Authors: Michel Koenig

In 1863, Nicholaus Friedreich, Professor of Medicine in Heidelberg, described a "degenerative atrophy of the posterior columns of the spinal cord" leading to progressive ataxia, sensory loss and muscle weakness, often associated with scoliosis, foot deformity, and cardiopathy.Not until the late 1970s were large series of patients analyzed to establish clear diagnostic criteria.Recessive inheritance was firmly established as an essential feature of Friedreich ataxia (FRDA).The Québec Collaborative Group identified the clinical features of typical FRDA and proposed them as diagnostic criteria. They were, however, too strict for the diagnosis of early cases. Harding distinguished the early signs and symptoms from those that may not be present at the onset, but that have to manifest as the disease evolves. These studies, as well as more recent ones, identified an important degree of clinical variability, both among and within the families. Atypical FRDA, including adult-onset Friedreich ataxia (LOFA)(MIM 229300), and Friedreich ataxia with retained reflexes (FARR), a variant in which tendon reflexes in the lower limbs are preserved,11 were recognized by genetic linkage studies to be part of the same entity. The identification of the most common FRDA mutation, an unstable hyperexpansion of a GAA triplet repeat polymorphism,12 clarified the origin and mechanism of the clinical variations.