Objective: To describe a rare case of rapidly progressive generalized dystonia parkinsonism due to FBXO7 gene mutation.

Background: Parkinson’s disease is a neurodegenerative disorder of usual onset after 60 years, with 18 genetic loci and 13 disease related genes been identified. FBXO 7 gene mutation associated Parkinsonian Pyramidal syndrome is very rare cause of early onset rapidly progressive parkinsonism with dystonia.

Method: 21 year male presented with acute change in speech and facial appearance with severe dysarthria, hypomimia, reduced eye blinking leading to red eyes. Opthalmology consult was first sought by the family where he was found to have dry eyes. The ophthalmologist suspected a depressive disorder and he was referred to psychiatrist. He was treated with escitalopram, clonazepam and quetiapine.  He developed symmetric rigid syndrome with hypomimia and tongue and chin tremor with no response to levodopa. Subsequently over the next 3 months, he developed severe generalised symmetric akinetic rigid syndrome followed by severe cervical dystonia followed by lower limb dystonia. Over the next 4 months , he developed severe generalised dystonia parkinsonism making him bed bound and requiring nasogastric tube for feeding. Over the next 2 months, he became mute and bed bound and subsequently succumbed to illness. He had no response to levodopa, dopa-agonists, trihexiphenydl, clonazepam, amantidine. methyl prednisolone.

Results: His MRI brain; serum copper[ free and total], ceruloplasmin, thyroid peroxidase [TPO] antibody, thyroid stimulating immunoglobulin, anti-GAD antibody, ammonia,  CSF for cell count, gram stain, oligoclonal bands, flowcytometry, cytology, HSV 1/2 PCR, bacterial culture HIV, VDRL, EEG, autoimmune and paraneoplastic antibody panel was negative. Whole genome sequencing panel was suggestive of heterozygous pathogenic mutation in FBXO 7 gene on chromosome 22q12-q13.

Conclusion: Deleterious FBXO 7 gene mutations are responsible for an autosomal recessive rapid onset dystonia parkinsonism. This is the first reported case of FBOX7 gene mutation associated dystonia parkinsonism from India.

References: 1. Kirk R, Laman H, Knowles PP, et al. Structure of a conserved dimerization domain within the F-box protein Fbxo7 and the PI31 proteasome inhibitor. J Biol Chem. 2008;283(32):22325-22335 2. Luo LZ, Xu Q, Guo JF, et al. FBXO7 gene mutations may be rare in Chinese earlyonset Parkinsonism patients. Neurosci Lett. 2010;482(2):86-89. 3. Di Fonzo A, Dekker MC, Montagna P, et al. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology. 2009; 72(3):240-245. 4. Schneider SA, Bhatia KP, Hardy J. Complicated recessive dystonia parkinsonism syndromes. Mov Disord. 2009;24(4):490-499

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/rapidly-onset-progressive-generalised-dystonia-parkinsonism-in-a-young-indian-male-with-rare-fbxo-7-genetic-mutation/