Vogel et al. (1985) reported a German kinship with clinical features of hereditary motor sensory neuropathy type 2 (HMSN2; see, e.g., CMT2A1; 118210) characterized by axonal swellings with neurofilament accumulations on peripheral nerve biopsy. There were at least ... Vogel et al. (1985) reported a German kinship with clinical features of hereditary motor sensory neuropathy type 2 (HMSN2; see, e.g., CMT2A1; 118210) characterized by axonal swellings with neurofilament accumulations on peripheral nerve biopsy. There were at least 9 affected family members spanning 5 generations; inheritance was autosomal dominant. Clinical features included pes cavus, gait abnormalities, peroneal muscle weakness and atrophy, hand weakness, hyporeflexia or areflexia, and distal sensory loss of tactile and vibratory sensations. EMG showed chronic denervation, and nerve conduction velocities (NCVs) were normal or mildly decreased. Sural nerve biopsy showed mild reduction in myelinated fibers, occasional small onion bulb formations, and swollen axons with neurofilament accumulation. Three of the most severely affected individuals had evidence of a cardiomyopathy. Vogel et al. (1985) distinguished the disorder in this family from autosomal recessive giant axonal neuropathy (GAN; 256850) by the mode of inheritance, later age at onset, absence of hair abnormalities, and absence of central nervous system involvement. Lus et al. (2003) reported an Italian family with autosomal dominant inheritance of Charcot-Marie-Tooth disease with giant axons. Clinical features were variable in severity, but included progressive weakness and atrophy of the hands, feet, and legs with a peroneal distribution, generalized hyporeflexia and areflexia, steppage gait, and distal loss of tactile and vibratory sensation. All patients had pes cavus since infancy, but other symptoms developed in adulthood and were slowly progressive. Motor and sensory NCVs were moderately to severely reduced. Sural nerve biopsy of 1 patient showed numerous giant axons with sporadic onion bulb formations. Molecular analysis excluded linkage to known CMT2 loci and mutations in known CMT2 genes, including NEFL (162280) and GAN (605379).