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Congenital Insensitivity to Pain Overview

, MB ChB, MRCP, MA, , MBBS, MRCP, MD, MA, and , MB ChB, FRCP, FMedSci.

Author Information

Initial Posting: .

Summary

The goals of this overview on congenital insensitivity to pain (CIP) are:

Goal 1.

To describe the clinical characteristics of congenital insensitivity to pain

Goal 2.

To review the causes of congenital insensitivity to pain

Goal 3.

To provide an evaluation strategy to identify the genetic cause of congenital insensitivity to pain in a proband

Goal 4.

To inform genetic risk assessment of family members of a proband with congenital insensitivity to pain

Goal 5.

To provide a brief summary of management of congenital insensitivity to pain

Clinical Characteristics of Congenital Insensitivity to Pain

Congenital insensitivity to pain (CIP) is an extremely rare phenotype characterized by the inability to perceive pain (absence of nociception) from birth. Individuals with CIP do not feel pain from any noxious stimuli, including inflammation and heat [Goldberg et al 2007]. This review does not cover conditions that cause a generalized sensory neuropathy.

Inability to feel pain leads to repeated injuries and prevents normal healing.

Characteristic Findings

Age-Related

Infants and young children

  • Self-mutilating injuries of the fingers (biting off fingertips) and oral cavity such as loss of the tongue tip, injuries to the inside of the teeth/gums, and avulsion of teeth are common (Figure 1A&B).
  • Cuts and bruises may be present.
  • Burns due to impaired temperature sensation [Cox et al 2006] can occur.
  • Recurrent otitis media may be due to selectively reduced immunity to Staphylococcus aureus (see Infections) [Shatzky et al 2000].
Figure 1.

Figure 1.

Examples of clinical findings in individuals with congenital insensitivity to pain (CIP) A. Typical loss of fingertips secondary to trauma, poor wound healing, and chronic Staphylococcal aureus infections in a child age nine years with NTRK1-CIP

Note: (1) Affected individuals may be able to differentiate large temperature changes, but are unable to sense if something is too hot or too cold. (2) A significant number of parents of affected children are suspected of physically abusing their child due to the nature of these injuries [Author, personal observation].

Older individuals

  • Painless fractures and joint damage frequently occur and can lead to permanent damage.
  • Bony deformities due to past fractures can occur.
    • Charcot joints (neuropathic arthropathy), most commonly of the ankles, hips, and lumbar spine, are almost universal (Figure 1C).
    • Charcot spine may present with progressive deformity or new motor and/or sensory deficits [Wheeler et al 2014, Staudt et al 2017].

Eyes

All affected individuals are at risk for corneal injuries due to absent corneal reflexes.

Permanent corneal scarring can develop and is best assessed through a slit-lamp examination.

Emotional tearing, as opposed to pain induced tearing, is likely to be present [Shatzky et al 2000].

Infections

Apparent selectively reduced immunity to Staphylococcus aureus has been observed in some affected individuals, leading to recurrent soft tissue infections, abscesses, and osteomyelitis.

Temperature Regulation, Anhidrosis, and Hyperhidrosis

Some individuals have anhidrosis (lack of sweating), which disturbs thermoregulation and can lead to recurrent episodes of unexplained fever [Indo et al 1996, Indo 2001] (see Table 1).

Marked hyperhidrosis may be seen in those affected individuals who have a heterozygous pathogenic c.2432T>C (p.Leu811Pro) variant in SCN11A [Woods et al 2015].

Hyperpyrexia can be fatal if untreated [Shatzky et al 2000].

Hypothermia can occur in cold conditions.

Development and Intellect

Development and intellect may be normal or delayed/disabled (see Table 1).

  • Individuals with CIP caused by biallelic pathogenic variants in SCN9A and PRDM12 typically have normal intellect.
  • Individuals with CIP caused by biallelic pathogenic variants in NTRK1 may have a variable degree of intellectual disability (see Table 1).
  • Hyperactivity, impulsivity, and attention deficit are common in children with biallelic pathogenic variants in NTRK1 [Levy Erez et al 2010].

