Friedreich's ataxia with chorea and myoclonus caused by a compound heterozygosity for a novel deletion and the trinucleotide GAA expansion

Abstract

Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting about 1 in 50,000 individuals. It is caused by mutations in the frataxin gene; 98% of cases have homozygous expansions of a GAA trinucleotide in intron 1 of the frataxin gene. The remaining 2% of patients are compound heterozygotes, who have a GAA repeat expansion in one allele and a point mutation in the other allele. FRDA patients with point mutation have been suggested to have atypical clinical features. We present a case of compound heterozygotes in a FRDA patient who has a deletion of one T in the start codon (ATG) of the frataxin gene and a GAA repeat expansion in the other allele. The patient presented with chorea and subsequently developed FRDA symptoms. The disease in this case is the result of both a failure of initiation of translation and the effect of the expansion. This novel mutation extends the range of point mutations seen in FRDA patients, and also broadens the spectrum of FRDA genotype associated with chorea.

Heart and Nervous System Pathology in Compound Heterozygous Friedreich Ataxia

“…GFAP immunoreactivity attributable to the central nervous system ends at the DR entry zone (J, inset, arrow). who also had chorea (10). One previously reported heterozygous FA patient had dystonia (4).…”

Differential Diagnosis of Chorea

“…Although deep tendon reflexes are normally lost, in some cases, they are abnormally increased, and there is spasticity with dystonic posturing. Rarely chorea can be seen, which may even be a presenting symptom prior to the development of other features [36,37].…”

Spinocerebellar degenerations

“…Presenting symptoms can be either gait ataxia with absent lower-extremity reflexes and upgoing toes, scoliosis, and pes cavus, or cardiomyopathy. It can rarely present with chorea or myoclonus (Hanna et al, 1998;Zhu et al, 2002;Spacey et al, 2004)). Ataxia of limbs and dyarthria usually follow gait ataxia by a few years.…”