|Year : 2019 | Volume
| Issue : 3 | Page : 308-310
Congenital insensitivity to pain in a 1-year-old boy
MK Navya, GV Pramod, GP Sujatha, L Ashok
Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere, Karnataka, India
|Date of Web Publication||30-Sep-2019|
Dr. M K Navya
Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
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.
Keywords: Congenital insensitivity to pain, PRDM12 gene, self-mutilation
|How to cite this article:|
Navya M K, Pramod G V, Sujatha G P, Ashok L. Congenital insensitivity to pain in a 1-year-old boy. J Indian Soc Pedod Prev Dent 2019;37:308-10
|How to cite this URL:|
Navya M K, Pramod G V, Sujatha G P, Ashok L. Congenital insensitivity to pain in a 1-year-old boy. J Indian Soc Pedod Prev Dent [serial online] 2019 [cited 2020 Apr 1];37:308-10. Available from: http://www.jisppd.com/text.asp?2019/37/3/308/268183
| Introduction|| |
Pain is an unpleasant sensation caused due to injury. It is a mechanism which warns us from injury or tissue damage and loss of pain sensation is a dangerous condition. Congenital insensitivity to pain (CIP) is one such condition in which the child cannot sense the pain and cause severe injuries which remains unnoticed or there can be self-mutilating behavior causing oral perioral injuries and injuries in extremities. Early identification of the condition is necessary to educate the parents regarding the state of their child and hence that proper preventive measures can be taken as this disease does not have proper treatment.
| Case Report|| |
A 1-year-old boy reported to the Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, with the complaint of ulcers in the hands and mouth for 1 month. Ulcers were insidious in onset, gradually progressing associated with pain, and the patient had the habit of biting himself. He also had a frequent history of fever. His family history revealed that his parents had consanguineous marriage (cousins) and he was their first child. His mother was pregnant for the second time during the visit. No other family members have a similar history. General physical examination of the patient for pain sensitivity revealed reduced sensation to pain. Decreased motor function of limbs was evident. On extraoral examination, brachycephaly was evident, flattening of the occiput, ulceration was evident on the right thumb extending from the interphalangeal junction till the tip of the thumb, about 2 cm × 1.5 cm roughly oval, irregular border, erythematous base, and crusting evident on the inferior aspect of the ulcer. Ulceration was also evident on the lower lip, involving most of the lower lip, diffuse borders with pseudomembrane formation. Bilateral submandibular lymphadenopathy was present [Figure 1]. On intraoral examination, diffuse ulcerations were evident involving the tip and ventral aspect of the tongue and lower anterior alveolar mucosa. Indentations of the upper primary teeth were evident on the lip as well as the alveolar mucosa suggesting a habit of self-mutilation. Primary central and lateral incisors were present in the upper arch, and 61 was labially displaced. Based on the history and clinical examination, CIP was suspected along with oral candidiasis, and the patient was referred to a pediatrician for further evaluation. Meanwhile, he was advised to use candid gum paint (clotrimazole 1% w/v) for oral lesions and candid cream (clotrimazole 1% cream) for ulceration in the hand 3–4 times daily to apply over the ulcers, also parents were advised to restrict the child from biting his hand. The patient then underwent genetic analysis which revealed a novel mutation in the exon 5 of PRDM12 gene and was interpreted as having hereditary sensory and autonomic neuropathy (HSAN). His clinical features were suggestive of HSAN type IV also called CIP. The patient was followed up for about 2 months and lesions healed completely with mild scars on the thumb with atrophy of the nails.
|Figure 1: Selfinflicted injuries on the lower lip, right thumb and lower alveolar mucosa and tip of the tongue|
Click here to view
After 6 months, the patient again visited the department with a loose tooth in the upper front teeth region. On evaluation, 52 had displaced apically and was mobile. The patient had difficulty in suckling. Furthermore, 51, 61, and 63 were carious [Figure 2]. Pseudomembrane formation was evident on the gingiva. The patient was then referred to the Department of Pedodontics for the extraction of the mobile tooth and appliance fabrication to prevent self-mutilation. The patient is still under treatment and kept under follow-up.
