This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bonkowsky, J. L.
Right arrow Articles by Swoboda, K. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bonkowsky, J. L.
Right arrow Articles by Swoboda, K. J.
Related Collections
Right arrow Genetics & Dysmorphology
PEDIATRICS Vol. 112 No. 3 September 2003, pp. e237-e241

ELECTRONIC ARTICLE

An Infant With Primary Tooth Loss and Palmar Hyperkeratosis: A Novel Mutation in the NTRK1 Gene Causing Congenital Insensitivity to Pain With Anhidrosis

Joshua L. Bonkowsky, MD, PhD*, Justine Johnson{ddagger}, John C. Carey, MD*, A. Gordon Smith, MD{ddagger} and Kathryn J. Swoboda, MD*,{ddagger}

* Departments of Pediatrics
{ddagger} Neurology, University of Utah School of Medicine, Salt Lake City, Utah

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.

Key Words: CIPA • NTRK1 • tooth loss • hyperkeratosis • insensitivity to pain

Abbreviations: CIPA, congenital insensitivity to pain with anhidrosis • NTRK1, neurotrophic tyrosine receptor kinase 1 gene • NGF, nerve growth factor • EMG, electromyography • PCR, polymerase chain reaction • bp, base pair

Received for publication Mar 10, 2003; Accepted May 22, 2003.