Clinical, pathological and molecular characterization of a Limb-girdle muscular dystrophy type 2I(LGMD-2I) cohort (P5.452)

Objective: Description of the clinical, pathological and molecular characteristics of patients with LGMD-2I diagnosed in CHUC between 2004–2017 through revision of clinical processes. Background: LGMDs are rare hereditary muscular diseases with a high clinical and genetic heterogeneity. The autosomal recessive forms are the most common ones, accounting for 90% of cases. It is estimated that the subtype LGMD-2I (FKRP gene) is the third most frequent subtype. Until now there are very few studies of clinical and molecular characterization of this subpopulation of LGMD. Design/Methods: Retrospective cohort study Results: Our sample consists of 8 patients, with a mean age of 45.9 years, 37% of the female gender, with a mean follow-up period of 18.9 years. Parental consanguinity was identified in 75% of the cases. The mean age at onset of symptoms was 15.1 years. Seven patients underwent muscle biopsy, with a mean interval between the first symptoms and muscle biopsy of 8.3 years. The biopsy revealed a dystrophic pattern in 57% of the cases, and immunohistochemistry was normal in all cases. Molecular diagnosis was performed in all patients, and the mean time between onset of symptoms and molecular diagnosis was 16 years. The most frequent mutation identified was g.826C> A, present in 87.5% of patients. The most frequent initial phenotype was LGMD present in 75% of patients, with the remaining patients presenting as an isolated hyperckemia. During follow-up, 62.5% of the patients have a restrictive respiratory pattern and 37.5% developed dilated cardiomyopathy. The mean time to lose gait autonomy was 36 years and the mean CK concentration was 4382 mg/dL. Conclusions: The clinical characterization of LGMD subtypes is of major importance to increase the information on the progression and clinical characteristics of each of these conditions. It also helps to optimize the multidisciplinary care that these patients require. Study Supported by: not applicable Disclosure: Dr. Sousa has nothing to disclose. Dr. Varela has nothing to disclose. Dr. Matos has nothing to disclose. Dr. Geraldo has nothing to disclose. Dr. Rebelo has nothing to disclose. Dr. Negrao has nothing to disclose.