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Canine Mendelian disease record

Musladin-Lueke syndrome (MLS)

Musladin-Lueke syndrome (MLS). Autosomal recessive. Observed in 7 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,555 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:001509-9615
Autosomal recessive
Likely pathogenic / pathogenic
Source dataset
Sniff Atlas v1.0.1 / DOI

The Likely pathogenic / pathogenic grade describes the documented variant's causality, per the Animal Variant Classification Guidelines (AVCG; Boeykens et al. 2024, Front Vet Sci), an ACMG/AMP-style framework curated in OMIA. It grades the variant, not any individual dog. See the full classification table.

The human connection

A model of human geleophysic dysplasia 1

This is the canine counterpart of geleophysic dysplasia 1 in people. 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: Any geleophysic dysplasia in which the cause of the disease is a mutation in the ADAMTSL2 gene.

In humans it is also called: GPHYSD1, ADAMTSL2 geleophysic dysplasia, Geleophysic dysplasia type 1.

MONDO:0009269 OMIM 231050

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

Renamed from Musladin-Lueke syndrome [3/6/2022]

Clinical features

As reported by Bader et al. (2010), this disorder "is characterized by short stature, thick, taut skin, and severely restricted joint mobility . . . Affected dogs also have broad skulls with wide-set slanted eyes, creased ears, a hopping, “tip-toe” gait, and pleasant temperaments." Additionally, cardiac disease has been reported as possibly associated with Muscladin-Lueke syndrome, but reports are inconsistent (Packer et al., 2017). [IT thanks DVM student Elizabeth Polley for contributions to this entry in April 2022]

Molecular genetics

Fine-mapping followed by sequencing of likely positional candidate genes resulted in Bader et al (2010) identifying the causal mutation as a missense mutation in ADAMTSL2: "(c.660C>T) predicted a non-synonymous change, converting an arginine to a cysteine at codon 221 (R221C), occurred in a highly conserved stretch of residues, and was computationally predicted to negatively impact protein structure and function". The publication of Bader et al. 2010 probably had an incorrect numbering of the cDNA in their variant designation. The correct variant designation should read XM_003639308.3:c.661C>T; p.Arg221Cys.

History

As reported by Bader et al. (2010), this disorder was "originally called “Chinese beagle syndrome” in the lay literature, and subsequently renamed after two noted beagle breeders, Musladin and Lueke"; see Musladin et al. (1990, 1998).

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 231050 Gene · OMIM 612277

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001509-9615, 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.

  1. Genetics of inherited skin disorders in dogs. · Vet J · 2022 · PMID 34861369
  2. Clinical phenotype of Musladin-Lueke syndrome in 2 Beagles. · J Vet Intern Med · 2017 · PMID 28158899

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.

Predict a litter

Set each parent's status for Musladin-Lueke syndrome (MLS) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Musladin-Lueke syndrome (MLS) looks like in your dog's breed.
Carrier frequency by breed

Top 7 well-sampled breeds (n ≥ 50)

Maximum 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.

0%3%5%
Beagle1.7% · n 5,282
Boston Terrier<0.1% · n 3,701
Pug<0.1% · n 5,154
American Staffordshire Terrier<0.1% · n 42,779
Labrador Retriever<0.1% · n 16,843
Golden Retriever<0.1% · n 12,876
German Shepherd<0.1% · n 15,637
n = 102,272 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Musladin-Lueke syndrome (MLS) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Beagle 1.7% 5,282
Boston Terrier <0.1% 3,701
Pug <0.1% 5,154
American Staffordshire Terrier <0.1% 42,779
Labrador Retriever <0.1% 16,843
Golden Retriever <0.1% 12,876
German Shepherd <0.1% 15,637

259 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

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 carrier 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:001509-9615.

  • 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:001509-9615 · Donner et al. 2023