OBJECTIVE: To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP). METHODS: Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents. RESULTS: The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously. CONCLUSION The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.
Channelopathies ; Child ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; NAV1.7 Voltage-Gated Sodium Channel/genetics* ; Pain Insensitivity, Congenital/genetics*

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, autosomal recessive disorder; affected patients are characterized by inability to feel pain and to sweat over the entire body, as well as by mental retardation. Because, in the oral examination, no specific findings on soft or hard tissue may be found except possible lesions due to self-mutilation, early recognition and diagnosis are essential for these patients. Pediatric dentists must be aware of the clinical manifestations and treatment considerations related to uncontrolled body temperature, tactile hyperesthesia and lack of pain reflex. In this case report, dental management of CIPA was suggested by presenting a 6-year follow-up of young patient.
Body Temperature ; Dentists ; Diagnosis ; Diagnosis, Oral ; Follow-Up Studies ; Hereditary Sensory and Autonomic Neuropathies ; Humans ; Hyperesthesia ; Hypohidrosis ; Intellectual Disability ; Pain Insensitivity, Congenital ; Reflex ; Sweat

To analyze the clinical manifestations and gene mutations in children with congenital insensitivity to pain with anhidrosis (CIPA), and review related literature. An infant diagnosed with congenital insensitivity to pain with anhidrosis was reported. The main clinical manifestations of the infant were painless, no sweat, and repeated fever. Peripheral blood of the infant and his parents was collected, and candidate variants were confirmed by Sanger sequencing. The results of molecular genetic analysis showed that there were compound heterozygous mutations (c.36G>A, c.851-33T>A) of neurotrophic tyrosine kinase receptor type 1 (NTRK1) in the infant. c.36G>A and c.851-33T>A were inherited from his father and mother, respectively. c.851-33T>A is a previously reported mutation, c.36G>A is an unreported mutation, which can lead to the tryptophan changing into a stop codon. According to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines, the mutation is interpreted as pathogenic, and the biological hazard is potentially harmful. Congenital insensitivity to pain with anhidrosis is a rare inherited disorder. Genetic molecular genetic analysis is helpful to diagnose and discover new gene mutations.
Channelopathies ; Humans ; Infant ; Mutation ; Pain Insensitivity, Congenital ; Receptor, trkA

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare disease that affects the sensory and autonomic nervous system. The patients do not have the ability to sense different sensations, such as pain, which tends to lead to different injuries. In addition, the patients suffer from fluctuations in body temperature due to autonomic involvement. The present case was a five-year-old girl with a neglected distal femur fracture. X-rays taken during the follow-up showed marked callus formation and pseudarthrosis of the distal femur. She had biting injuries of the tongue, auto-amputation of the fingers, some developmental delay and a history of recurrent fever with an unknown origin. The electrodiagnostic study was normal. The quantitative sudomotor axon reflex test revealed markedly reduced postganglionic sudomotor axonal responses at all sites recorded on the left. She was diagnosed with CIPA. As the initial presentation of CIPA involves the musculoskeletal system, orthopedic surgeons should have a high index of suspicion.
Autonomic Nervous System ; Axons ; Body Temperature ; Bony Callus ; Female ; Femur ; Fever ; Fingers ; Follow-Up Studies ; Hereditary Sensory and Autonomic Neuropathies ; Humans ; Musculoskeletal System ; Orthopedics ; Pain Insensitivity, Congenital ; Pseudarthrosis ; Rare Diseases ; Reflex ; Sensation ; Surgeons ; Tongue

No abstract available.
Hypohidrosis* ; Pain Insensitivity, Congenital*

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.
Pain Insensitivity, Congenital

Adolescent ; Female ; Humans ; Hypohidrosis ; diagnosis ; Male ; Pain Insensitivity, Congenital ; diagnosis ; Siblings

Female ; Humans ; Infant ; Mutation ; Pain Insensitivity, Congenital ; complications ; genetics ; pathology ; Receptor, trkA ; genetics

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare hereditary sensory and autonomic neuropathy. CIPA is characterized by inability to sweat, insensitivity to pain, self-mutilation, recurrent episodes of hyperpyrexia, mental retardation, and autonomic nervous system abnormality. Patients with CIPA may undergo surgery because of susceptibility to trauma, bony fracture and osteomyelitis due to insensitivity to pain. We report a child who had undergone anesthesia with total intravenous anesthesia. The anesthetic management of this condition is discussed.
Anesthesia ; Anesthesia, Intravenous ; Autonomic Nervous System ; Child* ; Hereditary Sensory and Autonomic Neuropathies* ; Humans ; Intellectual Disability ; Osteomyelitis ; Pain Insensitivity, Congenital* ; Propofol ; Sweat

PURPOSE: Congenital insensitivity to pain with anhidrosis(CIPA) is a rare form of autosomal recessive peripheral sensory neuropathy. Patients with CIPA show loss of pain sensation, which leads to corneal ulcers and opacities, self-mutilation of the tongue and fingertips, as well as fractures with subsequent joint deformities and chronic osteomyelitis. The purpose of this report is to highlight the fact that pressure sores also are a potential complication of CIPA. METHODS: This case report describes a patient presenting with pressure sores resulting from CIPA. A 5-year-old boy was referred to our department for the treatment of a 5x5cm sacral pressure sore as a result of a hip spica cast applied for the treatment of a left hip joint dislocation. He had a history suggesting CIPA such as multiple bony fractures, mental retardation, recurrent hyperpyrexia, anhidrosis, and clubbing fingers due to oral mutilation. A microscopic examination of the sural nerve showed mainly large myelinated fibers, a few small myelinated fibers and an almost complete loss of unmyelinated fibers. After wound preparation for two weeks, the exposed bone was covered with two local advancement flaps. RESULTS: Two weeks later, complete wound healing was achieved. A 16-month follow-up showed no recurrence. However, the patient presented with a new pressure sore on the left knee due to orthosis for the treatment of the left hip joint dislocation. CONCLUSION: The early diagnosis of CIPA and special care of pressure sores are important for preventing and treating pressure sores resulting from CIPA.
Child, Preschool ; Congenital Abnormalities ; Dislocations ; Early Diagnosis ; Fingers ; Follow-Up Studies ; Hereditary Sensory and Autonomic Neuropathies* ; Hip ; Hip Joint ; Humans ; Hypohidrosis ; Intellectual Disability ; Joints ; Knee ; Male ; Myelin Sheath ; Nerve Fibers, Myelinated ; Orthotic Devices ; Osteomyelitis ; Pain Insensitivity, Congenital* ; Pressure Ulcer* ; Recurrence ; Sensation ; Sural Nerve ; Tongue ; Ulcer ; Wound Healing ; Wounds and Injuries