Clinical and histopathological findings in myotonic muscular dystrophy type 2 (DM2): retrospective review of 49 DNA-confirmed cases (P1.124)

Objective: To review the clinical and histopathologic findings in a cohort of 49 DNA-confirmed myotonic dystrophy type 2 (DM2) patients from a tertiary neuromuscular center over a 24-year period. Background: DM2 is a rare and slowly progressive autosomal dominant myopathy due to a repeat expansion (CCTG)n in intron 1 of the CNBP gene at 3q21. Focused study on a US-based population is limited. Design/Methods: We reviewed the clinical presentation, muscle strength grading by MRC, Jamar hand grip dynamometry, electromyography (EMG), creatine kinase (CK) values, forced vital capacity (FVC), muscle histopathology, CCTG repeat expansion (bp) size for DM2 patients from 1992 to 2015. Muscle histopathology was graded based on myofiber size variability, internal nucleation, pyknotic nuclear clumps, necrosis, myofiber hypertrophy and atrophy. Results: Forty-nine patients, ages 15–72 years (48.29 ± 13.1), were evaluated. Twenty-six (54%) patients were men. Eleven patients had no weakness and 16 patients had severe weakness. Proximal lower extremity weakness was the most common presenting symptom, and hip flexors were the most frequently and severely affected muscle group. Knee extensor and elbow extensor involvement was common. Nine patients (18%) had clinical myotonia and 35 (71%) had myotonia on EMG. Grip forces ranged from 68.9–435.9 N (255.4 ± 99.6 N, n=27), FVC (% predicted) ranged from 36–100% (80.7 ± 18.2%, n=31) and CK values ranged 20–2000 units/L (581.7 ± 449.3, n= 36). Other findings included cataracts in 23 (47%), diabetes in 11 (22%), hypothyroidism in 8 (16%), hearing loss in 7 (14%), and cardiac arrhythmia in 5 (10%) patients. Correlation was low or negligible between CCTG repeat size (bp) and age of onset, muscle strength, CK values, and histopathology composite score. We noted significant correlation of severity of histopathology with weakness. Conclusions: This large cohort of DM2, evaluated over a 24-year-period in a single center, showed variation in clinical presentation and disease severity. Study Supported by: None applicable. Disclosure: Dr. Roy has nothing to disclose. Dr. Wu has nothing to disclose. Dr. Whitaker has nothing to disclose. Dr. Felice has nothing to disclose.