Genetic basis - caused by a splice mutation in the PKP1 gene, specifically c.202+1 G>C in intron 1-2. PKP1 encodes plakophilin-1, a protein essential for cell-cell adhesion in the skin, part of the desmosome complex. The mutation causes a splicing error, leading to a premature stop codon and production of a non-functional plakophilin-1 protein. Inherited in an autosomal recessive manner.

Pathophysiology - Loss of functional plakophilin-1 disrupts desmosome formation and epidermal cohesion, leading to fragile skin. This results in epidermal cell separation (acantholysis), skin sloughing upon mild trauma, and progressive skin fragility. Structural integrity between skin cells is severely compromised, causing desquamation and erosions.

Complications - Severe skin fragility leading to painful erosions, infections, and poor quality of life. High mortality in affected puppies. 

Clinical Presentation - Symptoms are present from birth, with extreme skin fragility. Clinical signs include thin, fragile, and pale/transparent skin on paws, nose, mouth, ears. Progressive sloughing of skin, thickened footpads with fissures, deformed nails/claws, partial hair loss or woolly hair. Inflammation and skin erosions worsen by around 3 months in areas of friction. Growth retardation and poor clinical prognosis; many puppies die within weeks, survivors often euthanized for welfare.

Inheritance - Autosomal recessive: affected dogs have two copies of the mutation. Carriers (one copy) are asymptomatic but can pass the mutation to offspring. Both parents of an affected dog are carriers.

Why This Matters to Breeders and Vets - Skin Fragility Syndrome is a severe, lethal hereditary disorder in Chesapeake Bay Retrievers. Identification of the PKP1 mutation allows accurate genetic testing for carriers and affected dogs. This supports informed breeding to avoid producing affected puppies and improves breed health management.