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hereditary sensory and autonomic neuropathy type 2 (HSAN2) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

hereditary sensory and autonomic neuropathy type 2

MONDO:0019941

Also known as:HSAN2Hereditary Sensory and Autonomic Neuropathy Type IIautosomal recessive sensory radicular neuropathy

Overview

Hereditary sensory and autonomic neuropathy, type 2 (HSAN2) is an inherited disorder characterized by profound and universal sensory loss involving large and small fiber nerves, and marked hypotonia.

ResearchLimited published research (3 articles)

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

The published clinical descriptions of hereditary sensory and autonomic neuropathy type II (HSAN2) are inconsistent, possibly in part as a result of reports that lack molecular genetic confirmation of the diagnosis. Clinically, WNK1-related HSAN2 (HSAN2A), RETREG1 (FAM134B)-related HSAN2 (HSAN2B), and KIF1A-related HSAN2 (HSAN2C) appear to be very similar. Autonomic dysfunction may be more pronounced in RETREG1-related neuropathy, and individuals with KIF1A-related HSAN2 also showed distal muscle weakness. SCN9A-related HSAN2 was reported in two families . Table 2. Hereditary Sensory and Autonomic Neuropathy Type II (HSAN2): Gene-Phenotype Correlations Feature | Associated Gene (HSAN2 Subtype)

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

No consensus clinical diagnostic criteria for hereditary sensory and autonomic neuropathy type II (HSAN2) have been published.

Suggestive Findings

Hereditary sensory and autonomic neuropathy type II (HSAN2) should be suspected in individuals with the following clinical and electrophysiologic findings and family history.

Clinical findings

Congenital or early-onset (1st to 2nd decade) sensory deficit

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 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for hereditary sensory and autonomic neuropathy type II (HSAN2) have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hereditary sensory and autonomic neuropathy type II (HSAN2), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Prognosis

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

GeneReviews

Surveillance Guidelines

The feet should be inspected daily for injuries and sources of wear. Affected individuals should be followed annually by centers with comprehensive care, such as those for diabetic foot care and/or Charcot-Marie-Tooth neuropathy, also known as hereditary motor and sensory neuropathy.

Source: GeneReviews — "Hereditary Sensory and Autonomic Neuropathy Type II"

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 2.

3 publications have been identified in PubMed for hereditary sensory and autonomic neuropathy type 2. Research spans Case Report / Case Series (100%).

Recent Publications

Ma S (2025). [PMID: 39710744](https://pubmed.ncbi.nlm.nih.gov/39710744/). *J Hum Genet*. [Case Report / Case Series]
Ragucci C (2025). [PMID: 41300170](https://pubmed.ncbi.nlm.nih.gov/41300170/). *Brain Sci*. [Case Report / Case Series]
Davion JB (2024). [PMID: 39553548](https://pubmed.ncbi.nlm.nih.gov/39553548/). *Heliyon*. [Case Report / Case Series]

Data assembled from 4 of 12 sources · Last updated Sep 18, 2026, 1:20 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:970

GARD

Genetic and Rare Diseases Info Center

GARD:3976

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

HSAN is a heterogeneous group of disorders in which pathogenic variants in other genes lead to overlapping clinical phenotypes. The distinction between HSAN and clinically similar congenital insensitivity to pain (CIP) is inconsistent. A list of genes implicated in other types of HSAN and/or CIP is provided in . Table 4. Disorders of Interest in the Differential Diagnosis of Hereditary Sensory and Autonomic Neuropathy Type II (HSAN2)

Gene	HSAN Classification	MOI	Typical Age at Onset	Clinical (Distinguishing) Features	Reference
ATL1	HSAN1	AD	Adulthood	Painless ulcers, fractures; involvement of upper motor neurons described	See HSN1D or allelic Spastic Paraplegia 3A.
ATL3	HSAN1	AD	Adulthood	Painless ulcers, fractures; spasticity in some persons; severely delayed wound healing; multiple fractures of foot skeleton	OMIM 615632
CLTCL1	Not classified	AR	Congenital	CIP, inability to feel touch, ID	OMIM 601273
DNMT1	HSAN1	AD	Adulthood	Loss of pain, ulcers; sensorineural hearing loss, progressive dementia, sensory ataxia	DNMT1-Related Disorder
DST	HSAN6	AR	Congenital	Autonomic involvement; alacrimia, feeding difficulties, contractures, hypomimia, severeDD/ID	OMIM 614653
ELP1	HSAN3	AR	Congenital	Predominant autonomic neuropathy; alacrimia, gastrointestinal dysfunction, vomiting, cardiovascular instability, blood pressure fluctuations, autonomic crises, scoliosis	—
Familial Dysautonomia FAAHP1 (FAAH-OUT)	CIP	ADAR	Congenital	Pain insensitivity impaired anxiety	OMIM 618377 FLVCR1
AR	Congenital	Painless injuries, psychomotor delay, anemia	—	—	—
NGF	HSAN5	AR	Congenital	See phenotype of HSAN4.	Congenital Insensitivity to Pain Overview
NTRK1	HSAN4	AR	Congenital	CIP w/anhidrosis, self-mutilations (biting the tongue, biting of fingertips), fever episodes (lack of sweat gland innervation), painless fractures, variable degree of ID, corneal lesions	NTRK1 Congenital Insensitivity to Pain with Anhidrosis
PRDM12	HSAN8	AR	Congenital	Pain insensitivity, facial injuries, sweating usually preserved, ID less common	Congenital Insensitivity to Pain Overview RAB7A
AD	Adulthood	Strong motor involvement, also classified as CMT2B	Charcot-Marie-Tooth Hereditary Neuropathy Overview	—	—
SCN11A	CIP/HSAN7	AD	Congenital	Predilection for skin ulcers to cervical region, pruritus, intestinal dysmotility, delayed motor development, joint hypermobility	Congenital Insensitivity to Pain Overview
SPTLC1	HSAN1	AD	Adulthood	Loss of pain (may be assoc w/lancinating pain); ulcerations, mutilations, mild motor involvement (may be pronounced in some persons)	SPTLC1-Related Hereditary Sensory Neuropathy
SPTLC2	HSAN1	AD	Adulthood	Similar to SPTLC1-HSN	OMIM 613640 ZFHX2

Source: GeneReviews — "Hereditary Sensory and Autonomic Neuropathy Type II"

WNK1 (HSAN2A)	RETREG1 (HSAN2B)	KIF1A (HSAN2C)	SCN9A (HSAN2D)
Sensory deficit	+++	+++	+++
Autonomic dysfunction	++	+++	++
Distal motor involvement	+	+	++

Kisho

hereditary sensory and autonomic neuropathy type 2

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Treatment of Manifestations

Clinical Guidance

Therapies Under Investigation

Clinical Trials

hereditary sensory and autonomic neuropathy type 2

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Treatment of Manifestations

Clinical Guidance

Therapies Under Investigation

Clinical Trials