Introduction
Muscle weakness in myotonic dystrophy type 1 (DM1) typically occurs in distal upper and lower limbs, neck and face muscles. Bulbar and respiratory muscle weakness evolves gradually. Proximal muscle weakness in the arms or shoulder girdle weakness may arise later in the disease and generally remains less pronounced than distal muscle weakness. Early pronounced involvement of the proximal muscles in DM1 has only rarely been reported [
1‐
4].
Similarly, scapular winging has received only little attention in DM1 [
5‐
7]. Scapular winging is one of the manifestations of scapular dyskinesis which refers to the alteration of the position and motion of the scapula, secondary to weakness or discoordination of the serratus anterior muscle and other scapular fixators [
8]. It thus points to a scapular dyskinetic motor profile and not to a movement disorder caused by a central nervous system disease. This dyskinesis results in an abnormal scapulohumeral rhythm in all three planes (Supplemental Fig. 1 and 2). Hamano et al. reported two members of the same family with adult-onset DM1 and scapular winging. On muscle MRI, marked atrophy of the serratus anterior and latissimus dorsi muscle was seen in both [
5]. In the patient reported by Masciullo et al., scapular winging was associated with the coexistence of FSHD1 [
6]. In the fourth patient, DM1 was suspected because of the positive family history in spite of the atypical presentation with scapular winging [
7]. These reports call for further research into the prevalence, features and pathophysiology of scapular dyskinesis in DM1.
We, therefore, performed a prospective cohort study of 33 patients with DM1 and pronounced, mostly asymmetric, abnormal scapular position and motion with more pronounced proximal than distal weakness. We systematically assessed DM1 severity and characteristics, shoulder girdle strength, maximal range of shoulder abduction and forward flexion, and evaluated the progression over time. The type of scapular dyskinesis was retrospectively classified [
8]. All patients were genetically tested for FSHD1, nine were tested for myotonic dystrophy type 2 (DM2), and in seven patients, the D4Z4 methylation was assessed, with subsequent sequencing of
SMCHD1 when appropriate. This study is expected to improve the recognition and understanding of shoulder girdle involvement in DM1, which eventually will contribute to better management of these patients.
Discussion
We here report the clinical features and progression over time of 33 patients with DM1 and pronounced, mostly asymmetrical scapular dyskinesis resulting from shoulder girdle weakness or discoordination of the scapular fixator muscles or both. This occurred in all subtypes of DM1 (from congenital to late onset), either as an early manifestation or later in the disease course. Genetic studies showed a concomitant FSHD1 mutation (D4Z4 repeat of 8–10 units) in 3 of 33 patients, and reduced methylation of the D4Z4 repeat (delta1: − 35) in 1 of 9 patients tested; however, in absence of a
SMCHDH1 mutation, therefore, excluding FSHD2. We conclude that shoulder girdle weakness with scapular dyskinesis is an inherent feature of DM1 in a small subset of patients. This study thus confirms the previous reports in single cases [
5,
7].
The DM1 patients with scapular dyskinesis were mildly to severely affected (MIRS 2:
n = 1; MIRS 3:
n = 2; MIRS 4:
n = 17; MIRS 5:
n = 11) and had otherwise typical DM1 features. The mean MIRS score at last evaluation was 4.2. We observed symmetrical facial weakness in 97%, dysarthria in 48%, respiratory muscle weakness for which non-invasive ventilation was required in 47%, and cardiac conduction defects leading to pacemaker use in 30%. Overall, these severity parameters are above the mean severity scores reported in an adult DM1 population (and in the registry cohort) [
16].
The retrospective evaluation of successive photographs and videos of 21 patients shed light on the abnormal position and motion of the scapula. Most patients showed a type 3 scapular dyskinesis (superior translation), some with overactivation of rhomboids, levator scapulae and minor pectoral muscles, which is likely to increase the tendency for anterior tilt, downward rotation, and internal rotation of the scapula. Recruitment of serratus anterior and trapezius descendens seemed very limited and decreased over time, disabling the scapula in stabilizing in posterior tilt, upward rotation and external rotation. This subsequently causes an increase in scapular dyskinesis. This pattern is very similar to our observations in FSHD patients. The scapular dyskinesis was in all cases associated with a progressive reduction of range of motion of shoulder abduction and forward flexion.
