Genetic and Family Studies in Friedreich's Ataxia

Abstract

SUMMARY:This study consists of two parts: I. A detailed genetic analysis of 35 sibships in which 58 individuals were affected with Friedreich’s ataxia; and 2. Clinical and laboratory examinations of parents and siblings, in an attempt at carrier detection and diagnosis of the pre-clinical state.The increased parental consanguinity, the lack of affected individuals in other generations, and the lack of significance of extrinsic etiological variables, all suggested an autosomal recessive mode of inheritance, and this was confirmed by formal genetic analyses, employing several different methods.Associated abnormalities in our series of 58 patients included cardiomyopathy (51.7%), diabetes melitus (19.0%), optic atrophy (5.2%), nerve deafness (5.2%) and congenital malformations (6.9%). The incidence of diabetes mellitus. congenital malformations, and epilepsy and lor febrile convulsions was elevated in first degree relatives of patients with Friedreich’s ataxia.Examinations in first degree relatives revealed an increased frequency of neurological and skeletal abnormalities (26.3%). but no abnormalities on neuro-ophthalmological examination. Frequent EMG abnormalities were noted in parents (56.3%). but not in siblings; and these could usually be attributed to extrinsic causes. There was an increased incidence of ECG abnormalities in both parents (50.0%) and siblings (25.0% and some of these abnormalities may represent cardiomyopathy. An increased frequency of EEG abnormalities was also recorded in parents (14.3%) and siblings (27.2%). but these were not specific. None of these examinations resulted in a practicable method of carrier detection or preclinical diagnosis.Since carrier detection is still not feasible, genetic counselling remains the only possible means of prevention of Friedreich’s ataxia.