Camptocormia as a Novel Phenotype in a Heterozygous POLG2 Mutation

Abstract

Mitochondrial dysfunction is known to play a key role in the pathophysiological pathway of neurodegenerative disorders. Nuclear-encoded proteins are involved in mtDNA replication, including DNA polymerase gamma, which is the only known replicative mtDNA polymerase, encoded by nuclear genes Polymerase gamma 1 (POLG) and Polymerase gamma 2 (POLG2). POLG mutations are well-known as a frequent cause of mitochondrial myopathies of nuclear origin. However, only rare descriptions of POLG2 mutations leading to mitochondriopathies exist. Here we describe a 68-year-old woman presenting with a 20-year history of camptocormia, mild proximal weakness, and moderate CK increase. Muscle histology showed COX-negative fibres. Genetic analysis by next generation sequencing revealed an already reported heterozygous c.1192-8_1207dup24 mutation in the POLG2 gene. This is the first report on a POLG2 mutation leading to camptocormia as the main clinical phenotype, extending the phenotypic spectrum of POLG2 associated diseases. This underlines the broad phenotypic spectrum found in mitochondrial diseases, especially in mitochondrial disorders of nuclear origin.

From Collar to Coccyx: Truncal Movement Disorders: A Clinical Review

“…Pleurothotonus or Pisa Syndrome is defined as >10 lateral spinal flexion on standing, relieved almost completely by passive mobilization or supine positioning, especially common in multiple system atrophy (MSA). 31,43 Approximately 10% of PD patients will also develop Pisa syndrome, with DA use being a risk factor. Tardive pleurothotonus is commonly described, and rarely can it be an isolated phenomenon without discernible cause.…”