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neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities

MONDO:0030947

Also known as:CONRIBAneurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities

Overview

GeneticsAutosomal dominant · CLCN6 (chr 1)

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: Motor delay, Global developmental delay, Difficulty breathing (respiratory insufficiency), and Gastrostomy tube feeding in infancy; and common findings: Long philtrum, Generalized hypotonia, Type 2 muscle fiber predominance, and Nystagmus and others. 26 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	5	Seizure, Cerebral visual impairment, Global developmental delay

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.

CLCN6 encodes Cl-/H+ antiporter 6 (869 aa). Voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the late endosome lumen. Highest expression in Brain Cerebellum (40.9 TPM) and Testis (38.9 TPM).

Neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities has been associated with mutations in the CLCN6 gene on chromosome 1.

The CLCN6 protein participates in CLCN6(1-49)-p-RAF1(279-648) fusion, CLCN6(1-49)-RAF1(279-648) fusion, and CLCN4/5/6 exchange Cl- for H+ pathways.

CLCN6 is classified as a druggable target (Druggable Genome and Ion Channel categories) with score 0.4.

Diagnosis

Genetic testing for CLCN6 is available. Testing is considered supportive for diagnosis.

Prognosis

Phenotype severity distribution: 4 always present features, 19 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 1:58 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:619173

Orphanet

European rare disease database

Orphanet:610573

GARD

Genetic and Rare Diseases Info Center

GARD:18023

Questions for Your Care Team

→Should I pursue genetic testing for CLCN6, 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?

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neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Medical References

External Resources

OMIM

Orphanet

GARD

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Questions for Your Care Team

Questions for Your Care Team

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