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Congenital Insensitivity to Pain with Anhidrosis.

Authors

Indo Y1.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.
2008 Aug 5 [updated 2014 Apr 17].

Author information

1
Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan

Excerpt

CLINICAL CHARACTERISTICS:

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), 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 CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.

DIAGNOSIS/TESTING:

The diagnosis of CIPA is suspected in infants and children with recurrent fever and biting of the tongue, lips, or fingers after eruption of the first teeth, and in older individuals with repeat traumatic injuries. Evaluation of sensory and autonomic functions (including pharmacologic tests) and skin and nerve biopsies were used in the past for clinical diagnosis, however, the diagnosis can now be confirmed by identification of biallelic pathogenic variants in NTRK1.

MANAGEMENT:

Treatment of manifestations: Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology. For anhidrosis: Monitoring body temperature helps to institute timely measures to prevent/manage hyperthermia or hypothermia. For insensitivity to pain: Modify as much as reasonable a child’s activities to prevent injuries. Inability to provide proper immobilization as a treatment for orthopedic injuries often delays healing; additionally, bracing and invasive orthopedic procedures increase the risk for infection. Methods used to prevent injuries to the lips, buccal mucosa, tongue, and teeth include tooth extraction, and/or filing (smoothing) of the sharp incisal edges of teeth, and/or use of a mouth guard. Skin care with moisturizers can help prevent palmar and plantar hyperkeratosis and cracking and secondary risk of infection; neurotrophic keratitis is best treated with routine care for dry eyes, prevention of corneal infection, and daily observation of the ocular surface. Interventions for behavioral, developmental, and motor delays as well as educational and social support for school-age children and adolescents are recommended. Prevention of secondary complications: Regular dental examinations and restriction of sweets to prevent dental caries; early treatment of dental caries and periodontal disease to prevent osteomyelitis of the mandible. During and following surgical procedures, potential complications to identify and manage promptly include hyper- or hypothermia and inadequate sedation, which may trigger unexpected movement and result in secondary injuries. Surveillance: Daily evaluation by parents and caregivers for early signs of otherwise unrecognized injury. Regular examinations by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology are recommended to help prevent serious injuries and initiate early treatment. Annual follow up at a center that fosters comprehensive care and communication between the various subspecialties that are needed for optimal care. Agents/circumstances to avoid: Hot or cold environments; hot or cold foods; hot showers or baths; jumping or high-impact activities and sports. Evaluation of relatives at risk: If the pathogenic variants in a family are known, molecular genetic testing can clarify the genetic status of at-risk infants, so that those who are affected can be monitored to avoid hyperpyrexia and its potential complications and oral injuries when the primary teeth erupt. If the pathogenic variants in the family are not known, monitoring of the body temperature of at-risk infants during the neonatal period (i.e., first 28 days of life) can help avoid hyperpyrexia.

GENETIC COUNSELING:

Congenital insensitivity to pain with anhidrosis (CIPA) results from the presence of two NTRK1 pathogenic variants. Typically one pathogenic variant is inherited from each parent (autosomal recessive inheritance); however, in some instances both pathogenic variants are from one parent (uniparental disomy). Autosomal recessive (AR) inheritance. 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. Uniparental disomy (UPD). The risk to sibs of an affected individual is not increased over that of the general population. For both AR inheritance and UPD, carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible once the pathogenic variants have been identified in an affected family member.

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