Abstract
Hereditary myelopathies are an important and likely underappreciated component of
neurogenetic disease. While previously distinctions have been made by age of onset,
the growing power and availability of high-quality neuroimaging and next-generation
sequencing are increasingly expanding classical phenotypes and diminishing the utility
of age-based classifications. Increasingly, cases of “atypical” disease presentations
are challenging past assumptions regarding the age of onset and survival in many disorders
and identifying allelic syndromes in others. Despite this, there is poor awareness
of the potential for spinal involvement in many diseases that typically affect the
brain. Broadly speaking, congenital myelopathies can be neuroanatomically grouped
into motor neuron, axonopathy, spinocerebellar, cerebroleukodystrophy, and pan-neuraxis
(generally central nervous system predominant with associated axonopathy) disorders.
Here, we review hereditary causes of myelopathy, organized by neuroanatomy, and highlight
atypical presentations. We discuss findings concerning an underlying genetic etiology
for myelopathy, as well as practical, technical, and ethical considerations of diagnostic
genetic testing.
Keywords
hereditary myelopathy - hereditary myelopathy - neurogenetic disease
