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hereditary sensory and autonomic neuropathy type 4 - Clinical Profile, Genes & Research | Kisho | Kisho

Organ System	Phenotype Count	Example Features
Eyes	5	Opacification of the corneal stroma, Corneal ulceration, Corneal scarring
Brain and nerves	5	Problems with involuntary body functions (abnormal autonomic nervous system physiology), Emotional lability, Intellectual disability
Skin	3	Nail dysplasia, Anhidrosis, Nail dystrophy
Bones and joints	2	Postural hypotension with compensatory tachycardia, Bone infection (osteomyelitis)
Arms and legs	1	Autoamputation of digits
Immune system	1	Abnormality of the immune system
Heart and blood vessels	1	Postural hypotension with compensatory tachycardia
Metabolism	1	Recurrent fever

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"

GeneReviews

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)

Genetic testing for NTRK1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for hereditary sensory and autonomic neuropathy type 4 has been reported in the published literature.

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 type 4. 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

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

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

GeneReviews

Clinical Guidance

Avoid the following:

Hot or cold environments; hot or cold foods; hot showers or baths
Jumping or high-impact activities and sports

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

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

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

Clinical Trials

View trials for hereditary sensory and autonomic neuropathy type 4

Explore Trials

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.

No clinical trials have been registered for hereditary sensory and autonomic neuropathy type 4.

133 publications have been identified in PubMed for hereditary sensory and autonomic neuropathy type 4. Research spans Review / Meta-Analysis (64%), Case Report / Case Series (15%), and Basic Science / Preclinical (13%).

Research Type	Count	% of Total
Research summaries	85	64%
Patient case studies	20	15%
Laboratory research	17	13%
Disease patterns and progression	6	5%
Other research	2	2%
Testing and diagnosis research	2	2%
Clinical study results	1	1%

Recent Publications

Papazachariou A (2026). [PMID: 41128447](https://pubmed.ncbi.nlm.nih.gov/41128447/). *Curr Opin Clin Nutr Metab Care*. [Review / Meta-Analysis]
Inaka S (2026). [PMID: 41492817](https://pubmed.ncbi.nlm.nih.gov/41492817/). *Pediatr Int*. [Basic Science / Preclinical]
Chang S (2026). [PMID: 41553922](https://pubmed.ncbi.nlm.nih.gov/41553922/). *Pacing Clin Electrophysiol*. [Review / Meta-Analysis]
AlHashem A (2026). [PMID: 41474134](https://pubmed.ncbi.nlm.nih.gov/41474134/). *Am J Med Genet A*. [Case Report / Case Series]
Amado C (2026). [PMID: 40975490](https://pubmed.ncbi.nlm.nih.gov/40975490/). *Ann Allergy Asthma Immunol*. [Review / Meta-Analysis]
Anderson EN (2026). [PMID: 41468891](https://pubmed.ncbi.nlm.nih.gov/41468891/). *Am J Hum Genet*. [Basic Science / Preclinical]
Najeeb A (2026). [PMID: 42238874](https://pubmed.ncbi.nlm.nih.gov/42238874/). *Skin Appendage Disord*. [Case Report / Case Series]
Benaroch LR (2026). [PMID: 41863776](https://pubmed.ncbi.nlm.nih.gov/41863776/). *JBJS Case Connect*. [Case Report / Case Series]
Buel KL (2026). [PMID: 41569909](https://pubmed.ncbi.nlm.nih.gov/41569909/). *FP Essent*. [Review / Meta-Analysis]
Sierra-Rivera A (2026). [PMID: 41400424](https://pubmed.ncbi.nlm.nih.gov/41400424/). *Lab Med*. [Case Report / Case Series]

Kisho

hereditary sensory and autonomic neuropathy type 4

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

hereditary sensory and autonomic neuropathy type 4

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team