NTRK1 gene-related congenital insensitivity to pain with anhidrosis: a nationwide multicenter retrospective study

Autor: Cecilia Altuzarra, Altynshash Jaxybayeva, Marta Gomez Garcia de la Banda, Bakhytkul Myrzaliyeva, Jon Andoni Urtizberea, Jean-Michel Vallat, Raluca Anca Tudorache, Meriem Tazir, Andoni Echaniz-Laguna, Alain Verloes, Susana Quijano-Roy, Bruno Francou
Rok vydání: 2021
Předmět:
Zdroj: neurogenetics. 22:333-341
ISSN: 1364-6753
1364-6745
DOI: 10.1007/s10048-021-00668-z
Popis: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease resulting from mutations in the NTRK1 gene encoding the neurotrophic tyrosine kinase-1 receptor. In this multicenter observational retrospective study, we investigated CIPA patients identified from French laboratories sequencing the NTRK1 gene, and seven patients were identified. Patients originated from France (2), Suriname (2), Mali (1), Kazakhstan (1), and Algeria (1). Mean age of patients was 9.8 years (4–20), four patients were female (57%), infant developmental milestones were delayed in four cases (57%), and four patients had a family history of consanguinity (57%). Mean age at diagnosis was 4.8 months (3–6), and all patients presented with pain insensitivity, anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, and autonomous nervous system impairment. Patients also showed an assortment of associated findings, including hyperactivity (86%), emotional lability (86%), joint deformities (71%), bone fractures (57%), abnormal sense of touch, vibration and position (50%), skin, hair and nails abnormalities (28%), and hypothermia episodes (28%). Two patients died at age 9 and 12 years from infection. In three cases, nerve conduction studies showed absent lower limbs sensory nerve action potentials. In one case, sensory nerve biopsy showed complete absence of unmyelinated fibers. Nine NTRK1 pathogenic variants were found, including three newly described mutations. This nationwide study confirms that NTRK1 gene-related CIPA is an extremely rare disorder and expands the genotypic spectrum of NTRK1 mutations.
Databáze: OpenAIRE
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