A retrospective review of LMNB1-related autosomal dominant leukodystrophy

Abstract

Introduction LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurodegenerative disorder caused by overexpression of LMNB1. We retrospectively reviewed charts of all ADLD patients seen at Mayo Clinic. Methods All available data from molecularly confirmed ADLD patients was reviewed. Results Of eight patients identified, three were male. Age at symptom onset ranged from 33 to 64 years. In males, the first symptom was erectile dysfunction (2/3) or neurogenic bladder (1/3) and, in females, weakness (3/5), bladder dysfunction (2/5), or depression (1/5). Diagnostic delay from symptom onset was a median of 6 (IQR 2.3–10) years. Other reported symptoms included cognitive difficulties (8/8), fatigue (7/8), sleep issues (4/8), mood disturbances (5/8), tremor (4/8), and migraine (4/8). Family history was positive in 6. All eight patients had LMNB1 duplication. Eighteen brain MRIs were reviewed from 7 patients. All showed symmetric confluent T2W deep cerebral and periventricular white matter hyperintensities with involvement of the posterior limb of the internal capsule, corpus callosum, corticospinal tract in brain stem, and superior and middle cerebellar peduncles. Seven spine MRIs from six patients showed moderate diffuse atrophy of the spinal cord. Conclusion Typical clinical symptoms and characteristic MRI changes should prompt genetic testing for ADLD.