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Congenital insensitivity to pain with anhidrosis (CIPA) is a rare disease which mainly affects infants, children and adolescents. As an autosomal recessive disorder, CIPA is also known as familial autonomic dysfunction type 2. The diagnosis of CIPA mainly relies on clinical observation and genetic testing. Currently there is lack of effective treatment, and it is mainly treated by cooling, anti-inflammatory and strengthened guardianization. This article has reviewed the literature and summarized the research on CIPA and progress made in its diagnosis and treatment, with an aim to improve the understanding of this disorder.

A 22-month-old girl of consanguineous parents was admitted with a high-grade fever. She was found to have insensitivity to painful stimuli and an absence of perspiration. She also displayed self-mutilating behaviour and was insensitive to cold/hot water on her body. On examination, there was loss of the tip of the tongue, missing teeth, generalised xerosis, and several ulcers at sites of minor trauma. She also had dysplastic nails and digital ulcers. Sensory examination demonstrated a complete lack of awareness of pain and temperature, vibration and fine touch were intact and lacrimation was normal. Differential diagnoses of hereditary sensory and autonomic neuropathy (HSAN), Lesch-Nyhan syndrome, hypohidrotic ectodermal dysplasia and leprosy were considered. Results of routine blood investigations including serum uric acid were normal. On performing clinical exome sequencing, the diagnosis of congenital insensitivity to pain with anhidrosis (CIPA) of autosomal recessive inheritance was confirmed. A novel, predicted to be pathogenic variant detected at exon 16 of the NTRK1 gene resulting in congenital insensitivity to pain with anhidrosis is reported. Abbreviations: CIPA: congenital Insensitivity to pain with anhidrosis; HSAN: hereditary sensory and autonomic neuropathy; NGF: nerve growth factor; NTRK1: neurotrophic tyrosine kinase receptor 1 gene; TrKA: tropomyosin receptor kinase A.

Rationale: Hereditary sensory and autonomic neuropathy type IV (HSAN IV) may be misdiagnosed because of low awareness among clinical professionals and overlap with other subtypes of congenital insensitivity to pain (CIP)., Patient: The patient was a 1-year-and-5-months-old boy whose main symptoms were delayed psychomotor development and recurrent fever. Whole-exome sequencing (WES) revealed a compound heterozygous mutation (c. 1927C > T, c. 851-33T > A) in the NTRK1 gene of the child. Pathological analysis showed decreased autonomic small nerve fibers, sparse hair follicles, and atrophy of the sweat glands. Sweat glands lack innervating nerve fibers. Brain magnetic resonance imaging (MRI) of the patient showed delayed myelination in the brain, slightly enlarged bilateral lateral ventricles, and patchy abnormal signals in the brain., Diagnosis: hereditary sensory and autonomic neuropathy type IV (HSAN IV)., Intervention: Inform parents about the illness and take good care of the child., Outcomes: The children had less self-harming behavior and no painless fractures during follow-up at 2 years., Lessons: This report describes the pathological and imaging features and clinical manifestations of a child with HSAN IV in early life to provide a reference for the early diagnosis of the disease. Early diagnosis can help avoid self-mutilation and painless injury and reduce wound infection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To describe ocular manifestations in children with congenital insensitivity to pain with and without anhidrosis (CIPA and CIP)., Methods: We reviewed records of eye examinations of 39 children diagnosed with CIPA or CIP. We collected clinical data, with particular attention to ocular surface findings. Corneal sensitivity was tested by presence of a blink reflex upon touching the cornea. Statistical analysis assessed differences in manifestations between the two conditions, and relationships among corneal sensitivity, presence of corneal opacities and visual acuity (VA)., Results: CIPA was diagnosed in 32 children and CIP in 7. The median follow-up periods were 50 months (CIPA group) and 94 months (CIP group). Corneal opacities were present in 23% of CIPA eyes and in 57% of CIP eyes. A blink reflex was positive in 52% of CIPA eyes and in 33% of CIP eyes. We recorded VA ≥20/25 in 36% of CIPA eyes, whereas all patients with CIP had VA ≤20/30. For the whole cohort, we found a negative correlation between a preserved blink reflex and the presence of corneal opacities, and a positive correlation between a preserved blink reflex and VA ≥20/25., Conclusion: Children with congenital insensitivity to pain are prone to develop corneal scarring. Patients with CIP tend to have more severe ocular surface disease than those with CIPA, probably due to more prevalent loss of corneal sensation. In both groups, a preserved blink reflex correlated with good vision. Affected children should have close follow-up to promptly treat ocular surface disease and prevent vision loss., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In this case report, we described the past history, clinical manifestations, genetic characteristics and cognitive evaluation of a boy with congenital insensitivity to pain with anhidrosis (CIPA) who developed autism spectrum disorder (ASD)., Case Presentation: The boy had an early onset of CIPA at the age of 48 months, and was later diagnosed with ASD at 5 years old. Developmental delays in communication, social skills and the presence of maladaptive behaviors were observed in the patient. Professional treatments significantly improved the developmental delays., Conclusions: This case demonstrated that ASD may develop in children with CIPA, and pediatricians should be aware that if they suspect or identify a child with CIPA that they should also be screened for ASD using similar examination and diagnostic tools as shown in the present report. Moreover, therapeutic interventions for ASD was helpful for the remission of both diseases., (© 2022. The Author(s).)

