Home About Journal AHEAD OF PRINT Current Issue Back Issues Instructions Submission Search Subscribe Blog    

Users Online: 288 
Print this page  Email this page Small font sizeDefault font sizeIncrease font size 

 Table of Contents    
Year : 2011  |  Volume : 45  |  Issue : 3  |  Page : 269-271
Congenital insensitivity to pain and anhidrosis

Department of Orthopaedics, Al Ameen Medical College and Hospital, Athani Road, Bijapur, Karnataka, India

Click here for correspondence address and email

Date of Web Publication 26-Apr-2011


Congenital insensitivity to pain and anhidrosis (CIPA) is a rare reported entity characterised by disturbance in the pain and temperature perception due to involvement of the autonomic and sensory nervous system. It is an autosomal recessive trait with several defects of the gene NTRK1 coding for the neurotrophic tyrosine kinase - a nerve growth factor receptor on chromosome 1q21-q22. Traumatic fractures are common and, because of lack of pain, may go unrecognised for prolonged periods, resulting in nonunion or pseudoarthrosis. A Charcot joint may be the end result. Treatment complications are very common in these patients and range from infection to wound breakdown to failure of fixation. We report here a rare case of CIPA in a 9-year-old girl and her younger male sibling with generalised absence of pain, anhidrosis and its orthopaedic implications.

Keywords: CIPA, congenital insensitivity to pain, HSAN type IV, malunion, pseudoarthrosis

How to cite this article:
Sasnur AH, Sasnur PA, Ghaus-ul RM. Congenital insensitivity to pain and anhidrosis. Indian J Orthop 2011;45:269-71

How to cite this URL:
Sasnur AH, Sasnur PA, Ghaus-ul RM. Congenital insensitivity to pain and anhidrosis. Indian J Orthop [serial online] 2011 [cited 2016 Oct 11];45:269-71. Available from: https://ijoonline.com/text.asp?2011/45/3/269/80047

   Introduction   Top

Congenital insensitivity to pain and anhidrosis (CIPA) is a rare disorder affecting autonomic nervous system, and therefore has been described as Hereditary Sensory and Autonomic Neuropathies (HSAN). [1] It presents to orthopaedic surgeons with nonunion and pseudoarthrosis following multiple fractures. [2],[3] The failure of internal fixation, infection and wound breakdown are common complications. Many of their wounds are largely self-inflicted act of curiosity.

The incidence of this disorder has been estimated to be 1 in 25,000 population. [4] We report here a rare case of CIPA in a 9-year-old girl and her younger male sibling with generalised absence of pain, anhidrosis and its orthopaedic implications.

   Case Report   Top

A 9-year-old girl presented with a painless and deformed right elbow [Figure 1]a since 5 years and a painless, deformed right ankle [Figure 1]b since 3 months The deformities of joints preceded with history of repeated trauma. Parents brought her with complaints of swelling in her right ankle and limp since 3 months. Over the past years they complain of her being insensate to pain, lack of tears, dry skin, recurring bouts of fever, constipation, biting tongue and ulcers over her back.

On examination she has generalised absence of pain perception, swollen right proximal forearm with abnormal mobility suggesting nonunion. Her right ankle joint appeared to be medially displaced [Figure 1]b. She had shortening of her right lower limb by 3 cms and had short limb gait. She had a bifid tongue [Figure 1]c, absence of most of the teeth, lack of response to painful stimulus, diminished temperature perception, normal touch perception, diminished deep reflexes, fluctuating blood pressure, multiple scars over the body [Figure 1]d and ligamentous laxity [Figure 1]e. Radiographs of her right elbow with forearm revealed atrophic nonunion of proximal ulna with displaced radial head [Figure 2]a and b suggesting old Monteggia fracture dislocation for which she was operated at the age of 6 years at another private hospital. Her right ankle X-rays revealed bimalleolar ankle fracture dislocation [Figure 2]c and d.
Figure 1: Clinical photograph of the patient shows deformity of the right elbow (a), right ankle (b), bifid tongue (c), multiple scars on the body (d), and ligamentous laxity (e)

Click here to view
Figure 2: X-ray of both bones forearm with elbow joint (anteroposterior views) (a, b) showing atrophic nonunion of proximal ulna with displaced radial head on right side. X-ray of the right ankle (anteroposterior and lateral views) shows nonunion (c, d), of bimalleolar fracture and internal fixation and for nounion fracture dislocation of right ankle (e,f)

Click here to view

Her parents are asymptomatic and have history of consanguineous marriage. There is no history of similar complaints from either of the parent's side. Their son who is seven years old (younger brother of our patient) also has history of tongue bites, lack of tears and insensate to pain but to a very lesser degree and does not present with Orthopaedic manifestations.

