To report shared clinical characteristics of people with genetically confirmed ADLD and promote understand the clinical disease course. 

ADLD was first described as a fatal mimicker of primary progressive multiple sclerosis and is under recognized. Onset is in the fourth to sixth decades with autonomic symptoms followed by pyramidal signs and ataxia. It is caused by LMNB1 duplication and, less commonly, an upstream promoter mutation.

Ten people with genetically confirmed ADLD evaluated at the University of Pittsburgh Medical Center between 2023-2025 were identified. Charts were reviewed for clinical presentation and disability accumulation, family history, and MRI findings. In a small subset of patients, patient reported outcomes and clinical metrics were obtained with the goal of following these patients over time as part of a prospective natural history study.

Eight patients had bladder symptom onset and other autonomic symptoms, followed by gait ataxia and progressive weakness and spasticity. Two patient presented with balance difficulty. All patients had similar MRI findings of symmetric T2 FLAIR hyperintensities extending from corticospinal tract to medulla oblongata, upper and middle cerebellar peduncles, and confluent signal in frontoparietal region with relative sparing of corpus callous and periventricular regions. In one patient's family, all 5 siblings had ADLD with bladder symptom onset followed ataxia and weakness. One patient presented with a de novo LMNB1 duplication, which was previously unreported in the literature. CSF from one patient was negative for oligoclonal bands. Dalfampridine has helped in two patients.

ADLD is a monogenic disorder caused by LMNB1 mutation. This case series highlights the homogeneity in clinical presentation and radiographic features. These findings inform the natural progression of the disease, a necessary precursor to developing therapies. This is also the first report of a novo mutation and warrants consideration of diagnosis with clinical and radiographic features without family history.