|Figure 2: Post 6 months, healing of lesion in the thumb and oral mucosa and apically displaced 52|
Click here to view
| Discussion|| |
PRDM12 is a 5-exon gene encoding a single protein isoform of 367 amino acids-containing a PR domain (related to the SET methyltransferase domain), three zinc fingers, and a C-terminal poly-alanine tract. PRDM12 is essential for pain-sensing in humans as pathogenic mutations cause congenital painlessness. CIP is an autosomal recessive genetic disease caused by a mutation in various different genes such as PRDM12 gene, SCN9A gene, and NTRK1 gene. It was first described by Swanson in 1963. Most of the cases of CIP have occurred in parents who had consanguineous marriage. Usually, in CIP, mutations in the NTRK1 gene, located on chromosome 1 that encodes the tyrosine kinase receptor for nerve growth factor are detected. This results in the failure of differentiation and migration of neural crest cells, leading to the complete absence of small myelinated and unmyelinated nerve fibers resulting in the loss of pain and temperature sensations. However, in our case, there was a mutation in the exon 5 of PRDM12 gene which causes a defect in the synthesis of PRDM protein which is an essential regulator for control of neural specification and neurogenesis.
According to a study conducted by Chen et al., a mutation in PDRM12 gene caused features similar to CIP and HSAN. Patients were unable to feel acute or inflammatory pain from birth and could not identify noxious heat or cold. Infants had a painless mutilating tongue, perioral, and finger lesions due to repeated self-biting and sustained multiple injuries as the result of repeated trauma and burns due to negligence. These features are similar to those of our case. Here also, the child was unable to sense pain and had a tongue, perioral lesions, and habit of self-mutilation.
The characteristic features of CIP are frequent episodes of fever, mental retardation, insensitivity to pain, and self-mutilating behavior. All these features were consistent in our case also. There was no sign of fracture and anhidrosis in our case. Hence, it cannot be classified as a Type IV HSAN, but it is considered as a type of HSAN on the basis of genetic analysis as well as the clinical features.
The management of such cases requires a multidisciplinary approach wherein an oral physician, pediatrician, and a pedodontist play a crucial role. Although CIP is a totally painless disorder, still it can lead to dangerous effects. There is no specific treatment for this condition only symptomatic management and preventive measures can be taken. Severe fever and traumatic complications require frequent medical attention. Children with CIP should be monitored closely to prevent injuries, burns, fractures, corneal ulceration, and self-mutilation. The parents should be educated about simple measures such as avoiding excessive wrapping, preventing dehydration, and measures to reduce hyperpyrexia, which reduce a lot of preventable deaths.
In this case, we identified the disease and gave symptomatic treatment to the patient and referred him to a pediatrician to evaluate further and carry out gene analysis following which treatment was initiated by the pediatrician. Later, when the patient reported with trauma to the tooth, then we evaluated and referred the patient to pedodontist for further evaluation and treatment planning. A proper clinical evaluation and genetic analysis are required to confirm the diagnosis. In the case of severe trauma to oral structures, a mouthguard can be given to the patient which in many reports have shown great results.
| Conclusion|| |
Loss of pain sensation is a dangerous condition wherein patient will not be able to perceive pain sensation leading to unnoticed wounds and fractures which can be life-threatening. CIP is one such condition and early identification if this is usually due to self-mutilating behavior and frequent hyperpyrexia. Genetic analysis is mandatory to identify the disease and symptomatic management along with education of parents regarding measures to be taken to prevent future injuries should be carried out. The management of the disease is a multidisciplinary approach where the dentists, as well as the pediatrician, have to contribute equally.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, et al.
Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet 2015;47:803-8.
Thakur LC, Chandran V, Anand KS. Congenital sensory neuropathy with anhidrosis. Indian Pediatr 1992;29:1046-8.
Udayashankar C, Oudeacoumar P, Nath AK. Congenital insensitivity to pain and anhidrosis: A case report from South India. Indian J Dermatol 2012;57:503.
] [Full text]
Chittka A, Nitarska J, Grazini U, Richardson WD. Transcription factor positive regulatory domain 4 (PRDM4) recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation. J Biol Chem 2012;287:42995-3006.
John D, Thomas M, Jacob P. Neurotrophic keratitis and congenital insensitivity to pain with anhidrosis – A case report with 10-year follow-up. Cornea 2011;30:100-2.
Peddareddygari LR, Oberoi K, Grewal RP. Congenital insensitivity to pain: A case report and review of the literature. Case Rep Neurol Med 2014;2014:141953.
Gupta B. Congenital insensitivity of pain with anhidrosis. Indian J Pediatr 2003;70:109-11.
Reilly MM. Classification and diagnosis of the inherited neuropathies. Ann Indian Acad Neurol 2009;12:80-8.
] [Full text]
[Figure 1], [Figure 2]