Calcaneal ulcer in a child with congenital insensitivity to pain syndrome

Tunçbi̇lek, Gökhan; Öztekin, Can; Kayıkçıoğlu, Aycan

doi:10.1080/02844310410004865

Cited by 8 publications

(8 citation statements)

References 8 publications

(11 reference statements)

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“…The first reference to a similar pathology was mentioned by Dearborn in 1932 [12], and it was published in 1963 by Swanson [13]. Tunçbilek et al (2005) determined three clinical representative findings: insensitivity to pain, inability to sweat and intellectual disability [14]. Indo et al (1996) associated CIPA pathogenesis with genetic loss-of-function mutations of the NTRK1 (neurotrophic receptor tyrosine kinase 1) gene [15].…”

Section: Introductionmentioning

confidence: 99%

Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report

et al. 2020

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Background: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Case presentation: Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The highaltitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, selfmutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. Conclusions: This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report

et al. 2020

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“…Since the first report on this pathology mentioned by Dearborn in 1932 (13) and published by Swanson in 1963(14), only a few hundred of cases have been reported worldwide. Each of these publications has provided a significant contribution to better understand the clinical and genetic aspects of this autosomal recessive disorder (8,12,(23)(24)(25)(26)(27)(28)30,31,(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

“…The first reference to a similar pathology was mentioned by Dearborn in 1932 (13), and it was published in 1963 by Swanson(14). Tunçbilek et al (2005) determined three clinical representative findings: insensitivity to pain, inability to sweat and intellectual disability (15). associated CIPA pathogenesis with genetic loss-offunction mutations of the NTRK1 (neurotrophic receptor tyrosine kinase 1) gene (16).…”

Section: Introductionmentioning

confidence: 99%

Genomic, Ancestral and Networking Analyses of a High-Altitude Native American Ecuadorian Patient with Congenital Insensitivity to Pain with Anhidrosis

López‐Cortés

Zambrano

Guevara-Ramírez

et al. 2019

Preprint

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Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Patients with CIPA lack the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we conducted a genomic analysis of 4,811 genes and 18,933 variants, including 54 mutations of NTRK1 in a high-altitude indigenous Ecuadorian patient with CIPA. As results, the patient presented 87.8% of Native American ancestry, 6.6% of African ancestry and 5.6% of European ancestry. The mutational analysis of the kinase domain of NTRK1 showed two pathogenic mutations, rs80356677 (Asp674Tyr) and rs763758904 (Arg602*). The genomic analysis showed 68 pathogenic and/or likely pathogenic variants in 45 genes, and two variants of uncertain significance in CACNA2D1 (rs370103843) and TRPC4 (rs80164537) genes involved in the pain matrix. The GO enrichment analysis showed 28 genes with relevant mutations involved in several biological processes, cellular components and molecular functions. In addition, the protein-protein interaction (PPi) networking analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix. In conclusion, this is the first time that a study associates genomic, ancestral and networking data in a high-altitude Native American Ecuadorian patient with consanguinity background in order to better understand CIPA pathogenesis.

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“…According to literature, the first step in the diagnosis of CIPA syndrome is consideration of the clinical presentation based on the combination of three basic signs: insensitivity to pain, anhidrosis, and mental retardation [ 3 , 4 ]. Other possible signs may be associated: impaired temperature sensation [ 5 ], facial alterations [ 6 ], mandibular osteolysis [ 7 ], dental caries [ 6 ], and premature tooth loss [ 6 ]; repetitive soft tissue and osseous infections of hematogenous origin [ 33 ], mainly caused by S. aureus [ 25 ]; self-mutilating behavior [ 7 ]; occasional microcephaly [ 5 , 24 ]; urine and fecal incontinence [ 11 ]; growth disturbances; and heterotopic ossification [ 7 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…The first reference to a similar pathology was mentioned by Dearborn in the early 1900s [ 1 ], and it was published in 1963 by Swanson [ 2 ]. Three clinical findings define the syndrome: insensitivity to pain, inability to sweat, and mental retardation [ 3 , 4 ]. Only a few hundreds of cases of CIPA have been recently published worldwide [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Update Review and Clinical Presentation in Congenital Insensitivity to Pain and Anhidrosis

Perez-Lopez

Cabrera-González

Iglesia

et al. 2015

Case Reports in Pediatrics

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Introduction. Congenital insensitivity to pain and anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV is an extremely rare syndrome. Three clinical findings define the syndrome: insensitivity to pain, impossibility to sweat, and mental retardation. This pathology is caused by a genetic mutation in the NTRK1 gene, which encodes a tyrosine receptor (TrkA) for nerve growth factor (NGF). Methods. The consultation of a child female in our center with CIPA and a tibia fracture in pseudoarthrosis encouraged us to carefully review literature and examine the therapeutic possibilities. A thorough review of literature published in Pubmed was done about CIPA and other connected medical issues mentioned in the paper. Conclusions. The therapeutic approach of CIPA remains unclear. The preventive approach remains the only possible treatment of CIPA. We propose two new important concepts in the therapeutic approach for these patients: (1) early surgical treatment for long bone fractures to prevent pseudoarthrosis and to allow early weight bearing, decreasing the risk of further osteopenia, and (2) bisphosphonates to avoid the progression of osteopenia and to reduce the number of consecutive fractures.

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Calcaneal ulcer in a child with congenital insensitivity to pain syndrome

Cited by 8 publications

References 8 publications

Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report

Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report

Genomic, Ancestral and Networking Analyses of a High-Altitude Native American Ecuadorian Patient with Congenital Insensitivity to Pain with Anhidrosis

Update Review and Clinical Presentation in Congenital Insensitivity to Pain and Anhidrosis

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