Objective: To describe a case of parkinsonian syndrome associated to C9Orf72 expansion followed by ALS development

Background: C9Orf72 expansions are known to be the most familial frequent cause of FTD and ALS. It has also been associated with movement disorders, as HD phenocopy, but also atypical Parkinsonism. These last patients have predominantly been described as suffering from hypokinetic-rigid syndrome without tremor, in association with upper motor neuron signs, cognitive dysfunction and psyquiatric syndromes among others. Previous references are found in literature, but not many cases have been described of the coexistence of parkinsonian syndrome followed by ALS

Method: 63 y.o woman consulted complaining about slowness of movements for the previous eight months. She was suffering from instability and gait disorder. She had recently been diagnosed with major depression. She had primary hypothyroidism treated with levothyroxine and seasonal asthma. No other personal history or treatment was recorded. She had an interesting family history. Her father, two aunts on her father’s side and one brother had died from ALS. Her sister was being studied for a speech disorder with suspicion of bulbar ALS. Her physical examination showed normal cranial nerves, sensitivity, strength, trophism and coordination. Her tendon reflexes were universally brisk. Plantar reflexes were flexor. It also showed moderate hypophonia and hypomimia, mild rigidity in both left limbs, moderate bradykinesia in all four limbs, moderate slowness arising from chair, global akinesia, no resting or postural tremor, pull test was normal. Her gait was slow with decreased arm swing, hight and length of steps.

Results: A complete laboratory analysis was performed finding no metabolic, vitamin, antibodies or serology alterations. Cranial MRI and DATSCAN were normal.  A test for C9Orf72 was requested for her and her sister, finding pathological number of repetitions of hexanucleotid in both. Six months after first visit she complained about weakness in upper limbs and exam confirmed mild atrophy of both of them. An electromyography was performed, and found denervation and active reinnervation in all explored muscles including bulbar and paraspinal.

Conclusion: Family history was the clue of diagnosing this patient even before she developed lower motor signs. We ought to keep in mind C9Orf72 expansions as possible cause of atypical Parkinsonism in the presence of family history of ALS or FTD

References: 1. CarloWilke. Hohn K Pomper Saskia Bisku Cornelia Puskás Daniela Berg, Matthis Synofzik. Atypical parkinsonism in C9Orf72 expansions: a case report and systematic review of 45 cases from literature J Neurol, 2016 Mar;263(3):558-74. doi: 10.1007/s00415-016-8021-7. Epub 2016 Jan 25 2. Cooper-Knock J, Frolov A, Highley JR, et al. C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study. Neurology. 2013;81(9):808-11. 3. Dejesus-Hernandez M, Rayaprolu S, Soto-Ortolaza AI, et al. Analysis of the C9orf72 repeat in Parkinson’s disease, essential tremor and restless legs syndrome. Parkinsonism Relat Disord. 2012;19(2):198-201

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsonian-syndrome-associated-to-c9orf72-expansion/