Hereditary motor and sensory neuropathy with myelin outfolding: clinical, genetic and neuropathological study of three cases.

We describe 3 patients affected by a congenital motor and sensory neuropathy with excessive myelin outfoldings (MOs). Clinical and electrophysiological features supported the diagnosis of hereditary motor and sensory neuropathy (HMSN). The genetic study failed to demonstrate either the duplication in chromosome 17p11.2 or the mutations at exons 1 and 2 of the myelin protein gene, PMP-22, recently observed in HMSN type Ia, and suggested an autosomal recessive (AR) inheritance. Sural nerve biopsy revealed a demyelinating process with prominent hypertrophic changes and excessive MOs formation. The percentage of MOs was significantly higher than in 3 age-matched HMSN Ia patients. MOs were morphologically and morphometrically different from tomacular-like thickenings of myelin. Myelin thickness was significantly lower than in the three HMSN Ia controls and linear regression showed a thinner myelin related to axon diameter. The reported cases demonstrate that HMSN with MOs is a well defined variant of HMSN and that a primary defect in the myelination process may be proposed as a possible pathogenic mechanism.