Other

Chronic anemia of unknown cause was observed in 22/28 Israeli affected individuals with congenital insensitivity to pain and anhidrosis [Shatzky et al 2000].

A few individuals have neuropathic pain, although this does not limit activities [Wheeler et al 2014; Author, personal observation].

Establishing the Clinical Diagnosis of Congenital Insensitivity to Pain

There are no consensus clinical diagnostic criteria for CIP. However, a diagnosis requires visible proof of lack of nociception in a conscious individual of normal intellectual ability. In those with intellectual disability CIP may be more difficult to diagnose clinically.

Clinical Examination

Nociception is assessed by applying painful stimuli, which in people with normal nociception would be so difficult to bear that they would move the part of the body away from the stimulus and/or express discomfort. The authors have experience of children being incorrectly judged to have insensitivity to pain after an inadequately painful stimulus.

  • The technique should not damage/scar prior to significant pain (e.g., sternal rub, which bruises before significant pain).
  • Application of 5-10 kg pressure with a pen pressed onto the nail bed (the nail bed blanches for a few seconds afterward) is reliable (see Figure 1D).

Assessment of the remainder of the peripheral and central nervous system is typically normal (touch, vibration and position sense, motor functions, and deep tendon reflexes).

Supportive Laboratory Findings

Routine nerve conduction studies and electromyogram are typically normal [Shatzky et al 2000].

For more information about autonomic function testing for CIP with anhidrosis, click here.

Nerve biopsy is not routinely performed in clinical practice. Skin biopsy to determine intra-epidermal nerve fiber density and autonomic innervation is performed in adults in some centers.

Causes of Congenital Insensitivity to Pain

All causes of CIP affect nociceptors (specialized peripheral sensory neurons) and either cause nonfunctional nociceptors or failure of nociceptor neurodevelopment [Nahorski et al 2015b]. Congenital insensitivity to pain is an extremely rare phenotype and the exact proportion of individuals with pathogenic variants in each gene within the whole population is not known.

Table 1.

Genes Associated with Congenital Insensitivity to Pain (CIP)

GeneProportion of Affected Individuals with Mutation of This GeneMOIDistinguishing Features
CLTCL1 1RareAR
  • Severe non-progressive learning disability
  • Delay in central nervous system myelination
  • One family reported
NGF 2RareAR
  • Variable phenotype
  • Individuals w/biallelic null variants may have anhidrosis, mild/moderate ID, prematurely aged appearance, ↑Staphylococcus aureus infections, & Charcot joints.
  • Individuals w/a homozygous missense variant had impairment of pain/temperature sensation & Charcot joints, normal intellect & normal sweating. 3
NTRK1 4CommonAR
  • Anhidrosis
  • Tendency to develop corneal ulcers that heal poorly 5
  • ID in a majority; always less intellectually able than unaffected family members
  • Predisposition to Staphylococcus aureus infections
  • Charcot joints
  • Dry skin w/lichenification
  • Also known as HSAN IV
PRDM12 6IntermediateAR
  • Non-global pain insensitivity in some
  • Absent corneal reflex & impaired tear production
  • Normal olfaction
  • Staphylococcus aureus infections
  • No Charcot joints
  • Some have difficulties w/temperature regulation in some
  • Known as HSAN VIII
SCN9A 7, 8CommonAR
  • Anosmia 9
  • Charcot joints
  • Normal corneal reflex and tear production
SCN11A 10RareAD
  • Delayed motor development
  • Mild muscle weakness
  • Joint hypermobility
  • Gastrointestinal dysfunction (intestinal hypoperistalsis or diarrhea)
  • Pruritis

HSAN = hereditary sensory and autonomic neuropathy

ID = intellectual disability

1.
2.
3.

Three individuals from a large northern Swedish family who were homozygous for the NM_002506​.2:c.661C>T, (p.Arg211Trp) pathogenic variant [Einarsdottir et al 2004]. A proportion of adults who were heterozygous for the NM_002506​.2:c.661C>T, (p.Arg211Trp) pathogenic variant in this family had mild or moderate problems with joint deformities but were not believed to actually be affected by CIP.

