How is Huntington disease-like 2 inherited?

Huntington disease-like 2 follows an autosomal dominant inheritance pattern. This means inheriting just one copy of the altered gene from either parent can cause the condition.

How rare is Huntington disease-like 2?

Huntington disease-like 2 is classified as very rare. The estimated prevalence is approximately <1 in 1,000,000. Because rare disease data can be limited, actual numbers may differ from published estimates.

How is Huntington disease-like 2 diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Huntington disease-like 2?

Information about treatment is currently limited for this condition.

What are the complications of Huntington disease-like 2?

Huntington disease-like 2 can lead to serious complications due to its effects on movement, mood, and thinking. As the disease progresses, individuals may face increasing difficulties with daily activities, which can impact their independence. Additionally, psychiatric problems may lead to challenges in relationships and social interactions.

How does Huntington disease-like 2 affect daily life?

Living with Huntington disease-like 2 can be challenging as it affects movement, mood, and cognitive abilities. People may find it hard to perform everyday tasks, manage their emotions, and remember things. Support from family, friends, and healthcare providers can help improve quality of life and assist with daily management.

What is the life expectancy for someone with Huntington disease-like 2?

Currently, there is limited information about the life expectancy of individuals with Huntington disease-like 2. The progression of the disease can vary from person to person, and more research is needed to understand its long-term effects. It is important for families to discuss individual cases with healthcare professionals for better insights.

Are there specialists who can help with Huntington disease-like 2?

Yes, individuals with Huntington disease-like 2 may benefit from seeing specialists who understand neurodegenerative disorders. Neurologists, psychiatrists, and therapists can provide support and guidance tailored to the specific symptoms of this condition. It's important to have a healthcare team that can address both physical and mental health needs.

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Huntington disease-like 2 (HDL2) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

Huntington disease-like 2

MONDO:0011671

Also known as:HDL2Huntington disease-like type 2Huntington's disease-like 2

Overview

Huntington disease-like 2 (HDL2) is a severe neurodegenerative disorder considered part of the neuroacanthocytosis syndromes characterized by a triad of movement, psychiatric, and cognitive abnormalities.

GeneticsAutosomal dominant · JPH3 (chr 16)

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: Inertia, Memory problems (memory impairment), Cerebral cortical atrophy, and Chorea and others. 19 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	17	Action tremor, Slowness of movement (bradykinesia), Dystonia

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.

JPH3 encodes junctophilin 3 (748 aa). Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Highest expression in Brain Cortex (113.4 TPM) and Brain Frontal Cortex BA9 (112.8 TPM).

Huntington disease-like 2 is associated with mutations in the JPH3 gene on chromosome 16.

JPH3 is classified as a druggable target (Ion Channel category) with score 0.0.

GeneReviews

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

Huntington disease-like 2 (HDL2) should be suspected in individuals – particularly of African descent or with African ancestry (even if distant) – who present with the following clinical and imaging features and family history typical of Huntington disease (HD) but do not have a disease-causing CAG expansion (i.e., reduced-penetrance allele or full-penetrance allele) in HTT.

Clinical features

Progressive motor disability featuring involuntary movements (especially chorea) and affecting voluntary movement (e.g., gait, speech, swallowing). Rigidity and bradykinesia may predominate in the later stages of the disease.

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 Huntington disease-like 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Systematic clinical practice guidelines for Huntington disease-like 2 (HDL2) have not been established, though potential treatment, primarily based on Huntington disease (HD) therapeutics, have been summarized . The following recommendations are based on the authors' personal experience managing individuals with this disorder combined with standard practices for HD treatment. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with HDL2, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Huntington Disease-Like 2: Recommended Evaluations Following Initial Diagnosis

Prognosis

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

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

Huntington Disease-Like 2: Recommended Surveillance

System/Concern | Evaluation | Frequency

Movement disorder

| • Assessment of fine motor gross motor skills incl gait (using UHDRS or CQNE)

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 Huntington disease-like 2.

18 publications have been identified in PubMed for Huntington disease-like 2. Research spans Epidemiology / Natural History (44%), Case Report / Case Series (33%), and Review / Meta-Analysis (11%).

Research Type	Count	% of Total
Disease patterns and progression	8	44%

Data assembled from 7 of 12 sources · Last updated Sep 19, 2026, 2:43 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:606438

Orphanet

European rare disease database

Orphanet:98934

GARD

Genetic and Rare Diseases Info Center

GARD:16874

Questions for Your Care Team

→Should I pursue genetic testing for JPH3, 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 Huntington disease-like 2

Huntington disease-like 2 (HDL2) is a severe neurodegenerative disorder that affects movement, mood, and thinking. It is part of the neuroacanthocytosis syndromes, a group of conditions that share similar features including unusual blood cell shapes and neurological issues. This condition is characterized by a triad of movement difficulties, psychiatric problems, and cognitive decline.

People with Huntington disease-like 2 can experience a range of symptoms including problems with movement, changes in mood and behavior, and difficulties with memory and thinking. These symptoms reflect the complex nature of the condition, affecting several areas of health.

