Clinical Information

Inherited peripheral neuropathies are common neurologic disorders that represent a spectrum of diseases with different etiologies. Based on the pattern of inheritance and nerve conduction studies, there are 3 major categories of inherited peripheral neuropathies with isolated nerve involvement. The first group is hereditary motor and sensory neuropathy, also referred to as Charcot-Marie-Tooth (CMT) disease. Individuals with CMT typically present with slowly progressive muscle weakness and atrophy, primarily affecting the distal extremities. The second group is hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy if autonomic dysfunction is absent. They predominantly feature slowly progressive loss of multimodal sensation and autonomic dysfunction, with the most common features of HSANs being the loss of sensation of pain and temperature. The third group is distal hereditary motor neuropathy, which is characterized by length-dependent lower motor neuron dysfunction. The clinical phenotype is variable but includes progressive weakness and atrophy of the distal muscles, foot deformities, and decreased reflexes. Inherited peripheral neuropathies may also show involvement of the central nervous system (brain or spinal cord), as seen in hereditary spastic paraplegia with neuropathy, or they may be part of a systemic syndromic or metabolic disorder.

The inherited peripheral neuropathies are a relatively common and heterogeneous group of disorders. Due to the considerable overlap in the clinical phenotypes of various neuropathies, it is often difficult to distinguish these specific inherited disorders from sporadic, idiopathic, or acquired forms of neuropathy without genetic testing. Additionally, peripheral neuropathy may be part of an inherited systemic syndromic or metabolic disorder caused by genes in metabolic pathways. Therefore, multigene panels can be an efficient and cost-effective way to establish a molecular diagnosis for individuals with peripheral neuropathy.