title: An infant with primary tooth loss and palmar hyperkeratosis: a novel mutation in the NTRK1 gene causing congenital insensitivity to pain with anhidrosis.
abstract: Patients with congenital insensitivity to pain and anhidrosis (CIPA), caused by mutations in the NTRK1 gene, can be difficult to diagnose because of their variable presentation, the lack of simple diagnostic tests, and the paucity of cases reported in North America. We describe a 1-year-old infant who had tooth loss and palmar hyperkeratosis as the primary manifestations of CIPA. He was initially evaluated by a pediatric dentist and epidermal dysplasia syndromes were considered, but insensitivity to pain was suspected after a skeletal survey revealed an unrecognized skull fracture. Nerve conduction studies were normal, as was his response to subdermal histamine injection. Sequence analysis of his NTRK1 gene revealed 2 mutations: 1 mutation is novel, while the other has been described previously in a patient of northern European descent. An antibody directed against NTRK1 revealed persistent expression in keratinocytes, consistent with the mutations in this patient. Skin biopsy specimens revealed a lack of epidermal and sweat gland innervation. Immunohistochemistry of skin biopsy specimens, together with routine nerve conduction studies, can provide quick and reliable confirmation if CIPA is clinically suspected.
authors.affiliation: Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Bonkowsky
authors.forename: Justine
authors.initials: J
authors.lastname: Johnson
authors.forename: John C
authors.initials: JC
authors.lastname: Carey
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Smith
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Swoboda
mesh_terms: D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics*; D006801:Humans; D007007:Hypohidrosis / Q000235:genetics*; D007223:Infant; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D009154:Mutation; D000699:Pain Insensitivity, Congenital / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D016388:Tooth Loss / Q000235:genetics*
chemical_list: D020917:Receptor, trkA