4.
5.
6.
7.
8.

Pathogenic variants are typically truncating, although one missense variant and one in-frame deletion have been described [Cox et al 2010].

9.
10.

The pathogenic NM_014139​.2:c.2432T>C (p.Leu811Pro) variant was found in three affected individuals and was de novo in each case. The pathogenic NM_014139​.2:c.3904C>T, (p.Leu1302Phe) variant was found in an affected mother and two children. All six of these individuals had hyperhidrosis [Leipold et al 2013, Phatarakijnirund et al 2016].

Table 2.

Other Disorders to Consider in the Differential Diagnosis of Congenital Insensitivity to Pain (CIP)

DisorderGene(s)MOIClinical Features of the Disorder
Overlapping w/CIPDistinguishing from CIP
HereditaryHypohidrotic ectodermal dysplasiaEDA
EDAR
EDARADD
XL
AR
AD
  • Lack of sweating (overlap w/NTRK1- & NGF-CIP)
  • Risk of hyperthermia
Insensitivity to pain not a feature
Lesch-Nyhan syndromeHPRT1XLProgressive self-injurious behavior (biting fingers, hands, lips, cheeks; banging the head or limbs)
  • Hyperuricemia
  • Progressive, severe DD/ID
  • Abnormal involuntary movements
COL1A1/2-related osteogenesis imperfectaCOL1A1
COL1A2
ADMultiple fractures
  • Fractures cause pain
  • Fractures occur w/minimal or absent trauma
  • Associated w/other features incl blue sclera, short stature, joint hypermobility, deafness
Familial dysautonomia (also known as HSAN III)ELP1 (IKBKAP)ARReduced pain from birthGastrointestinal dysfunction, vomiting crises, recurrent pneumonia, cardiovascular & temperature instabiity
MPV17-related hepatocerebral mitochondrial DNA depletion syndromeMPV17AR
  • Absent pain responses from birth
  • DD (can be seen in NTRK1 & NGF-CIP)
  • Infantile-onset liver dysfunction typically → liver failure
  • Failure to thrive, lactic acidosis, & hypoglycemia
  • More severe neurologic involvement; may incl white matter abnormalities on MRI & seizures
AcquiredLeprosy 1NANA
  • Insensitivity to pain
  • Painless injuries
  • Skin lesions (hypopigmented macules, nodules, plaques, or diffuse skin infiltration)
  • Enlargement of peripheral nerves
  • Localized (not universal) insensitivity to pain
Non-accidental / abusive injuryNANAMultiple unexplained injuries
  • Normal response to pain (although caregivers may deny this)
  • Different pattern of injuries (proportionate to size and development of child)

HSAN = hereditary sensory and autonomic neuropathy

DD = developmental delay

ID = intellectual disability

NA = not applicable

1.

Prevalence

The prevalence of the CIP phenotype is unknown. Consideration of this diagnosis has increased considerably due to the identification of more causative genes and increased awareness from medical/scientific publications and media stories. Fewer than 30 cases are known in the UK [Authors, personal observation], giving an estimated prevalence of one in a million.

Evaluation Strategy to Identify the Genetic Cause of Congenital Insensitivity to Pain

The diagnosis of a specific Mendelian form of congenital insensitivity to pain is established in a proband with a suggestive history and/or presenting findings and a heterozygous pathogenic variant in SCN11A or biallelic pathogenic variants in one of the other genes listed in Table 1. The diagnosis can be difficult to establish on clinical grounds alone before age five years.

Molecular genetic testing approaches can include a combination of targeted gene testing (multigene panel or single-gene testing) and genomic testing (comprehensive genomic sequencing).