Background: Congenital insensitivity to pain is a rare autosomal recessive condition characterized by insensitivity to painful stimuli due to absence of sensory and sympathetic post ganglionic neurons in the skin and skeletal system leading to lack of protective sensation and altered joint propioception. This study was performed to assess hand and wrist manifestations of patients with congenital insensitivity to pain in the Maltese Islands. Methods: Records of public and private hospitals were reviewed to identify patients suffering from this condition. A review of notes, patients, and imaging was performed. A Disabilities of the Arm, Shoulder, and Hand score was obtained to assess level of function. Results: Nine patients were identified. Mean age of diagnosis was 8.9 years. Interphalangeal joints were most commonly affected. Multiple spontaneous or posttraumatic fingertip ulceration occurred in 5 patients. Anhidrosis resulted in more protracted ulcers and infections, requiring amputation of distal and middle phalanges due to osteomyelitis. The wrist joint was less commonly involved and showed more complex joint involvement. Conclusion: The hand and wrist are involved in different ways, with fingertip ulceration leading to potential infection and osteomyelitis in the hand, whereas the wrist joint is involved in cases of increased axial loading and load transfer, such as following prolonged use of walking and mobility aids. The latter should be borne in mind during management of lower limb conditions. Hand care and hygiene is important in all patients, especially in cases of anhidrosis due to the increased rate of ulceration and osteomyelitis requiring surgical intervention. Despite the severity of the condition, patients report good overall function.

Purpose: To report the findings of a comprehensive eye examination from an individual with congenital insensitivity to pain because of loss-of-function mutations in the SCN9A gene., Methods: Ophthalmologic examination and confocal microscopy were performed on a patient with congenital insensitivity to pain., Results: A 39-year-old man with compound heterozygous mutations in the SCN9A gene underwent examination. Cochet-Bonnet esthesiometry readings averaged 38 mm (SD 8 mm) in the right eye and 55 mm (SD 7 mm) in the left eye. Other corneal findings included mild conjunctival lissamine green staining, nonvisually significant corneal scars, mild anterior basement membrane dystrophy, and a tear breakup time of 3 seconds in each eye. In vivo confocal microscopy of the corneal subbasal nerve plexus revealed relatively normal corneal nerve morphology, but a reduction in corneal nerve fiber density., Conclusions: An individual with loss-of-function mutations in SCN9A had reduced corneal nerve fiber density but normal corneal mechanoreception., Competing Interests: A. Delwig is an employee of SiteOne Therapeutics. S. G. Waxman is a consultant to SiteOne. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Paul Ferdinand Schilder was born in Vienna in 1886 and died in New York in 1940. Today he is remembered particularly as a psychoanalyst and a psychotherapist. His research in neuroscience, however, was also both comprehensive and innovative. For example, he is considered to be the first to describe Schilder's disease, which was named after him. This article focuses on pain asymbolia, which was also first described by Schilder, and is currently little known and considered to be rarely encountered. Pain asymbolia is a central impairment of pain experience with no negative affective-emotional component. The basis of Schilder's discovery and the differential diagnosis of pain asymbolia was the detailed examination of eleven medical cases between 1928 and 1930. His publications on the condition are characterized by meticulousness, progressive thinking and critical reflection. He nosologically assigned pain asymbolia to the group of agnosias and integrated it into the concept of body image, which was a central issue in his entire scientific work. This article additionally addresses the question of whether Schilder's assumptions are still valid today and what consequences might arise from this.

