P109 - CARDIAC FEATURES OF HOMOZYGOUS LEMD2 MUTATION

Background: LEMD2 is an inner nuclear membrane protein involved in the organization of the nuclear envelope across different tissue types. Common pathogenic LEMD2 gene variants have been identified in the Hutterite population, manifesting as juvenile cataracts and a cardiomyopathy with distinct MRI features in homozygous individuals[1] referred to as Juvenile Onset Cataracts type 46 with or without Arrhythmic Cardiomyopathy (CTRCT46; OMIM 212500).

METHODS AND RESULTS: We conducted a case series on a subset of a previously established cohort[2] of 12 Hutterite individuals affected by CTRCT46, with one additional participant with a de novo diagnosis. We prospectively followed 11 patients for evidence of development and progression of myocardial involvement over a 7 year follow up between 2018 and 2025. Outcomes included new and worsening left ventricular (LV) systolic dysfunction, MRI evidence of scar progression, development of arrhythmias, initiation and response to pharmacologic therapies, implantable cardio-defibrillator (ICD) insertion and mortality.
Age ranged from 10 to 57 years old. Five patients developed new LV systolic dysfunction and were offered primary prevention ICD. The progression of LV dysfunction did not consistently correlate with the amount of delayed enhancement on MRI. One patient sustained recurrent episodes of ventricular tachycardia requiring ICD therapy. One patient developed profound peripartum worsening of baseline cardiomyopathy. Three patients exhibited MRI findings of new or progressive delayed enhancement without a corresponding decline in systolic function. One patient with an initial presentation of sustained VT, died due to progressive biventricular failure. Only one participant (age 12) did not exhibit abnormal MRI findings.

Conclusion: CTRCT46 is associated with cardiomyopathy and juvenile cataracts in the Hutterite population. Cardiac involvement was observed in 10 of 11 subjects in follow up. Most common manifestations were distinct early onset inferolateral LV delayed enhancement and biventricular dysfunction.