IllnessFriedreich-Ataxie, Einzelgenanalyse

Repeat analysis in the first stage, sequencing in the second stage if a heterozygous repeat expansion is detected.

Parallel processing possible in certain cases, please note with reasons on request.

For atypical courses or age >25 years at first manifestation: consider panel ID AP0018 (hereditary ataxias).

Friedreich's ataxia (FRDA) is a genetic disease caused by biallelic pathogenic variants in the FXN gene (see below) and is associated with progressive functional impairment of several organs. The nervous system is primarily affected, which manifests as slowly progressive ataxia that usually begins before the age of 25 (mean age of onset: 10-15 years). Accompanying symptoms may include dysarthria, muscle weakness, loss of muscle reflexes, loss of positional and vibratory sensation, bladder dysfunction and, later on, a spastic increase in muscle tone (especially in the lower extremities) with secondary foot deformities (e.g. pes cavus). Cardiomyopathy occurs in about 60% of those affected and diabetes mellitus in 30%. Around 25% of those affected have an atypical course of the disease, e.g. with older age at first manifestation, pure spastic paraparesis or preserved tendon reflexes. Life expectancy is reduced compared to the general population, with the most common cause of death being cardiomyopathy. The disease follows an autosomal recessive pattern of inheritance. The age of onset and the severity of the course of the disease appear to correlate inversely with the repeat length of the shorter expansion, but are nevertheless highly variable between individuals, even within the same family.

FRDA is diagnosed by detecting biallelic pathogenic variants in FXN. The most common variant, which is found on both alleles in approximately 96% of individuals with FRDA, is a GAA repeat expansion in intron 1 of FXN. In the remaining 5%, compound heterozygosity is found with a GAA repeat expansion on one allele and an intragenic variant on the other allele.

Source:

https://www.ncbi.nlm.nih.gov/books/NBK1281/