Congenital insensitivity to pain is an umbrella term used to describe a group of rare genetic diseases also classified as hereditary sensory autonomic neuropathies. These conditions are intriguing, with the potential to shed light on the poorly understood relationship concerning nociception and the experience of pain. However, the term congenital insensitivity to pain is epistemologically incorrect and is the product of historical circumstances. The term conflates pain and nociception and, thus, prevents researchers and caregivers from grasping the full dimensions of these conditions. The aims of this article were to review the epistemological problems surrounding the term, to demonstrate why the term is inaccurate and to suggest a new term, namely, congenital nociceptor deficiency. The suggested term better reflects the nature of the conditions and incorporates current understandings of nociception. PERSPECTIVE: The umbrella term congenital insensitivity to pain conflates pain and nociception, which is epistemologically unacceptable. We suggest a new term, namely, congenital nociceptor deficiency, that overcomes this problem and is concordant with current neurobiological knowledge., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Congenital analgesia is a rare condition, reporting in the international literature in rare cases since 1932, when it was first described. Its cause has been the subject of development of multiple theories and studies through the years. Currently various studies and experiments as its origin point mutation in the gene encoding SC9NA sodium channels, which have an important role in nociceptive transmission signals in the human body. The purpose of this study is to present two cases that were valued in the department of pediatric orthopedics at UMAE HTYOLV, patients whose insensitivity to pain has produced significant injuries that were once cause for valuation of the hospital.

Background: Hereditary sensory and autonomic neuropathy type VIII is a rare autosomal recessive inherited disorder. Chen et al. recently identified the causative gene and characterized biallelic mutations in the PR domain-containing protein 12 gene, which plays a role in the development of pain-sensing nerve cells. Our patient's family was included in Chen and colleagues' study. We performed a literature review of the PubMed library (January 1985 to December 2016) on hereditary sensory and autonomic neuropathy type I to VIII genetic disorders and their orofacial manifestations. This case report is the first to describe the oral manifestations, and their treatment, of the recently discovered hereditary sensory and autonomic neuropathy type VIII in the medical and dental literature., Case Presentation: We report on the oral manifestations and dental management of an 8-month-old white boy with hereditary sensory and autonomic neuropathy-VIII over a period of 16 years. Our patient was homozygous for a mutation of PR domain-containing protein 12 gene and was characterized by insensitivity to pain and thermal stimuli, self-mutilation behavior, reduced sweat and tear production, absence of corneal reflexes, and multiple skin and bone infections. Oral manifestations included premature loss of teeth, associated with dental traumata and self-mutilation, severe soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary teeth, and mandibular osteomyelitis., Conclusions: The lack of scientific knowledge on hereditary sensory and autonomic neuropathy due to the rarity of the disease often results in a delay in diagnosis, which is of substantial importance for the prevention of many complications and symptoms. Interdisciplinary work of specialized medical and dental teams and development of a standardized treatment protocols are essential for the management of the disease. There are many knowledge gaps concerning the management of patients with hereditary sensory and autonomic neuropathy-VIII, therefore more research on an international basis is needed.

Terminal and interstitial deletions of the distal segment of the long arm of chromosome 4 (Cr4q del) are not common genetic disorders. The severity of the phenotype is correlated with the size of the deletion because small deletions have little clinical impact, whereas large deletions are usually associated with multiple congenital anomalies, postnatal growth failure, and moderate to severe intellectual disability. Alteration in pain tolerance has not been included among these features, also in case of large deletions. The purpose of this report is to document a case of a child affected by interstitial Cr4q del, expressing pain insensitivity as clinical feature not previously described. We also offer a discussion on genetic disorders featuring pain insensitivity/indifference., Case Report: A Caucasian girl aged 12 came to our observation for a developmental delay with multiple congenital abnormalities and moderate intellectual disability (IQ 47). A de novo interstitial Cr4 del between band q31.3 and q32.2 (Cr4 del q31.3 to q32.2) was found. The child also expresses no evidence of pain perception to injures which normally evoke pain. Consequently, she is affected by severe disability caused by painless injuries and self-injurious behaviours, such as excessive self-rubbing and scratching. The neurological examination manifested high pain threshold with preserved tactile sensitivity., Conclusions: This is the first report of pain insensitivity in a patient with a specific genetic deletion involving the interstitial region of the distal long arm of Cr4. Moreover, this report could serve as a useful model to better understand mechanisms of pain perception and its modulation.

