Clinical features of Friedreich's ataxia: classical and atypical phenotypes

Abstract

One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia.

Intrathecal Baclofen Therapy for Painful Muscle Spasms in a Patient with Friedreich’s Ataxia

“…FA is a degenerative disease involving the sensory neurons, dorsal root ganglia, the dorsal columns of the spinal cord and corticospinal tract [2]. Therefore, FA muscle spasms could be generated either at the cerebral or spinal level.…”

“…Therefore, a possible role in spinal cord atrophy [6] which is related to the number of GAA mutation repetitions in the frataxin gene [2] and its subsequent mitochondrial dysfunction [1] should be considered and possibly studied in the future.…”

“…Painful muscle spasms and spasticity have been reported in 11–15% of FA cases as part of the symptomatology [2]. Unfortunately, the pathophysiological characteristics of muscle spasms in FA are not well explored and understood, while effective treatment options are lacking [3].…”

“…It is an autosomal recessive disease which, in its typical form, presents in patients younger than 20 years old, with ataxia, weakness, lower limb areflexia, extensor plantar response, decreased vibratory sensation and dysarthria. It can potentially lead to cardiomyopathy and diabetes [2]. In the past, FA was a clinical diagnosis; however, nowadays it is documented through a specific genetic mutation of the frataxin gene [1].…”

Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms

“…The major neurological manifestations include limb and gait ataxia, dysarthria, and pyramidal signs. Spasticity and painful spasms have been reported in up to 15% of patients with FA [2]. …”