Targeted gene testing requires the clinician to develop a hypothesis as to which specific gene(s) are likely to be involved, whereas genomic testing does not. Targeted testing is feasible based on phenotype in anyone older than approximately age five years (because of the difficulties of assessing subtle problems of intellectual developmental, sweating, temperature sensing, and autonomic features in infants and young children), with the exception of SCN11A (see Serial single-gene testing following).

Serial single-gene testing. The phenotype may guide the choice of which gene(s) to analyze first. Consider performing sequence analysis of:

  • SCN11A first in a newborn with severe intestinal hypomotility.
  • SCN9A first in an individual with normal intelligence who has anosmia.
  • PRDM12 first in an individual with normal intelligence, staphylococcal infections, and hypohidrosis.
    Because some individuals with NTRK1-CIP and NGF-CIP have minimal learning problems, sequence analysis of these two genes should be considered next if molecular genetic testing of SCN9A and PRDM12 yield no pathogenic variants.
  • NTRK1 and NGF first in an individual with evidence of learning problems or late development, staphylococcal infections, and hypohidrosis. Unexplained fever due to anhidrosis (the inability to sweat) is a characteristic and often initial feature (more so in hot climates).

If no pathogenic variant in SCN11A is found through sequence analysis OR if no or only one pathogenic variant is found through sequence analysis of the remainder of the genes listed in Table 1, gene-targeted deletion/duplication analysis should be considered.

Note: Whole-gene deletions have been reported in individuals with NGF-CIP [Fitzgibbon et al 2009] and SCN9A-CIP [Author, personal observation].

A multigene panel that includes genes for CIP and other genes of interest (see Table 2) may be considered. Note: The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Comprehensive genomic testing (when available) including exome and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation).

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Genetic Risk Assessment

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Congenital insensitivity to pain (CIP) is inherited in an autosomal recessive manner, with the exception of SCN11A-CIP, in which two rare pathogenic variants with an autosomal dominant inheritance pattern have been reported.

Risk to Family Members – Autosomal Recessive Inheritance

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of one CIP-related pathogenic variant).
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Heterozygotes (carriers) are asymptomatic and are not at risk for developing the disorder.

Offspring of a proband. The offspring of an individual with CIP are obligate heterozygotes (carriers) for a pathogenic variant in a CIP-related gene.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier of a CIP-related pathogenic variant.

Carrier (Heterozygote) Detection

Carrier testing for at-risk relatives requires prior identification of the CIP-related pathogenic variants in the family.

Risk to Family Members – Autosomal Dominant Inheritance (SCN11A-CIP)

See SCN11A in Table 1 for information on this very rare condition.

Parents of a proband

  • Some individuals diagnosed with SCN11A-CIP have an affected parent.
  • Some individuals diagnosed with SCN11A-CIP have the disorder as the result of a de novo SCN11A pathogenic variant. Information on the frequency of de novo pathogenic variants is currently very limited.
  • Molecular genetic testing is recommended for the parents of a proband with an apparent de novo pathogenic variant.
  • If the pathogenic variant found in the proband cannot be detected in leukocyte DNA of either parent, possible explanations include a de novo pathogenic variant in the proband or germline mosaicism in a parent. Though theoretically possible, no instances of germline mosaicism have been reported.

Sibs of a proband

  • The risk to the sibs of the proband depends on the genetic status of the proband's parents.
  • If a parent of the proband is affected, the risk to the sibs is 50%. Based on currently available, but limited, information, SCN11A-CIP appears to be completely penetrant. Phenotypic variability within families has not been reported.
  • If the parents have been tested for the SCN11A pathogenic variant identified in the proband and:
  • If the parents have not been tested for the SCN11A pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. The sibs of a proband with clinically unaffected parents are still at increased risk for SCN11A-CIP because of the possibility of reduced penetrance in a parent or the theoretic possibility of parental germline mosaicism [Rahbari et al 2016].

