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autosomal dominant nonsyndromic hearing loss 3B - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

autosomal dominant nonsyndromic hearing loss 3B

MONDO:0012975

Also known as:DFNA3BGJB6 autosomal dominant nonsyndromic deafnessautosomal dominant deafness 3B

Overview

Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the GJB6 gene.

GeneticsAutosomal dominant · GJB6 (chr 13)

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: Adult onset sensorineural hearing impairment.

Organ System	Phenotype Count	Example Features
Ears	1	Adult onset sensorineural hearing impairment

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.

GJB6 encodes gap junction protein beta 6 (261 aa). One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell Highest expression in Esophagus Mucosa (199.5 TPM) and Vagina (198.1 TPM).

Autosomal dominant nonsyndromic hearing loss 3B is associated with mutations in the GJB6 gene on chromosome 13.

GJB6 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

Hidrotic ectodermal dysplasia 2 (HED2, Clouston syndrome) should be considered after infancy in individuals with the following clinical features:

Nail dystrophy (malformed, thickened, small nails); an essential feature of the syndrome. In approximately 30% of affected persons, nail dystrophy may be the only obvious finding during the physical examination at a specific time.
Hypotrichosis (partial or total alopecia). The scalp hair is sparse, pale, fine, and brittle, or may be completely absent. The eyebrows are sparse or absent. The eyelashes are short and sparse. Axillary and pubic hair is sparse or absent.

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 autosomal dominant nonsyndromic hearing loss 3B. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hidrotic ectodermal dysplasia 2 (HED2, Clouston syndrome), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 5.

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 5:45 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:612643

GARD

Genetic and Rare Diseases Info Center

GARD:18130

Questions for Your Care Team

→Should I pursue genetic testing for GJB6, 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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Clinical Guidance

Hidrotic ectodermal dysplasia 2 (HED2, Clouston syndrome) is characterized by dystrophy of the nails, alopecia (partial or total), hyperpigmentation of the skin (especially over the joints), palmoplantar hyperkeratosis, and clubbing of the fingers. Sweat glands, sebaceous glands, and teeth are normal. The clinical manifestations are highly variable even within the same family. To date, more than 150 individuals with HED2 have been identified [, , , , , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Hidrotic Ectodermal Dysplasia 2: Frequency of Select Features

Feature	% of Personsw/Feature	Comment
Alopecia	100%	Hair often sparse fine w/progressive thinning alopecia in adulthood; Involvement of eyebrows, lashes, axillary pubic hair
Dystrophic nails	100%	Typically present from birth or early childhood; often short, thick slow growing; May be cone shaped or triangular; may be assoc w/finger clubbing Palmoplantar
keratoderma	70%	Onset usually from early childhood to adolescence; when present, may be focal or diffuse; Often has a cobblestoned appearance w/multiple small fissures Hair. In infancy, the scalp hair is fine, wiry, brittle, patchy, and pale.

Source: GeneReviews — "Hidrotic Ectodermal Dysplasia 2"

GeneReviews

Differential Diagnosis

Various types of hidrotic ectodermal dysplasia exist, and it is likely that new types will be described . Hidrotic ectodermal dysplasia 2 (HED2) must be differentiated from other ectodermal dysplasias that can affect nails and hair . Table 4. Ectodermal Dysplasias in the Differential Diagnosis of Hidrotic Ectodermal Dysplasia 2

Gene(s)	Disorder	MOI	Clinical Characteristics	Comment / Distinguishing Features
WNT10A	Hypohidrotic ectodermal dysplasia (HED)1	XLARAD	Hypotrichosis: thin, lightly pigmented, slow-growing scalp hair; Hypohidrosis: deficient sweating w/episodes of hyperthermia; Hypodontia: few abnormally formed teeth erupt, later than average	Hypohidrosis dental abnormalities are the major distinguishing features.; Eyelid papules may develop in WNT10A-HED.
GJB2	Keratitis-ichthyosis-deafness syndrome (OMIM 148210)	AD	Sensorineural deafness; Photophobia, corneal ulceration scarring; Progressive hyperkeratotic plaques palmoplantar hyperkeratosis; Sparse hair nail dystrophy: less pronounced than in HED2	Sensorineural deafness ocular changes are the major differentiating features.
HOXC13	Ectodermal dysplasia 9, hair/nail type (OMIM 614931)	AR	Generalized congenital atrichia; Nail dystrophy	Absent palmoplantar keratoderma KRT6A KRT6B KRT6C KRT16
KRT17	Pachyonychia congenita (PC)	AD	Hypertrophic nail dystrophy w/subungual hyperkeratosis; Variably present: oral leukokeratosis, pilosebaceous cysts, palmoplantar hyperhidrosis, follicular keratoses on the trunk extremities, natal teeth	Absence of hypotrichosis or atrichia is the main distinguishing feature.; Palmoplantar keratoderma is focal in PC (vs diffuse in most cases of HED2).
KRT74	Ectodermal dysplasia 7, hair/nail type (OMIM 614929)	AR	Generalized hypotrichosis or atrichia; Nail dystrophy	Absent palmoplantar keratoderma
KRT85	Ectodermal dysplasia 4, hair/nail type (OMIM 602032)	AR	Sparse or absent scalp hair; Absent eyebrows, eyelashes, pubic axillary hair; Nail dystrophy	Absent palmoplantar keratoderma AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked EDA pathogenic variants are associated with X-linked HED. EDAR, EDARADD, and WNT10A pathogenic variants are associated with autosomal dominant and autosomal recessive HED.

Source: GeneReviews — "Hidrotic Ectodermal Dysplasia 2"

Kisho

autosomal dominant nonsyndromic hearing loss 3B

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Establishing the Diagnosis

Differential Diagnosis

Integument

Hypotrichosis

Therapies Under Investigation

Clinical Trials

autosomal dominant nonsyndromic hearing loss 3B

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Establishing the Diagnosis

Differential Diagnosis

Integument

Hypotrichosis

Therapies Under Investigation

Clinical Trials