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Congenital insensitivity to pain and anhidrosis syndrome: two cases involving a brother and sister

Zhang, Yimin; Jiang, Xin; Liu, Jianyong

doi: 10.3760/cma.j.issn.0366-6999.20141450
Clinical practice
Free
SDC

Department of Orthopaedics, Weifang People's Hospital, Weifang, Shandong 261041, China (Zhang YM, Jiang X and Liu JY)

Correspondence to: Dr. Zhang Yimin, Department of Orthopaedics, Weifang People's Hospital, Weifang, Shandong 261041, China (Tel: 86–536–8192240. Email: ymzh69@hotmail.com)

(Received June 23, 2014)

Edited by Hao Xiuyuan

Congenital insensitivity to pain and anhidrosis (CIPA) is a rare entity. CIPA patients are subjected to repeated injuries, which are easily neglected. There is no specific treatment for CIPA, but supervision by parents and patient training are important to avoid further damage and to maintain quality of life. We present two cases of CIPA involving a brother and sister, whose parents did not have a consanguineous marriage.

Case 1: The brother, aged 15 years, was admitted to our hospital in 2007 whose parents complained that the boy had severe instability and recurrent swelling of the bilateral knee joints. Physical examination showed that the knee joints were quite swollen and lax. Results were positive for the floating patella test, the anterior drawer test, the posterior drawer test, and the lateral stress test. The boy appeared slightly mentally retarded, but his mother told us that he had a good memory for digits, such as remembering phone numbers. He liked to raise up one leg straight up over his head and he could communicate with others who had an amicable attitude toward him, just reacting slightly slowly. A preoperative X-ray confirmed lax and degenerative knee joints (Figure 1A). Bacteriological culture of articular fluid was negative. To obtain stability of the lower extremities to keep from stumbling and falling, the decision was made to perform arthrodesis on the knee joints, although the epiphyseal lines were not totally shut. During the operation, we found that the cartilage was severely damaged, with synovial inflammatory hyperplasia and massive exudation. The anterior cruciate ligament and posterior cruciate ligament were absent, and the soft tissue around the knee joints was quite flabby (Figure 1B). Following debridement of the knee joints, external fixator was used for bone to bone fusion. Preoperatively, high fever persisted for 5 days, with resistance to any measures. Weight-bearing activity began in 3 months, and the external fixator was removed 8 months following total bony fusion proven with X-ray. At the follow-up, the boy could walk with two straight knees without flexion and extension. The lower extremities look shorter compared with the upper part of his body.

Figure 1.

Figure 1.

Case 2: The sister, aged 14 years, came to our hospital in 2012 because of a left closed tibiofibular fracture following a high jump. The girl also felt no pain with anhidrosis as usual. The diagnosis of CIPA was made in this girl, too. Open reduction and internal fixation with a titanium plate were performed successfully. Similar to her brother, a high fever occurred after operation for 4 days with resistance to any countermeasures. The girl was discharged 12 days after suture removal. Six weeks later, X-ray showed that the fracture line was blurred. We suggested that she walk with weight bearing, regardless of her low painful response. Three months later, she came again with her mother and complained of bony enlargement with no pain in the fracture position. X-ray showed delayed union with angulation deformity and visible fracture line with some bony callus around. The upper two nails were both broken because of shear force. We prescribed external fixation with cast for another 8 weeks but this had no effect. A second operation had to be performed including the removal of original plate and screws and fracture ends debridement, iliac bone graft, and internal fixation with another compression plate. This time, the girl was advised to avoid early loading for at least 3 months until the fracture had completely healed as shown by clinical and radiographical evidence. Finally, a good result was obtained. It was worth mentioning that the girl appeared to be normal mentally and was just a little taciturn. She often studied her junior middle school textbooks, including Chinese, English, and mathematics, and sometimes liked to play games on her mobile phone.

CIPA was first mentioned by Dearborn in 1932 and described systematically by Swanson in 1963. It is extremely rare with autosomal recessive inheritance, termed hereditary sensory autonomic neuropathy (HSAN) type IV.

CIPA can be diagnosed by clinical and paraclinical tests together. A genetic test is the definitive confirmation for diagnosis. However, early cognition regarding CIPA is not common, even for doctors, with less than 60 cases reported in the literature.1 Recurrent episodes of hyperpyrexia after birth are the typical symptom, and the rate of death from hyperpyrexia is 20% within 3 years of age.2 Multiple joint deformities (many are similar to Charcot joints) often occur as a complication of painless intra-articular fractures with increasing age.3 Some patients have prominent inclination toward self-mutilation, leading to injuries of the tongue, hands, lips, and oral mucosa and even permanent tooth germ loss by biting.4

Currently, there is no standard treatment for CIPA patients.4 The most crucial factor is early diagnosis and supervision by family members, in order to let the CIPA patients obtain effective protection from self-mutilation and other damage to maintain quality of life.5

Pain is a protective mechanism from damage. However, people with CIPA cannot feel pain1 because the gene encoding the neurotrophic tyrosine-kinase receptor is mutated in a manner that interferes and halts autophosphorylation. This prevents signals of pain and temperature from being sent to the brain.6

In our cases, the diagnosis was made clinically and laboratorily. The brother, who was slightly mentally retarded, was subject to laxity and instability of the knee joints because of absence of pain protection. The sister, who appeared to have normal intelligence, had to suffer fracture operation twice because of pain absence. We speculate that if the girl had appropriate supervision during the early period of rehabilitation after the first operation, the second internal fixation could have been avoided.

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REFERENCES

1. Ali N, Sharma S, Sharma S, Kamal Y, Sharma S. Congenital insensitivity to pain with anhidrosis (HSAN Type IV), extremely rare syndrome that can be easily missed by bone and joint surgeons: a case report. Iran J Pediatr 2012; 22: 559-563.
2. Gupta B. Congenital insensitivity of pain with anhidrosis. Indian J Pediatr 2003; 70: 109-111.
3. Mobini M, Javadzadeh A, Forghanizadeh J. Neuropathic osteoarthropathy in a patient with congenital insensitivity to pain. Arch Iran Med 2009; 12: 599-602.
4. Rasmussen P. The congenital insensitivity-to-pain syndrome (analgesia congenita): report of a case. Int J Paediatr Dent 1996; 6: 117-122.
5. Emad MR, Raissi GR. Congenital insensitivity to pain with anhidrosis: a case report. Electromyogr Clin Neurophysiol 2003; 43: 409-411.
6. Mardy S, Miura Y, Endo F, Matsuda I, Indo Y. Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor. Hum Mol Genet 2011; 10: 179-188.
Keywords:

congenital insensitivity to pain and anhidrosis; knee; fracture

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