Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder of the

nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...

which prevents the feeling of

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

or temperature, and prevents a person from sweating. Cognitive disorders are commonly coincident. CIPA is the fourth type of

hereditary sensory and autonomic neuropathy 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. They are less common than Charcot-Marie-Tooth disease. Classif ...

(HSAN), and is also known as HSAN IV.

Signs and symptoms

Signs of CIPA are present from infancy. Infants may present with

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s 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. Those affected are unable to feel pain and temperature. The absence of pain experienced by people with CIPA puts them at high risk for accidental self-injury.

Corneal ulcer Corneal ulcer is an inflammatory or, more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal Stroma of cornea, stroma. It is a common condition in humans particularly in the ...

ation occurs due to lack of protective impulses. Joint and bone problems are common due to repeated injuries, and wounds heal poorly.

Cause

CIPA is caused by a genetic mutation that prevents the formation of nerve cells which are responsible for transmitting signals of pain, heat, and cold to the brain. The disorder is inherited in an autosomal recessive fashion. CIPA is caused by a mutation in

NTRK1 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'' gen ...

, a gene encoding the neurotrophic

tyrosine kinase receptor Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase ...

. NTRK1 is a receptor for

nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was on ...

(NGF). This protein induces outgrowth of

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

s and

dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...

s and promotes the survival of

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

nic sensory and sympathetic neurons. The mutation in NTRK1 does not allow NGF to bind properly, causing defects in the development and function of

nociceptive Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...

reception.

Mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

l abnormalities in muscle cells have been found in people with CIPA. Skin biopsies show a lack of innervation of the

eccrine gland Eccrine sweat glands (; from Greek ''ekkrinein'' ' secrete'; sometimes called merocrine glands) are the major sweat glands of the human body, found in virtually all skin, with the highest density in palm and soles, then on the head, but much les ...

s and nerve biopsies show a lack of small

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

ated and unmyelinated fibers.

Diagnosis

Diagnosis is made based on clinical criteria and can be confirmed with genetic testing.

Treatment

There is no treatment for CIPA. Attention to injuries to prevent infection and worsening is necessary.

Epidemiology

The condition is inherited and is most common among Negev Arabs aka

Negev Bedouins The Negev Bedouin ( ar, بدو النقب, ''Badū an-Naqab''; he, הבדואים בנגב, ''HaBedu'im BaNegev'') are traditionally pastoral nomadic Arab tribes (Bedouin), who until the later part of the 19th century would wander between Sau ...

. Approximately 20% of people with CIPA die of hyperthermia by age 3.

Signs and symptoms

Cause

Diagnosis

Treatment

Epidemiology

References

Further reading