Peripheral neuropathy in hereditary spastic paraplegia caused by REEP1 variants
- 106 Downloads
SPG31 is a hereditary spastic paraplegia (HSP) caused by pathogenic variants in the REEP1 gene. The phenotype (SPG31) has occasionally been described with peripheral nervous system involvement, in additional to the gradually progressing lower limb spasticity that characterizes HSP. The objective of this study was to characterize patients with pathogenic REEP1 variants and neurophysiologically assess the extent of peripheral nerve involvement in this patient group. Thirty-eight index cases were molecular-genetically tested, yielding two previously reported pathogenic REEP1 variants and a novel missense variant, in a total of four index patients. Three of four probands and five additional family members underwent nerve conduction studies, electromyography, quantitative sensory testing, and examination of the autonomic nervous system. None of the examined patients had completely unremarkable results of peripheral nerve studies. Most showed electrophysiological signs of carpal tunnel syndrome, and one patient demonstrated a multifocal compression neuropathy. Autonomic testing revealed no severe dysfunction, and findings were limited to adrenergic function. HSP caused by pathogenic REEP1 variants may be accompanied by a generally mild and subclinical polyneuropathy with a predisposition to compression neuropathy, and should be considered in such cases.
KeywordsHereditary spastic paraplegia REEP1 SPG31 Nerve conduction studies Polyneuropathy Carpal tunnel syndrome
The study was supported by Ludvig and Sara Elsass Foundation and the Novo Nordisk Foundation.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no competing interests.
- 9.Rosenfalck P, Rosenfalck A (1975) Electromyography—sensory and motor conduction. Findings in normal subjects. Publications from the Laboratory of Clinical Neurophysiology, CopenhagenGoogle Scholar
- 13.Novak P (2011) Quantitative autonomic testing. J Vis Exp 19(53):2502Google Scholar
- 14.Sletten D, Grandinetti A, Weigand S et al (2015) Normative values for sudomotor axon reflex testing using QSWEAT™. Neurology 84(14 Suppl.):P1.282Google Scholar
- 18.Campbell WW, Carroll DJ, Greenberg MK et al (1999) Practice parameter for electrodiagnostic studies in ulnar neuropathy at the elbow: American Academy of Electrodiagnostic Medicine, American Academy of Neurology, American Academy of Physical Medicine and Rehabilitation. Muscle Nerve 22(suppl 8):S171–205Google Scholar
- 19.England JD, Gronseth GS, Franklin G (2005) Distal symmetric polyneuropathy: a definition for clinical research: report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 64(2):199–207CrossRefGoogle Scholar