General description

LMNB1-related autosomal dominant leukodystrophy is a progressive neurological disorder characterized by the degeneration of white matter in the central nervous system. It typically begins in adulthood, often in the fourth or fifth decade, with autonomic dysfunction. This can manifest as bladder or bowel problems, low blood pressure upon standing, erectile dysfunction, and less commonly, impaired sweating.

As the disease progresses, patients typically develop pyramidal signs such as spasticity, increased muscle tone, and hyperreflexia, primarily affecting the lower limbs. Cerebellar signs, including gait instability, difficulty with rapid alternating movements, intention tremor, and nystagmus, often appear concurrently. Sensory deficits, particularly in the lower limbs, are also common. In later stages, pseudobulbar palsy can occur, leading to difficulties with speech, swallowing, and emotional control. While cognitive function is usually preserved or mildly impaired early in the disease, dementia and psychiatric symptoms may develop over time.