‘Pseudo-dominant’ Inheritance in Friedreich’s Ataxia: Clinical and Genetic Study of a Brazilian Family (P2.033)

Objective: To evaluated a family with pseudo-dominant inheritance in Friedreich’s ataxia (FRDA). Background: FRDA is an autosomal recessive inherited disorder characterized by progressive ataxia, hypertrophic cardiomyopathy, skeletal abnormalities, areflexia, loss of vibratory and position sense. The wide spectrum of disease may lead to diagnostic challenge and in such scenario the inheritance pattern is a clue to diagnose. A rare pattern observed in some families is the pseudodominant pattern which is in general characterized by phenotypic variation and could provoke difficulty in the correct diagnose. Methods: We evaluated a Brazilian family of Italian descent with marked variation of phenotype. Pedigree was described Results: The father developed progressive ataxia at 30 years of age and at 68 years, he had dysarthria, dysphagia, generalized ataxia, dysmetria and loss of deep tendon reflexes. He could not sit without support, as walking or standing. MRI was normal and echocardiogram showed cardiomyopathy. DNA analysis showed two expanded alleles with more than 700 GAA repeats each one. Of three children, two were affected. The 39-year-old man began to have difficulties with balance in his 22. He presented impaired speech, dysphagia, horizontal nystagmus and head tremor. There were loss of vibration sensation and tendon reflexes. He exhibited truncal ataxia and could not stand even with support. There were scoliosis and cardiomyopathy. DNA showed one allele with 700 GAA repeats and the other with 900 repeats. The index case first exhibited clumsiness in handwriting at the age of 26, followed by progressive unsteadiness of gait. She had slurred speech, square wave jerks, postural tremor in the hands and loss of knee reflex. MRI and echocardiogram were normal. DNA analysis showed: one allele with 350 GAA repeats and the other with 1000 repeats. Conclusions: The family presented is a relatively rare observation of pseudodominant inheritance of FRDA, which provided the opportunity to investigate the molecular basis of intra-familial clinical polymorphism of this disease. Disclosure: Dr. Moro has nothing to disclose. Dr. Martinez has nothing to disclose. Dr. Moscovich has nothing to disclose. Dr. Karuta has nothing to disclose. Dr. Munhoz has nothing to disclose. Dr. Arruda has nothing to disclose. Dr. Raskin has nothing to disclose. Dr. Germiniani has nothing to disclose. Dr. Teive has nothing to disclose.