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Canine Mendelian disease record

X-Linked Ectodermal Dysplasia (XHED)

X-Linked Ectodermal Dysplasia (XHED). X-linked recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,665 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier
OMIA:000543-9615
X-linked recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human X-linked hypohidrotic ectodermal dysplasia

Dogs with this condition carry a change in EDA. In people, changes in the same gene cause X-linked hypohidrotic ectodermal dysplasia. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: An X-linked form of ectodermal dysplasia which results from mutations of the gene encoding ectodysplasin.

In humans it is also called: XHED, anhidrotic ectodermal dysplasia X-linked, Christ-Siemens-Touraine syndrome, ectodermal dysplasia 1, hypohidrotic, X-linked, hypohidrotic ectodermal dysplasia X-linked.

MONDO:0010585 OMIM 305100 Mechanism (DisMech) →

Human mechanism pathograph for X-linked Hypohidrotic Ectodermal Dysplasia is curated in DisMech (Monarch Initiative), joined by exact Mondo id. That page is about people. It is not a treatment plan for a dog.

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

X-linked ectodermal dysplasia is an inherited skin condition characterized by absent or abnormal teeth, hypotrichosis, and absent sweat glands. Other signs include decreased tear production, decreased mucociliary clearance, and symmetrical hairlessness. Affected animals are more susceptible to pulmonary infectious disease than normal dogs. Chronic nasal and ocular discharges are common, as are corneal ulceration and chronic demodecosis. The causative mutation is a point mutation in the ectodysplasin (EDA, also called ED1) gene. The mode of inheritance is X-linked recessive. Breeding of affected animals or known carriers is not recommended. Edited by Dr. Margret Casal

Clinical features

Affected animals are born with symmetrical hairlessness on the forehead and over the dorsal pelvic area. There is often a history of ophthalmia neonatorum (infection behind closed eye lids in neonates). Affected animals have absent or abnormal secondary hairs (Casal et al., 2005, Mauldin et al., 2009). A large number of teeth are missing. Premolars are rarely present and canines, when present, are thinner than normal and pointed outward. Teeth that are present are conically shaped. Most notably molars and incisors, when present, are misshapen and small (Lewis et al., 2010). Signs also include absent sweat glands, decreased tear production, decreased mucociliary clearance in the respiratory tract and symmetrical hypotrichosis. Affected dogs are more susceptible to pulmonary infectious disease than normal dogs. Chronic nasal and ocular discharge are common, as are corneal ulcerations (Casal et al., 2005, Casal et al., 2007, Mauldin et al., 2009).

Molecular genetics

By adopting a comparative positional cloning approach, involving a linkage analysis as described in the Mapping section, Casal et al. (2005) discovered that the causative mutation of XHED in the colony of German shepherd dogs described by Casal et al. (1997) is a "nucleotide substitution (G to A) in the splice acceptor site of intron 8 . . . In the presence of the A residue, a cryptic acceptor site within exon 9 is used, leading to a frame shift and use of a premature stop codon that truncates the translation of both isoforms, EDA-A1 and EDA-A2, resulting in the absence of the TNF-like homology domain, the receptor-binding site of ectodysplasin." Using the genetic variant nomenclature of 2015, the causative variant can be described as c.910-1G>A (OMIA variant 361). In each of three affected mixed-breed dogs (two of which were brothers) from Israel, Waluk et al. (2016) reported that "the whole genome sequence data did not reveal any non-synonymous EDA variant in the affected dogs"but "the EDA transcript in the affected dogs lacked 103 nucleotides encoded by exon 2. We speculate that this exon skipping is caused by a genetic variant located in one of the large introns flanking this exon, which was missed by whole genome sequencing with the illumina short read technology. The altered EDA transcript splicing most likely causes the observed ectodermal dysplasia in the affected dogs. . . . The variant designation for this frame-shifting exon skipping on the transcript level is r.385_487del. The predicted variant on the protein level is p.Met129Valfs*112 and the predicted mutant protein lacks the functionally important collagen-like and TNF-signaling domains" (OMIA variant 1458). Hadji Rasouliha et al. (2018) reported a single base-pair deletion in the EDA gene (NM_001014770.2:c.842delT; NP_001014770.1:p.Leu281HisfsTer22) as the likely causal variant "in a litter of Dachshund puppies, of which four male puppies showed clinical signs of XLHED" (OMIA variant 1017). Vasiliadis et al. (2018) independently investigated the same Dachshund family and identified the same variant. Vasiliadis et al. (2018) described the variant as c.458delT as they referred to the ENSEMBL annotation, which lacks the first exon of the EDA gene. A comparison of the ENSEMBL and NCBI annotations of the canine EDA gene is given in Figure S1 of Hadji Rasouliha et al. (2018).

Pathology

Ectodysplasin A is a key component in ectodermal appendage formation. The gene is transcribed as several splice variants, two of which encode the proteins EDA-A1 and EDA-A2. EDA-A1 binds the receptor EDAR. Anhidrotic ectodermal dysplasia is caused by failure of the ligand-receptor interaction during the development of skin and its appendages, which is necessary for correct development of hair follicles and tooth buds (Kowalczyk et al., 2011, Casal et al., 2005). Histological examination of hairless skin and foot pads shows an absence of hair follicles, adnexal structures, and eccrine glands. Bronchial, tracheal, and esophageal glands are also absent (Casal et al., 1997, Casal et al., 2007, Mauldin et al., 2009). Epidermal hyperpigmentation and orthokeratotic hyperkeratosis are common findings (Moura et al., 2004).

Prevalence

Because the mode of inheritance is X-linked recessive, the condition occurs more often in males.

Inheritance

Casal et al. (1997) showed that this disorder is X-linked recessive. Mosaic expression in females heterozygous for the causative mutation is possible (Casal et al., 2005). Moura et al. (2020) reported an interesting case of an affected male and its mother, both of whom were dead by the time the researchers gained access to the data, which precluded any DNA testing. From pedigree information alone, Moura et al. (2020) reported that "Through Bayesian inference, it was possible to establish that this case originated from a new mutation, with a 99.99% probability of the mother of the proband not being a carrier."

Control

Breeding of affected animals or known carriers is not recommended.

Genetic testing

There is a test available to detect the causative mutation in the German Shepherd and in Dachshund.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 305100 Gene · OMIM 300451

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000543-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as X-linked hypohidrotic ectodermal dysplasia (MONDO:0010585).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (doi:10.25910/2AMR-PV70, CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 22.

  2. Genetics of inherited skin disorders in dogs. · Vet J · 2022 · PMID 34861369

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Your breed

See what X-Linked Ectodermal Dysplasia (XHED) looks like in your dog's breed.
Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The variant frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:000543-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:000543-9615 · Donner et al. 2023