A study of neural and extraneural findings in a large family with Friedreich's ataxia

From a review of the literature and a consideration of the findings in this study, the following conclusions appear to be justified. 1. (1) Neurological findings in Friedreich's ataxia are of 3 general types: those found fairly constantly and in earlier stages of the disease; those found less frequently and usually later in the course of the illness; those tending to occur within given pedigrees and reflecting a hereditary predisposition in the family to degeneration of specific parts of the nervous system involved. 2. (2) Commonest findings among members of the family studies were: scoliosis, nystagmus, dysdiadochokinesia, mirror motion, fanning of toes with neutral response of the great toe, reduced reflexes, high arches and extraocular palsies. Those findings which correlate best with numbers of other findings were: reduced reflexes, hypermetria, intention tremor, sensory changes, nystagmus and extensor plantar responses. 3. (3) Neurological and musculo-skeletal defects are evaluated by a system of weighted criteria based on the literature. The incidence of significant numbers of these stigmata among persons qualifying for evaluation was 28 in 112 or 25%, with an equal distribution between sexes. Presence of significant numbers of stigmata in these persons is interpreted as a genetic potentiality for development of heredo-degenerative disease. In some cases, findings may represent a single dose effect of a lone recessive gene. 4. (4) Exogenous factors, representing physiological stresses, exert a phenotypic influence and are often found to precipitate onset of Friedreich's ataxia. 5. (5) It is suggested that variations among findings in Friedreich's ataxia result from the effect of differences in the fundamental constitutions of the individuals involved. These separately inherited genes, acting as genetic modifiers on the gene(s) primarily responsible for the clinical disease, may produce their own manifestations which, when present, not only constitute a part of the clinicopathologic state, but also reflect in part the genetic milieu wherein the ataxia-bearing gene(s) work their effect.