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hereditary sensory and autonomic neuropathy (CIP) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

hereditary sensory and autonomic neuropathy

MONDO:0015364

Also known as:CIPHSANcongenital insensitivity to pain

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Overview

An instance of sensory peripheral neuropathy that is caused by an inherited modification of the individual's genome.

Clinical Trials4 registered · 2 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

GeneReviews

Clinical Guidance

NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) is characterized by profound sensory loss affecting pain and temperature perception, absence of sweating (anhidrosis), and intellectual disability. Anhidrosis. Because sweating plays an important role in maintaining normal body temperature, anhidrosis (the failure to sweat) disturbs thermoregulation in hot environmental conditions and increases susceptibility to recurrent febrile episodes . Recurrent episodic fevers, usually the first clinical sign of NTRK1-CIPA, can begin in infancy or early childhood depending on environmental temperature. Recurrent febrile convulsions are also observed in some affected infants. Occasionally, hypothermia is observed in cold environments.

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) should be suspected in individuals with the following clinical findings and family history.

Clinical findings

Source: GeneReviews — "NTRK1 Congenital Insensitivity to Pain with Anhidrosis"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for hereditary sensory and autonomic neuropathy. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with NTRK1 Congenital Insensitivity to Pain Disorders

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

In addition to daily evaluation by parents and caregivers for early signs of otherwise unrecognized injury, regular examinations by a pediatrician, orthopedist, dentist, dermatologist, and ophthalmologist are recommended to assess and advise on various physical, mental, and behavioral problems. For details, see Table 6, Congenital Insensitivity to Pain Overview.

Source: GeneReviews — "NTRK1 Congenital Insensitivity to Pain with Anhidrosis"

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

4 clinical trials registered, 2 recruiting. Interventions under study include other interventions and drug therapy. Pipeline includes 2 PHASE2. Research is primarily sponsored by academic and government institutions.

102 publications have been identified in PubMed for hereditary sensory and autonomic neuropathy. Research spans Case Report / Case Series (53%), Basic Science / Preclinical (21%), and Review / Meta-Analysis (12%).

Research Type	Count	% of Total
Patient case studies	54

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 9:43 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:140471

GARD

Genetic and Rare Diseases Info Center

GARD:12688

Questions for Your Care Team

→Are any of the 4 active clinical trials a good fit for my situation?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Differential Diagnosis

The differential diagnosis of NTRK1 congenital insensitivity to pain with anhidrosis (NTRK1-CIPA) includes other genes associated with congenital insensitivity to pain (see Congenital Insensitivity to Pain Overview) as well as other hereditary disorders and acquired conditions with clinical manifestations similar to those of NTRK1-CIPA. Table 2. Hereditary Disorders in the Differential Diagnosis of NTRK1-CIPA

Gene(s)	Disorder	MOI	Clinical Features of Differential Disorder
COL1A1/2-related osteogenesis imperfecta	AD	Multiple fractures	Fractures cause pain occur w/minimal or no trauma.; Assoc w/other features incl blue sclera, short stature, joint hypermobility, deafness EDA EDAR EDARADD
Hypohidrotic ectodermal dysplasia	XLARAD	Hypohidrosis; Risk of hyperthermia	Insensitivity to pain not a feature ELP1 (IKBKAP)
Familial dysautonomia (HSAN III)	AR	pain from birth	GI dysfunction, vomiting crises, recurrent pneumonia, cardiovascular temperature instability HPRT1
Lesch-Nyhan syndrome	XL	Progressive self-injurious behavior (biting fingers, hands, lips, cheeks; banging the head or limbs)	Hyperuricemia; Progressive, severe DD/ID; Abnormal involuntary movements MPV17
MPV17-related hepatocerebral mitochondrial DNA depletion syndrome	AR	Absent pain responses from birth; DD	Infantile-onset liver dysfunction typically liver failure; failure to thrive, lactic acidosis, hypoglycemia; More severe neurologic involvement; may incl white matter abnormalities on MRI seizures
NGF	NGF-CIPA1 (HSAN V)	AR	Insensitivity to pain, anhidrosis, ID1,2
Disorder	Overlapping Clinical Features	Clinical Features of the Disorder Distinguishing from NTRK1-CIPA Leprosy1	Insensitivity to pain; Painless injuries
Absence of anhidrosis Non-accidental/abusive injury	Multiple unexplained injuries	Normal response to pain (although caregivers may deny this); Different pattern of injuries (proportionate to size development); Absence of anhidrosis 1. ,	—

Source: GeneReviews — "NTRK1 Congenital Insensitivity to Pain with Anhidrosis"

System/Concern	Evaluation	Comment
Anhidrosis	Physical exam of the skin	Assess for dry skin palmoplantar hyperkeratosis (often assoc w/cracking); determine if individual is using skin moisturizer daily. Regulation of body
temperature	Inquire about history of hyperthermia or hypothermia.	Insensitivity to pain
Multiple unintentional injuries	Physical exam of whole body	Assess for bruises, cuts, burns, as well as fingertip biting.
Orthopedic injuries	Exam of bones joints by an orthopedist	Assess for fractures, avascular necrosis, septic arthritis/osteomyelitis, self-mutilation, joint subluxation, Charcot neuroarthropathy, leg length discrepancy, scoliosis.
Dental risks for injury	Exam for oral lesions	Assess for traumatic lingual injuries, burns, self-biting, auto-extraction of teeth, overall dental health.
Neuropathic keratitis	Ophthalmologic exam	Assess for superficial punctate keratopathy corneal ulceration/perforation/infection.
Developmental delay	Neurologic exam standardized tests for developmental milestones	Assess for DD ID, incl defects in conceptual thinking abstract reasoning.
Behavioral problems	Formal eval of cognitive adaptive functions	Assess for social behaviors emotional disturbances; ADHD.
Genetic counseling	By genetics professionals1	To inform affected persons families re nature, MOI, implications of NTRK1-CIPA in order to facilitate medical personal decision making Family support/resources

Kisho

hereditary sensory and autonomic neuropathy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

hereditary sensory and autonomic neuropathy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications