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 µm and 5.33 ± 1.48 µm (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.

Keywords:
Congenital insensitivity to pain with anhidrosis, Hereditary sensory and autonomic neuropathy type IV, NTRK1, Histopathology, Morphometry
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© 2004 S. Karger AG, Basel
2004
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