| Congenital insensitivity to pain with anhidrosis | |
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| Charcot joints are shown in this boy with CIPA. | |
| Causes | Genetic mutations |
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder of the nervous system which prevents the feeling of pain or temperature and prevents a person from sweating. Cognitive disorders are commonly coincidental. CIPA is the fourth type of hereditary sensory and autonomic neuropathy (HSAN), and is also known as HSAN IV.
Signs of CIPA are present from infancy. Infants may present with seizures related to an abnormally high body temperature. Since people with this condition are unable to sweat, they are unable to properly regulate their body temperature. [1] Those affected are unable to feel pain and temperature. [2] [3]
The absence of pain experienced by people with CIPA puts them at high risk for accidental self-injury. Corneal ulceration occurs due to lack of protective impulses. [4] Joint and bone problems are common due to repeated injuries, and wounds heal poorly. [5]
Delayed developmental milestones in early years may be observed. [6] Patients often have severe learning difficulties, irritability, hyperactivity, self-injurious behaviour, and cognitive impairment, [6] but patients with normal intelligence have also been reported. [6]
CIPA is caused by a genetic mutation that prevents the formation of nerve cells responsible for transmitting signals of pain, heat, and cold in the brain. The disorder is inherited in an autosomal recessive fashion. [6]
CIPA is caused by a mutation in NTRK1, [6] a gene encoding the neurotrophic tyrosine kinase receptor. [7] NTRK1 is a receptor for nerve growth factor (NGF). This protein induces outgrowth of axons and dendrites and promotes the survival of embryonic sensory and sympathetic neurons. The mutation in NTRK1 does not allow NGF to bind properly, causing defects in the development and function of nociceptive reception. [3]
Mitochondrial abnormalities in muscle cells have been found in people with CIPA. Skin biopsies show a lack of innervation of the eccrine glands [4] and nerve biopsies show a lack of small myelinated and unmyelinated fibers. [4] [8] [3]
Diagnosis is made based on clinical criteria, supported by nerve biopsy findings of reduced unmyelinated and small myelinated fibres, and can be confirmed with genetic testing. [1] [2]
The absence of or significantly reduced sweating in CIPA patients can be used for a differential diagnosis. [6]
Sadly, there is no treatment for CIPA. Attention to injuries to prevent infection and worsening is necessary. [1]
Some patients with CIPA have been operated on without anesthesia, [9] but the patient's anxiety might still need to be alleviated in these cases. [9]
Patients might have tactile hyperesthesia, in which case anesthesia is necessary. [9]
Bradycardia, hypotension, and hyperthermia also require management/attention, before, during and after surgery. [9]
Worldwide several hundred cases have been reported, but the exact prevalence is unknown. [6]
The condition is inherited and is most common among Negev Arabs aka Negev Bedouins. [4] For Japan, the prevalence is estimated at 1/600,000–950,000. [6]
Approximately 20% of people with CIPA die of hyperthermia by age 3. [4]
Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).
Congenital insensitivity to pain (CIP), also known as congenital analgesia, is one or more extraordinarily rare conditions in which a person cannot feel physical pain. The conditions described here are separate from the HSAN group of disorders, which have more specific signs and cause. Because feeling physical pain is vital for survival, CIP is an extremely dangerous condition. It is common for people with the condition to die in childhood due to injuries or illnesses going unnoticed. Burn injuries are among the more common injuries.
Familial dysautonomia (FD), also known as Riley–Day syndrome, is a rare, progressive, recessive genetic disorder of the autonomic nervous system that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons in the autonomic and sensory nervous system.
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the NTRK1 gene.
Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, peripheral nerves, and organs. The role of these nerves is to innervate some skin sensations and help control autonomic function. It is estimated that 15–20 million people in the United States have some form of peripheral neuropathy.
Hypoalgesia or hypalgesia denotes a decreased sensitivity to painful stimuli.
