Skeletal complications in congenital insensitivity to pain with anhidrosis: a case series of 14 patients and review of articles published in Japanese

Zhang, Yasu; Haga, Nobuhiko

doi:10.1007/s00776-014-0595-2

Cited by 31 publications

(36 citation statements)

References 17 publications

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“…(58,61) CIP fractures occur primarily in the femur and tibia. (51,53) In 2014, Haga and Zhang (62) reported 14 CIP patients with anhydrosis (HSAN type IV) caused by NTRK1 mutation, and identified the most common skeletal complications to be fractures (91%) and Charcot joints (29%), both involving primarily the lower limbs. Fractures were particularly frequent between ages 1-7 years.…”

Section: V) Discussionmentioning

confidence: 99%

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Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9

Phatarakijnirund

Mumm

McAlister

et al. 2016

Bone

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Congenital insensitivity to pain (CIP) comprises the rare heritable disorders without peripheral neuropathy that feature inability to feel pain. Fracturing and joint destruction are common complications, but lack detailed studies of mineral and skeletal homeostasis and bone histology. In 2013, discovery of a heterozygous gain-of-function mutation in SCN11A encoding voltage-gated sodium channel 1.9 (Nav1.9) established a distinctive CIP in three unrelated patients who suffered multiple painless fractures, self-inflicted mutilation, chronic diarrhea, and hyperhidrosis. Here, we studied a mother and two children with CIP by physical examination, biochemical testing, radiological imaging including DXA, iliac crest histology, and mutation analysis. She suffered fractures primarily of her lower extremities beginning at age two years, and had Charcot deformity of both ankles and joint hypermobility. Nerve conduction velocity and biopsy and electromyography were normal. Her children had recurrent major fractures beginning in early childhood, joint hypermobility, and chronic diarrhea. She had an excoriated external nare, and both children had hypertrophic scars from scratching. Skin collagen studies were normal. Radiographs revealed fractures and deformities. However, lumbar spine and total hip BMD Z-scores, biochemical parameters of mineral and skeletal homeostasis, and iliac crest histology of the mother (after in vivo tetracycline labeling) were normal. Genomic DNA from the children revealed a unique heterozygous missense mutation in exon 23 (c.3904C>T, p.Leu1302Phe) of SCN11A that is absent in SNP databases and alters an evolutionarily conserved amino acid. This autosomal dominant CIP reflects the second gain-of-function mutation of SCN11A. Perhaps joint hypermobility is an unreported feature. How mutation of Nav1.9 causes fracturing remains unexplained. Lack of injury awareness is typically offered as the reason, and was supported by our unremarkable biochemical, radiological, and histological findings indicating no skeletal pathobiology. However, low-trauma fracturing in these patients suggests an uncharacterized defect in bone quality.

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Section: V) Discussionmentioning

confidence: 99%

“…Fractures were particularly frequent between ages 1-7 years. (62) Osteomyelitis, resulting from repeated minor trauma and biting of the digits, can also be found in CIP, but is usually restricted to toes and fingers, and leads to autoamputation. (53) …”

Section: V) Discussionmentioning

confidence: 99%

Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9

Phatarakijnirund

Mumm

McAlister

et al. 2016

Bone

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“…In recent days, two cases of CIPA patients who continue treatment have been reported [21]. Generally, effective CIPA treatment has been established within the framework of family education and patient education [22]. Early detection of the disease using techniques such as prenatal genetic screening and amniocentesis is the only way to prevent the birth of an affected child, because treatment is not available [23].…”

Section: Discussionmentioning

confidence: 99%

Congenital insensitivity to pain syndrome accompanied by neglected orthopedic traumas and complications

et al. 2017

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Pain is a protective mechanism. Congenital insensitivity to pain syndrome is a very rare disease in which there is no ability to feel physical pain. It has been reported that it occurs with an incidence of 1 in 125 million newborn. Patients with congenital insensitivity to pain may have various orthopedic complications such as recurrent fractures, osteomyelitis and neuropathic joints. The most frequently affected body parts are lower extremities. Besides, curvature of spine can be seen. Injuries in epiphyseal points may cause incompatibility of extremity. Charcot joints may develop, which can lead to neuropathic arthropathy as a result of insensitivity to pain. Here, we present a patient with traumatic fracture-dislocation on left hip that neglected the treatment, had a bilateral femur fracture and then had septic arthritis of knee.

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“…Musculoskeletal complications are frequent in HSAN‐IV and ‐V, and include repeated fractures and joint dislocations, arthritis and osteomyelitis, avascular necrosis, and Charcot arthropathy, mainly in the lower extremities . A review of Japanese patients with HSAN‐IV showed that fractures are frequent between 1 and 7 years of age, whereas other complications have no apparent age relationship …”

Section: Complications and Their Managementmentioning

confidence: 99%

“…Fractures and dislocations develop in HSAN‐IV and ‐V, even without any apparent trauma or following minor trauma, such as short falls (Fig. ) . Although the reason for these fractures and dislocations has not been clarified, decreased sensation, including deep sensation, intellectual disability, and mutilating behavior, may be related.…”

Section: Complications and Their Managementmentioning

confidence: 99%

Hereditary sensory and autonomic neuropathy types IV and V in Japan

Haga

Kubota

Miwa

2015

Pediatrics International

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Hereditary sensory and autonomic neuropathy (HSAN) is a group of genetic disorders involving varying sensory and autonomic dysfunction. HSAN types IV and V are characterized by congenital generalized loss of pain and thermal sensation. HSAN type IV is additionally accompanied by decreased sweating and intellectual disability. From 2010 to 2013, we (members of the Japanese Research Group on Congenital Insensitivity to Pain) carried out research on HSAN types IV and V. Research by this group included epidemiological data, examination of clinical findings, solutions of disease etiology, investigation of complications and development of their management. Complications were categorized into musculoskeletal complications, oral/dental complications, dermal complications, ocular complications, complications resulting from impaired thermal control, anesthetic considerations, other complications possibly related to autonomic dysfunction, and abnormal mental development and behavior. Treatment and care for patients with HSAN types IV and V require a wide range of knowledge and experience, and a multidisciplinary team approach. Therefore, we produced the "Guideline of Total Management and Care for Congenital Insensitivity to Pain (Ver.1)" in 2012, to provide information for medical specialists based on our knowledge and experience. This guideline includes medical issues, as well as descriptions of social participation and welfare. This review outlines the situation of HSAN types IV and V in Japan, and the recommendations of treatment and care for patients, mostly based on research conducted by the Japanese Research Group.

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Skeletal complications in congenital insensitivity to pain with anhidrosis: a case series of 14 patients and review of articles published in Japanese

Cited by 31 publications

References 17 publications

Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9

Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9

Congenital insensitivity to pain syndrome accompanied by neglected orthopedic traumas and complications

Hereditary sensory and autonomic neuropathy types IV and V in Japan

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