Inherited Neuropathies

Abstract

The inherited neuropathies are a common and heterogeneous group of slowly progressive disorders affecting motor, sensory, and autonomic nerves. These hereditary conditions can be confined to the peripheral nervous system, termed the primary hereditary neuropathies, or can occur as part of a multisystem disease. Identification of systemic involvement is necessary to distinguish the primary and secondary hereditary neuropathies to prevent the misdiagnosis of potentially treatable entities. Recent genetic and technological advances have dramatically improved our understanding of the underlying pathophysiology of these inherited neuropathies and hence provide the correct milieu for the future development of disease-modifying therapies. This review provides clinical, neurophysiological, genetic, pathophysiological, and treatment insights into the primary inherited neuropathies, and those associated with multisystem diseases, including porphyria and mitochondrial disorders.

Current and future applications of ultrasound imaging in peripheral nerve disorders

“…CMT1B: In demyelinating CMT1B, due to mutations in Myelin Protein Zero (MPZ), the median and vagus nerve CSAs were enlarged compared to normal individuals[ 156 ]. However, across the spectrum of CMT caused by mutations in MPZ, which can cause a demyelinating (CMT1B), axonal (CMT2I/2J) or intermediate (CMTDID) phenotype[ 157 ], the CSA of only the demyelinating subgroup was found to be enlarged in the median and ulnar nerves, in particular at proximal nerve sites[ 158 ]. Similarly the C5 nerve root CSA was enlarged in both the demyelinating and intermediate groups[ 158 ].…”

“…CMT1X: CMT1X, the second most common form of CMT, is an X-linked intermediate CMT associated with mutations in gap junction-associated protein B1[ 157 ]. Initial reports, which evaluated median nerves to the mid forearm, did not find any significant differences between median nerve CSA and fascicle diameters in CMTX cohorts and healthy controls[ 27 , 150 ].…”

“…CMT2: CMT2 is a heterogenous group, with axonal neurophysiology, comprising of both autosomal dominant and recessive mutations in over 52 genes[ 157 ]. Axonal neuropathies are typically characterised by NMUS as having reduced or normal nerve dimensions, thought secondary to progressive axonal drop out[ 15 ].…”

Orphan Peripheral Neuropathies

“…For with oligogenic inheritance [10]. Additionally, NGS has a cost-depth trade-off [10], that is, it can screen a small number of genes with good read depth or a large number with less depth [10]. length-dependent, sensory-motor axonopathy [13].…”

“…Overview of orphan, complex hereditary neuropathieswith high variability between regions of investigation. According to a study from the UK, >90% of the CMTs are due to mutations in these four genes[10].These include HNPP, GAN, hereditary plexopathy, and the hereditary SFNs. With the exception of HNPP, which is due to duplications/deletions in PMP22 these neuropathies are very rare.Neuropathy may be also a feature in non-classified1133SCAs, such as those due to mutations in SETX[111].RFC1 was discovered as the cause of CANVAS [128].…”