Congenital pain insensitivity is a rare genetic disorder characterized by the inability to perceive pain. Since affected individuals do not respond appropriately to painful situations, they engage in self-mutilating behavior such as biting of the oral mucosa and fingers and sustain injuries such as burns, fractures, and joint dislocations.
Congenital pain insensitivity (CPI) is an autosomal recessive disorder characterized by the inability to discern physical pain although the ability to feel a stimulus is intact . This rare ailment is considered to be a part of the hereditary sensory and autonomic neuropathies (HSAN) . CPI is a genetically heterogeneous disease caused by mutations in the SCN9A , NTRK1 , and NGFB genes . If left undetected and unaddressed, this condition can affect the patient's overall health and result in serious outcomes.
The clinical presentation reflects which gene is affected. Generally, the cases demonstrate a lack of pain perception with burns, bone fractures, joint dislocations, and other injuries . Moreover, they engage in self-mutilation by biting on their tongue, lips, and digits   resulting in laceration and ulceration of oral mucosa and scarring of the cheeks  . Additionally, affected individuals may exhibit mental retardation and developmental delays with varying degrees. Also common are behavioral issues and emotional lability. Furthermore, patients may be prone to developing neurotrophic keratitis, corneal ulcerations and scarring, and even infection.
Painless injuries induce severe consequences such as recurrent disease and repeated fractures. Specifically, sufferers are susceptible to developing osteomyelitis, acroosteolysis, and Charcot joints. Additionally, they may develop oral ulcers and other lesions, which further lead to infections, oral bleeding, and malnutrition . If not treated, poor outcomes such as failure to thrive are likely .
Jaw & Teeth
- Decreased Sweating
Over time, this lack of pain awareness can lead to an accumulation of injuries and health issues that may affect life expectancy. 0000970 Anosmia Lost smell 0000458 Autosomal recessive inheritance 0000007 Hypohidrosis Decreased ability to sweat Decreased [rarediseases.info.nih.gov]
HSAN type IV is characterized by anhidrosis, absent or markedly decreased sweating [ 1 – 3, 12, 13, 55 – 58 ]. [ojrd.biomedcentral.com]
- Neuropathic Arthropathy
Repeated trauma to joints results in progressive inflammation, damage, and deformity of the affected joints (Charcot joint or neuropathic arthropathy). The large, weight-bearing joints are especially prone to this complication. [rarediseases.org]
- Recurrent Fractures
Death from hyperpyrexia within the first three years of life may occur in 20% of these cases.  Insensitivity to pain is profound and results in deep ulceration on the knees and elbows, overuse of bones and joints leading to recurrent fractures, osteomyelitis [e-ijd.org]
- Indifference to Pain
[…] to pain congenital pain indifference indifference to pain, congenital, autosomal recessive pain insensitivity, congenital Dabby R. [ghr.nlm.nih.gov]
Other names for congenital insensitivity to pain include: asymbolia for pain channelopathy-associated insensitivity to pain CIP congenital analgesia congenital insensitivity to pain congenital pain indifference indifference to pain, congenital, autosomal [thinkgenetic.com]
A syndrome characterized by indifference to PAIN despite the ability to distinguish noxious from nonnoxious stimuli. Absent corneal reflexes and INTELLECTUAL DISABILITY may be associated. [connects.catalyst.harvard.edu]
There is indifference to pain, but this is usually far less of a problem than the autonomic dysfunction. Intelligence is usually normal, but emotions can be unstable. [contact.org.uk]
A twenty one year review of a case of congenital indifference to pain. J Bone Joint Surg Br 1975;57:241-3. [ PUBMED ] [ FULLTEXT ] 13. Abell JM, Hayes JT. Charcot knee due to congenital insensitivity to pain. [ijoonline.com]
- Poor Coordination
The NCS and nerve biopsy are normal. 1 Familial dysautonomia (HSAN-Type-III) also comprises of nystagmus, hypotonia, areflexia and poor coordination. 6 Asymbolia for pain usually has damaged insular cortex evident on magnetic resonance imaging of brain [apicareonline.com]
Type 3 (HSAN-III) features include, hypotonia, hypothermia, poor coordination and temperature regulation with indifference to pain. [neurosciencefundamentals.unsw.wikispaces.net]
Infants and young children with an impaired response to pain and repeated harmful behaviors should be evaluated for this medical entity. The workup will include the patient's history and presentation, a complete physical exam (including a focus on neurologic, oral, and eye tests), and specialized studies.
