Autosomal Dominant Variant of Alport Syndrome Shows Unexpected Severity, Study Shows

People with the autosomal dominant variant of Alport syndrome can also experience severe symptoms, and may be more prevalent than previously thought, researchers reported.

The study, “Study of the True Clinical Progression of Autosomal Dominant Alport Syndrome in a European Population,” was published in the online journal Kidney and Blood Pressure Research.

Alport syndrome is a genetic inherited disease characterized by kidney disease, hearing loss, and eye abnormalities. The autosomal dominant Alport syndrome represents 5% of all cases of Alport syndrome. But what does this mean, autosomal dominant?

An inherited genetic disorder (meaning it is passed through generations) has several mechanisms of transmission. One of them is via an autosomal dominant pattern, which means that if you inherit the abnormal gene from only one parent, you can get the disease (hence the term dominant).

Patients with autosomal dominant Alport syndrome present differences in the clinical symptoms when compared to other forms of the disease (recessive inheritance pattern and the X chromosome-linked pattern). Contrary to these, autosomal dominant Alport syndrome is recognized as less severe.

This means that clinical evolution is less aggressive, the renal symptoms (hematuria and proteinuria) appear at later stages of life, and the disease progresses slowly toward chronic kidney failure which, in very few cases, reaches end-stage chronic kidney failure. Furthermore, hearing loss in these cases is also mild, appearing only in adulthood.

Researchers performed a descriptive observational and retrospective clinical study with 19 patients from five families with a clinical diagnosis of autosomal dominant Alport Syndrome. They analyzed the expression of the symptoms in the different families, and compared the results with what was previously published.

In the tested group of patients, they detected that renal symptoms appeared at a young age, with a progression toward end-stage chronic kidney disease at a median age of 31. Hearing loss also appeared at early ages (median age of 28.5). Additionally, they observed ocular lenticonus-like injuries, which have been only described in other inheritance patterns.

These results show that, at least in this cohort of patients, the dominant autosomal pattern is accompanied with severe symptoms, similar to those as detected in the other two forms of the disease (recessive inheritance pattern and the X chromosome-linked pattern).

These findings also suggest that Alport syndrome symptoms are variable, which may lead to many unnoticed cases. Moreover, the severest cases may actually occur in dominant autosomal pattern but are erroneously diagnosed as recessive, meaning that the real prevalence of dominant forms is probably higher than the current estimated 5%.