Infantile-Onset Myelin Protein Zero–Related Demyelinating Neuropathy Presenting as an Upper Extremity Monoplegia,☆☆

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We describe an infant with an early-onset demyelinating neuropathy who presented with an upper extremity monoplegia and progressive asymmetric weakness. Neurophysiologic testing revealed a generalized severe neuropathy with marked slowing of nerve conduction. The disproportionate severity and asymmetry of upper extremity involvement at presentation was atypical of inherited neuropathies, and an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was considered. Nerve biopsy showed severe depletion of large myelinated fibers without inflammatory cells, and focally folded myelin sheaths were seen on electron microscopy. Genetic testing revealed a de novo heterozygous mutation in the myelin protein zero gene.

Introduction

Early-onset demyelinating neuropathies in childhood are uncommon and present a considerable diagnostic challenge. Although most have a genetic basis, acquired inflammatory neuropathies can also occur in early infancy. We report a child who presented in infancy with an upper extremity monoplegia, but who had widespread slowing of nerve conduction on neurophysiologic testing. Although a diagnosis of infantile chronic inflammatory demyelinating polyneuropathy was initially considered, features on the nerve biopsy were more consistent with an inherited neuropathy, and she was ultimately found to have a de novo heterozygous mutation of the myelin protein zero (MPZ) gene.

Section snippets

Case Report

An 11-month-old female infant was referred with a 5-month history of decreased spontaneous movement of the left upper limb and generalized hypotonia. From 6 months of age, her parents noted decreasing use of the left upper limb. She reached across the midline with her right upper limb to grasp objects. Although she could hold objects placed directly into her left hand, she had no proximal movement and was unable to reach for toys on the left side. Hypotonia was also noted from the first 2

Discussion

This patient has an infantile-onset demyelinating neuropathy due to a de novo mutation in the MPZ gene. Demyelinating neuropathies of infantile onset are uncommon, have a broad differential diagnosis, and usually have a genetic basis. Genetic causes include early-onset forms of demyelinating CMT, as well as neuropathies associated with a range of metabolic conditions and disorders of central nervous system myelin.3

The terminology used to define the etiology of early-onset demyelinating

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Institution where the work was performed: Department of Neurology, Royal Children׳s Hospital, Melbourne, Australia.

☆☆

E.M.Y. is supported by a National Health Medical Research Council, Australia (NHMRC) Early Career Fellowship (APP1073323). G.A.N. receives Grant support from the National Health Medical Research Council, Australia (APP104668). M.M.R. receives Grant support from the National Health Medical Research Council, Australia under The Centres of Research Excellence scheme (APP1031893). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.

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