Genetic Disorders


Collie Eye Anomaly (CEA)

CEA is an inherited disease affecting several breeds.  The choroid is the layer of tissue in the eye responsible for supplying blood and nutrients to the Retina. In dogs affected with CEA, the choroid does not develop properly and is therefore thinner than normal.  The severity of the condition can vary from dog to dog.  In mild cases, affected dogs may only show signs of collie eye anomaly on eye exam between about 5 and 12 weeks of age, just prior to normal, age-related pigmentation of the retina which often masks the characteristic, disease-related changes. After this time period, mildly affected dogs may be impossible to distinguish from normal dogs on eye exam. (a phenomenon often referred to as "going normal") and may not display obvious vision deficits.  In more severely affected dogs, clinical signs include malformations of the eye and/or optic nerve (colobomas), retinal detachment, intraocular bleeding, and subsequent blindness.  Both mild and severe forms of CEA are associated with the same NHEJ1 gene Mutation.  Therefore, predicting the potential severity of the disease in an affected puppy is difficult as mildly affected parents may produce offspring that are severely affected.

Cone Degeneration (CD)

CD is an inherited eye disease affecting dogs.  Affected dogs develop day blindness (blindness in bright light) and Photophobia (light sensitivity) between 8 to 12 weeks after birth due to degeneration of cells in the eye called cone photoreceptors which are responsible for vision in bright light. Affected dogs have normal vision in low light and structures of the inner eye appear normal on eye exam. Normal cone cell function can be seen on Electroretinogram (ERG) before six weeks of age, but becomes abnormal between 6 to 12 weeks of age and is completely absent in affected adult dogs signifying complete loss of Cone Cells. The cells responsible for vision in low light called Rod photoreceptors are not affected and thus, affected dogs will still be able to see normally in low light throughout life.

Canine Degenerative Myelopathy (DM)

DM is an inherited neurologic disorder caused by a Mutation of the SOD1 gene in dogs.  This mutation is found in many breeds of dog, though it is not clear for some breeds whether all dogs carrying two copies of the mutation will develop the disease.  The variable presentation between breeds suggests that there are environmental or other genetic factors responsible for modifying disease expression. The average age of onset for dogs with degenerative myelopathy is approximately nine years of age.  Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog, but will progress until the dog is no longer able to walk. The gait of dogs affected with degenerative myelopathy can be difficult to distinguish from the gait of dogs with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of disease, dogs may lose fecal and urinary continence and the forelimbs may be affected.  Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of symptoms. Affected small breed dogs often progress more slowly than affected large breed dogs and owners may postpone euthanasia until the dog is paraplegic.

Hereditary Cataracts (HC)

Hereditary Cataracts (Australian Shepherd Type) is an inherited eye disease affecting dogs. Cataracts are opacities in the lens of the eye caused by structural changes in lens proteins. A normal lens allows light to pass through it to the Retina in the back of the eye. Light cannot pass through the parts of the lens affected by cataracts and vision becomes blurry.  Dogs with Hereditary cataracts (Australian Shepherd type) most commonly present between 2 to 7 years of age with small cataracts that are visible on a veterinary eye exam.  In dogs that inherit one copy of the mutation, cataracts develop slowly and on rare occasion, may lead to complete blindness.  However, it has been speculated that dogs carrying two copies of the mutation are more likely to develop a more rapidly progressing and severe Cataract. Of note, not all forms of cataracts are inherited and environmental factors such as UV damage can also play a role in the severity of disease.  This specific mutation in the HSF4 gene shows Incomplete Penetrance, meaning that not all dogs inheriting two copies of the mutation develop clinical disease. This suggests that other unknown genetic or environmental factors may play a role in modifying disease development and progression.

Multidrug Resistance 1 (MDR1)

Multiple resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs such as the Toy Australian Shepherd.  The mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly.  This, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*) they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs.  Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications.  DRUGS KNOWN TO CAUSE NEUROLOGICAL SIGNS RELATED TO THE MDR1 MUTATION: Acepromazine, Butorphanol, Doxorubicin, Emodepside, Erythromycin, Ivermectin, Loperamide, Milbemycin, Moxidectin, Rifampin, Selamectin, Vinblastine and Vincristine.

Canine Multifocal Retinopathy 1, (CMR1)

Multifocal Retinopathy 1 is an inherited disorder of the Retina affecting multiple breeds of dog.  Affected dogs typically present between 11 and 16 weeks of age with multiple discrete circular areas of retinal detachment with underlying fluid accumulation that are visible on an eye exam performed by a veterinarian.  These blister-like lesions are typically found in both eyes and can appear gray, tan, orange, or pink and vary in number, size and location.  Progression of retinal changes is usually slow and new lesions are not noted after 6 to 12 months of age.  Occasionally as affected dogs age, lesions appear to heal and are no longer visible on an eye exam.  Generally the dog's vision is not affected although vision loss has been described in some cases of multifocal retinopathy 1. 

Progressive Retinal Atrophy ( PRA-PRCD)

Progressive retinal Atrophy, progressive Rod-Cone degeneration (PRA-PRCD) is a late onset, inherited eye disease affecting many breeds of dog.  PRA-PRCD occurs as a result of degeneration of both rod and cone type Photoreceptor Cells of the Retina, which are important for vision in dim and bright light, respectively. Evidence of retinal disease in affected dogs can first be seen on an Electroretinogram around 1.5 years of age for most breeds, but most affected dogs will not show signs of vision loss until 3 to 5 years of age or later.  The rod type cells are affected first and affected dogs will initially have vision deficits in dim light (night blindness) and loss of peripheral vision.  Over time affected dogs continue to lose night vision and begin to show visual deficits in bright light.  Other signs of progressive retinal atrophy involve changes in reflectivity and appearance of a structure behind the retina called the Tapetum that can be observed on a veterinary eye exam.  Although there is individual and breed variation in the age of onset and the rate of disease progression, the disease eventually progresses to complete blindness in most dogs.   Other inherited disorders of the eye can appear similar to PRA-PRCD.  Genetic testing may help clarify if a dog is affected with PRA-PRCD or another inherited condition of the eye.