SPPD - Split Paw Pad Disease

SPPD ("Split Paw Pad Disease") is a rarely diagnosed disease that begins with the detachment of the paw pads on several paws and increases in severity due to subsequent secondary infections. It manifests at a young age and has been described for various breeds. The cause is thought to be congenital disorders of horn formation in the epidermis. As a result, exertion can lead to detachment of the superficial layers of the epidermis.
In two families of German Shepherds with a common ancestor, several offspring were found to have SPPD. In these, a mutation in a gene (KRT5) involved in horn formation was identified as a possible trigger for SPPD in this breed. The identification of the original animal implies that only animals with this sire in their pedigree are potential carriers of this mutation and tests can be limited to the lineages within this pedigree.
In the affected animals from the families, the symptoms of SPPD appeared between 6 and 12 months of age. The spectrum ranged from mild skin peeling to more severe ulcerated lesions on the paw pads. This variability in clinical presentation indicates the complexity of the disease, which is also reflected in the inheritance of the mutation as autosomal dominant with incomplete penetrance. With this type of inheritance, cases are also possible in which the mutation is present but the affected animals show no symptoms.
At the molecular level, the mutation consists of an 18 bp in-frame deletion (KRT5:c.988_1005del). This leads to the loss of six amino acids in the L12 linker domain of the encoded KRT5 protein - a crucial element for skin development in mammals. In carrier animals, both the altered gene and an intact copy are active and, possibly in interaction with other, as yet unknown genes, cause the different manifestations.
Until further clarification of the significance of the mutation beyond the families described, it is recommended that dogs that are likely to carry the mutation on the basis of their pedigree be tested regardless of their clinical appearance in order to detect hidden carriers.
 

• Lameness may be the first clinical sign even before lesions/ulcers are visible on the skin of the paw pads.
• Visible lesions on one or more paws associated with lameness
• Detachment of the skin on the paw pads after long walks

Histology: cleft formation in the outer layers of the epidermis of the skin

German Shepherd Dogs and mongrels in which animals from the affected lineages have been involved.

The test is based on a PCR-based amplification of the DNA section where the mutation is located. This test determines if the KRT5:c.988_1005del mutation is present in the KRT5 genes. This targeted approach ensures that only the relevant section of DNA is amplified for further analysis.

Application:

• Identification of asymptomatic carrier animals
• Differential diagnosis in cases with paw pad lesions

Result: n/n  | homozygous normal – healthy

The tested animal does not have the KRT5:c.988_1005del mutation that potentially causes the split paw pad disease phenotype and cannot pass it on to offspring. When mated with a heterozygous animal (carrier), 50% of the offspring will be heterozygous and 50% will be homozygous wildtype.  

Result: n/SPPD  | heterozygous – potentially affected

The animal carries the mutant allele in one of the two copies of the KRT5 gene and will transmit it to 50% of its offspring. The tested animal is potentially affected. Carrier animals can be affected by lesions of the paw pads or be completely free from symptoms. There is a possibility of symptom-free animals developing SPPD at a later stage. Carrier animals are advised to not be used for breeding. 

Rietmann, S.J., Lange, A., Soto, S., Thom, N., Manz, E., Jagannathan, V., Mayer, U. and Leeb, T. (2024), KRT5in-frame deletion in a family of German Shepherd dogs with split paw pad disease resembling localized epidermolysis bullosa simplex in human patients. Anim Genet. https://doi.org/10.1111/age.13444