No relevant excess prevalence of myotonic dystrophy type 2 in patients with suspected fibromyalgia syndrome

Highlights

• Myotonic dystrophy type 2 (DM2) was established in only one out of 398 patients with suspected fibromyalgia (FMS).

• This is not considered to be a relevantly excessive prevalence of DM2 in patients with suspected FMS.

• This implies that patients with suspected FMS should not routinely be tested for DM2.

• The DM2 patient had slight proximal weakness, but no cataract, clinical myotonia or elevated creatin kinase.

• This case demonstrates once again how difficult it can be to establish DM2 as the diagnosis.

Abstract

Myotonic dystrophy type 2 (DM2) is a rare, autosomal dominant, multisystem disorder with proximal weakness, myotonia, pain and cataract as important symptoms. Given the assumed underreporting of DM2 in the Netherlands combined with the predominant role of pain in DM2 as well as in fibromyalgia syndrome (FMS), we hypothesized there will be an excess prevalence of DM2 in patients with (suspected) FMS. Our objective was to determine the prevalence of DM2 in patients with suspected FMS. A prevalence of 2% was considered a relevant excess frequency.

Between November 2011 and April 2014, 398 patients with suspected FMS who had been assessed by a rheumatologist participated in this cross-sectional study. 95% of the study population was female, with a mean age of 42 years. The final ICD-9 diagnoses were collected, in 96% the diagnosis was FMS. 92% met the 2010 American College of Rheumatology (ACR) diagnostic criteria for FMS. A questionnaire including neuromuscular symptoms was completed. Creatine kinase was determined, and genetic testing for DM2 was conducted in all patients. DM2 was established in only one patient (0.25%, 95% CI 0.04–1.4%), thus disapproving our hypothesis of a relevant prevalence of 2%. Our results suggest that patients with suspected FMS should not routinely be tested for DM2.

Introduction

Myotonic dystrophy type 2 (DM2) is a rare, dominantly inherited multisystem disorder, with proximal limb weakness, myotonia, pain, and cataract as the core clinical features [1], [2]. It is caused by an unstable CCTG repeat expansion in the CNBP (formerly ZNF9) gene on chromosome 3q21.3 [3]. Confirming the diagnosis by genetic testing is important for both genetic counselling as well as for cardiac monitoring because cardiac arrhythmias are common and may be prevented by implantation of a pacemaker [4].

DM2 seems to be underreported in the Netherlands. There are only 45 known genetically proven DM2 patients from 17 different families (16,600,000 Dutch inhabitants, a prevalence of 1:370,000). This contrasts with an estimated prevalence in Germany of 1:20,000 and even 1:1830 in Finland [5], [6]. DM2 is difficult to recognize, not only due to the unfamiliarity with the disorder by most clinicians but also because of the heterogeneous phenotype and the rather aspecific onset [2], [7]. The average delay between onset of symptoms and genetic confirmation of DM2 is 14 years [8].

DM2 shows some remarkable clinical similarities to fibromyalgia syndrome (FMS). FMS is a chronic disorder with an estimated prevalence of 2%, characterized by generalized musculoskeletal pain, and fatigue, and often with various associated symptoms [9], [10]. Striking similarities between the two conditions are widespread fluctuating pain, a high frequency of fatigue and gastrointestinal symptoms [2], [10], [11], [12], [13], [14], [15]. 4.4% of the Dutch DM2 patients were formerly diagnosed with FMS (unpublished data). In addition, a Finnish study reported that 2 out of 63 (3%) FMS patients had underlying DM2 as the explanation for their complaints [16]. We therefore hypothesized that there will be an excess frequency of DM2 in patients with suspected FMS.