Neuropediatrics 2017; 48(04): 282-293
DOI: 10.1055/s-0037-1603518
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Hereditary Neuropathies: Update 2017

Sabine Rudnik-Schöneborn
1  Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria
Michaela Auer-Grumbach
2  Department of Orthopaedics, Medical University of Vienna, Vienna, Austria
Jan Senderek
3  Friedrich-Baur-Institut, LMU Munich, Munich, Germany
› Author Affiliations
Further Information

Publication History

06 April 2017

12 April 2017

Publication Date:
08 June 2017 (online)


Hereditary neuropathy is an umbrella term for a group of nonsyndromic conditions with a prevalence of approximately 1:2,500. In addition to the most frequent form, Charcot–Marie–Tooth's disease (CMT, or hereditary motor and sensory neuropathy), there are additional entities such as hereditary neuropathy with liability to pressure palsies (HNPP), hereditary motor neuropathies (HMNs), and hereditary sensory and autonomic neuropathies (HSANs). With the exception of HNPP, which is almost always caused by defects of the PMP22 gene, all other forms show genetic heterogeneity with altogether close to 100 genes involved. Mutation detection rates vary considerably, reaching up to 80% in demyelinating CMT (CMT1) but are still as low as 10 to 30% in axonal CMT (CMT2), HMN, and HSAN. Based on current information, analysis of only four genes (PMP22, GJB1, MPZ, MFN2) identifies 80 to 90% of CMT-causing mutations that can be detected in all known disease genes. For the remaining patients, parallel analysis of multiple neuropathy genes using next-generation sequencing is now replacing phenotype-oriented multistep gene-by-gene sequencing. Such approaches tend to generate a wealth of genetic information that requires comprehensive evaluation of the pathogenic relevance of identified variants. In this review, we present current classification systems, specific phenotypic clues, and genetic testing algorithms in the different subgroups of hereditary neuropathies.