Alport syndrome

Genetic testing offers the opportunity for early pre-symptomatic diagnosis, antenatal testing, and pre-implantation genetic diagnosis. Patients with a confirmed or suspected diagnosis should be referred for genetic counselling, where the different options for antenatal diagnosis can be explained and genetic testing carried out.

Direct sequencing and deletion analysis of all the Alport syndrome-associated genes is available with many laboratories offering this as part of a larger gene panel by next generation sequencing.[21]Savige J, Ariani F, Mari F, et al. Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Pediatr Nephrol. 2019 Jul;34(7):1175-89. https://orbi.uliege.be/handle/2268/235913 http://www.ncbi.nlm.nih.gov/pubmed/29987460?tool=bestpractice.com It should ideally be carried out after genetic counselling. The mutation detection rate in Alport syndrome-associated genes is high for patients who meet diagnostic criteria. Therefore, it is valuable to confirm the clinical diagnosis and to provide information for other family members. Ideally genetic testing is used only when clinical suspicion of Alport syndrome is high and not as a screening test. Interpretation of results may be problematic if a sequence variant of unknown significance is found. Genotype-phenotype correlations are strong for X-linked Alport syndrome. Positive linkage or mutation analysis can be used to provide predictive, diagnostic, or prenatal testing. For predictive and prenatal testing referral to a clinical geneticist is required. In some centres, in addition to prenatal diagnosis, pre-implantation genetic diagnosis may be offered.

Secondary prevention is mostly concentrated on preventing the complications associated with hypertension and chronic kidney disease. A low-salt, high-fibre, low-cholesterol diet that is tailored to renal function should be followed and reviewed yearly. Smoking must be avoided and full support given to encourage cessation. Patients should take measures to reduce the risk of noise-induced hearing loss. All new symptoms such as ankle oedema, urinary discomfort and pain, chest pain, visual disturbance, and hearing loss should be reported to a physician for further evaluation. This may allow early intervention and treatment of medical complications.