CMT 4F Four novel cases of periaxin-related neuropathy and review of the liter

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Four novel cases of periaxin-related neuropathy and review of the literature.

http://www.ncbi.nlm.nih.gov/pubmed/21079185

Marchesi C, Milani M, Morbin M, Cesani M, Lauria G, Scaioli V, Piccolo G,

Fabrizi GM, Cavallaro T, Taroni F, Pareyson D.

Unit of Clinic of Central and Peripheral Degenerative Neuropathies, Department

of Clinical Neurosciences, Carlo Besta Neurological Institute IRCCS Foundation,

Via Celoria 11, 20133 Milan, Italy

Abstract

OBJECTIVE: To report 4 cases of autosomal recessive hereditary neuropathy

associated with novel mutations in the periaxin gene (PRX) with a review of the

literature. Periaxin protein is required for the maintenance of peripheral nerve

myelin. Patients with PRX mutations have early-onset autosomal recessive

demyelinating Charcot-Marie-Tooth disease (CMT4F) or Déjèrine-Sottas neuropathy

(DSN). Only 12 different mutations have been described thus far.

METHODS: Case reports and literature review.

RESULTS: Four patients from 3 unrelated families (2 siblings and 2 unrelated

patients) were affected by an early-onset, slowly progressive demyelinating

neuropathy with relevant sensory involvement. All carried novel frameshift or

nonsense mutations in the PRX gene. The 2 siblings were compound heterozygotes

for 2 PRX null mutations (p.Q547X and p.K808SfsX2), the third patient harbored a

homozygous nonsense mutation (p.E682X), and the last patient had a homozygous

2-nt insertion predicting a premature protein truncation (p.S259PfsX55).

Electrophysiologic analysis showed a severe slowing of motor nerve conduction

velocities (MNCVs, between 3 and 15.3 m/s) with undetectable sensory nerve

action potentials (SNAPs). Sural nerve biopsy, performed in 2 patients,

demonstrated a severe demyelinating neuropathy and onion bulb formations.

Interestingly, we observed some variability of disease severity within the same

family.

CONCLUSIONS: These cases and review of the literature indicate that PRX-related

neuropathies have early onset but overall slow progression. Typical features are

prominent sensory involvement, often with sensory ataxia; a moderate-to-dramatic

reduction of MNCVs and almost invariable absence of SNAPs; and pathologic

demyelination with classic onion bulbs, and less commonly myelin folding and

basal lamina onion bulbs.