Investigating phenotypic variability patterns in myotonic dystrophy type 2 in a neuromuscular referral center retrospective cohort.

We aimed at investigating the presence of patterns that account for the phenotypic variability in a myotonic dystrophy type 2 (DM2) retrospective cohort at the Mass General Brigham Neuromuscular Centers. We collected the presence or absence of 23 clinical variables at symptom onset and diagnosis (n = 67 patients) and follow-up (n = 37 patients). We first identified set/s of variables (factors or cluster/s) representative of the large research data pool at onset by performing factor analyses, then assigned each patient to the cluster for which they had the highest computed total factor score. Twelve variables grouped into two distinct clusters that, based on their variable content, we named as proximal myotonic myopathy (PROMM)-DM2 or non-PROMM-DM2. Patients assigned to non-PROMM-DM2 more frequently had clinical myotonia and positive family history, and less frequently multiorgan involvement. Most patients (67.2 %) remained assigned to same cluster during disease course and 11 non-PROMM eventually transitioned to PROMM-DM2. Dyslipidemia and early cataracts (both in PROMM-DM2 cluster) were the earliest extramuscular manifestations that occurred during disease course and they accounted for the conversion of up to 8 out of 11 non-PROMM to PROMM converters. Identification of phenotypically homogeneous patient subgroups may help investigating DM2 prognosis and disease biomarkers in future prospective studies.