Linkage and mutation analyses, MRI, EEG and EMG were performed in 6 patients with giant axonal neuropathy (GAN) from 3 consanguineous families examined at Hacettepe University, Ankara, Turkey, and centers in France. All patients had a progressive sensory motor peripheral neuropathy, mental retardation, cerebellar ataxia, pyramidal tract signs, cranial nerve abnormalities, and “frizzly” hair. Onset of symptoms varied from 3.5 to 4.5 years of age. Distal limb weakness was the initial complaint, and 4 patients were wheelchair bound by 9-10 years. Facial diplegia, ptosis, and high forehead were prominent features, 2 female patients had early breast development, and 5 showed scoliosis, pectus carinatum, and pes equino-valgus. Ankle jerks were absent, and pain and light touch sensation impaired. EEGs were abnormal in 3 patients, and EMG abnormalities were consistent with SMAN in 4. MRIs in 4 patients showed diffuse periventricular and cerebellar demyelination and atrophy. Cavum septi pellucidi and vergae abnormalities were also characteristic. Sural nerve biopsy in 1 and skin biopsy in 2 patients showed giant axons and accumulation of whorled filaments in cytoplasm of fibroblasts, respectively. GAN mutations (R293X or a novel mutation, 1502+1 G>T) were present in all families, and linkage to chromosome 16q24.1 was confirmed by haplotype analysis. [1]
COMMENT. Giant axonal neuropathy is a recessive neuroectodermal degenerative disorder affecting the peripheral and central nervous systems as well as the skin and hair. These authors and others have located the GAN locus to chromosome 16q24.1, and a homogeneous clinical presentation in 6 patients and 3 families is linked to 2 GAN mutations.