Multiple system atrophy in a patient with primary ciliary dyskinesia

We present the case of a patient with primary ciliary dyskinesia who later developed clinically probable multiple system atrophy. Multiple system atrophy is a sporadic neurodegenerative disorder clinically characterised by various combinations of parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal sign. Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia and results in chronic bronchitis, bronchiectasis, chronic rhinosinusitis, chronic otitis media, situs inversus, and male infertility. Most of the causative genes for primary ciliary dyskinesia encode proteins that are part of the heavy or intermediate chain of axonemal dynein in ciliary outer dynein arms. We hypothesised that axonemal dynein dysfunction in primary ciliary dyskinesia results in reduced autophagy, accompanied by impaired cytoplasmic dynein function, which in turn accelerates -synucleinopathy in multiple system atrophy. Furthermore, we contemplated a potential association between primary cilia and neuronal function. Although it is not yet clear if a causal link between multiple system atrophy and primary ciliary dyskinesia exists, further investigation into the relationship between axonemal dynein dysfunction in primary ciliary dyskinesia and α-synucleinopathy should be conducted. Neurology Asia 2013; 18(1) : 103 – 105 Address correspondence to: Satoshi Yamashita, MD, PhD, Department of Neurology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. Tel.: +81-96-373-5893, Fax: +81-96-373-5895, E-mail: [email protected] INTRODUCTION Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder clinically characterised by any combination of parkinsonism and autonomic, cerebellar, and pyramidal signs. Pathologically, this disorder is defi ned by cell loss, gliosis, and glial cytoplasmic inclusions in several central nervous system structures. Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease of motile cilia that is clinically characterised by recurrent respiratory tract infections, male infertility, and randomisation of left–right body asymmetry. Patients with PCD show mutations in the heavy/intermediate chain of axonemal dynein. Here, we present a case study of a patient with PCD who later developed clinically probable MSA. We also discuss the possible association of axonemal dynein with MSA pathology.