SCA2 presenting as an ataxia-parkinsonism-motor neuron disease syndrome

Abstract

The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national). All subjects were provided with the approved informed consent. Spinocerebellar ataxia type 2 (SCA2) is characterized by progressive cerebellar ataxia, slow saccadic eye movements and peripheral neuropathy. Atypical SCA2 phenotypes with prominent dementia, an amyotrophic lateral sclerosis-like presentation, and levodopa-responsive parkinsonism are also encountered 1 . The definite diagnosis of SCA2 is based on clinical symptoms and molecular genetic testing to detect an abnormal CAG trinucleotide repeat expansion of the ATXN2 gene on chromosome 12q1 . The protein synthesized by ATXN2 is known as ataxin-2 that is involved in RNA metabolism and translation regulation 1 . Herein we report an unusual case of SCA2 presenting as an ataxia-parkinsonism-motor neuron disease (MND) syndrome. CASEA 46-year-old Brazilian man of Italian ancestry, presented for consultation because of progressive gait instability and muscle cramps that started 18 months before. He also developed rapidly progressive muscle weakness few months before his first appointment. His family history revealed affected individuals (ataxia) within first and second generations. On neurological examination, there were mild dysarthria, slow saccades, mild limb and gait ataxia, parkinsonism, brisk reflexes and bilateral Babinski sign. He also presented muscle weakness in upper limbs, diffuse fasciculations and atrophy involving upper limbs, chest and face. Genetic testing confirmed the diagnosis of SCA2 with 40 CAG repeats. Brain magnetic resonance imaging (MRI) disclosed cerebellar and brainstem atrophy (Figure). Electroneuromyography showed denervation activity at rest, with fasciculation, fibrillation and positive sharp wave potentials in the bulbar, cervical, thoracic and lumbosacral regions. Nerve conduction studies showed normal sensory and motor nerve conduction velocities and reduced amplitudes of the motor potentials. We introduced riluzole 50 mg b.i.d. as treatment for amyotrophic lateral sclerosis (ALS). DISCUSSIONFew previous studies have described the association of SCA2 with MND. Infante et al.2 reported a case of a 61 years-old woman with SCA2 diagnosis who developed a levodopa-responsive parkinsonism after 6 months of the ataxia-onset of symptoms, but later on disease course Figure. Sagittal T 1 brain MRI disclosing cerebellar and brainstem atrophy. This imaging finding is frequently seen in SCA2.

Intermediate CAG Repeat Expansion in the ATXN2 Gene Is a Unique Genetic Risk Factor for ALS−A Systematic Review and Meta-Analysis of Observational Studies

“…Other mechanisms may also influence this comparison. For example, the co-occurrence of fALS with SCA2, or with Parkinson disease, would lead to non-diagnosis of ALS in fALS [72], [82], [83], thus underestimating the occurrence of the intermediate CAG repeats among familial ALS cases.…”

Neonatal SCA2 Presenting With Choreic Movements and Dystonia With Dystonic Jerks, Retinitis, Seizures, and Hypotonia

“…It is classically characterized by progressive cerebellar ataxia, slow saccadic eye movements, and peripheral neuropathy. The definitive diagnosis of SCA2 is based on genetic testing, when abnormal CAG trinucleotide repeat expansion of the ATXN2 gene is detected . CAG repeat extension is unstable in intergenerational transmission, showing a tendency to further expansion over successive generations.…”

“…Almost all types of movement disorders may be observed in SCAs. The most frequent extrapyramidal signs observed in SCA2 include parkinsonism and dystonia . However, there is no report of neonatal‐onset SCA2 presenting with choreic movements and dystonia with dystonic jerks.…”

“…Normal CAG alleles range from 15 to 32 repeats. The disease usually presents with adult‐onset progressive cerebellar ataxia, dysarthria, nystagmus, slow saccadic eye movements, and peripheral neuropathy . Childhood onset is uncommon and is frequently associated with larger triplet expansions (>100 repeats) and presents with multisystem involvement beyond the aforementioned neurologic symptoms, such as developmental delay, hypotonia, pigmentary retinopathy, seizures, dysphagia, and early death .…”

“…The disease usually presents with adult-onset progressive cerebellar ataxia, dysarthria, nystagmus, slow saccadic eye movements, and peripheral neuropathy. 1,2 Childhood onset is uncommon and is frequently associated with larger triplet expansions (>100 repeats) and presents with multisystem involvement beyond the aforementioned neurologic symptoms, such as developmental delay, hypotonia, pigmentary retinopathy, seizures, dysphagia, and early death. [3][4][5][6] Herein, we describe a patient with neonatal-onset SCA2 that presented with choreic movements and dystonia with dystonic jerks, retinitis, seizures, and hypotonia as prominent clinical features instead of ataxia, resembling a global encephalopathy.…”