Descriptions of Diseases for which the University of Missouri Canine Genetics Laboratory Offers DNA Testing
(Listed by disease name)

Adult-onset Neuropathy (AON)

Disease description: Adult-onset neuropathy (AON) of English Cocker Spaniels and Field Spaniels is characterized by progressive weakness due to a neuropathy. Signs typically begin between 7.5 and 9 years of age and consist first of an uncoordinated gait or wobbling in the hind limbs. The stance in the hind limbs is wide-base and the hocks will drop lower to the ground. The weakness eventually progresses to also involve the front limbs. When affected dogs become nonambulatory in all limbs, they may develop difficulty in swallowing. The neurologic signs progress over 3 to 4 years, more slowly than those of degenerative myelopathy. The disease is inherited as an autosomal recessive trait.

Breeds affected: English Cocker Spaniel, Field Spaniel

Reference: University of Missouri Canine Genetics Lab discovery. Not yet published.

Gene: Not yet published.

Alpha-mannosidosis (AMAN)

Disease description: Doberman Pinscher alpha-mannosidosis is an early-onset progressive neurodegenerative disease. By 2 months of age, affected dogs are clumsy and unstable on their feet, falling over frequently. By 7 months of age mild cognitive impairment, proprioceptive ataxia, asymmetric reduced menace responses, moderate divergent strabismus, and diffuse brain atrophy detected by MR imaging are apparent. By 8 months of age motor function deteriorated to ambulatory paraparesis and visual impairment was observed. Over the course of the disease progression, the owners reported that an affected dog developed aggressiveness toward other dogs, became intolerant of grooming and bathing, exhibited compulsive behaviors, including circling, and would vocalize inappropriately. The affected dog also became progressively uncoordinated and developed difficulty navigating stairs. As the disease progressed an affected dog exhibited dementia and apparent hallucinatory behavior characterized by trying to interact with non-apparent stimuli or reacting to open areas/empty spaces. Due to the progression of neurological signs, owners will likely elect euthanasia by 14 months of age.

Breeds affected: Doberman Pinscher

Reference:

Bullock G, Johnson GS, Pattridge SG, Mhlanga-Mutangadura T, Guo J, Cook J, Campbell RS, Vite CH, Katz ML. A Homozygous MAN2B1 Missense Mutation in a Doberman Pinscher Dog with Neurodegeneration, Cytoplasmic Vacuoles, Autofluorescent Storage Granules, and an α-Mannosidase Deficiency . Genes 14:1746, 2023.

Gene: MAN2B1

Copper Toxicosis (CT)

Disease description: Copper is an essential micronutrient important in maintaining normal metabolism and liver function. Copper toxicosis is an inherited metabolic disorder characterized by elevated tissue copper levels that can lead to liver failure. Signs of copper toxicosis may include abdominal pain and swelling, Loss of appetite (anorexia), vomiting and diarrhea, jaundice (yellowing of the skin and eyes), weight loss, depression and lethargy, excessive thirst and frequent urination, bleeding from the nose or mouth, blood in the urine, and altered mental state.

Breeds affected: Bedlington Terrier

Reference:

Haywood S, Swinburne J, Schofield E, Constantino-Casas F, Watson P. Copper toxicosis in Bedlington terriers is associated with multiple independent genetic variants. Veterinary Record. 193(4):e2832, 2023.

Gene: COMMD1

Dancing Doberman Syndrome (D-Dobe)

Disease description: Dancing Doberman disease is a disorder of the Doberman Pinscher with varying age of onset from a few months to middle age. This disease is characterized by intermittent flexion of one or both pelvic limbs while standing. Signs usually begin in a single limb. The contralateral pelvic limb may become affected. Affected dogs develop weakness and atrophy of the distal pelvic limb musculature and may prefer to sit. The disease insidiously progresses over several years. Chronically, affected dogs may develop postural reaction deficits. 

Breed affected: Doberman Pinscher

Reference: University of Missouri Canine Genetics Lab discovery. Not yet published.

Gene: Not yet published.

Degenerative Encephalopathy (DEN)

Disease description: Nova Scotia Duck Tolling Retrievers suffering from degenerative encephalopathy exhibit progressive neurological dysfunction starting at four months to five years of age. The most consistent clinical sign is profound sleep derangement characterized by frequent episodes of marked involuntary movements during sleep. The duration of episodes typically ranged from a few seconds to 15-30 minutes, although some owners report occasional episodes lasting longer than one hour. The episodes were reported to occur up to 10 times in a sleep period. The dogs make running movements, sometimes lifting their heads and frequently vocalize. Some owners also report that the dog would be difficult to awaken from sleep. The dogs learned basic obedience but had difficulty with advanced training. Affected dogs showed increased anxiety and heightened awareness, which sometimes manifested as noise phobia or obsessive-compulsive activity. With progression of the disease, some dogs began having aggressive interactions, or lacked self-control, with other dogs and sometimes their owners. Some owners reported abnormal swimming motion (the dog adopting a vertical position in water), while others felt this was part of normal learning to swim. The owners also reported reduced tail movement and gait abnormalities. One dog was reported to have been urinary and fecally incontinent. Affected dogs are frequently euthanized due to progressive debilitating behavior anomalies.