Background: Congenital insensitivity to pain and anhidrosis (CIPA) is a rare clinical condition characterized by the absence of normal subjective and objective responses to noxious stimuli in patients with intact central and peripheral nervous systems., Case Presentations: Two patients with CIPA are reported. The first patient was a 13-year-old girl who presented to our hospital with multiple joint destructions secondary to osteomyelitis. The second patient was a 10-year-old boy who presented with multiple hand lesions and right leg osteomyelitis. Our patients were treated with multiple debridements and intravenous antibiotics according to our hospital protocol., Conclusion: Early recognition of the disease is important. The treatment for this condition is focused more on the prevention of bone injuries and joint infection, as opposed to a cure. There are no standard techniques or guidelines available to treat this rare disease. Overall, effective CIPA treatment is built around family education and patient training.

Background: Congenital insensitivity to pain (CIP) is a rare extreme phenotype characterised by an inability to perceive pain present from birth due to lack of, or malfunction of, nociceptors. PRDM12 has recently been identified as a new gene that can cause CIP. The full phenotype and natural history have not yet been reported., Methods: We have ascertained five adult patients and report their clinical features., Results: Based on our findings, and those of previous patients, we describe the natural history of the PRDM12-CIP disorder, and derive diagnostic and management features to guide the clinical management of patients., Conclusions: PRDM12-CIP is a distinct and diagnosable disorder, and requires specific clinical management to minimise predictable complications., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

An emerging class of mitochondrial disorders is caused by mutations in nuclear genes affecting mitochondrial dynamics and function. One of these is the DNM1L gene encoding the dynamin-related protein 1 (DRP1), which is pivotal in the mitochondrial fission process. Here, we describe a patient with a novel dominant-negative, de novo DNM1L mutation, which expands the clinical spectrum. The patient reported here exhibits a chronic neurological disorder, characterized by postnatal microcephaly, developmental delay, and pain insensitivity. Muscle biopsy disclosed decreased respiratory chain complex IV activity. Exome sequencing showed a de novo heterozygous c.1084G>A (p.G362S) mutation. Subsequent studies of patient skin fibroblasts showed markedly impaired mitochondrial fission and a partial respiratory chain defect while peroxisomal morphology remained intact. Human foreskin fibroblasts over-expressing the mutant DNM1L gene displayed aberrant mitochondrial morphology. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Loss of pain perception can result from neurodevelopmental defects, degeneration of nociceptive fibers, or altered excitability of sensory neurons. Hereditary neurodegeneration leading to pain loss is classified as sensory and autonomic neuropathy (HSAN). Mutations in approximately 15 genes have been identified in the group of HSAN disorders. Hallmark of the disease is a liability to injury because of impaired acute pain as a warning system to prevent harm. The clinically overlapping "congenital insensitivity to pain (CIP)" is caused by mutations in voltage-gated sodium channels, which control the excitability of nociceptors. However, mutations in the latter genes can also result in disorders with increased pain susceptibility. This review summarizes the clinical presentation of HSAN and pain-related channelopathies and discusses the underlying disease mechanisms.

Hereditary sensory and autonomic neuropathy (HSAN) IV is a rare autosomal recessive disorder which is characterized by a decrease in the number of myelinated and non-myelinated nerve fibers of peripheral nerves which causes diminished or absent pain sensation leading to increase in self-mutilative habits. A retrospective study of eight cases ranging from age group of 4 to 17 years for oral and digital signs and symptoms is presented. All the patients showed congenital insensitivity to pain and anhidrosis. Oral self-mutilations, such as autoextraction of teeth and severe bite injuries (with resultant scarring) of the finger tips and oral soft tissues (tongue, lip, and buccal mucosa) were found in most patients. Our study suggests that early diagnosis and specific treatment plan are important for prevention of characteristic of the oral as well as digital trauma associated with this disorder.

Congenital indifference to pain is a rare and debilitating congenital disease. Individuals with the disorder may have one or a combination of sensory or autonomic deficits, which can range from lack of mechanical nociception, diminished ability to detect heat and cool stimulation, to the devastating and fatal form which includes autonomic dysfunction. It is important for radiologists to be able to recognize the radiographic presentations of this rare disorder, as delay in diagnosis can lead to extensive and sometimes unnecessary workup. We present a case of congenital indifference to pain initially interpreted as a mass of the distal femur.

