How is Alexander Disease (Discovered in the Labrador Retriever) inherited in dogs?

Alexander Disease (Discovered in the Labrador Retriever) follows a Autosomal recessive inheritance pattern, associated with the GFAP gene.

Is there a genetic test for Alexander Disease (Discovered in the Labrador Retriever)?

Alexander Disease (Discovered in the Labrador Retriever) is associated with the GFAP gene. Where a validated DNA test for the causal variant is available, it can identify dogs carrying the variant before breeding. Per-breed variant frequency figures are published in the Sniff Atlas (242,664 dogs screened).

What is the human equivalent of Alexander Disease (Discovered in the Labrador Retriever)?

OMIA links Alexander Disease (Discovered in the Labrador Retriever) to its human counterpart in OMIM (OMIM 203450), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Alexander Disease (Discovered in the Labrador Retriever)

Q: How well studied is Alexander Disease (Discovered in the Labrador Retriever) in dogs?

OMIA curates 13 peer-reviewed references for Alexander Disease (Discovered in the Labrador Retriever). The full, linked citation list is on this page.

Alexander Disease (Discovered in the Labrador Retriever). Autosomal recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,664 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:001208-9615
Inheritance: Autosomal recessive
Linked gene: GFAP
Human counterpart: In humans, this gene is GFAP. OMIM 137780 In people, GFAP appears tolerant of loss-of-function variation (gnomAD v4.1 constraint, LOEUF 0.99). Constraint measures intolerance to loss-of-function only and does not indicate importance; some tolerant genes cause disease through other mechanisms. In people, variants in the GFAP gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human Alexander disease

Dogs with this condition carry a change in GFAP. In people, changes in the same gene cause Alexander disease. 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: Alexander disease (AxD) is a rare neurodegenerative disorder of the astrocytes comprised of two clinical forms: AxD Type I and Type II manifesting with various degrees of macrocephaly, spasticity, ataxia and seizures and leading to psychomotor regression and death.

In humans it is also called: ALXDRD, alexanders leukodystrophy, AxD.

MONDO:0008752 OMIM 203450 Mechanism (DisMech) →

Human mechanism pathograph for Alexander Disease 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.

Clinical features

Alexander disease is a progressive fatal neurodegenerative disease. The observed cases have been found in younger dogs, usually <12 months of age (Wrzosek et al., 2015). Early signs may begin as incoordination, a head tilt, knuckling on limbs, issues with balance, nystagmus and an aversion to touch (Wrzosek et al., 2015). As the disease progresses clinical features are ataxia and paresis in the hindlimbs (Kobatake et al., 2020) and in later stages tetraparesis (Van Poucke et al., 2016). Some patients may experience spastic front limbs along with vestibular signs (e.g., head tilt, strabismus) and myoclonic jerks of the head and cervical regions (Van Poucke et al., 2016). Generalised muscle atrophy, stiffness, regurgitation, increasing difficulty in swallowing and changes in vocalisation can be observed (Van Poucke et al., 2016; Kobatake et al., 2020). [IT thanks DVM students Bri Pepper and Carmen Tu for contributions to this entry in April 2022]

Molecular genetics

Van Poucke et al. (2016): "c.719G>A nucleotide substitution resulting in a p.Arg240His substitution was considered to be causal, because it is orthologous to the heterozygous de novo dominant c.716G>A (p.Arg239His) hotspot variant in man, proven to cause a severe phenotype. In addition, the variant was not found in 50 unrelated healthy Labrador retrievers."

Pathology

Blood examinations reveal no remarkable changes for both complete blood counts and serum biochemistry (Wrzosek et al., 2015, Kobatake et al., 2020). Gross pathological changes are not always obvious in all cases (Wrzosek et al., 2015; Van Poucke et al., 2016), but can include diffuse atrophy of brain and spinal cord (Kobatake et al., 2020), discoloured foci in the brain and spinal cord (Ito et al., 2010) and lateral ventricle enlargement (Alemañ et al., 2006; Weissenböck et al., 1996). Histopathological examination reveals eosinophilic round, club-shaped or elongated deposits that are consistent with Rosenthal fibers (eosinophilic corkscrew bundles), occurring in the astrocytes throughout the central nervous system (Weissenböck et al., 1996; Alemañ et al., 2006; Van Poucke et al., 2016). The Rosenthal fibers are immunopositive for glial fibrillary acidic protein (GFAP). The astrocytes also present with large nuclei, prominent nucleoli, and a glassy eosinophilic cytoplasm (Wrzosek et al., 2015; Van Poucke et al., 2016) and are often distributed around blood vessels in the white matter, beneath the pia matter and subependymal areas (Alemañ et al., 2006; Van Poucke et al., 2016). Demyelination in the brain may or may not be present (Alemañ et al., 2006). [IT thanks DVM students Bri Pepper and Carmen Tu for contributions to this entry in April 2022]

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 203450 Gene · OMIM 137780

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001208-9615, 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 Alexander disease (MONDO:0008752).

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 13.

Development of cost-effective PCR-RFLP methods for screening Mendelian disorders in Chihuahua dogs. · F.U. Vet. J. Health Sci. · 2026
An overview of canine inherited neurological disorders with known causal variants. · Animals (Basel) · 2023 · PMID 38003185
Diagnostic features of type II fibrinoid leukodystrophy (Alexander disease) in a juvenile Beagle dog. · J Vet Intern Med · 2023 · PMID 36799664
Long-term survival of a dog with Alexander disease. · J Vet Med Sci · 2020 · PMID 33055453
A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. · Eur J Hum Genet · 2016 · PMID 26486469
A Labrador Retriever diagnosed with Alexander’s disease and the identification of the causal GFAP mutation. · J Comp Pathol · 2016

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 Alexander Disease (Discovered in the Labrador Retriever) 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 Wilson 95% confidence intervals. 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

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

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:001208-9615.
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.

Gene page: GFAP, cited identity, disease associations, and the human-gene bridge.
Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:001208-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated July 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001208-9615 · Donner et al. 2023 · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018)