Introduction

Giant axonal neuropathy (GAN) is a rare condition involving abnormal intracellular intermediate filament aggregation. Since intermediate filaments are abundant in neurons of the central and peripheral nervous system, it is not surprising that significant neurologic dysfunction results from such an abnormality. The predominant intermediate filament of neurons is known as neurofilament. In GAN, intermediate filaments of multiple cell types cluster abnormally. Other organ systems, including the skin, can be involved. Most of the well-documented cases in the literature have strikingly unusual hair that is curly, kinky or frizzled. In this sense, GAN can be considered a ‘neurocutaneous’ disorder. Berg, Asbury and colleagues first described GAN in 1972 (Berg et al., 1972; Asbury et al., 1972). Since then, approximately 30 additional cases have been published.

Clinical manifestations

GAN affects both the central and peripheral nervous systems. Typically, the early manifestations of the disease involve the peripheral nervous system and are present in infancy. Some children have delay in motor milestones, while others have normal early development then become clumsy after 2 or 3 years of age. The onset of symptoms almost always occurs prior to age seven. With time, progressive weakness in the lower extremity followed by the upper extremity proceeds. Incoordination is prominent. Scoliosis, dysarthria and other cranial nerve dysfunction follows. In most cases, cognitive impairment (dementia) and spasticity occur in the second decade. A few cases develop epileptic seizures.