We present a case study of a 10-year-old child with severe burns that were misinterpreted as inflicted burns. Because of multiple injuries since early life, the family was under suspicion of child abuse and therefore under supervision of the Child Care Board for 2 years before the boy was burned. Because the boy incurred the burns without feeling pain, we conducted a thorough medical examination and laboratory testing, evaluated detection and pain thresholds, and used MRI to study brain morphology and brain activation patterns during pain between this patient and 3 healthy age- and gender-matched controls. We found elevated detection and pain thresholds and lower brain activation during pain in the patient compared with the healthy controls and reference values. The patient received the diagnosis of hereditary sensory and autonomic neuropathy type IV on the basis of clinical findings and the laboratory testing, complemented with the altered pain and detection thresholds and MRI findings. Hereditary sensory and autonomic neuropathy IV is a very rare congenital pain insensitivity syndrome characterized by the absence of pain and temperature sensation combined with oral mutilation due to unawareness, fractures, and anhidrosis caused by abnormalities in the peripheral nerves. Health care workers should be aware of the potential presence of this disease to prevent false accusations of child abuse., (Copyright © 2014 by the American Academy of Pediatrics.)

Congenital insensitivity to pain is a rare hereditary sensory and autonomic neuropathy (HSAN). This disorder is an autosomal recessive condition: since 1996, mutations attributed to this entity have been found in the neurotrophin tyrosine-kinase gene receptor on chromosome 1. The authors report 3 cases of congenital insensitivity to pain. In these 3 sisters of consanguineous parents, the clinical investigation showed total absence of pain and temperature sensations with preservation of all other sensory modalities, mental retardation, but in contrast to HSAN type IV, there was no anhidrosis. The neurophysiological investigation revealed an isolated axonal sensory polyneuropathy in the 3 patients. The clinical and neurophysiological investigations were normal in both parents and the brother. The physiopathology of this entity is discussed. We suggest a particular form of HSAN type IV with preservation of transpiration or a new entity of congenital insensitivity to pain, which should be analyzed genetically., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare disorder, most often of genetic origin., Case Report: The authors present the case of two siblings, 10 and 13 years old, both followed-up since the age of 2 for CIPA diagnosed after discovering insensitivity to pain during iterative falls, burns, and of severe oro-digital self-mutilating behavior. Sural nerve biopsy and an electromyogram confirmed the diagnosis., Discussion: CIPA with anhidrosis is a very rare disease. It is characterized by unexplained fever episodes, anhidrosis, pain insensitivity, self-mutilating behavior, and sometimes mental retardation. Complications of this insensitivity (non-treated fractures, burns, and oro-digital mutilation) may be lethal. Treatment remains preventive. The patient must observe a very strict hygiene. Prevention for maxillofacial involvement consists in breaking the cycle of oral self-mutilation., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the frequency of mandibular osteomyelitis (OM) in patients with congenital insensitivity to pain with anhidrosis (CIPA) and to relate its appearance to possible risk factors., Methods: The records of 33 patients were reviewed for data concerning events of jaw OM, oral trauma, maxillofacial interventions, or OM of long bones., Results: Eighteen percent of the patients had mandibular OM. Of the six patients, preceding oral laceration was documented in one and tooth extraction in two. Seventy percent of the patients had OM of the limbs, but only 15% overlapped, having both jaw and limb OM. Half of the patients with mandibular OM had also OM of the limbs during the following year. There seems to be a correlation between high frequency of limb OM (at least 5 events per patient) and appearance of mandibular OM., Conclusion: The incidence of mandibular OM is very high among patients with CIPA and can result in pathologic fracture and the need for open reduction and internal fixation. The reason for this phenomenon is presently not clear. Preventive and therapeutic strategy for CIPA patients should be undertaken to minimize this severe complication., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Osseous injuries are a major facet of child abuse and in most patients radiographic imaging plays a major role in diagnosis. While some injuries are typically produced as a result of excessive and inappropriate force other injuries are nonspecific in terms of their causation, but become suspicious when the history provided by the caretakers is inconsistent with the type of injury produced., Questions/purposes: I detail the radiographic imaging of the more characteristic of the highly specific injuries, discuss the major issues that relate to some moderate- or low-specificity injuries, and describe several diseases that mimic abuse., Methods: A review of the current and recent literature focused on the radiographic imaging of child abuse was performed by searching the National Library of Medicine database at pubmed.gov. Keywords used included: radiology, fracture, child abuse, and/or nonaccidental trauma., Results: Injuries that are highly specific for the diagnosis of abuse include metaphyseal corner fractures, posteromedial rib fractures, and sternal, scapular, and spinous process fractures. Lesions of moderate specificity include, among other injuries, multiple fractures of various ages and epiphyseal separations. Long-bone fractures and clavicular fractures, while common, are of low specificity. In addition to the appropriate accurate diagnosis of these injuries, several diseases and syndromes may mimic abuse due to the similarity in the radiographic picture., Conclusions: Stratification of fractures sustained in child abuse according to specificity and an understanding of the several diseases that mimic abuse are helpful in the accurate diagnosis of child abuse., Level of Evidence: Level V, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease characterized by anhidrosis, insensitivity to noxious stimuli, and mental retardation. Mutations in the NTRK1 gene are associated with the pathogenesis of CIPA. In this study, we performed a clinical and genetic analysis on the NTRK1 gene in four Korean patients with CIPA. All patients had typical clinical manifestations of CIPA, including anhidrosis, recurrent fever, absent pain perception, and developmental delay. Sequencing analysis revealed one predominant mutation, c.851-33T>A, in four affected alleles and three novel mutations, including c.287+2dupT, c.2155G>A (p.Glu719Lys), and c.1218delC (p.Pro407ArgfsX), in each affected allele. For one patient, who was heterozygous for c.851-33T>A, another mutation could not be identified, suggesting that a possible hidden intronic or large genomic mutation may have been present. This study extends the spectrum of mutations in the NTRK1 gene and confirms that Korean patients with CIPA have the same genetic background as other ethnicities.

