Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by 
autosomal recessive mutations in the GAN gene on chromosome 16q24.1. Mutations 
in the GAN gene lead to functional impairment of the cytoskeletal protein 
gigaxonin and a generalized disorder of intermediate filaments, including 
neurofilaments in axons. Tightly curled hair is a common but not universal 
feature of Giant Axonal Neuropathy. The pathogenesis of curly hair is unknown, 
although disruption of keratin architecture is thought to play a role. As part 
of a broader natural history study of Giant Axonal Neuropathy, we found that the 
absence of curly hair is correlated with superior motor function (p=0.013) when 
controlling for age, as measured by the Gross Motor Function Measure. 
Theoretically, higher levels of functional gigaxonin protein or compensatory 
mechanisms could produce fewer abnormalities of neurofilaments and keratin, 
accounting for this phenotype. We suggest that straight-haired patients with 
Giant Axonal Neuropathy are potentially underdiagnosed due to their divergence 
from the classic phenotype of the disease. Due to their non-specific features of 
an axonal neuropathy, these patients may be misdiagnosed with 
Charcot-Marie-Tooth Disease type 2. Genetic testing for Giant Axonal Neuropathy 
should be considered in relevant cases of Charcot-Marie-Tooth Disease type 2.