Biopsy of the skin and nerves can confirm the diagnosis by revealing distinctive findings . Specifically, microscopic analysis of the skin may show the abnormal functioning of nerves innervating eccrine sweat glands while examination of the nerve tissue may demonstrate a diminished quantity of unmyelinated small-diameter fibers. Another exam is characterized by applying pressure with a pen onto the patient's nail bed. Note that an absent withdrawal response is a result of the lack of pain perception . Clinicians may perform the axonal flare test, in which an intradermal histamine injection results in a characteristic skin response. An electromyogram (EMG) will typically yield normal results . Genetic testing is not routinely done since there are many mutations associated with CPI.
Treatment depends on the patient's age and intelligence, as well as the parent's attitude and cooperation. [pediatricneurosciences.com]
HSAN is described additionally to be a genetic disorder created through mutations with no cure or treatment. Although there is therapy to deal with the symptoms, it does not deal with the disorder, and there is no definitive treatment to each child. [neurosciencefundamentals.unsw.wikispaces.net]
[…] and prognosis No specific treatment is available for CIP 1,7. [radiopaedia.org]
Treatment Self treatment : Most simple boils can be treated at home. Ideally, the treatment should begin as soon as a boil is noticed. Early treatment may prevent later complications. [livingnaturally.com]
[…] reported the following features 9 : acro-osteolysis within the first year of life (100%) limb fractures with prominent periosteal reaction and exuberant callus (100%) osteomyelitis (50%) brain volume loss with mild ventriculomegaly (50%) Treatment and prognosis [radiopaedia.org]
The prognosis for independent function depends on the degree of disease expression and the ability to control the secondary clinical problems. Prognosis and goals There are a number of hereditary and sensory and autonomic neuropathies (HSAN). [ojrd.biomedcentral.com]
The etiology and pathogenesis of CIP depends on the specific type of HSAN. For example: HSAN2D (channelopathy-associated congenital insensitivity to pain) : patients have homozygous mutations in the SCN9A gene 4,7. [radiopaedia.org]
Common syndromes with unknown etiology (e.g., intercostal neuralgia). B. Painful polyneuropathies (including acute-onset and slow-onset distal symmetrical polyneuropathies) HIV (Schiffito et al. 2002; Luciano et al. 2003). [shiga-med.ac.jp]
[…] insensitivity to pain to experience it for the first time.  Similar effects were observed in Na v 1.7 null mice treated with naloxone.  As such, opioid antagonists like naloxone and naltrexone may be effective in treating the condition.  Epidemiology [en.wikipedia.org]
Epidemiology HSAN IV is extremely rare among most populations with the exception of the Japanese and Israeli-Bedouins. The prevalence is unknown, but it was seen the disorder is more diffused in cultures in which intermarriage is accepted. [flipper.diff.org]
Despite the discovery of these two channels and their modes of action, the pathophysiology of pain perception is incompletely understood. To date, mutations in Nav1.7 (OMIM 603415) have been implicated in three pain-related syndromes in humans. [karger.com]
Endorphins are molecules in your body that when released, prevent nerve cells from releasing more pain signals. [thetartan.org]
In certain extreme cases, the child's baby teeth are extracted to prevent self mutilation of tongue, lips and fingers until they grow their adult teeth. Figure 4. [neurosciencefundamentals.unsw.wikispaces.net]
Common practices can be: • prevention of self-mutilation by smoothing or extracting teeth; • prevention of debilitating orthopedic problems by daily evaluation for early signs of unrecognized injury; • prevention of neurotrophic keratitis with tarsorrhaphy [flipper.diff.org]
Tea tree oil : Tea tree oil is purported to have antiseptic properties, and has been used traditionally to prevent and treat infections. [livingnaturally.com]
The parents need to be educated about simple measures like avoiding excessive wrapping, preventing dehydration, and measures to reduce hyperpyrexia, which reduce lot of preventable deaths. [e-ijd.org]
- Peddareddygari LR, Oberoi K, Grewal RP. Congenital Insensitivity to Pain: A Case Report and Review of the Literature. Case Rep Neurol Med. 2014;2014:141953.
- Genetics Home Reference (GHR). Congenital insensitivity to pain. http://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain. Accessed May 22nd, 2017.
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- Zhang S, Malik Sharif S, Chen Y-C, et al. Clinical features for diagnosis and management of patients with PRDM12 congenital insensitivity to pain. J Med Genet. 2016;53(8):533-535.