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Abstract
Objective: To identify the clinical features of Japanese patients with suspected hereditary sensory and autonomic neuropathy (HSAN) on the basis of genetic diagnoses.
Methods: On the basis of clinical, in vivo electrophysiologic, and pathologic findings, 9 Japanese patients with sensory and autonomic nervous dysfunctions were selected. Eleven known HSAN disease–causing genes and 5 related genes were screened using a next-generation sequencer.
Results: A homozygous mutation, c.3993delGinsTT, was identified in exon 22 of SCN9A from 2 patients/families. The clinical phenotype was characterized by adolescent or congenital onset with loss of pain and temperature sensation, autonomic nervous dysfunctions, hearing loss, and hyposmia. Subsequently, this mutation was discovered in one of patient 1's sisters, who also exhibited sensory and autonomic nervous system dysfunctions, with recurrent fractures being the most predominant feature. Nerve conduction studies revealed definite asymmetric sensory nerve involvement in patient 1. In addition, sural nerve pathologic findings showed loss of large myelinated fibers in patient 1, whereas the younger patient showed normal sural nerve pathology.
Conclusions: We identified a novel homozygous mutation in SCN9A from 2 Japanese families with autosomal recessive HSAN. This loss-of-function SCN9A mutation results in disturbances in the sensory, olfactory, and autonomic nervous systems. We propose that SCN9A mutation results in the new entity of HSAN type IID, with additional symptoms including hyposmia, hearing loss, bone dysplasia, and hypogeusia.
GLOSSARY
- CIP=
- channelopathy-associated insensitivity to pain;
- CMAP=
- compound muscle action potentials;
- HSAN=
- hereditary sensory and autonomic neuropathy;
- NaV1.7=
- voltage-gated sodium channel;
- dbSNP=
- single nucleotide polymorphism database;
- SCV=
- sensory nerve conduction velocity;
- SCN9A=
- sodium channel, voltage-gated, type 9, α;
- SNAP=
- sensory nerve action potentials
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received November 2, 2012.
- Accepted in final form January 18, 2013.
- © 2013 American Academy of Neurology
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