Abstract
Congenital pain insensitivity syndrome with anhidrosis (CIPA, MIM 256800 ) or hereditary sensory and autonomic neuropathy (HSAN) type IV is a rare autosomal recessive disease. CIPA has characteristic symptoms such as failure to respond to painful stimuli, lack of thermal sensitivity, decreased or absent sweating (anhidrosis), varying degrees of reduced intellectual disability, musculoskeletal fractures, and joint deformities. A 4-year-old female patient diagnosed with CIPA syndrome presented to our clinic with the complaint of self-harm with her anterior teeth. In the clinical examination, sores were detected on the child’s hands, fingers, mouth, and tongue. The front teeth of the patient, which caused the trauma, were extracted. In the 6-month follow-up, the patient’s wounds healed. In this case report, the treatment of a patient with CIPA syndrome who was severely self-harming is described.
1
Introduction
Congenital pain insensitivity syndrome with anhidrosis (CIPA, MIM 256800 ) or hereditary sensory and autonomic neuropathy (HSAN) type IV is a rare autosomal recessive disease [ ]. The incidence of CIPA is estimated to be between 130 and 210 individuals in Japan, which corresponds to approximately one in 600,000 to 950,000 people [ ]. CIPA is caused by a mutation in the neuropathic tyrosine kinase receptor type 1 (NTRK 1) gene, which encodes tropomyosin-related kinase A acting as a receptor for nerve growth factor (NGF) [ ]. NGF is involved in the development and function of sympathetic and sensory neurons involved in immune and inflammatory function after tissue injury [ ]. As a result of defective NGF proteins, the development of myelinated and unmyelinated peripheral autonomic nerve fibers is impaired [ ]. Loss of pain sensation and anhidrosis are seen in CIPA syndrome due to the absence of these nerve fibers [ ]. CIPA has characteristic findings such as failure to respond to painful stimuli, lack of thermal sensitivity, decreased or absent sweating (anhidrosis), varying degrees of reduced intellectual disability, musculoskeletal fractures, and joint deformities [ ]. Since there is no pain sensitivity in this syndrome, self-injury behavior such as biting the tongue and lip, painless fractures, bruises, infection of wound sites, osteomyelitis, and digital amputations are seen [ , ].
This case report aimed to describe the oral findings and treatment of a patient with CIPA syndrome.
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Case report
A 4-year-old female patient presented to the Faculty of Dentistry of University with the complaint of injury due to chewing her tongue. Consent was obtained from the patient’s parents that the case would be reported, and the Declaration of Helsinki was followed in the follow-up of the case. According to the anamnesis taken from the patient, she was diagnosed with CIPA syndrome and had a tendency to self-harm. In the clinical examination, in addition to the signs of hyperactivity and mental retardation, bite wounds and scar tissue on her cheek, tongue, arms, and fingers, and extensive dental caries were observed ( Fig. 1 ). The patient was 90 cm and 19 kg. The patient’s parents were seventh-generation relatives, indicating a distant familial connection spanning six generations back to a common ancestor. Despite this distant consanguinity, no other cases of this syndrome were reported within the extended family lineage. Her mother had been treated for hypothyroidism throughout her pregnancy. There were no complications during the delivery of the patient, but she was hospitalized for 10 days after delivery due to infection. The patient had an atrial septal defect when she was born and it healed later. The patient did not have a febrile seizure before, and there was no deformity or sweating in her head and eyes. In the patient several joint-related symptoms were observed, including frequent joint dislocations and deformities, which are commonly associated with the condition due to the lack of protective pain sensations. Additionally, the patient experienced cyclical vomiting, a recurrent issue often linked to autonomic dysfunction in CIPA. The patient’s treatment regimen included various medications aimed at managing autonomic dysregulation and gastrointestinal symptoms. Ongoing medical follow-up was crucial to monitor potential complications, including orthopedic and gastrointestinal issues. The patient’s family played a vital role in their care, providing consistent support and ensuring adherence to medical advice, which is essential given the complex nature of CIPA and the patient’s vulnerability to injury and other complications. Her family did not remember when the child’s first tooth erupted, but she started hurting herself with her teeth around the age of one.
The patient’s teeth 64 and 74 were extracted under general anesthesia. Root canal treatment was performed for teeth 54, 55, 65, 75, 84, and 85. A stainless steel crown was applied to tooth 54 and compomer filling to tooth 53, all of which were conducted by another dentist at a private dental clinic.
In the oral examination of the patient, it was determined that the teeth numbered 51, 52, 53, 54, 55, 61, 62, 63, 65, 75, 83, 84, and 85 were in the mouth ( Fig. 2 ).
The family stated that the child avulsed a few teeth by biting on a cloth or a hard object. Since teeth 71, 72, 73, 81, and 82 were not in the mouth, these teeth were thought to be avulsed. Caries was detected in teeth 51, 61, and 62 ( Fig. 2 ). Biting wounds were detected on the tongue and lips ( Figs. 3 and 4 ).
No radiographs were taken. The patient’s teeth 51, 61, and 62 were extracted without local anesthesia ( Fig. 5 ). Due to the patient’s inability to regulate body temperature, special precautions were taken to prevent hyperthermia, as CIPA patients face a risk of elevated body temperature during stressful procedures. The treatment environment was kept cool, and the patient was monitored closely to manage any potential increase in body temperature [ ]. Based on the clinical examination, including palpation, mobility, and percussion tests, there were no signs of active infection in the patient. Therefore, the use of antibiotics was not deemed necessary. The absence of symptomatic indicators such as swelling, tenderness, or abnormal mobility suggested that the carious lesions, although severe, did not warrant antibiotic therapy. Post-extraction, a broad-spectrum antibiotic was prescribed orally to mitigate the risk of infection. The parents were advised to apply chlorhexidine-containing spray to heal the oral wounds after extraction.
