Pulsating Enophthalmos in Neurofibromatosis 1 Pulsating Enophthalmos in Neurofibromatosis 1

Lehn A, Airey C, Boyle R. — Wed, 01 May 2013 00:00:00 GMT

A 49-year-old man with neurofibromatosis 1 (NF1) presented to the neurology outpatient clinic with headaches and visual disturbance. He had typical clinical features of neurofibromatosis and was noted to have a pulsating enophthalmos. This had first been noted in childhood, when he was hospitalized for the removal of a spinal neurofibroma. Apart from severe, disabling headaches, he has not had any other major complications from NF1. His family history was notable for his mother, his siblings, and both his children all being affected by NF1, although with widely variable phenotypes.

Proximal Dominant Hereditary Motor and Sensory Neuropathy With Proximal Dominance Association With Mutation in the TRK-Fused Gene Neuropathy Associated With TRK-Fused Gene Mutation

Lee S, Lee H, Park J, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) has been reported as a rare type of autosomal dominant adult-onset Charcot-Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since 1997, and the causative gene has not been found.

Objectives

To identify the genetic cause of HMSN-P in a Korean family and determine the pathogenic mechanism.

Design

Genetic and observational analysis.

Setting

Translational research center for rare neurologic disease.

Participants

Twenty-eight individuals (12 men and 16 women) from a Korean family with HMSN-P.

Main Outcome Measures

Whole-exome sequencing, linkage analysis, and magnetic resonance imaging.

Results

Through whole-exome sequencing, we revealed that HMSN-P is caused by a mutation in the TRK-fused gene (TFG). Clinical heterogeneities were revealed in HMSN-P between Korean and Japanese patients. The patients in the present report showed faster progression of the disease compared with the Japanese patients, and sensory nerve action potentials of the sural nerve were lost in the early stages of the disease. Moreover, tremor and hyperlipidemia were frequently found. Magnetic resonance imaging of the lower extremity revealed a distinct proximal dominant and sequential pattern of muscular involvement with a clearly different pattern than patients with Charcot-Marie-Tooth disease type 1A. Particularly, endoneural blood vessels revealed marked narrowing of the lumen with swollen vesicular endothelial cells.

Conclusions and Relevance

The underlying cause of HMSN-P proves to be a mutation in TFG that lies on chromosome 3q13.2. This disease is not limited to Japanese descendants, and marked narrowing of endoneural blood vessels was noted in the present study. We believe that TFG can affect the peripheral nerve tissue.

AMA Publishing Group: Neuropathy Topic Collection

Pulsating Enophthalmos in Neurofibromatosis 1 Pulsating Enophthalmos in Neurofibromatosis 1

Proximal Dominant Hereditary Motor and Sensory Neuropathy With Proximal Dominance Association With Mutation in the TRK-Fused Gene Neuropathy Associated With TRK-Fused Gene Mutation