How is Charcot-Marie-Tooth disease, axonal, Type 2HH inherited?

Charcot-Marie-Tooth disease, axonal, Type 2HH follows an autosomal dominant inheritance pattern. This means inheriting just one copy of the altered gene from either parent can cause the condition.

How is Charcot-Marie-Tooth disease, axonal, Type 2HH diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Charcot-Marie-Tooth disease, axonal, Type 2HH?

Information about treatment is currently limited for this condition.

What complications can arise from Charcot-Marie-Tooth disease, axonal, Type 2HH?

Information about complications specific to Charcot-Marie-Tooth disease, axonal, Type 2HH is currently limited. However, like other types of Charcot-Marie-Tooth disease, it may lead to muscle weakness and difficulty with movement over time. It's important to monitor any changes and discuss concerns with a healthcare provider.

How does Charcot-Marie-Tooth disease, axonal, Type 2HH affect daily life?

Daily life with Charcot-Marie-Tooth disease, axonal, Type 2HH can vary from person to person. Some individuals may experience challenges with walking or balance, which can impact activities. It’s helpful to work with healthcare providers to find ways to manage these challenges and maintain independence.

What is the life expectancy for someone with Charcot-Marie-Tooth disease, axonal, Type 2HH?

Information about life expectancy for Charcot-Marie-Tooth disease, axonal, Type 2HH is currently limited. Generally, many people with Charcot-Marie-Tooth disease live normal or near-normal lifespans. It’s important to focus on managing symptoms and maintaining a good quality of life.

Should family members get tested for Charcot-Marie-Tooth disease, axonal, Type 2HH?

Since Charcot-Marie-Tooth disease, axonal, Type 2HH has a genetic component, family members may consider genetic testing. This can help determine if they carry the gene change associated with the condition. Discussing testing options with a genetic counselor can provide valuable information and support.

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Charcot-Marie-Tooth disease, axonal, Type 2HH - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

Charcot-Marie-Tooth disease, axonal, Type 2HH

MONDO:0030458

Also known as:CMT2HH

Overview

GeneticsAutosomal dominant · JAG1 (chr 20)

ResearchLimited published research (1 article)

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.

Features include always present findings: Stridor, Vocal cord paresis, and Centrally nucleated skeletal muscle fibers; and common findings: Impaired temperature sensation, Distal muscle weakness, Impaired pain sensation, and Pes cavus and others. 27 total HPO annotations.

Organ System	Phenotype Count	Example Features
Muscles	8	Triceps weakness, Low muscle tone (hypotonia), Distal muscle weakness

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

JAG1 encodes jagged canonical Notch ligand 1 (1,218 aa). Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Highest expression in Artery Tibial (202.9 TPM) and Artery Coronary (150.2 TPM).

Charcot-Marie-Tooth disease, axonal, Type 2HH is associated with mutations in the JAG1 gene on chromosome 20.

The JAG1 protein participates in JAG1 gene expression is inhibited by RUNX3, Expression of JAG1 during nephron development, and NOTCH1 t(7;9)(NOTCH1:M1580_K2555) does not bind JAG1 pathways.

JAG1 is classified as a druggable target (Druggable Genome and Growth Factor categories) with score 8.7.

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

Clinical diagnostic criteria for Alagille syndrome (ALGS) have been published .

Suggestive Findings

ALGS should be suspected in individuals with any combination of the following histologic findings, major clinical features, and/or family history. The histologic finding of bile duct paucity (an increased portal tract-to-bile duct ratio) on liver biopsy. Although considered to be the most important and constant feature of ALGS, bile duct paucity is only identified in 65% of biopsies done in the first three months of life. In the newborn, a normal ratio of portal tracts to bile ducts, bile duct proliferation, or histology suggestive of neonatal hepatitis may be observed. Eventually, bile duct paucity is present in about 95% of individuals .

