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Hereditary insensitivity to pain with anhidrosis(CIPA)

MedGen UID:
6915
Concept ID:
C0020074
Disease or Syndrome
Synonyms: CIPA; Familial dysautonomia, type 2; FAMILIAL DYSAUTONOMIA, TYPE II; Hereditary sensory and autonomic neuropathy 4; Hereditary Sensory and Autonomic Neuropathy Type IV; HSAN 4; HSAN Type IV; Insensitivity to pain, congenital, with anhidrosis; Neuropathy, congenital sensory, with anhidrosis
SNOMED CT: Swanson-Buchanan-Alvord neuropathy syndrome (62985007); Congenital insensitivity to pain, anhidrosis and mental retardation (62985007); Congenital sensory neuropathy with anhidrosis (62985007); Hereditary sensory and autonomic neuropathy type IV (62985007); Hereditary sensory and autonomic neuropathy, type IV (62985007); HSAN IV (62985007); Autosomal recessive hereditary sensory neuropathy (62985007); Hereditary insensitivity to pain with anhidrosis (62985007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): NTRK1 (1q23.1)
 
Monarch Initiative: MONDO:0009746
OMIM®: 256800
Orphanet: ORPHA642

Definition

NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of NTRK1-CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common. [from GeneReviews]

Additional description

From MedlinePlus Genetics
Congenital insensitivity to pain with anhidrosis (CIPA) has two characteristic features: the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.\n\nAn inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.\n\nNormally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).\n\nIn addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older.  https://medlineplus.gov/genetics/condition/congenital-insensitivity-to-pain-with-anhidrosis

Clinical features

From HPO
Autoamputation of digits
MedGen UID:
343770
Concept ID:
C1852289
Finding
Acral ulceration
MedGen UID:
1648438
Concept ID:
C4732740
Finding
A type of digital ulcer that manifests as an open sore on the surface of the skin at the tip of a finger or toe.
Postural hypotension with compensatory tachycardia
MedGen UID:
376790
Concept ID:
C1850438
Finding
Abnormal autonomic nervous system physiology
MedGen UID:
8511
Concept ID:
C0013363
Disease or Syndrome
A functional abnormality of the autonomic nervous system.
Self-mutilation
MedGen UID:
19925
Concept ID:
C0036601
Injury or Poisoning
The act of injuring one's own body to the extent of cutting off or permanently destroying a limb or other essential part of a body.
Mood swings
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or out of proportion to events and circumstances.
Pain insensitivity
MedGen UID:
488855
Concept ID:
C0344307
Finding
Inability to perceive painful stimuli.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a state of constantly being unusually or abnormally active, including in situations in which it is not appropriate.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Postural hypotension with compensatory tachycardia
MedGen UID:
376790
Concept ID:
C1850438
Finding
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
A broad category of disorders characterized by an impairment to the intelligence an individual possesses. These impairments can result from trauma, birth, or disease and are not restricted to any particular age group.
Decreased number of small peripheral myelinated nerve fibers
MedGen UID:
870470
Concept ID:
C4024916
Finding
Neuropathic arthropathy
MedGen UID:
13919
Concept ID:
C0003892
Disease or Syndrome
Chronic progressive degeneration of the stress-bearing portion of a joint, with bizarre hypertrophic changes at the periphery. It is probably a complication of a variety of neurologic disorders, particularly tabes dorsalis, involving loss of sensation, which leads to relaxation of supporting structures and chronic instability of the joint. (Dorland, 27th ed)
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Corneal scarring
MedGen UID:
83899
Concept ID:
C0349702
Finding
Replacement of corneal tissue with scar tissue as a result of injury to the deeper layers of the cornea.
Keratitis
MedGen UID:
44013
Concept ID:
C0022568
Disease or Syndrome
Inflammation of the cornea.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Abnormality of the immune system
MedGen UID:
867388
Concept ID:
C4021753
Pathologic Function
An abnormality of the immune system.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Anhidrosis
MedGen UID:
1550
Concept ID:
C0003028
Disease or Syndrome
Inability to sweat.
Lichenification
MedGen UID:
452108
Concept ID:
C0023653
Pathologic Function
Thickening and hardening of the epidermis seen with exaggeration of normal skin lines.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
Poor wound healing
MedGen UID:
377525
Concept ID:
C1851789
Finding
A reduced ability to heal cutaneous wounds.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Acral ulceration
MedGen UID:
1648438
Concept ID:
C4732740
Finding
A type of digital ulcer that manifests as an open sore on the surface of the skin at the tip of a finger or toe.
Corneal ulceration
MedGen UID:
40486
Concept ID:
C0010043
Disease or Syndrome
Disruption of the epithelial layer of the cornea with involvement of the underlying stroma.
Keratitis
MedGen UID:
44013
Concept ID:
C0022568
Disease or Syndrome
Inflammation of the cornea.
Recurrent corneal erosions
MedGen UID:
56353
Concept ID:
C0155119
Disease or Syndrome
Corneal scarring
MedGen UID:
83899
Concept ID:
C0349702
Finding
Replacement of corneal tissue with scar tissue as a result of injury to the deeper layers of the cornea.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary insensitivity to pain with anhidrosis
Follow this link to review classifications for Hereditary insensitivity to pain with anhidrosis in Orphanet.

Recent clinical studies

Diagnosis

Berkovitch M, Copeliovitch L, Tauber T, Vaknin Z, Lahat E
Pediatr Neurol 1998 Sep;19(3):227-9. doi: 10.1016/s0887-8994(98)00047-2. PMID: 9806143

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