Congenital insensitivity (HSAN) to pain is a rare disorder, which affects the body's painprotective mechanism and predisposes the patient to increased risk and incidence of traumatic injuries. Currently, 5 types of hereditary sensory and autonomic neuropathies have been identified, depending upon different patterns of sensory and autonomic dysfunction, peripheral neuropathy, clinical features, and genetic abnormalities. The purpose of this report is to present the case of a 10-year-old boy with congenital insensitivity to pain (hereditary sensory autonomic neuropathy [HSAN] type V) with dental implications. History, clinical features, nerve conduction studies, and electron microscopy revealed no reaction to painful stimuli, a self-mutilating habit, multiple missing teeth, and an absence of small, unmyelinated fibers, thus indicating HSAN type V. Management included patient counseling and use of a mouthguard to prevent further damage and restore function.

We report the case of a 43-year-old woman referred for evaluation of worsening gait. Her initial evaluation led to a diagnosis of a Charcot spine and 2 spinal stabilization surgeries. Because no clear cause for the Charcot spine could be determined from the patient's history or initial evaluation, an extensive diagnostic work-up was undertaken, which ultimately led to a diagnosis of congenital insensitivity to pain with anhydrosis (CIPA). This diagnosis was known and confirmed by the patient's parents but was unknown to the patient and her treating physicians. Unique to this case is not only the significant medical implications and the value of the re-diagnosis and confirmation of this rare condition, but also the rarer occurrence of a Charcot spine in a person with CIPA.

Sensory phenotype was assessed in a young girl affected by congenital insensitivity to pain (CIPA) scheduled for an open surgical drainage. The sensory profile showed that only the Abeta fibers were functioning normally, whereas Adelta and C fibers did not respond to nociceptive stimuli. On the basis of these findings and the results of cardiovascular reflexes, she was submitted to abscess incision and debridement under midazolam sedation alone. She did not report pain or other discomfort during surgery. The sensory (and sympathetic) assessment may have a high potential value in planning anesthesia and analgesia in children with CIPA. This psychophysical procedure could be introduced as standard component of clinical evaluation before surgery.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, hereditary, autonomic recessive disorder. The inability to perceive pain results from loss of nociceptive afferents, while anhidrosis is caused by loss of innervation to the sweat glands. Insensitivity to pain and mental retardation lead to self-inflicted injuries, corneal lacerations, painless bony fractures, joint deformities with consequent chronic osteomyelitis, and septic arthritis. There are only a few reports on the anesthetic management for patients with CIPA. We describe the anesthetic management of a young woman with CIPA receiving bilateral arthrodesis of the ankle.