The systematic assessment of shoulder girdle strength and function which has been performed in IM from 2000 to 2017 enables a rough speculation of the scapular dyskinesis in DM1: 30 patients among a population of 900 patients suggests a prevalence of 3%. This might be an underestimation since only patients with more proximal than distal weakness were included, whereas scapular dyskinesis may also occur in patients with pronounced distal weakness. Furthermore, patients with scapular dyskinesis type 1 with still shoulder abduction MRC > 3 were not included either. The three cases detected in the Netherlands in 2015–2017 confirm the existence of this manifestation in another population.
The recognition of this DM1 phenotype, although rare, is important for timely management since clinicians might neglect the testing of muscles that are not considered to be typically involved in a specific disease. Similarly, patients might fail to report the limitation in shoulder movements since they consider it part of their muscle disease. Furthermore, one patient was initially misdiagnosed with FSHD by a neurologist specialized in neuromuscular diseases. Only after genetic testing, FSHD was excluded leading to consider the DM1 diagnosis. In five patients the scapular dyskinesis was the presenting symptom, and in all other patients it developed after DM1 was diagnosed, with a mean disease duration of 11 years. This underlines the importance of shoulder girdle function testing in all DM1 patients on annual checkup.
Patients with winging report diffuse neck, shoulder girdle, and upper back pain, which may be debilitating, associated with abduction and overhead activities [
17]. First, it is important to differentiate between patients that show scapular dyskinesis as a consequence of muscle weakness and patients that show disorganization of activation in scapular stabilizers. The latter group may be treated with motor control therapy, which would enable them to relearn correct activation patterns [
18]. This training is expected to improve the stabilization of the scapula on the thoracic wall and possibly protecting the re-activated musculature against accelerated dystrophy due to inactivity. Furthermore, scapular dyskinesis due to muscle weakness of the scapular fixators is most obvious during active movements and is usually absent at rest [
19]. Furthermore, decreased shoulder abduction and forward flexion can also be caused by weakness of the axial muscles. In these patients presenting with camptocormia, symmetrical scapular dyskinesis and a limitation of shoulder abduction and forward flexion, support of paraspinal muscles (by lying down or sitting straight on a chair with backrest) reduces the limitations in shoulder movements and resolves scapular dyskinesis. This makes postural therapy a viable option to explore in further research.
At the onset of this study, we had different hypothesis on the causes of shoulder girdle involvement. The first hypothesis, coexistence of DM1 and FSHD1, was based on the fact that the two diseases are the two most common inherited myopathies in adulthood and were simultaneously detected in one of the previous case reports [
6]. We tested all patients, and only in three patients (1, 2 and 3; 9%) FSHD1 was genetically confirmed. Remarkably, all three had a D4Z4 repeat size (8–10 units) that is found in the normal population with a frequency of 1–3% [
20,
21]. Therefore, this finding might as well be coincidental. A second hypothesis, coexistence of DM1 and DM2 was also rejected based on negative genetic testing for DM2 in nine patients.
To look for other explanations and, additional genetic analysis was performed based on the clinical similarity with FSHD. FSHD2, which is the cause of FSHD in less than 5% of the patients [
13], was excluded by D4Z4 CpG methylation analysis in eight out of nine patients. In only one patient, we found D4Z4 hypomethylation and a permissive 4qA allele, but without identifying a pathogenic SMCHD1 variant [
14]. Hence, the hypothesis of a FSHD2 mutation or D4Z4 hypomethylation otherwise as explanation for scapular dyskinesis in DM1 seems unlikely based on these results, but remains to be rejected in a larger group of patients. Together, these findings suggest that the molecular mechanism is independent of the known FSHD pathophysiology in most patients.
There are a number of limitations. First, DNA samples were unavailable in four patients. This limited the screening for FSHD1 and 2, and DM2, which should be part of diagnostic analysis in all DM1 patients with pronounced shoulder girdle weakness or scapular dyskinesis who do not have a D4Z4 repeat contraction. Second, we have taken only subsequent photographs in most patients, while videos would have enabled a more accurate assessment of scapular dyskinesis. Our preferred next research step would, therefore, be a comparative trial on the effect of targeted physical therapy on scapular dyskinesis in both DM1 and FSHD patients, including quantitative clinical assessment and imaging (MRI or muscle ultrasound) before and after treatment [
22,
23]. Furthermore, such study will allow estimating the prevalence of this condition.
In short, this study demonstrates that scapular dyskinesis resulting from shoulder girdle weakness or altered coordination or both occurs in a subgroup of DM1 patients. Although coexistence of FSHD1 needs to be excluded, scapular dyskinesis is inherent to DM1 in most patients, independent of the DM1 type. This knowledge is essential for adequate management.