Giant Axonal Neuropathy: Clinical, Radiological, and Genetic Features

Abstract

Introduction: Giant axonal neuropathy (GAN) is an inherited neurodegenerative disorder caused by mutations in the GAN gene. It affects both the central and peripheral nervous systems. We discuss clinical, electrophysiological, radiological and genetic features in three new unrelated patients with GAN.

Methods: Three pediatric patients with suspected GAN were included. The diagnosis was considered in patients with early onset polyneuropathy and characteristic hair with central nervous system involvement or suggestive neuroimaging findings. Biochemical, metabolic and electrophysiological investigations were performed. Diagnosis was confirmed by targeted sequencing of the GAN gene.

Results: All the three patients were found to have biallelic mutations in GAN gene. Peripheral neuropathy, characteristic hair, and cerebellar dysfunction were present in all three while bony deformities, cranial nerve involvement and intellectual disability were seen variably. Neuroimaging showed a spectrum of findings which are discussed.

Conclusion: GAN is a clinically and radiologically heterogeneous disease where genetic testing is necessary for a definite diagnosis and counselling. With facilities for testing becoming increasingly available, the spectrum is likely to expand further.

Keywords: GAN; Giant axonal neuropathy; gigaxonin; hereditary neuropathy; magnetic resonance imaging; sensory neuropathy.

Figure 1

Characteristic hair seen in the three patients

Figure 2

Magnetic resonance imaging brain. (a-c) T2-weighted axial section, T2-weighted sagittal section, and fluid-attenuated inversion recovery axial section of patient 2 showing demyelination in frontoparietal and cerebellar white matter. Cavum septum pellucidum is seen. Dentate nucleus and globus pallidus hyperintensities are appreciated. (d) Extensive periventricular white matter hyperintense changes seen on fluid-attenuated inversion recovery axial section of patient 1. (e and f) Fluid-attenuated inversion recovery axial sections show involvement of dentate nucleus and parieto-occipital white matter in patient 3