Intradermal injection of 0.1 ml of 1:1000 solution of histamine produced a wheal but no pain and no axon flare around it. Nerve conduction velocity was normal, serum creatinine phosphokinase level was elevated and findings of the remaining investigations were within normal limits. The patient was operated at the age of nine years for bimalleolar fracture dislocation. Open reduction and internal fixation with malleolar screws and multiple K-wire was done [Figure 2]e and f. Post-operatively, the limb was immobilised in a below knee slab for 6 weeks. Intra-operative and post-operative recovery was uneventful. However, there were no radiological signs of fracture healing after 6-8 weeks, and she was allowed to ambulate with the help of ankle braces. The fracture did not unite even at one year followup. She had right tibial shortening and managed to walk with limp. At 2 year follow-up she presented with pain and swelling in her right ankle and she was diagnosed as septic arthritis of right ankle joint. She had progressed from pain insensitivity to painful ankle joint, for which she underwent surgical debridement and implant removal. Intra-operatively, implants were buried inside the callus, but fracture resulted in pseudoarthrosis. The nonunion of the proximal right ulna was left alone, as she did not present with any complaints.

   Discussion   Top

Hereditary peripheral neuropathies have been classified based on their clinical characteristics, mode of inheritance, electrophysiological features, metabolic defects, and specific genetic markers. [5] The most consistent and distinctive feature of an HSAN is loss of pain and perception.

HSAN Type I is most common autosomal dominant inheritance with genetic locus on 9q22.1-q22.3, in SPTLC1 gene, [6] characterised by progressive degeneration of dorsal ganglia and motor neurons, leading to distal sensory loss and later in the course of disease, distal muscle wasting and weakness. Symptoms manifests in second to fourth decade of life with slowly progressive numbness, paraesthesias and sensory defects, and plantar ulcers, with less obvious motor deficit. [6]

HSAN Type II is an autosomal recessive trait characterised by loss of pain, temperature, pressure and touch sensation following large and small nerve fibre involvement. This is a disease of infancy and early childhood, with distal numbness in the upper and lower limbs and a glove and stocking sensory loss. The causative gene HSN2 on chromosome 12q13.33, has been recently reported in five Canadian families. [7]

HSAN Type III or riley day syndrome or familial dysautonomia is one of the many names for this autosomal recessive disorder, which occurs exclusively in Ashkenazi Jewish families. It has an incidence of 27 in 100000 population, but is very rare in other ethnic groups. [8] The genetic locus has been mapped to chromosome 9 q31-q33 . [8] These patients present with diminished or absent pain and temperature perception but normal touch perception. They present with anhidrosis, decreased lacrimation, tongue ulcerations, recurrent gastrointestinal (GI) upset, diminished or absent deep tendon reflexes, poorly controlled temperature, a fluctuating blood pressure and an absent axon reflex. Orthopaedic manifestations include gait abnormalities, fractures, charcot joints, osteomyelitis, scoliosis and ligamentous laxity. [8] There is characteristic absence of fungiform papillae of the tongue and can later develop finger nail dystrophy. [6]

HSAN Type IV is an autosomal recessive disorder associated with several defects of the gene NTRK1 coding for the neurotrophic tyrosine kinase. [6] This type IV is also called CIPA. First described in 1951, results from a defect in neural crest differentiation and the first-order afferent system responsible for pain and temperature sensation. Clinical suspicion arises when symptoms begin early in infancy, which include profound loss of pain sensitivity leading to injuries, self-mutilation and osteomyelitis. [9] Loss of oral sensation leads to mutilation of the face and mouth, as seen in our patients. Mild-to-moderate mental retardation, episodic hyperthermia associated with seizures, and anhidrosis are some of the prominent features. Early death from hyperpyrexia occurs in up to 20% of patients, and septicaemia is a frequent occurrence. The histamine test shows no axon flare response, and there is no tear formation and sweating with pilocarpine. Seyon et al. [10] have called CIPA, the "mystery of broken bones" after the patient who was wrongly diagnosed as suffering with osteogenesis imperfecta due to recurring fractures since the age of 4.

HSAN Type V is an autosomal recessive disorder phenotypically similar to HSAN IV presenting with loss of pain and temperature sensation, but other sensations preserved. It is caused by mutation in the nerve growth factor beta gene on chromosome 1. The main difference between HSAN IV and HSAN V was thought to be the pattern of nerve fibre loss, and the greater severity of anhidrosis in HSAN IV and lack of mental retardation in patients with HSAN V. [6]

We were unable to carry out genetic tests, but we believe that diagnosis primarily depends on clinical examinations and specific sensory and autonomic assessments. Our findings on clinical examination are consistent with HSAN Type IV. Although there is no mention of curative treatment in such patients, Bar-On et al. describes preventive measures for orthopaedic complications such as the use of special footwear, periods of non-weight-bearing, surgical wide debridement and curative osteotomy for deformity. [8] Krettek et al. encourages to treat initially with non-operative methods and then, if the fracture does not unite on time and there are signs of hypertrophic nonunion, to fix with internal fixation. [11] Jacob et al advices regarding protective footwear, clothing, avoidance of injuries and prompt treatment of wounds and infections is crucial. [6] Congenital indifference to pain is a problem that is difficult to control and appears impossible to treat, as there are no specific guidelines for fracture treatment. Recurrent injuries can be lessened by preventive measures and vigilant attention by the parents.As described by Drummond et al., CIPA patients tend to progress from pain indifference to gradual recovery of pain sensibility. [12] They strive to be normal as they grow and learn to respond to painful stimuli and hence acquire a pattern of appropriate behavioural responses. [13]

A rare case of HSAN Type IV, CIPA showing the usual features of biting lips, tongue and self-mutiliation, repeated fractures, nonunions with anhidrosis is presented here. Patient initially presented with indifference to pain and later progressing to gradual recovery of normal pain sensibility. Both fractures resulted in nonunion despite adequate operative interventions.