Offspring of a proband. Each child of an individual with SCN11A-CIP has a 50% chance of inheriting the SCN11A pathogenic variant. Based on currently available (limited) information, SCN11A-related CIP appears to be completely penetrant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the SCN11A pathogenic variant or is clinically affected, his or her family members may be at risk.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the CIP-related pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • National Library of Medicine Genetics Home Reference
  • Tomorrow: The Japan Association of Patients with Congenital Insensitivity to Pain with Anhidrosis (CIPA)
    Provides information about CIPA (HSAN IV) in Japanese
    Kitami 8-15-35-307
    Tokyo 157-0067
    Japan
    Phone: 03-5761-2860
    Fax: 03-5761-2861
    Email: cipa@tomorrow.or.jp

Management

Treatment of Manifestations

No consensus treatment or surveillance guidelines have been developed.

Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology (see Congenital Insensitivity to Pain with Anhidrosis).

Table 3.

Treatment of Manifestations in Individuals with Congenital Insensitivity to Pain

ManifestationTreatmentConsiderations/Other
Dental and oral lesionsTooth extraction and/or filing (smoothing) of sharp incisal edges [Bodner et al 2002]; use of a mouth guard [Hutton & McKaig 2010]
Bone fracturesStandard treatmentTreatment w/an external fixator may lead to potential serious infectious complications.
Bone and joint deformityCorrective osteotomyProlonged & intensive monitoring is necessary to avoid deformity or incomplete healing.
Leg length discrepancyShoe lift or epiphysiodesis [Bar-On et al 2002]The value of surgical intervention needs to be weighed against nonsurgical approaches incl close monitoring [Kim et al 2013].
Dry eyesLubricating eye drops or ointmentsSurgical treatment of neurotrophic keratitis has not been successful [Yagev et al 1999].
Longstanding infectionsWide surgical debridement
Ulcerating foot lesionsStandard treatmentAppropriate footwear & periods of non-weight bearing may be appropriate.
HyperthermiaDirect cooling in a bath or w/a cooling blanketControl of environmental temperatures is essential.
HypothermiaWarming by a blanketControl of environmental temperatures is essential.
Skin dryness and crackingTopical moisturizer (lotion or cream)Untreated dry skin can lead to skin infections, which increase the risk for serious infections (cellulitis or osteomyelitis).

Global Developmental Delay / Intellectual Disability Educational Issues

The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.

Global developmental delay / intellectual disability educational issues may be seen in those with CTCL1-CIP, NGF-CIP, or NTRK-CIP.

Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the United States, early intervention is a federally funded program available in all states.

Ages 3-5 years. In the United States, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.

Ages 5-21 years

  • In the United States, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.
  • Discussion of transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life. Some issues to consider:

  • Private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
  • In the United States:
    • Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
    • Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Social/Behavioral Issues

Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavioral management strategies or providing prescription medications when necessary.

Irritability, hyperactivity, impulsivity, and acting-out behaviors typically improve with age.

Prevention of Primary Manifestations

Table 4.

Prevention of Primary Manifestations in Individuals with Congenital Insensitivity to Pain

ManifestationPreventionConsiderations/Other
Injuries occurring around the homeStair gates; soft-round edging on tables & protruding objects; guard all heating devices; close supervision of younger children in the kitchen
Injuries occurring at schoolInform personnel at school of the diagnosis; seek help when an accident occurs but the child does not seem hurt.
Self-inflicted injuriesEducation of affected individuals about their condition.Communicating w/other families of individuals w/CIP (especially affected adults)
Corneal abrasionAt least annual ophthalmologic evaluation; artificial tears
  • Artificial tears are particularly helpful to those w/PRDM12-CIP
  • All individuals w/congenital corneal anesthesia have had SCN9A-CIP [Author, personal observation].
Staphylococcus aureus infections
  • Good hand hygiene & care; use of antiseptic soaps; early use of topical antibiotics
  • Investigation of swollen joints, limping, & limb underuse for infection by x-ray & C-reactive protein
Affects those w/NTRK1-, NGF-, CLTCL1-, & PRDM12-CIP; infections are specific for S. aureus only.

Prevention of Secondary Complications

Table 5.