Cholinergic urticaria or also known as (CholU) and CU, is a rare form of hives (urticaria) that is triggered by an elevation in body temperature, breaking a sweat, or exposure to heat. It is also sometimes called exercise-induced urticaria or heat hives. The condition is considered to be one of the many rarest forms of allergies known to medical science.
Hypohidrosis is a medical condition in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyperhidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosis include hyperthermia, heat stroke and death. An extreme case of hypohidrosis in which there is a complete absence of sweating and the skin is dry is termed anhidrosis. The condition is also known as adiaphoresis, ischidrosis, oligidria, oligohidrosis and sweating deficiency.
Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A and B are myelinated. Group C fibers include postganglionic fibers in the autonomic nervous system (ANS), and nerve fibers at the dorsal roots. These fibers carry sensory information.
Sudomotor function refers to the autonomic nervous system control of sweat gland activity in response to various environmental and individual factors. Sweat production is a vital thermoregulatory mechanism used by the body to prevent heat-related illness as the evaporation of sweat is the body’s most effective method of heat reduction and the only cooling method available when the air temperature rises above skin temperature. In addition, sweat plays key roles in grip, microbial defense, and wound healing.
Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.
Hereditary sensory neuropathy, type II also known as HSN2 is a region of a parent protein which in humans is encoded by the WNK1 gene. It is a transcript variant of the WNK1 gene that is selectively expressed in nervous system tissues, and during development. Mutations in this exon of the WNK1 gene have been identified as causative in genetic neuropathy syndromes, and in inherited pain insensitivity.
Nav1.8 is a sodium ion channel subtype that in humans is encoded by the SCN10A gene.
Idiopathic pure sudomotor failure (IPSF) is the most common cause of a rare disorder known as acquired idiopathic generalized anhidrosis (AIGA), a clinical syndrome characterized by generalized decrease or absence of sweating without other autonomic and somatic nervous dysfunctions and without persistent organic cutaneous lesions.
Acquired idiopathic generalized anhidrosis (AIGA) is characterized by generalized absence of sweating without other autonomic and neurologic dysfunction. Other symptoms include facial flushing, headaches, disorientation, lassitude, hyperthermia, weakness, and palpitations.
Group A nerve fibers are one of the three classes of nerve fiber as generally classified by Erlanger and Gasser. The other two classes are the group B nerve fibers, and the group C nerve fibers. Group A are heavily myelinated, group B are moderately myelinated, and group C are unmyelinated.
Hereditary sensory and autonomic neuropathy type I or hereditary sensory neuropathy type I is a group of autosomal dominant inherited neurological diseases that affect the peripheral nervous system particularly on the sensory and autonomic functions. The hallmark of the disease is the marked loss of pain and temperature sensation in the distal parts of the lower limbs. The autonomic disturbances, if present, manifest as sweating abnormalities.
PR domain zinc finger protein 12 is a protein that in humans is encoded by the PRDM12 gene. This gene is normally switched on during the development of pain-sensing nerve cells. People with homozygous mutations of the PRDM12 gene experience congenital insensitivity to pain (CIP). PRMD12 is a part of a larger domain that mediate histone methyltransferases. Enzymes target gene promoters in order to control gene expression.
Peripheral mononeuropathy is a nerve related disease where a single nerve, that is used to transport messages from the brain to the peripheral body, is diseased or damaged. Peripheral neuropathy is a general term that indicates any disorder of the peripheral nervous system. The name of the disorder itself can be broken down in order to understand this better; peripheral: in regard to peripheral neuropathy, refers to outside of the brain and spinal cord; neuro: means nerve related; -pathy; means disease. Peripheral mononeuropathy is a disorder that links to Peripheral Neuropathy, as it only effects a single peripheral nerve rather than several damaged or diseased nerves throughout the body. Healthy peripheral nerves are able to “carry messages from the brain and spinal cord to muscles, organs, and other body tissues”.
Marsili syndrome is an extremely rare genetic disorder which is characterized by symptoms similar to those reported on individuals with congenital insensitivity to pain with anhidrosis. It can be fatal if it goes unnoticed/undiagnosed.
| Authority control databases: National |
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