TY - JOUR

T1 - Peripheral neuropathy in hereditary spastic paraplegia caused by REEP1 variants

AU - Toft, Anders

AU - Birk, Steffen

AU - Ballegaard, Martin

AU - Dunø, Morten

AU - Hjermind, Lena E

AU - Nielsen, Jørgen E

AU - Svenstrup, Kirsten

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Carpal Tunnel Syndrome/etiology

KW - Child

KW - Female

KW - Humans

KW - Male

KW - Membrane Transport Proteins/genetics

KW - Middle Aged

KW - Neural Conduction/physiology

KW - Pedigree

KW - Phenotype

KW - Polyneuropathies/etiology

KW - Spastic Paraplegia, Hereditary/complications

KW - Young Adult

U2 - 10.1007/s00415-019-09196-1

DO - 10.1007/s00415-019-09196-1

M3 - Journal article

C2 - 30637453

VL - 266

SP - 735

EP - 744

JO - Deutsche Zeitschrift fur Nervenheilkunde

JF - Deutsche Zeitschrift fur Nervenheilkunde

SN - 0939-1517

IS - 3

ER -