Thesis defense Judith van Vliet (Donders series 378)

15 May 2019

Myotonic dystrophy type 2 The challenging diagnosis of a complex disease

Myotonic dystrophy type 2 (DM2) is a rare, dominantly inherited, multisystem disorder, typically presenting in adult life. Core clinical features are proximal muscle weakness, pain, myotonia and early-onset cataract. Other characteristics are sleep disturbances and involvement of the heart and endocrine system. The phenotype of DM2 is highly variable. The clinical features show some striking similarities to fibromyalgia syndrome (FMS), a common disorder with widespread pain. The aim of this thesis was to broaden our knowledge about epidemiological aspects and the phenotype of DM2; not only to get a better understanding of its complicated pathophysiology, but also to be able to shorten the diagnostic delay and to improve symptomatic management.

In the first part, we established the DM2 mutation in only one patient of almost 400 examined patients with suspected fibromyalgia. This was not considered as a relevant excess prevalence, and therefore we do not recommend to routinely test the DM2 mutation in patients with suspected FMS. Also, abnormal creatine kinase and thyroid stimulating hormone values were rare in patients with suspected FMS and did not result in alternative diagnosis.

In the second part, we focused on the multisystem aspects of DM2. The prevalence of pain was 65% in patients with DM2. The severity of pain was significantly correlated to several aspects of health-related quality of life. Quantitative sensory testing demonstrated the presence of generalized hyperalgesia in DM2. Gastrointestinal dysfunction was found to be common in patients with DM2, with a high frequency of abdominal pain and constipation. Also, mild dysphagia was demonstrated in patients with DM2, generally not leading to aspiration pneumonia or short weight. Finally, sensorineural hearing impairment was established as a feature of DM2, resembling early presbycusis. The results are discussed in the third part and a proposed flowchart of aid is presented on when to consider DM2 as diagnosis.