A Case of Severe Early-Onset Neuropathy Caused by a Compound Heterozygous Deletion of the PMP22 Gene: Clinical and Neurographic Aspects.

Abstract

Heterozygous deletions of the gene PMP22 are associated to hereditary neuropathy with liability to pressure palsies (HNPP), a demyelinating neuromuscular disease causing variable transitory focal muscles weakness. Deletions involving both copies of PMP22 cause more severe phenotypes, with early-onset neuropathy and impairment in motor development. We report a patient with a severe early-onset demyelinating neuropathy, caused by two different inherited deletions of PMP22, whose parents had an HNPP. The patient showed neurological signs and delay in motor development but normal intellective abilities. A motor and sensitive conduction study showed severe signs of demyelination, suggestive for Dejerine Sottas Syndrome (DSS). The patient s father had a typical HNPP caused by a heterozygous 17p11.2 deletion, encompassing PMP22. The patient s mother reported no neuropathic symptoms, but in a nerve conduction studies, parents and several relatives showed signs of sensory-motor deficit with focal slowing of conduction at common sites of entrapment. Quantitative analysis of PMP22, performed in our patient by multiplex ligation-dependent probe amplification, revealed a compound heterozygous status with the same deletion of the father and a deletion of PMP22 exon 5, after proved to be inherited from the mother. Therefore, when we face an early-onset, severe form of neuropathy, we have to consider rare forms of hereditary neuropathy caused by homozygous or compound heterozygous mutations in PMP22, even if parents are asymptomatic; an exhaustive family history and an electrodiagnostic study are essential to guide genetic tests and to make a diagnosis.