Hereditary Neuropathies

This article describes the clinical features, genetic causes, and diagnostic strategies of inherited peripheral neuropathies, and highlights how recent developments are reshaping the management of these disorders.

Multiple new genetic causes of hereditary neuropathies have been identified, deepening insight into peripheral nerve biology and enabling the first clinical trial targeting a recessive form of genetic neuropathy. Concurrent advances in next-generation sequencing have substantially improved diagnostic yield. In parallel, several disease-modifying therapeutic approaches are being evaluated in human studies. Progress in targeted therapies, particularly for familial amyloid neuropathy, provides a framework for the development of innovative treatments across the spectrum of genetic neuropathies.

Inherited peripheral neuropathies are among the most common genetic neuromuscular disorders worldwide, yet diagnosis remains challenging because of marked genetic and phenotypic heterogeneity. Charcot-Marie-Tooth disease is now linked to pathogenic variants in more than 100 genes encoding proteins essential for Schwann cell biology and peripheral axonal function. Additional inherited neuropathies present as multisystem disorders, including familial amyloid neuropathy and neuropathies associated with metabolic or other genetic conditions. Advances in sequencing technologies and refined genotype-phenotype correlations are transforming the diagnosis of inherited neuropathies.