Aim: To apply a standardized protocol for the orofacial evaluation of two adult siblings (one male and one female) with Hereditary Sensory Radicular Neuropathy (HSRN) that presented with dental problems., Summary: The systematic evaluation consisted of (a) clinical questionnaire; (b) radiographs [orthopantomography and computarized tomography (CT)]; (c) orofacial psychophysical tests (pain, thermal, mechanical and electrical sensation); and (d) histology of gingiva and pulp (optical and transmission electronic microscopy). The female patient had complete insensitivity to orofacial pain and partial facial heat sensitivity, and received dental treatment without anaesthesia or pain. She had a severe and painless jaw infection due to pulp necrosis in tooth 37. The male patient had partial insensitivity to orofacial pain and required anaesthesia for dental treatment. Histological examination of gingivae and pulpal tissue revealed an altered proportion of unmyelinated and myelinated sensory nerve fibres., Key Learning Points: * Patients with HSRN may present with significant, silent dental disease. * A standard protocol is helpful when evaluating such patients. * If the opportunity arises, evaluation of pulp tissue may reveal an altered proportion of myelinated and unmyelinated nerve fibres. This may avoid the more estabilished sural nerve biopsy.

Introduction: Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a rare autosomal recessive disorder featuring recurrent fever episodes, inability to sweat, absent response to noxious stimuli, self mutilating behavior and mental retardation. It has been associated with mutations in the NTRK1 gene, located in 1q21-22 and encoding a high-affinity NGF receptor., Case Report: An 8-year-old boy, the first son of consanguineous parents, presented with hypotonia, episodic hyperpyrexia and global developmental delay since the neonatal period. In addition to these signs, typical of CIPA, he displayed some other not previously described in this disease, such as facial dysmorphism, a severe swallowing disorder and a myogenic EMG pattern, that led to the initial suspicion of a muscle disorder. Molecular genetics studies uncovered a mutation c.C2011T in exon 15 of the NTRK1 gene. Genetic counselling was possible in the following pregnancy of the couple, where the female fetus was found to harbour the mutation in heterozygosity. The subsequent diagnosis of a congenital myasthenic syndrome in this sister led to neurophysiological re-evaluation of the probandus, in whom a myasthenic pattern of muscle activation was also found., Conclusions: A patient with CIPA and congenital myasthenic syndrome is described. CIPA must be the first diagnostic hypothesis when assessing a patient with insensitivity to pain, anhidrosis and self-mutilation. Given the rather homogeneous presentation of CIPA, the occurrence of atypical myopathic manifestations should raise the suspicion of a concurrent disorder. The present consanguineous kindred illustrates a rare instance of transmission of two mutated alleles giving rise to two unrelated, infrequent neurological syndromes.

Unlabelled: We report a case of hereditary sensitive neuropathy associated with insensitivity to pain in an infant., Case Report: The girl was born after a normal full term pregnancy. She was hospitalized in the neonatal period because of hypotonia and recurrent cyanotic episodes due to false passage. The diagnosis of insensitivity to pain was suspected at nine months of age, as parallel with dentition, multiple mutilations of the tongue and the fingers were observed. The diagnosis was confirmed by biopsy taken from the sural nerve which showed a rarefaction of small myelinated fibres whereas unmyelinated fibres remained unaltered. At the age of six years, the general condition was good and the neurologic developement was satisfactory, neurotrophic and urologic complications currently being the main problem., Conclusion: A multidisciplinary and specialized care associated with parental compliance was necessary to minimize the complications of this potentially severe disorder.

Congenital insensitivity to pain (hereditary sensory and autonomic neuropathy [HSAN] type V) is a rare disorder of pain perception in which pain sensation is absent from birth, with no other neurologic deficits. We report five Saudi patients (three male and two female) age 10 months to 23 years who lacked pain sensation from birth but have normal appreciation of other sensory modalities. They are from four related families who are descended from one grandfather. The patients had sustained many painless injuries resulting in fractures and disfigurement, but otherwise are completely normal.

We present a rare case of necrotising fasciitis in an infant with congenital insensitivity to pain syndrome. The aetiology, diagnosis and management of necrotising fasciitis in children are compared with those in adults. In contrast to adults, children affected by necrotising fasciitis are usually previously healthy and have no predisposing factors. Early diagnosis, intravenous antibiotics and aggressive surgical debridement are mandatory for an optimal outcome., (Copyright 2002 The British Association of Plastic Surgeons.)

Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It mimics a number of other syndromes categorized under peripheral sensory neuropathies, often making early diagnosis difficult. Two cases from the middle east are presented, highlighting possible diagnostic, and management difficulties.