Huntington disease-like 2 is linked to genetic changes involving the JPH3 gene. This genetic factor is an important part of understanding the condition, although more detailed mechanisms about how it causes the disease are still being studied. Associated genes include JPH3.

← Back to All Diseases

GeneReviews

Differential Diagnosis

The differential diagnosis of Huntington disease-like 2 (HDL2) is the same as for Huntington disease (HD), and is based on the co-occurrence of: (1) movement abnormalities (chorea, dystonia, and/or parkinsonism) reflecting basal ganglia dysfunction, dementia, and psychiatric disturbances; and (2) autosomal dominant inheritance. The most obvious diagnosis to exclude is HD. HD and other genetic disorders to consider are summarized in . Table 3. Genetic Disorders of Interest in the Differential Diagnosis of Huntington Disease-Like 2

Gene(s)	Disorder	MOI	Features of Disorder
Huntington disease	AD	Clinically indistinguishable from HDL2	Possibly greater thalamic volume than in HDL2 (unlikely to be diagnostically useful in single cases) APP PSEN1
PSEN2	Early-onset familial Alzheimer disease (See Alzheimer Disease Overview.)	AD	Dementia
DRPLA	AD	Progressive movement disorder dementia; Psychiatric disturbances	Prominent ataxia myoclonus; Extremely rare outside of Japanese populations ATP7B
Wilson disease	AR	Movement disorders; Psychiatric disorders	Liver disease; Kayser-Fleischer rings; Copper abnormalities; Note: Exclusion is essential, as Wilson disease is treatable. ATXN2
Spinocerebellar ataxia type 2	AD	Dystonia or chorea (38%); Dementia (37%); Parkinsonism; Oculomotor dysfunction	Cerebellar ataxia is the prominent movement disorder. ATXN3
Spinocerebellar ataxia type 3	AD	Chorea (rare) C9orf72	—
C9orf72 frontotemporal dementia /or amyotrophic lateral sclerosis	AD	Choreiform movement disorders; Dementia; Neuropsychiatric manifestations	Extrapyramidal manifestations CLN3 CLN5 CLN6 CLN8 CTSD CTSF DNAJC5 GRN KCTD7 MFSD8 PPT1 TPP1
Neuronal ceroid lipofuscinoses	ARAD	Movement disorder	Usually AR w/childhood onset; rarely AD w/adult onset FTL
Neuroferritinopathy	AD	Chorea; Dystonia; Speech swallowing deficits	Dementia rare; From disease onset, all affected persons have evidence of excess brain iron accumulation on T2-weighted MRI. MAPT
MAPT-related frontotemporal dementia	AD	Parkinsonian manifestations; Dementia; Behavioral psychiatric manifestations	Not assoc w/chorea
NKX2-1	Benign hereditary chorea (See NKX2-1-Related Disorders.)	AD	Chorea
Pantothenate kinase-associated neurodegeneration	AR	Parkinsonism; Dystonia; Dementia	Childhood onset w/early falls visual disturbances; MRI features PDGFB PDGFRB SLC20A2
XPR1	Primary familial brain calcification (familial idiopathic basal ganglia calcification)	AD	Progressive movement disorder (clumsiness,...

Source: GeneReviews — "Huntington Disease-Like 2"

System/Concern	Evaluation	Comment
Psychiatric	Assessment for psychiatric manifestations	—
Genetic counseling	By genetics professionals 1	To obtain a pedigree inform affected persons their families re nature, MOI, implications of HDL2 to facilitate medical personal decision making
Nutrition	Assessment for nutritional status; referral to nutritionist as needed	Assure adequate intake in setting of swallowing abnormalities. Family support
resources	By clinicians, wider care team, family support organizations	Assessment of family social structure to determine need for:; Community or; Social work involvement; Home nursing referral; Legal assistance (e.g.
Huntington Disease-Like 2: Treatment of Manifestations Manifestation/Concern	Treatment	Considerations/Other
Movement disorders	Pharmacologic agents may suppress abnormal movements. The most common choices are tetrabenazine its derivatives; consider also low-dose neuroleptic agents, e.g., fluphenazine or haloperidol.	Tremor in 1 persons was suppressed w/clonazepam. However, clonazepam, levodopa/carbidopa, anticholinergics, typical atypical neuroleptics were not effective in other persons.

Huntington disease-like 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Movement disorder

Research Landscape

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is Huntington disease-like 2?

What are the symptoms of Huntington disease-like 2?

What causes Huntington disease-like 2?

How is Huntington disease-like 2 inherited?

How rare is Huntington disease-like 2?

How is Huntington disease-like 2 diagnosed?

Are there treatments for Huntington disease-like 2?

What are the complications of Huntington disease-like 2?

How does Huntington disease-like 2 affect daily life?

What is the life expectancy for someone with Huntington disease-like 2?

Are there specialists who can help with Huntington disease-like 2?

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Cognitive issues

Dysphagia

Psychiatric manifestations

Community

Recent Publications

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