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 Charcot-Marie-Tooth disease, axonal, Type 2HH. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for Alagille syndrome (ALGS) have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with ALGS, the evaluations summarized (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

To date, surveillance guidelines for ALGS have not been published. In the absence of published guidelines, recommendations to monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations are based on the authors' personal experience managing individuals with this disorder . Table 7. Alagille Syndrome: Recommended Surveillance

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 Charcot-Marie-Tooth disease, axonal, Type 2HH.

2 publications have been identified in PubMed for Charcot-Marie-Tooth disease, axonal, Type 2HH. Kisho has analyzed 1 by research type. Research spans Case Report / Case Series (100%).

Recent Publications

She QY (2024). [PMID: 39027568](https://pubmed.ncbi.nlm.nih.gov/39027568/). *Heliyon*. [Case Report / Case Series]

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 1:11 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:619574

Questions for Your Care Team

→Should I pursue genetic testing for JAG1, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

FAQ

Frequently Asked Questions

Common questions about Charcot-Marie-Tooth disease, axonal, Type 2HH

Information about overview is currently limited for this condition.

Information about symptoms is currently limited for this condition.

This condition has a genetic component. Research has identified a change in the gene JAG1 that is associated with Charcot-Marie-Tooth disease, axonal, Type 2HH. Additional details about its causes, including other potential genetic factors or risk factors, are currently limited. Associated genes include JAG1.

← Back to All Diseases

GeneReviews

Clinical Guidance

Alagille syndrome (ALGS) is a multisystem disorder with a wide spectrum of clinical variability ranging from life-threatening liver or cardiac disease to only subclinical manifestations (e.g., butterfly vertebrae, posterior embryotoxon, characteristic facial features) . Some individuals present with an isolated feature (e.g., cardiac disease, aneurysmal disease) . Clinical variability is seen even among individuals from the same family . To date, more than 700 individuals with ALGS have been found to have a pathogenic variant in JAG1 or NOTCH2 . lists the phenotypic features associated with this condition. Table 2. Alagille Syndrome: Frequency of Select Features

Feature	% of Persons w/Feature	Comment
Hepatic abnormality	95%	Bile duct paucity; conjugated hyperbilirubinemia; chronic cholestasis characterized by pruritus, xanthomas, fat-soluble vitamin deficiencies; end-stage liver disease
Cardiac manifestations	90%-97%	Most commonly including peripheral pulmonary stenosis tetralogy of Fallot
Posterior embryotoxon	78%-89%	—
Vertebral anomalies	33%-93%	—
Characteristic facies	20%-90%	—
Renal manifestations	39%	Renal malformations kidney disease
Vascular	15%-30%	Intracranial bleeds, systemic vascular anomalies, other, including moyamoya disease Onset. Individuals with ALGS who have severe liver or cardiac involvement are most often diagnosed in infancy.

Source: GeneReviews — "Alagille Syndrome"

Kisho

Charcot-Marie-Tooth disease, axonal, Type 2HH

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Gastrointestinal

Cardiovascular

Skeletal

Renal

Growth

Development

Genetic counseling

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Charcot-Marie-Tooth disease, axonal, Type 2HH

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is Charcot-Marie-Tooth disease, axonal, Type 2HH?

What are the symptoms of Charcot-Marie-Tooth disease, axonal, Type 2HH?

What causes Charcot-Marie-Tooth disease, axonal, Type 2HH?

How is Charcot-Marie-Tooth disease, axonal, Type 2HH inherited?

How is Charcot-Marie-Tooth disease, axonal, Type 2HH diagnosed?

Are there treatments for Charcot-Marie-Tooth disease, axonal, Type 2HH?

What complications can arise from Charcot-Marie-Tooth disease, axonal, Type 2HH?

How does Charcot-Marie-Tooth disease, axonal, Type 2HH affect daily life?

What is the life expectancy for someone with Charcot-Marie-Tooth disease, axonal, Type 2HH?

Should family members get tested for Charcot-Marie-Tooth disease, axonal, Type 2HH?

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Gastrointestinal

Cardiovascular

Skeletal

Renal

Growth

Development

Genetic counseling

Clinical Guidance

Therapies Under Investigation

Clinical Trials