Alport syndrome

Genetic testing offers the opportunity for early presymptomatic diagnosis, prenatal testing, and preimplantation genetic diagnosis. Patients with a confirmed or suspected diagnosis should be referred for genetic counseling, where the different options for prenatal 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 counseling. 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. If there are existing genetic test results, do not perform repeat testing unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[22]American College of Medical Genetics and Genomics. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 ​[internet publication]. https://web.archive.org/web/20230326143738/https://www.choosingwisely.org/societies/american-college-of-medical-genetics-and-genomics

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 centers, in addition to prenatal diagnosis, preimplantation 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-fiber, 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 edema, 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.