Pragmatic Diagnosis of Hereditary Neuropathies

Hereditary neuropathies are a clinically and genetically heterogeneous groups of neuropathies. Among the hereditary neuropathies, those forms associated with sensory and motor symptoms (hereditary sensorimotor neuropathy, and HMSN, also known as Charcot-Marie-Tooth-disease, CMT) are the most common. With an incidence of 1: 2 500, they are among the group of orphan diseases. In the field of clinical neurology, they represent the most common neurogenetic disorder. However, there are also purely sensory forms, with or without autonomic symptoms (HSAN), or pure motor hereditary neuropathies (dMHN) as well as hereditary neuropathy with liability to pressure palsies (HNPP). In recent years, genetic testing has made enormous advances so that genetic testing is now an integral part of the diagnosis of patients with hereditary neuropathies. Both clinically and genetically extremely heterogeneous, the assignment of hereditary neuropathies is difficult with more than 80 potentially disease-causing genes. Nevertheless, over 90 % of all genetically assured CMTs are clarified by mutations in 4 genes (PMP22, Cx32, MPZ and MFN2). We present here a brief overview of hereditary neuropathies and a pragmatic guideline for molecular genetic diagnostics. In addition, we present and discuss possibilities of further diagnostics, which we believe should be done in specialized centers.