Pontine autosomal dominant microangiopathy with leukoencephalopathy in a Hispanic man without a family history

To describe a case of pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL), a rare COL4A1-related cerebral small vessel disease, in a Hispanic man with atypical clinical and radiographic features that posed diagnostic challenges.

Case report and literature review.

A 49-year-old Hispanic man of Mexican ancestry without a family history or conventional cardiovascular risk factors developed recurrent ischemic events and multiple cranial nerve palsies beginning at age 35. Brain MRI demonstrated recurrent acute and chronic lacunar infarcts predominantly involving the pontine, thalamus, and basal ganglia, progressive supratentorial and infratentorial white matter hyperintensities, cerebral microbleeds, and a cervical spinal cord lesion. Despite repeated CSF analyses lacking inflammatory markers, he was treated for presumed multiple sclerosis and other inflammatory etiologies and continued to experience neurologic decline despite immunosuppressive therapies. Genetic testing identified a heterozygous pathogenic COL4A1 3' untranslated region variant (c.*31G>T), confirming the diagnosis of PADMAL.

PADMAL may present without a family history and with atypical features such as cervical spinal cord involvement and cranial nerve palsies, mimicking inflammatory or demyelinating disorders. Early consideration of hereditary cerebral small vessel disease and timely genetic testing may prevent unnecessary immunotherapy and facilitate appropriate vascular-focused management.