%0 Review
%T Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: Case reports and a review of the literature.
%A Cho JH
%A Hwang S
%A Kwak YH
%A Yum MS
%A Seo GH
%A Koh JY
%A Ju YS
%A Yoon JH
%A Kang M
%A Do HS
%A Kim S
%A Kim GH
%A Bae H
%A Lee BH
%J Mol Genet Genomic Med
%V 12
%N 4
%D 2024 Apr
%M 38581121
%F 2.473
%R 10.1002/mgg3.2430
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.