Background Myotonic dystrophy type 2 (DM2) is a dominantly inherited multiorgan disease caused by a CCTG repeat expansion within intron 1 of cellular nucleic acid-binding protein gene (CNBP). DM2 is likely underrecognized and often diagnosed years after patient’s first symptoms; this may be due to its variable or mild phenotype at onset. We aimed at investigating the existence of more than one DM2 phenotype at initial presentation and how different clinical patterns at onset evolve during the disease course.
Methods We reviewed the electronic medical records of 67 DM2 patients and collected the presence or absence of 23 clinical variables at onset, diagnosis, and last follow-up. Factor analysis and principal component analysis were performed to determine whether more than one set of interdependent variables (clusters) could be identified as distinct DM2 phenotype at onset. Fisher’s exact test and unpaired t-test were used to compare clinical features across identified phenotypes.
Results Two distinct DM2 phenotypes were identified at onset; classical and atypical. Classical DM2 phenotype was observed in 68.7% of patients in our cohort and was composed of proximal muscle weakness, cataracts, thyroid dysfunction, hypertension, diabetes, dyslipidemia, and benign tumors. Dyslipidemia, muscle weakness and cataracts were the clinical manifestations that appeared to occur early in the disease course. Atypical phenotype was composed of facial, neck and distal muscle weakness, alopecia, and white matter changes on brain MRI. Interestingly, patients with atypical phenotype less frequently had multiorgan involvement and more frequently had a positive family history for DM2 at onset. Most patients (69%) maintained same phenotypic pattern during the disease course.
Discussion In addition to a classical phenotype, we have identified an atypical DM2 phenotype at initial presentation that resembles that of a patient with myotonic dystrophy type 1. A DM2 diagnosis may be more easily missed in patients with atypical phenotype.