Congenital Insensitivity to Pain with Anhidrosis (CIPA) is an extremely rare congenital disorder characterized by severe clinical and oral manifestations. The aim of this case report is to present the dental and systemic findings in two adult siblings diagnosed with CIPA, highlighting their shared genetic condition yet differing oral manifestations. This report is notable for the patients’ advanced age and provides comparative insight into variations in dentition, periodontal status, and cooperation during dental care. These features highlight the importance of long-term follow-up in CIPA patients by shedding light on the oral and systemic changes that may emerge with advancing age. A 20-year-old male and his 22-year-old sister, both diagnosed with CIPA, presented to the Faculty of Dentistry at Niğde Ömer Halisdemir University for dental examination. The male patient showed plaque and calculus buildup, moderate gingival inflammation with bleeding, widespread staining from past iron use, and a tongue scar likely due to self-injury. He had a dolichofacial profile and missing mandibular central incisor (#31). Despite no previous dental treatment, he cooperated well and full-mouth scaling was completed. The female patient had more severe oral issues, including heavy plaque and calculus, generalized gingival recession, poor gum health, and several missing teeth. She had a brachycephalic facial pattern and restricted mouth opening due to scarring. Radiographs showed missing upper and lower central incisors (#21 and #31). Due to limited cooperation, only anterior scaling was done, and further treatment was advised under sedation or general anesthesia. Systemically, both siblings had typical CIPA findings: insensitivity to pain and temperature, recurrent high fever due to lack of sweating, joint deformities, and fingertip amputations. They also had moderate-to-severe intellectual disability, were unable to walk independently, and needed full-time caregiver support. This case emphasizes the significance of oral and systemic alterations that can manifest in CIPA patients during adulthood. The presence of notable dental anomalies in the absence of multiple carious lesions, oral ulcerations, or missing permanent teeth distinguishes these adult cases from most CIPA reports typically documented in childhood. Additionally, a certain level of treatment compliance particularly in the male patient further emphasizes the uniqueness of this report. The findings underscore the necessity for long-term monitoring and highlight the importance of individualized dental care and follow-up strategies in managing CIPA patients.

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. Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing. 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. 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.

Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disease characterized by insensitivity to pain, anhidrosis, and intellectual disability. CIPA is caused by a genetic mutation in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene on chromosome 1. The anhidrosis leads to cutaneous changes such as skin dryness, lichenification, and impetiginization. Moreover, patients with CIPA may experience repeated trauma and recalcitrant eczema due to excessive scratching of wounds on their skin, because they do not feel any pain. Severe whole-body eczema in a patient with CIPA may be overlooked, leading these patients to be frequently diagnosed with atopic dermatitis and common eczema. Indeed, in patients with treatment-resistant or atypically distributed eczema and underlying anhidrosis, CIPA should be considered as a potential causative disease. Increased awareness of CIPA among dermatologists is necessary to ensure that patients receive an appropriate diagnosis. Herein, we report a rare case of generalized xerotic eczema in a patient with CIPA.

Congenital insensitivity to pain (CIP) is a rare autosomal recessive genetic condition which causes reduced pain sensation, thermal sensation, and habit of self-mutilation. It is a life-threatening condition where due to reduced pain sensation, patient might not understand the severity of the injury which can eventually lead to death. Such people live a compromised life and can also affect them psychologically. Here, we are reporting a case of an infant with clinical features suggestive of CIP with a mutation in exon 5 of PRDM12 gene. The child has minimal response to pain along with self-mutilation and mental retardation.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive heterogeneous disorder mainly caused by mutations in the neurotrophic tyrosine receptor kinase 1 gene ( NTRK1) and characterized by insensitivity to noxious stimuli, anhidrosis, and intellectual disability. We herein report the first north Han Chinese patient with CIPA who exhibited classic phenotypic features and severe intellectual disability caused by a homozygous c.851-33T>A mutation of NTRK1, resulting in aberrant splicing and an open reading frame shift. We reviewed the literature and performed in silico analysis to determine the association between mutations and intellectual disability in patients with CIPA. We found that intellectual disability was correlated with the specific Ntrk1 protein domain that a mutation jeopardized. Mutations located peripheral to the Ntrk1 protein do not influence important functional domains and tend to cause milder symptoms without intellectual disability. Mutations that involve critical amino acids in the protein are prone to cause severe symptoms, including intellectual disability.