve` (FMA:53431).
Hypertension
MedGen UID:
635666
Concept ID:
C0497247
Finding
A finding of increased blood pressure; not necessarily hypertensive disorder
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Finding
A disorder characterized by laboratory test results that indicate blood in the urine.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
abnormal presence of protein in urine
Hypophosphatemia
MedGen UID:
505125
Concept ID:
CN001946
Finding
An abnormally decreased `phosphate` (CHEBI:18367) concentration in the `blood` (FMA:9670).
Azotemia
MedGen UID:
505130
Concept ID:
CN001955
Finding
An increased concentration of `nitrogen compounds` (CHEBI:51143) in the `blood` (FMA:9670).

Term Hierarchy

Professional guidelines

PubMed

Hertz JM, Thomassen M, Storey H, Flinter F
Eur J Hum Genet 2012 Jun;20(6) Epub 2011 Dec 14 doi: 10.1038/ejhg.2011.237. [Epub ahead of print] PMID: 22166944Free PMC Article

Recent clinical studies

Etiology

Kruegel J, Rubel D, Gross O
Nat Rev Nephrol 2013 Mar;9(3):170-8. Epub 2012 Nov 20 doi: 10.1038/nrneph.2012.259. [Epub ahead of print] PMID: 23165304
Niaudet P
Nat Rev Nephrol 2010 Dec;6(12):736-43. Epub 2010 Sep 28 doi: 10.1038/nrneph.2010.122. [Epub ahead of print] PMID: 20877305
Hertz JM
Dan Med Bull 2009 Aug;56(3):105-52. PMID: 19728970
Marcocci E, Uliana V, Bruttini M, Artuso R, Silengo MC, Zerial M, Bergesio F, Amoroso A, Savoldi S, Pennesi M, Giachino D, Rombolà G, Fogazzi GB, Rosatelli C, Martinhago CD, Carmellini M, Mancini R, Di Costanzo G, Longo I, Renieri A, Mari F
Nephrol Dial Transplant 2009 May;24(5):1464-71. Epub 2009 Jan 7 doi: 10.1093/ndt/gfn681. [Epub ahead of print] PMID: 19129241
Ilan T, Shohat T, Tobar A, Magal N, Yahav M, Halpern GJ, Rechavi G, Shohat M
Isr Med Assoc J 2001 Jul;3(7):488-91. PMID: 11791413

Diagnosis

Beicht S, Strobl-Wildemann G, Rath S, Wachter O, Alberer M, Kaminsky E, Weber LT, Hinrichsen T, Klein HG, Hoefele J
Gene 2013 Sep 10;526(2):474-7. Epub 2013 May 31 doi: 10.1016/j.gene.2013.05.045. [Epub ahead of print] PMID: 23732293
Ohtsubo H, Morisada N, Kaito H, Nagatani K, Nakanishi K, Iijima K
Pediatr Nephrol 2012 Jul;27(7):1189-92. Epub 2012 Feb 21 doi: 10.1007/s00467-012-2125-9. [Epub ahead of print] PMID: 22350371
Artuso R, Fallerini C, Dosa L, Scionti F, Clementi M, Garosi G, Massella L, Epistolato MC, Mancini R, Mari F, Longo I, Ariani F, Renieri A, Bruttini M
Eur J Hum Genet 2012 Jan;20(1):50-7. Epub 2011 Sep 7 doi: 10.1038/ejhg.2011.164. [Epub ahead of print] PMID: 21897443Free PMC Article
Jiang YS, Ehara T
Ultrastruct Pathol 2010 Aug;34(4):199-206. doi: 10.3109/01913121003725739. PMID: 20594039
Marcocci E, Uliana V, Bruttini M, Artuso R, Silengo MC, Zerial M, Bergesio F, Amoroso A, Savoldi S, Pennesi M, Giachino D, Rombolà G, Fogazzi GB, Rosatelli C, Martinhago CD, Carmellini M, Mancini R, Di Costanzo G, Longo I, Renieri A, Mari F
Nephrol Dial Transplant 2009 May;24(5):1464-71. Epub 2009 Jan 7 doi: 10.1093/ndt/gfn681. [Epub ahead of print] PMID: 19129241

