Beom Hee Lee

Background Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss‐of‐function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self‐mutilating behavior, and intellectual disability. Methods Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing. Results CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3–8 years). Two patients exhibited self‐mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851‐33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574‐156_850+1113del (exons 5‐7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851‐33T>A (p.?) mutations and compound heterozygous for c.851‐33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1 . The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574‐156_850+1113del (exons 5‐7 del) displayed a late onset and milder clinical manifestation. Conclusion All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.