Peripheral neuropathies of infancy

Abstract

Over a 33-year period, 260 patients (< 17 years of age; 119 males, 141 females) from New South Wales, Australia who had peripheral neuropathies confirmed by nerve biopsy, were studied. Of these, 50 infants presented with symptoms or signs of neuropathy under 1 year of age: including 24 patients with demyelinating neuropathies and 21 axonal neuropathies; a further five patients had spinal muscular atrophy with associated secondary sensory axonopathy. Nineteen infants had hereditary motor sensory neuropathy, of whom 13 had myelin protein mutations confirmed by molecular genetic studies. Peripheral neuropathy is not an unusual diagnosis in infancy. Awareness of this association will aid early diagnosis and prognosis as well as facilitate interventional patient management.

Genetic spectrum of hereditary neuropathies with onset in the first year of life

“…In other patients, clinical presentation consists of early foot deformities, delay in early motor milestones, distal sensory loss and weakness with progressive gait difficulties (Plante-Bordeneuve and Said, 2002; Wilmshurst et al ., 2003; Burns et al ., 2009). These early and severely affected patients are often isolated in their family, obscuring the inheritance pattern; either de novo mutations in dominant genes or recessive alleles inherited from unaffected parents are at play (Gabreels-Festen, 2002; Plante-Bordeneuve and Said, 2002; Parman et al ., 2004).…”

“…The disease history and electrophysiology may provide hints in that direction. Acquired causes, however, are proportionally less common than hereditary causes (Connolly, 2001; Wilmshurst et al ., 2003). More often, peripheral neuropathies in very young children may be seen as part of a syndromic (metabolic) hereditary disorder.…”

“…More often, peripheral neuropathies in very young children may be seen as part of a syndromic (metabolic) hereditary disorder. Although other clinical features than those of the peripheral neuropathy usually dominate the phenotype, severe demyelinating neuropathy leading to motor development delay may be observed as the initial and only clinical sign in these disorders (Wilmshurst et al ., 2003; Ryan and Ouvrier, 2005; Scherer, 2006; Landrieu et al , 2011).…”

“…Performing such examinations is challenging in very young children, and normal values vary significantly in the first 5 years of life due to ongoing maturation of the PNS and limb growth. For this reason, results of nerve conduction studies must be interpreted with utmost caution (Garcia et al ., 2000; Wilmshurst et al ., 2003). …”

Novel MPZ mutations and congenital hypomyelinating neuropathy

“…Some patients may eventually require a wheelchair for mobilization however data pertaining to long-term outcome is limited. MPZ mutations account for a large proportion of all inherited peripheral neuropathies that present during infancy [16]. The “classic” demyelinating phenotype (CMT1B) typically presents in the first decade with gait impairment, frequent falling and/or foot deformity.…”