Therapy

Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, McCrary Sisk C, Lam C
Pediatr Nephrol 2013 May;28(5):737-43. Epub 2012 Dec 4 doi: 10.1007/s00467-012-2372-9. [Epub ahead of print] PMID: 23207876
Noone D, Licht C
Pediatr Nephrol 2013 Jul;28(7):1025-36. Epub 2012 Aug 18 doi: 10.1007/s00467-012-2272-z. [Epub ahead of print] PMID: 22903660
Wang F, Zhao D, Ding J, Zhang H, Zhang Y, Yu L, Xiao H, Yao Y, Zhong X, Wang S
J Mol Diagn 2012 Nov;14(6):586-93. Epub 2012 Aug 21 doi: 10.1016/j.jmoldx.2012.06.005. [Epub ahead of print] PMID: 22921432
Bollée G, Dahan K, Flamant M, Morinière V, Pawtowski A, Heidet L, Lacombe D, Devuyst O, Pirson Y, Antignac C, Knebelmann B
Clin J Am Soc Nephrol 2011 Oct;6(10):2429-38. Epub 2011 Aug 25 doi: 10.2215/CJN.01220211. [Epub ahead of print] PMID: 21868615Free PMC Article
Ciccarese M, Casu D, Ki Wong F, Faedda R, Arvidsson S, Tonolo G, Luthman H, Satta A
Nephrol Dial Transplant 2001 Oct;16(10):2008-12. PMID: 11572889

Prognosis

Zallocchi M, Johnson BM, Meehan DT, Delimont D, Cosgrove D
Am J Pathol 2013 Oct;183(4):1269-80. Epub 2013 Aug 2 doi: 10.1016/j.ajpath.2013.06.015. [Epub ahead of print] PMID: 23911822Free PMC Article
Hertz JM
Dan Med Bull 2009 Aug;56(3):105-52. PMID: 19728970
Marcocci E, Uliana V, Bruttini M, Artuso R, Silengo MC, Zerial M, Bergesio F, Amoroso A, Savoldi S, Pennesi M, Giachino D, Rombolà G, Fogazzi GB, Rosatelli C, Martinhago CD, Carmellini M, Mancini R, Di Costanzo G, Longo I, Renieri A, Mari F
Nephrol Dial Transplant 2009 May;24(5):1464-71. Epub 2009 Jan 7 doi: 10.1093/ndt/gfn681. [Epub ahead of print] PMID: 19129241
Vizjak A, Ferluga D
Srp Arh Celok Lek 2008 Dec;136 Suppl 4:323-6. PMID: 20804103
Hood JC, Dowling J, Bertram JF, Young RJ, Huxtable C, Robinson W, Savige J
Nephrol Dial Transplant 2002 Nov;17(11):1897-908. PMID: 12401844

Clinical prediction guides

Strasser K, Hoefele J, Bergmann C, Büscher AK, Büscher R, Hoyer PF, Weber S
Nephrol Dial Transplant 2012 Nov;27(11):4236-40. doi: 10.1093/ndt/gfs468. PMID: 23144074
Hertz JM
Dan Med Bull 2009 Aug;56(3):105-52. PMID: 19728970
Vizjak A, Ferluga D
Srp Arh Celok Lek 2008 Dec;136 Suppl 4:323-6. PMID: 20804103
Hood JC, Dowling J, Bertram JF, Young RJ, Huxtable C, Robinson W, Savige J
Nephrol Dial Transplant 2002 Nov;17(11):1897-908. PMID: 12401844
Jefferson JA, Lemmink HH, Hughes AE, Hill CM, Smeets HJ, Doherty CC, Maxwell AP
Nephrol Dial Transplant 1997 Aug;12(8):1595-9. PMID: 9269635

Recent systematic reviews

Mora A, Michalickova K, Donaldson IM
BMC Bioinformatics 2013 Feb 11;14:47. doi: 10.1186/1471-2105-14-47. [Epub ahead of print] PMID: 23398688Free PMC Article
Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F
J Am Soc Nephrol 2013 Feb;24(3):364-75. Epub 2013 Jan 24 doi: 10.1681/ASN.2012020148. [Epub ahead of print] PMID: 23349312
Kashtan CE, Ding J, Gregory M, Gross O, Heidet L, Knebelmann B, Rheault M, Licht C; Alport Syndrome Research Collaborative
Pediatr Nephrol 2013 Jan;28(1):5-11. Epub 2012 Mar 30 doi: 10.1007/s00467-012-2138-4. [Epub ahead of print] PMID: 22461141Free PMC Article
Savige J
Nat Rev Nephrol 2012 May 29;8(7):375-6. doi: 10.1038/nrneph.2012.109. [Epub ahead of print] PMID: 22641079
Cheong HI, Park HW, Ha IS, Choi Y
Pediatr Nephrol 2000 Feb;14(2):117-21. PMID: 10684360

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