One hundred and thirty two individuals at risk for hereditary motor and sensory neuropathy (HMSN) type I from 11 unrelated families were evaluated by physical examination. Motor conduction velocity (MCV) studies of median and/or peroneal nerves were performed on 99 of them. Seventy-three subjects were found to be affected. In all age categories including the first decade of life, the ratio of affected individuals at risk did not significantly differ from the expected 1:1 ratio; that is, penetrance of the gene was complete. The majority of affected members in the first decade had no clinical features considered diagnostic of peroneal muscular atrophy syndrome, and full clinical expression developed in the second decade. Marked slowing of MCV was already present in the early years of life, even as young as 6 months. Moreover serial MCV studies carried out throughout the first year of life in an affected girl showed no physiological increase in conduction velocity. For purposes of genetic counseling, our experience suggests that, starting from 6 months of age, a clinically and electrophysiologically normal subject has a zero risk of having inherited the HMSN type I gene. However given the limited numbers in this series, infants at risk with normal clinical evaluation and MCVs should be followed up yearly up to 5 years of age.

A family with hereditary motor and sensory neuropathy (HMSN) type II is described in which 10 affected and 17 unaffected members in three generations were examined. The peak age of onset was in the second decade. In the youngest generation, the proportion of affected to unaffected individuals at risk significantly differed from the expected 50%. There was slight slowing of conduction velocities in 36% of nerves; however, only 3 out of 10 affected members had entirely normal conduction studies. The amplitude of the sensory potentials of median and peroneal nerves was almost uniformly reduced. In all affected patients electromyography of anterior tibial muscles showed signs of neurogenic involvement. Histological study of two sural nerves and a sciatic nerve and its branches revealed loss of myelinated fibres with a proximal-to-distal gradient in this fibre loss, clusters of small regenerating fibres, and atrophic axons. Postmortem study of the proband showed loss of anterior horn and dorsal root ganglion neurons in the lumbar and sacral segments and degeneration of the fasciculus gracilis. Morphometric evaluation of L5 ventral and dorsal roots revealed a normal number of myelinated fibres, diameter histograms being shifted to the left because of a significant loss of large myelinated fibres and regeneration. These anatomical findings are consistent with the hypothesis that HMSN type II represents a primary neuronopathy affecting motor and sensory neurons.

Advances in molecular genetics in hereditary neuropathies, and mainly in Charcot-Marie-Tooth disease, have enriched our knowledge of this heterogeneous group of disorders. In spite of this there remain important and basic issues, such as an updated and revised classification of Charcot-Marie-Tooth disorders, the better delineation of phenotypic-genotypic correlations, and further research to map as yet non-localized loci or to identify unknown gene mutations.

syndrome High-dose IV immunoglobulin for peripheral neuropathy associated with Sjögren's This information is current as of