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Canine Mendelian disease record

Fetal Onset Neuroaxonal Dystrophy (FNAD)

Fetal Onset Neuroaxonal Dystrophy (FNAD). Autosomal 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:002153-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;

This canine condition is studied as a natural model of Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; in people; it is not the same as a human Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; diagnosis. Studying dogs can move medicine forward for everyone; the canine disease remains the subject.

In people, the disease is described as: An autosomal recessive sub-type of Charcot-Marie-Tooth disease caused by compound heterozygous or homozygous mutation(s) in the MFN2 gene, encoding mitofusin-2. This condition is more severe and has an earlier onset as compared to Charcot-Marie-Tooth disease type 2A2A.

In humans it is also called: CMT2A2B, Charcot-Marie-Tooth disease type 2A2B.

MONDO:0014906 OMIM 601152OMIM 609260

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Closely related human conditions exist for this gene. 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 2026-08-27.

Summary

Neuroaxonal dystrophy is a disorder of CNS development with motor neuron degeneration characterized by fetal-onset neuromuscular dysfunction causing joint contracture and respiratory failure at birth. Affected animals present with scoliosis, arthrogryposis, cerebellar, pulmonary, and spinal cord hypoplasia, respiratory failure, and thinning of the patellar tendon. The condition is lethal, and was first observed in a colony of laboratory dogs following the mating of a purebred Giant Schnauzer with a Beagle. Edited by John C. Fyfe, D.V.M., Ph.D.

Clinical features

Signs include fetal akinesia, scoliosis, arthrogryposis, cerebellar hypoplasia, pulmonary hypoplasia, respiratory failure, thinning of the patellar tendon, and spinal cord hypoplasia. The condition is lethal (Fyfe et al., 2010).

Molecular genetics

The likely causal variant is a 3 bp deletion in exon 14 of MFN2, the gene that codes for mitofusin 2. This c.1617_1619delGGA deletion is predicted to lead to the loss of a glutamate residue on the protein level, p.Q539del (Fyfe et al., 2011).

Pathology

Mitofusin 2 is a multifunctional, membrane bound GTPase found in mitochondria and endoplasmic reticulum. It acts with mitofusin 1 to mediate fusion of the outer mitochondrial membrane. Alone, it mediates mitochondrial-ER contacts, autophagosome genesis, and mitochondrial transport in axons. Affected dogs have very low levels of MFN2 in the brainstem, cerebrum, kidneys, and cultured fibroblasts. The defects are tissue-specific (Fyfe et al., 2011). Histopathologic changes in affected dogs include swollen axons and spheroids in brainstem and spinal cord tracts, patchy loss of Purkinje cells, reduced cerebellar foliation, and multifocal thinning of the external granular cell layer. Loss of neurons in the deep cerebellar nuclei, spheroids and loss of myelinated axons in spinal roots and peripheral nerves, increased apoptosis of skeletal muscle myocytes, and fibro-fatty connective tissue proliferation around joints can also be seen (Fyfe et al., 2010).

Prevalence

The condition has only been observed in a colony of laboratory dogs following the mating of a purebred Giant Schnauzer with a Beagle (Fyfe et al., 2010).

Control

Breeding of known carriers is not recommended. Siblings of affected dogs and dogs that have produced affected puppies should be tested for the causative mutation.

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 601152 Disease · OMIM 609260 Disease · OMIM 617087 Gene · OMIM 608507

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:002153-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

OMIA curates the disease definition, the clinical description and the reference list. The cross-species disease identity is Monarch's. Sniff renders these and adds the breed-level frequencies, the plain-language summary, and a stated reason wherever a number is missing.

The evidence

Published references

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

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 Fetal Onset Neuroaxonal Dystrophy (FNAD) 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:002153-9615.

  • 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:002153-9615 · Donner et al. 2023