High prevalence of carpal tunnel syndrome in individuals with rare nerve growth factor-beta mutation.

Mikael Ridderström,Oumie Thorell,Theofilos Magounakis,Håkan Olausson,Saad S Nagi,Jan Minde,Mats Svantesson

doi:10.1093/braincomms/fcaa085

Abstract

In Sweden, a large family with a point mutation in the nerve growth factor-beta gene has previously been identified. The carriers of this mutation have reduced small-fibre density and selective deficits in deep pain and temperature modalities. The clinical findings in this population are described as hereditary sensory and autonomic neuropathy type V. The purpose of the current study was to investigate the prevalence of carpal tunnel syndrome in hereditary sensory and autonomic neuropathy type V based on clinical examinations and electrophysiological measurements. Furthermore, the cross-sectional area of the median nerve at the carpal tunnel inlet was measured with ultrasonography. Out of 52 known individuals heterozygous for the nerve growth factor-beta mutation in Sweden, 23 participated in the current study (12 males, 11 females; mean age 55 years; range 25–86 years). All participants answered a health questionnaire and underwent clinical examination followed by median nerve conduction study in a case–control design, and measurement of the nerve cross-sectional area with ultrasonography. The diagnosis of carpal tunnel syndrome was made based on consensus criteria using patient history and nerve conduction study. The prevalence of carpal tunnel syndrome in the hereditary sensory and autonomic neuropathy group was 35% or 52% depending on whether those individuals who had classic symptoms of carpal tunnel syndrome but negative nerve conduction studies were included or not. Those who had a high likelihood of carpal tunnel syndrome based on classic/probable patient history with positive nerve conduction study had a significantly larger median nerve cross-sectional area than those who had an unlikely patient history with negative nerve conduction study. The prevalence of carpal tunnel syndrome was 10–25 times higher in individuals heterozygous for the nerve growth factor-beta mutation than the general Swedish population. Further studies are needed to better understand the underlying pathophysiological mechanisms.

Highlights

Hereditary sensory and autonomic neuropathies are rare genetic conditions that can be classified into five subtypes (HSAN I to V) based on their mode of inheritance, natural history, pathology, biochemical and neurophysiological features, and degree of autonomic involvement (Dyck et al, 1983)
The aim of the current study was to determine the prevalence of carpal tunnel syndrome (CTS) in the heterozygous group, using the aforementioned consensus criteria (Rempel et al, 1998), and to measure the cross-sectional area (CSA) of the median nerve at the carpal tunnel inlet with ultrasonography
We found that individuals heterozygous for a point mutation in the nerve growth factor-beta (NGFB) gene resulting in HSANV have a very high prevalence of CTS

Summary

Introduction

Hereditary sensory and autonomic neuropathies are rare genetic conditions that can be classified into five subtypes (HSAN I to V) based on their mode of inheritance, natural history, pathology, biochemical and neurophysiological features, and degree of autonomic involvement (Dyck et al, 1983). We have previously identified a large family residing in northern Sweden with a condition best fitting the HSANV subtype (Minde et al, 2004). They have a point mutation in the gene encoding nerve growth factor-beta (NGFB) on chromosome 1p11.2-p13.2, and the pattern of inheritance is autosomal recessive (Einarsdottir et al, 2004). Heterozygous carriers – the focus of the current study – have milder symptoms than their homozygous counterparts, a moderate reduction in Aδ and C fibers in sural nerve biopsies, and the clinical picture ranges from asymptomatic cases to Charcot arthropathy starting in adult life (20 to 30-year-old in some cases) but is most common above 70 years (Minde et al, 2009). The prevalence of CTS in the general population in Sweden is estimated to be 2.1 to 3.6% (Atroshi et al, 1999)

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