How is Cleft Palate (DLX6-related) inherited in dogs?

Cleft Palate (DLX6-related) follows a Autosomal recessive inheritance pattern, associated with the DLX6 gene. It has been observed in 1 of 266 breeds screened in the Sniff Atlas.

Is there a genetic test for Cleft Palate (DLX6-related)?

Cleft Palate (DLX6-related) is associated with the DLX6 gene. Where a validated DNA test for the causal variant is available, it can identify carriers before breeding. Per-breed carrier frequency figures are published in the Sniff Atlas (242,492 dogs screened).

What is the human equivalent of Cleft Palate (DLX6-related)?

OMIA links Cleft Palate (DLX6-related) to its human counterpart in OMIM (OMIM 261800), the bridge to the deeper human-medicine literature for the same underlying biology.

How well studied is Cleft Palate (DLX6-related) in dogs?

OMIA curates 4 peer-reviewed references for Cleft Palate (DLX6-related). The full, linked citation list is on this page.

Canine Mendelian disease record

Cleft Palate (DLX6-related)

Cleft Palate (DLX6-related). Autosomal recessive. Observed in 1 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,492 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:001919-9615
Inheritance: Autosomal recessive
Linked gene: DLX6
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human isolated Pierre-Robin syndrome

Dogs with this condition carry a change in DLX6. In people, changes in the same gene cause isolated Pierre-Robin syndrome. 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: Pierre-Robin syndrome (or Pierre-Robin sequence) is characterized by triad of orofacial morphological anomalies consisting of retrognathism, glossoptosis and a posterior median velopalatal cleft.

In humans it is also called: glossoptosis, micrognathia, and cleft palate, isolated Pierre Robin sequence, Pierre Robin Sequence.

MONDO:0009869 OMIM 261800

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

See 'OMIA:001140-9615 : Cleft lip with or without cleft palate, ADAMTS20-related' for a different form of clef palate in Nova Scotia Duck Tolling retrievers.

Clinical features

As reported by Wolf et al. (2014), this syndrome is best summarised as "relative mandibular brachygnathia and cleft palate". As detailed by the same authors, in the syndrome specified as CP1 "clefts were characterized by abnormal or missing palatine fissures, missing or small palatine processes of the maxilla, and small, missing, or abnormally shaped palatine bones . . . The nasal septum was absent or poorly developed. . . .variation from the normal angulation of the condylar process [of mandibles] was observed". These same authors also reported that "CP1 NSDTRs [Nova Scotia Duck Tolling Retrievers] had relatively shorter mandibles by an average of 5.46 mm when compared to the normal NSDTRs".

Molecular genetics

Among the 21 positional candidate genes in the region to which this disorder was mapped (see Mapping section), Wolf et al. (2014) identified two (DLX5 and DLX6) as functional candidates (being transcription factors involved in craniofacial development; and containing causal mutations in mice). Sanger sequencing of the coding regions and conserved introns of these two genes in 1 affected and 1 unaffected Nova Scotia Duck Tolling Retriever revealed a "2056 bp [LINE-1] insertion . . . within a highly conserved region of DLX6 intron 2 at cfa14.25016716" as the most likely causal mutation. As reported by the same authors, "The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6." Genotyping for this mutation in a range of families in which the disorder is segregating confirmed it as causal.

Prevalence

As reported by Wolf et al. (2014), "Within the NSDTR breed, 96 dogs were genotyped and 80 NSDTRs did not carry the insertion, while the remaining 16 NSDTRs were heterozygous for the insertion. To determine if the insertion was shared among other breeds, 35 affected dogs from 20 other breeds and 284 unaffected dogs from 69 breeds were genotyped. No carriers were identified. This is consistent with a fully penetrant autosomal recessive causative mutation that is private to the NSDTR breed."

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 261800 Gene · OMIM 600030

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001919-9615, 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.

Management of dental and oral developmental conditions in dogs and cats. · Vet Clin North Am Small Anim Pract · 2022 · PMID 34838248
A numerical classification system for cleft lip and palate in the dog. · J Small Anim Pract · 2017 · PMID 28887848
Morphological evaluation of clefts of the lip, palate, or both in dogs. · Am J Vet Res · 2017 · PMID 28738009
A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. · PLoS Genet · 2014 · PMID 24699068

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 Cleft Palate (DLX6-related) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A

Parent B

NNClear

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 Cleft Palate (DLX6-related) looks like in your dog's breed.

Carrier frequency by breed

Top 1 well-sampled breeds (n ≥ 50)

Maximum carrier 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.

0%5%10%

Nova Scotia Duck Tolling Retriever0.82% · n 61

0.82%n 61

n = 61 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 Cleft Palate (DLX6-related) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Nova Scotia Duck Tolling Retriever	0.82%	[0.1%, 7.4%]	61

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

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 carrier 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:001919-9615.
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.

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:001919-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated June 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001919-9615 · Donner et al. 2023