Prevention of Secondary Manifestations in Individuals with Congenital Insensitivity to Pain

ManifestationPreventionConsiderations/Other
Inability to use pain as an indicator in diagnosing or assessing injury severityLaminated information letters/MediAlert braceletsConsider providing a laminated letter confirming the diagnosis, stating the pathogenic variant(s), & giving advice on diagnosis & treatment
Osteomyelitis of the mandibleEarly treatment of dental caries & periodontal diseaseRegular dental examinations & restriction of sweets
Bone & joint injury due to strenuous activity when an individual has poor baseline conditioningActivities that lead to increased strength, balance, & body awarenessDancing (particularly ballet), swimming, cycling, & non-traumatic martial arts may be considered.
Inadequate sedation in the postoperative period may trigger unexpected movement, causing secondary injury.Adequate sedation during proceduresTachycardia & hypertension in the postoperative period should raise consideration of the possibility of inadequate sedation.
Hyper- or hypothermiaCareful monitoring of temperature during the perioperative period

Surveillance

In addition to regular evaluations by a pediatrician and dermatologist (to assess and advise on skin infections/injuries) the measures in Table 6 are recommended.

Table 6.

Recommended Surveillance for Individuals Congenital Insensitivity to Pain

ManifestationEvaluationFrequency/Comment
Dental caries/tooth damageDental careRegular examinations (at least every 6 months)
Early injuriesEvaluation by parents & caregivers for signs of unrecognized injuryDaily
Bone healthPrompt investigation & treatment of orthopedic consequences of CIP by a named orthopedic surgeonAt least yearly, or more frequently depending on bony injuries
Corneal damageOphthalmology evaluationAt least annually, or more frequently as indicated
Hyper- or hypothermiaMonitoring of body temperature may allow timely treatment of hyper- or hypothermia.As needed

Agents/Circumstances to Avoid

Avoid the following:

  • Jumping, high-impact/contact sports, pastimes and jobs that involve the potential for blunt injury or severe bone and joint trauma
    The paucity of males with CIP who are older than age 20 years correlates with behaviors fueled by inability to feel pain (e.g., greater risk taking, deliberately picking fights, participation in extreme sporting events).
  • Hot or cold environments; hot or cold foods, hot showers or baths; heating blankets, particularly in the perioperative period

Pregnancy Management

Women with CIP are able to become pregnant and bear children normally.

Obstetric staff must be made aware of the diagnosis of CIP. Labor progresses normally, but will be painless, while other senses (stretch and touch) are intact. A delay in detecting pelvic fractures in an affected woman in the postnatal period has been reported [Wheeler et al 2014].

Therapies Under Investigation

Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for information on clinical studies for a wide range of diseases and conditions.

Other

Individuals with CIP typically learn that others have pain and tend to respond to others' pain normally. They often learn to simulate having pain in appropriate situations; e.g., being tackled during football.

The possibility that naloxone may temporarily relieve CIP analgesia has been suggested [Minett et al 2015]. While this medication could be of use in detecting the source of injury/illness in an affected individual, it may also expose the affected person to widespread pain from accumulated injuries.

References

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  • Bodner L, Woldenberg Y, Pinsk V, Levy J. Orofacial manifestations of congenital insensitivity to pain with anhidrosis: a report of 24 cases. ASDC J Dent Child. 2002; 69:293-6, 235. [PubMed: 12613315]
  • Carvalho OP, Thornton GK, Hertecant J, Houlden H, Nicholas AK, Cox JJ, Rielly M, Al-Gazali L, Woods CG. A novel NGF mutation clarifies the molecular mechanism and extends the phenotypic spectrum of the HSAN5 neuropathy. J Med Genet. 2011;48:131–5. [PMC free article: PMC3030776] [PubMed: 20978020]
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Chapter Notes

Author Notes

AP+CGW run a clinical and advice service for diagnosis and management of CIP.

Acknowledgments

We thank families with congenital insensitivity to pain and colleagues for advice in writing this paper.

Revision History

  • 8 February 2018 (ma) Review posted live
  • 29 July 2017 (cgw) Original submission
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