Screening
Family screening
Relatives of an index case with suspected or confirmed Alport syndrome can be offered screening. Identification of at-risk relatives will depend on the likely mode of inheritance. If this is unclear then all first-degree relatives can be offered screening with urinalysis, BP estimation, and assessment of renal function.
In X-linked Alport syndrome (XLAS) all affected family members should be identified using cascade genetic testing where possible.[23] The daughters of affected males will all be affected. Screening can initially be carried out using urinalysis and BP measurement, and where the familial mutation is known this can be used to offer predictive and diagnostic tests. A single urine test can be offered to males but up to 3 are required in females.
Early detection of hypertension, proteinuria, and renal failure offer the opportunity to intervene and potentially slow the progression of renal disease and reduce the risk of developing cardiovascular disease. Screening of males and females with a family history is indicated, as the lifetime risk of developing renal failure is 100% and 15% to 30%, respectively.[29][44]
The age of screening depends on the individual's sex and the presence of symptoms and comorbidities. Male siblings of an affected male with XLAS, who are at 50% risk, should be screened as early as possible after discussion with the parents in parallel with screening the mother if she has not previously been tested. Female siblings should also be screened as early as possible despite the fact that symptoms typically appear at a later age, as use of an ACE inhibitor may slow disease progression once microalbuminuria has developed.
Children of females with XLAS should also be offered screening as above.
Screening advice is typically based on individual clinical assessment by nephrologists and clinical geneticists. Expert guidelines for the management of Alport syndrome also contain guidance on family screening.[5][23][30]
In autosomal-recessive Alport syndrome (ARAS) cascade screening should be offered to parents and siblings. All offspring of a patient with ARAS are obligate carriers and therefore likely to develop microscopic hematuria. Both parents may have microscopic hematuria. Siblings have a 1:4 chance of having ARAS and a 2:3 chance of being a carrier if they do not clinically have ARAS. Most carriers have microscopic hematuria. Carriers of ARAS are typically not considered as potential kidney donors although this may be reviewed after careful clinical, pathological, and molecular evaluation.[23][45]
In autosomal dominant Alport syndrome, all first-degree relatives should be offered screening as above.
In autosomal digenic Alport syndrome screening and advice will depend on whether the COL4A3 and COL4A4 are in cis or trans.
Population screening
There are no indications for screening the healthy population. The diagnosis may rarely be made during population screening for hearing loss and microscopic hematuria.
Use of this content is subject to our disclaimer