Titinopathies

Abstract

In this issue of Neurology , Udd et al.1 add another chapter to the evolving story of titinopathies. Distinct titin mutations are known to cause dilated cardiomyopathy, but investigation of the skeletal muscle disease that is now also known to be a titinopathy dates back to the 1980s when a form of limb-girdle dystrophy was recognized in a multigeneration consanguineous family in the geographically isolated Larsmo archipelago off the west coast of Finland. All affected members proved to be descendants of the same ancestor parents born in the 17th century. By 1991, it became apparent that some members of the same family had a milder distal myopathy selectively affecting the anterior tibial muscles, although computed tomography showed focal fatty replacement in some proximal as well as distal muscles. Patients with limb-girdle weakness from the same family presented in the first decade and progressed over the next 20 years to wheelchair confinement whereas the tibial muscular dystrophy (TMD) variant presented in the third or fourth decade but progressed slowly. From these observations it was not possible to distinguish between the TMD and …