Collaboration Leads to Solutions for Heritable Disease: Microphthalmia Syndrome in the Portuguese Water Dog

Collaboration Leads to Solutions for Heritable Disease: Microphthalmia Syndrome in the Portuguese Water Dog

The AKC Canine Health Foundation (CHF) is a nonprofit organization that works to improve the health of ALL dogs by funding scientific research and sharing health information to help prevent, treat, and cure canine disease. Thanks to the Foundation’s history of collaboration with breed Parent Clubs, research funding continues to aid scientists’ exploration of heritable conditions that affect specific dog breeds. This work improves diagnostic and treatment strategies available in the veterinary clinic, and helps breeders manage harmful genetic mutations to improve the overall health of their breed.

A great example of this collaborative process is the recent unraveling of a heritable disease seen in Portuguese Water Dogs (PWD). Since the mid-1980s, PWD breeders reported puppies with small eyes and delayed growth. The disease was called Puppy Eye Syndrome and included abnormalities in the eyes and other body systems that would shorten the lifespan of affected dogs.

Long-time PWD breeder Linda Carey saw Puppy Eye Syndrome occasionally, but when a litter she produced had four puppies that did not do well, she knew something serious was happening. The puppies had varied clinical signs, such as small size, blindness, and struggling to nurse or a ravenous appetite. Necropsy (an animal autopsy) results showed severe internal bleeding—a finding which is now known to be caused by low platelet numbers typical of this syndrome.

“I became a detective to determine what happened to these puppies,” Linda says. “I started researching the disease and pedigrees of affected dogs and it all started to come together. These puppies were often passed off as ‘poor doers,’ but there was a real disease process in play.”

To understand this syndrome and improve the health of their breed, the Portuguese Water Dog Club of America and the Portuguese Water Dog Foundation worked with CHF to fund research exploring its mode of inheritance and developing a genetic test that could help breeders manage the underlying genetic mutation(s) (CHF Grant 02403-MOU: Microphthalmia and Delayed Growth Syndrome in the Portuguese Water Dog). Dr. Margret Casal and her team at Penn Vet published some of the first scientific literature describing what was originally called Puppy Eye Syndrome in the PWD, and is now known as Microphthalmia Syndrome.

With the availability of a genetic test for the mutation that causes Microphthalmia Syndrome in the Portuguese Water Dog, breeders can manage this heritable disease.

“The Portuguese Water Dog Club of America did a lot of fundraising and work to get DNA samples submitted for the research at Penn Vet,” Linda continues. “Our members are very motivated to solve health problems and very active at searching for solutions!”

Clinical signs of Microphthalmia Syndrome in the PWD include abnormal development of the front part of the eye, abnormal tooth enamel, stunted growth, anemia, and low platelet counts. Although the syndrome is present at birth, puppies may not be diagnosed until examined by an ophthalmologist at 7-8 weeks of age. Pedigree analysis showed that both males and females can be affected by this syndrome, and two normal parents could produce affected puppies. This suggested an autosomal recessive mode of inheritance; meaning that a puppy must inherit two copies of the mutated gene, one from each parent, to develop the condition.

Genetic studies identified a region on chromosome 4 associated with Microphthalmia Syndrome in the PWD. This region contains an insertion mutation affecting protein production and degradation—essentially there is extra genetic material inserted which disrupts the normal function of this section of DNA and the proteins and body processes that it directs. After identifying this mutation, researchers tested a large group of PWDs and confirmed that it causes Microphthalmia Syndrome through autosomal recessive inheritance. A genetic test for this mutation is now available through PennGen (vet.upenn.edu/PennGen) to help PWD breeders avoid choosing mating pairs that will produce affected offspring. And it appears to be a success! As of May 2024, the harmful mutation is present in 8.8% of PWD DNA samples tested, but only 0.7% of these dogs have two copies and experience clinical disease. This means that while the mutation is present in a significant portion of the population, the actual number of dogs suffering from the disease is relatively low, demonstrating the power that genetic tests have in helping breeders manage heritable disease.

Linda continues to breed PWDs and works to produce healthy, happy puppies. “If you really love your dog, you want a healthy dog and you want to do the best for them,” she says. “Donating to health research and working with CHF helps the future health of our breed.”

Thanks to the dedicated efforts of the Portuguese Water Dog Club of America, the Portuguese Water Dog Foundation, CHF, and Penn Vet researchers, we have a firm understanding of Microphthalmia Syndrome in the PWD, and breeders are using this knowledge to produce healthier dogs. Working together, we will continue to help all dogs live longer, healthier lives. Join us at: akcchf.org.