Congenital insensitivity to pain with anhidrosis in Taiwan: a morphometric and genetic study

Abstract

Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by insensitivity to pain, anhidrosis, recurrent hyperpyrexia, mild mental retardation, and self-mutilating behavior. We report 2 brothers, aged 20 and 18 years, who suffered from phenotypes of CIPA. Both brothers had a branch site mutation in intron 7 (IVS7-33 T-->A) of the neurotrophic tyrosine kinase receptor type 1 gene. The electrophysiological studies showed no significant abnormal findings in sensory evoked potentials, motor evoked potentials to transcranial magnetic stimulation, or heart rate variations; sympathetic skin responses were absent. Morphometric study of their sural nerve histopathology revealed normal myelinated fiber density, 8,082 fibers/mm2 and 5,637 fibers/mm2 (normal 6,141 +/- 421); decreased unmyelinated fiber density, 2,537 fibers/mm2 and 2,211 fibers/mm2 (normal 28,578 +/- 8,669); increased axon size, 4.41 +/- 1.59 microm and 5.33 +/- 1.48 microm (normal 3.73 +/- 1.45), and increased axon diameter (A)/myelin thickness (M) ratio (A/M), 3.47 +/- 1.42 and 2.70 +/- 1.07 (normal 2.49 +/- 0.93). Scatterplot analysis of the G ratio (axon diameter:fiber diameter) did not show consistent results in the relationship between axon size and myelin thickness. In conclusion, the neuropathy of our CIPA patients included a marked reduction of small myelinated and unmyelinated fibers and a relatively increased axon size. This is the first CIPA family encountered in Taiwan.