Hereditary neuropathy with liability to pressure palsies and amyotrophic lateral sclerosis

Abstract

A 56-year-old male with recurrent painless focal neuropathies and a family history of peripheral neuropathy of unknown etiology presented with progressively worsening of impaired sensations and weakness in his lower extremities. His initial electrodiagnostic evaluation was suggestive of severe sensory and motor peripheral polyneuropathy. The genetic testing was performed for familial causes of peripheral neuropathy as there was a family history of peripheral neuropathy of unknown etiology. The patient was found to have 1.5-Mb deletion in the PMP22 gene which was confirmatory of hereditary neuropathy with liability to pressure palsies (HNPP). He developed progressive upper and lower extremity weakness, bulbar dysfunction and widespread fasciculations during the course of his illness. He was subsequently diagnosed with amyotrophic lateral sclerosis (ALS). This is the second reported case of HNPP associated with ALS. We discuss significant clinical and electrodiagnostic findings of this interesting case.

The Peripheral Nervous System in Amyotrophic Lateral Sclerosis: Opportunities for Translational Research

“…Recent evidence has challenged such traditional view of selective neuronal loss demonstrating widespread extra-motor involvement in ALS and implying that neuronal populations other than MNs may also be affected (Geser et al, 2008; Brettschneider et al, 2013; McCluskey et al, 2014). Furthermore, an expanded clinical spectrum has now been recognized, as overlapping phenotypes with other neuromuscular disorders (Sabatelli et al, 2016), including peripheral neuropathies, have been described (Rajabally and Jacob, 2008; Bhatt et al, 2009; Sawa et al, 2012). Although in clinical practice MNDs should be differentiated from other peripheral nervous system (PNS) disorders, sensory and autonomic neurons in the dorsal root ganglia (DRG) and lower MNs in the ventral horns share important challenges, as proper stability and functioning of their long projections throughout the body requires a protective environment and efficient communication between the central nervous system (CNS) and the outermost areas of these cells.…”

Fasciculations in human hereditary disease

“…Among hereditary neuropathies fasciculations were described in patients carrying mutations in the PMP22 gene [12], the MNF2 gene [13], the TKF-gene [14], and the TTR or gelsolin genes, the two latter are responsible for hereditary amyloid polyneuropathies [15.16]. In hereditary neuropathies fasciculations occur most frequently in limb muscles, except for familial amyloidosis in which also bulbar muscles can be affected.…”

Case of hereditary neuropathy with liability to pressure palsies presenting progressive muscular atrophy with lower motor neuron degeneration in the spinal cord and the brainstem

“…There are two cases of HNPP with cranial nerve involvements, but without PMA: a 40‐year‐old female case of HNPP with the involvement of the trigeminal, facial and hypoglossal nerves, and a case of 7‐year‐old boy having a homozygous deletion of PMP22 , who had the LMN impairment in the cranial nerves of VII and III, sensory disturbance in extremities . Additionally, three cases of patients with HNPP and ALS have been reported (Table ) . Compared with these cases, the presenting patient developed PMA symptoms more gradually without any upper motor neuron signs.…”

“…PMP22 is a myelin protein that regulates proliferation and apoptosis of Schwann cells that form compact myelin . Although three cases of HNPP with amyotrophic lateral sclerosis (ALS) have been reported, little is known about the role of PMP22 in the central nervous system (CNS) . Here, we report a case of HNPP with bulbar palsy and PMA in all extremities, associated with a deletion in the PMP22 gene.…”