Cure KCNH1 Foundation

Cycle 3

Web:

https://www.curekcnh1.org/

Contact:

KCNH1-related epileptic encephalopathy is an ultra-rare neurological disorder caused by a mutation in the KCNH1 gene; exact prevalence is unknown, and there are probably many cases that are undiagnosed due to lack of access to genetic testing, but currently there are under 100 known cases in the world. Some cases lead to severe, early-onset, intractable (unresponsive to medications) seizures and encephalopathy (widespread disease of the brain that results in altered structure and function).

Last updated 04/30/2026

Clinical

Disease Class

Channelopathies

Ciliopathies

Epilepsy and seizure disorders

Intellectual disability and developmental syndromes

Neurological diseases

Body Systems

Digestive

Integumentary / Exocrine

Muscular / Skeletal

Nervous / Sensory

Respiratory

Organs

Bones

Brain

Hair

Intestines

Lungs

Mouth / teeth

Muscles

Nails

Nerves

Nose

Spinal cord

Known Genetic Link

Yes, one or more genes directly cause the condition

Causative Genes

KCNH1

Contributory Genes

None specified / unknown

Type of Inheritance

Autosomal dominant

Newborn Screening

Disease Mechanism(s)

Abnormal channel conductance

Altered channel kinetics

Cell signaling defects

Cilia dysfunction

Ion channel dysfunction

Age of Onset

Prebirth

Average Age at Diagnosis

Early childhood (age 1+-5)

Life Expectancy

Adolescence (12-17)

Adulthood (age 18-64)

Middle childhood (6-11)

Affected Sex(es)

Female

Intersex

Male

National Prevalence

11-50

Global Prevalence

101-1000

National Incidence

Less than 10

Global Incidence

Less than 10

Symptoms / Phenotypes

abnormal digit morphology

autism

craniofacial abnormalities

developmental delay

feeding difficulties

gastrointestinal disorders

gingival overgrowth

hypertrichosis

intellectual delay / global developmental delay

movement disorders / ataxia / tremor

seizures / epilepsy

sleep disorders

speech problems / apraxia

Biomarkers

Diagnostic

Existing Therapies

Off-Label Drug Use

Therapies in Development

Antisense oligonucleotide (ASO) therapy

Other (please specify)

· Two CRISPR base editing programs, targeting different KCNH1 variants (one currently being screened in mice, one in very early preclinical development)

Repurposed drug

· Imipramine and aripiprazole

Small molecule therapy (novel small molecule drugs)

· Two programs in preclinical development

Therapeutic Development Stages

In preclinical development

Therapeutic Development Role

Access to registry or natural history study

Data sharing

Funding

Outcome measures development

Recruitment and outreach to patients

Recruitment and outreach to trial sites / physicians

Results dissemination (including publications)

Sample provision

Study protocol design and/or review (includes selection of outcome measures)

Organizational & Research

Cell Lines

Fibroblasts

iPSCs

Cell Lines, Institution

Northwestern University

Transcripta Bio

Cell Lines, Involvement

Designed

Funded

Own

Cell Lines, share

Some of our cell lines are freely available

Disease Model

Mouse

Organoids

Disease Model, Involvement

Consulted

Disease Model, share

Organizational Challenges

Funding! Also analysis of our patient data (Citizen EHR, and registry results)

Clinical Trial Role

Recruitment and outreach, patients

Clinical Trial Types

Phase 1

Biobank, Institution

Van Andel Institute

Biobank, Involvement

Own

Center of Excellence, Institution

None

Registry

Yes, we have a registry that we created

Data Collected, Registry

Clinical data

Electronic health records/electronic medical records

Genetic data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Both

Platform, Registry

Matrix

Natural History Study

No, we do not have a natural history study, but we plan to create or collaborate on one

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

ICD Codes

No, we do not have any ICD codes

Diagnostic Guidelines

Science Advisory Board Policies

No policies

Research Network Policies

Has CRN but no policies

Patient Priority Survey

Research Roadmap

Yes we have a Research Roadmap, and will share policies

Europe