   References   Top

1. Axelrod FB, Gold-von Simson G. Hereditary sensory and autonomic neuropathies: Types II, III and IV. Orphanet J Rare Dis 2007;2:39.  Back to cited text no. 1
2. Bar-On E, Weigl D, Parvari R, Katz K, Weitz R, Steinberg T. Congenital insensitivity to pain. Orthopaedic manifestations. J Bone Joint Surg Br 2002;84:252-7.  Back to cited text no. 2
3. Guidera KJ, Multhopp H, Ganey T, Ogden JA. Orthopaedic manifestation in congenitally insensate patients. J Pediatr Orthop 1990;10:514-21.  Back to cited text no. 3
4. Hereditary sensory autonomic neuropathy and anaesthesia: A case report. Indian J Anaesth 2007;51:528-30.  Back to cited text no. 4
5. Dyck PJ. Neuronal atrophy and degeneration predominantly affecting peripheral sensory and autonomic neurons. In: Dyck PJ, editor. Peripheral neuropathy. Philadelphia: Saunders; 1993. p. 1065.  Back to cited text no. 5
6. Jacob A, Sarada C, Thomas SV. Painless injuries in a child; Hereditary sensory and autonomic neuropathy. Ann Indian Acad Neurol 2006;9:39-41.  Back to cited text no. 6
  Medknow Journal  
7. Lafreniere RG, MacDonald ML, Dube MP, MacFarlane J, O'Driscoll M, Brais B, et al. Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates. Am J Hum Genet 2004;74:1064-73.  Back to cited text no. 7
8. Bar-On E, Floman Y, Sagiv S, Katz K, Pollak RD, Maayan C. Orthopaedic manifestations of familial dysautonomia: A review of one hundred and thirty six patients. J Bone Joint Surg Am 2000;82-A:1563-70.  Back to cited text no. 8
9. MacEwen GD, Floyd GC. Congenital insensitivity to pain and its orthopaedic implications. Clin Orthop Relat Res 1970;68:100-7.  Back to cited text no. 9
10. Sathiaseelan S, Rayar U. The mystery of the broken bones. CMAJ 2003;169:1189-90.  Back to cited text no. 10
11. Krettek C, Glüer S, Thermann H, Lewis DA, Schweitzer S, Tscherne H. Non-union of the ulna in a ten month old child who had Type IV hereditary sensory neuropathy. A case report. J Bone Joint Surg Am 1997;79:1232-4.  Back to cited text no. 11
12. Drummond RP, Rose GK. A twenty one year review of a case of congenital indifference to pain. J Bone Joint Surg Br 1975;57:241-3.  Back to cited text no. 12
13. Abell JM, Hayes JT. Charcot knee due to congenital insensitivity to pain. J Bone and Joint Surg. 1964; 46-A:1287-1291.  Back to cited text no. 13

Correspondence Address:
Prakash A Sasnur
Department of Orthopaedics, Al Ameen Medical College Hospital, Athani Road, Bijapur - 586 108, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

Crossref citations 3
PMC citations 2

DOI: 10.4103/0019-5413.80047

Rights and Permissions


  [Figure 1], [Figure 2]

This article has been cited by
1 Hereditary sensory and autosomal peripheral neuropathy-type IV: case series and review of literature
D. P. Ashwin,G. D. Chandan,Handa Kaur Jasleen,G. C. Rajkumar,K. B. Rudresh,R. Prashanth
Oral and Maxillofacial Surgery. 2015;
[Pubmed] | [DOI]
2 Animal Disenhancement for Animal Welfare: The Apparent Philosophical Conundrums and the Real Exploitation of Animals. A Response to Thompson and Palmer
Arianna Ferrari
NanoEthics. 2012; 6(1): 65
[Pubmed] | [DOI]
3 A case report of congenital insensitivity to pain and anhidrosis (CIPA)
Karimi, M. and Fallah, R.
Iranian Journal of Child Neurology. 2012; 6(3): 45-48
4 Animal Disenhancement for Animal Welfare: The Apparent Philosophical Conundrums and the Real Exploitation of Animals. A Response to Thompson and Palmer
Ferrari, A.
NanoEthics. 2012; 6(1): 65-76


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
  • Sasnur AH
  • Sasnur PA
  • Ghaus-ul RM
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

    Case Report
    Article Figures

 Article Access Statistics
    Viewed 5150    
    Printed 105    
    Emailed 3    
    PDF Downloaded 113    
    Comments  [Add]    
    Cited by others  4    

Recommend this journal