The psychiatric literature contains anecdotal reports of diminished pain sensitivity in schizophrenia that date back to Kraepelin. Yet, the phenomenon of pain insensitivity in schizophrenia remains largely unstudied. For example, it is not clear if pain insensitivity is a consequence of the illness or if it is also present in the well relatives of schizophrenia patients. To explore this issue, we examined pain thresholds and pain tolerances in healthy young adults. Compared with controls with no family history of psychopathology (n=21), participants with a family history of schizophrenia (n=32) showed elevated pain thresholds and pain tolerances to finger pressure. Pain insensitivity was also significantly correlated with elevated scores on measures of self-referential thinking, magical ideation, and perceptual disturbances. Finally, a sizeable minority (19%) of well relatives of schizophrenia patients showed extreme pain insensitivity compared to other participants. The pattern of findings suggests that pain insensitivity may warrant further exploration as a potential marker of underlying liability to psychosis.

Congenital insensitivity to pain with anhidrosis (CIPA), a rare and severe disorder, comprises absence of sensation to noxious stimuli, inability to sweat, and recurrent episodes of hyperthermia. It has a relatively high prevalence in the consanguineous Israeli-Bedouins. Clinical studies of 28 patients are reported here. Using the linkage analysis approach, we linked the disease in 9 of 10 unrelated Israeli-Bedouin families with CIPA to the TrkA gene, which encodes the receptor for nerve growth factor. In one family, linkage was excluded, implying that another gene, yet unidentified, is involved. Two new mutations in the tyrosine kinase domain of the TrkA gene were identified in our CIPA patients: a 1926-ins-T in most of the southern Israeli-Negev CIPA patients, and a Pro- 689-Leu mutation in a different isolate of Bedouins in northern Israel. Eight prenatal diagnoses were made in the southern Israeli-Negev Bedouins, two by linkage analysis and six by checking directly for the 1926-ins-T mutation. Three polymorphisms in the TrkA protein kinase encoding domain were also observed., (Copyright 2000 Wiley-Liss, Inc.)

Congenital corneal anesthesia (CCA) is an uncommon condition difficult to diagnose. We report the case of a 9-month-old girl who presented bilateral congenital corneal anesthesia. The child had a corneal ulcer which had been unresponsive to adapted local treatment. Self-inflicted corneal injuries were present. Local treatment and arm splints led to quick healing. CCA occurs either alone or in association with neurological diseases (familial dysautonomia) or systemic congenital abnormalities (Goldenhar Gorlin syndrome). It is important to search for corneal anesthesia in children with chronic ulcerations of the cornea and self-inflicted injuries. Early diagnosis is important due to the risk for the visual prognosis. Short and longterm prevention of self-inflicted corneal injuries should be associated with a local treatment to assure rapid healing and a relapse free outcome.

Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive disorder, is characterized by insensitivity to pain, self-mutilating behaviour, anhidrosis and recurrent hyperpyrexia. It is a hereditary sensory and autonomic neuropathy, also classified as HSAN, due to a defect of the receptor for nerve growth factor. CIPA is the first human genetic disorder caused by a defect in the neurotrophin signal transduction system. This is the first clinical report of CIPA patients characterized on molecular grounds. The clinical phenotypes of our patients show that CIPA is characterized by a multisystem involvement besides the nervous system, including bone fracture with slow healing, immunologic abnormalities, such as low response to specific stimuli, chronic inflammatory state ending in systemic amyloidosis. The molecular characterization allows a better understanding of most of the clinical features.

As physicians and nurses, we have a fundamental obligation to consider patient welfare above all else. The case presented demonstrates the depth of this obligation. Our patient, who was diagnosed during infancy with congenital indifference to pain, can neither feel nor perceive the meaning of pain. Congenital indifference to pain is a rare disorder, which is characterized by normal intelligence, development, and sensation despite an absence of pain perception. There is no cure and treatment difficulties are plentiful. Educating and maintaining an open, consistent relationship with the family and caregivers is essential to reduce the morbidity of this condition.

Three children with congenital insensitivity to pain are described. Self-injuries of the tongue and fingers occurred during dentition. At infancy and early childhood fever of unknown origin and/or pneumoniae were observed in all children. All of them also suffered from osteomyelitis of various bones treated with antibiotics and surgery. The tibia and metatarsals were involved in one case, the tibia, metatarsals and the femur in second child and the jaw plus metatarsals in the third case. In one child the hip has been dislocated twice after minor trauma, lumbar arthropathy, distal femoral epiphyseal fusion causing shortening of the extremity by 4.5 cm, osteochondritis dissecans of the medial femoral condyle, elbow deformity after displaced fracture of the lateral humeral condyle and post-traumatic cataract were observed.