Anoctaminopathies: the least severe clinical forms are particularly frequent

Anotacmin-5, also called TMEM16, is a transmembrane protein encoded by the ANO5 gene. Dominant mutations of this gene are responsible for a developmental anomaly (gnathodiaphyseal dysplasia), whereas recessive mutations are responsible for muscular degeneration of varying severity. This can be summarised as a simple elevation of creatine phosphokinase (CPK) or lead to much more deficient distal myopathy (overlaps with Miyoshi myopathy) or Limb Girdle Muscular Dystrophy (LGMD 2L, according to the current international nomenclature). The pathophysiology of these disorders is still poorly understood, with anoctamine-5 playing a role in the production of ion channels, but also in the processes of fusion and membrane repair.

In an article published in February 2017, researchers at the Institute of Myology describe the clinical and paraclinical data of a large cohort of patients in whom recessive mutations of the ANO5 gene have been demonstrated using high-throughput sequencing in a panel of genes. Twenty patients out of the thirty-eight studied had no known muscle deficiency but a simple elevation of CPK (on average about five times the normal), combined or not with myalgia or stress intolerance. The onset of symptoms was generally after 20 years of age. Cardiac muscle is rarely affected in this form of neuromuscular disease. The authors believe that abnormalities in the ANO5 gene may be a frequent cause of isolated hyperCKemia.

Papadopoulos C, Laforêt P, Nectoux J,. Hyperckemia and myalgia are common presentations of anoctamin-5-related myopathy in French patients. Muscle Nerve. 2017 Feb 10. doi: 10.1002/mus.25608. [Epub ahead of print]