Breed affected: Nova Scotia Duck Tolling Retriever

Reference: University of Missouri Canine Genetics Lab discovery. Submitted for publication.

Gene: RB1CC1

Degenerative Myelopathy (DM1 & DM2)

Disease description: Canine degenerative myelopathy (DM) is a late-onset disease characterized initially by loss of coordination (ataxia) and spastic weakness in the hind limbs typically starting at 8 to 10 years of age. Over 6 months to 2 years after the onset of signs, progressive paralysis spreads to affect all limbs. In late stages of dogs may become incontinent and develop respiratory impairment. DM is similar to some forms of human ALS. The disorder occurs in many breeds, in which it is associated with a mutation in the SOD1 gene. However, not all dogs that are homozygous for the SOD1 risk variant develop the disease. SOD1-associated DM appears to occur in almost all breeds, but the risk of developing DM among dogs homozygous for the risk allele varies significantly between different breeds. The disease is particularly prevalent in Boxers, Chesapeake Bay Retrievers, German Shepherds, and Corgis. The SOD1 risk variant is the same in all affected breeds except in Bernese Mountain dogs which have a different SOD1 risk variant.

Breeds affected: All

References:

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Long S, March PA, Olby NJ, Khan S, O’Brien DP, Lindblad-Toh K and Coates JR. Genome-wide association analysis identifies a SOD1 missense mutation in dogs with degenerative myelopathy: A spontaneous animal model for amyotrophic lateral sclerosis. Proc. Nat. Acad. Sci. USA, 106:2794-2799, 2009.

Wininger FA, Zeng R, Johnson GS, Katz ML, Johnson GC, Bush WW, Jarboe JM and Coates, JR: Degenerative Myelopathy in a Bernese Mountain Dog with a Novel SOD1 Missense Mutation. J. Vet. Intern. Med.25:1166-1170, 2011.

Gene: SOD1a and SOD1b

Degenerative Myelopathy Risk Modifier (DMRM)

Disease description: Canine degenerative myelopathy (DM) is a late-onset disease characterized initially by loss of coordination (ataxia) and spastic weakness in the hind limbs typically at 8 to 10 years of age. Over 6 months to 2 years after the onset of signs, progressive paralysis spreads to affect all limbs. In late stages of dogs may become incontinent and develop respiratory impairment. The disorder occurs in many breeds, including Pembroke Welsh Corgis (PWCs), in which it is associated with a mutation in the SOD1 gene. However, not all PWCs that are homozygous for the SOD1 risk variant develop the disease. This suggested that there might be other genetic variants that modify the risk of developing DM among dogs that are homozygous for the SOD1 risk variant. Ivansson and colleagues found that in PWCs, alternate variants in the SP110 gene modify the risk of developing DM among dogs homozygous for the risk allele. Dogs that are homozygous for the SOD1 risk variant and have one or two copies of the SP110 risk variant are significantly higher risk of developing DM than dogs that do not have any copies of the SP110 risk variant.

Breeds affected: Pembroke Welsh Corgi

Reference:

Ivansson EL, Megquier K, Kozyreva SV, Izabella EM, Körbergc B, Swofford R, Koltookian M, Tonomura N, Zeng R, Kolicheskie AL, Hansen L, Katz ML, Johnson GC, Johnson GS, Coates JR, Lindblad-Toh K. Variants within SP110 modify risk of canine degenerative myelopathy: a model for amyotrophic lateral sclerosis. Proc Nat Acad Sci (USA), PNAS, E3091-E3100, 2016.

Gene: SP110

Dental-skeletal-retinal anomaly (DSRA)

Disease description: DSRA in Cane Corsos is characterized by abnormalities in the development and growth of the skeleton and teeth, which are markedly brittle, discolored, or translucent. The disease also entails progressive retinal degeneration resulting in vision loss.

Breeds affected: Cane Corso

Reference:

Christen M, Booij-Vrieling H, Oksa-Minalto J, de Vries C, Kehl A, Jagannathan V, Leeb T. MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA). Genes (Basel). 12(10), 2021 09 25.

Gene: MAI3

Dilated Cardiomyopathy (DCM)

Disease description: Standard and Giant Schnauzers with a variant in the RBM20 gene suffer from left-sided congestive heart failure with a median age of onset of 1.5 years in males and 2.4 years in females. The median survival time after diagnosis of congestive heart failure was 13 days in males and 62 days in females .

Breeds affected: Standard Schnauzer, Giant Schnauzer

Reference:

Leach SB, Briggs M, Hansen L, Johnson GS. Prevalence, geographic distribution, and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs. Journal of Veterinary Cardiology. 40:119-125, 2022.

Gene: RBM20

Dyserythropoietic Anemia & Myopathy Syndrome (DAMS)

Disease description: Dyserythropoietic Anemia and Myopathy Syndrome (DAMS) in English Springer Spaniels is an early onset disorder characterized by impaired opening of the mouth, difficulty swallowing, muscle atrophy, progressive weakness, cardiomyopathy, and anemia. Affected dogs have low activity levels and ability to exercise relative to unaffected dogs of the same breed. Other clinical signs that may appear include difficulty in lapping water, aspiration pneumonia, seizures, and chronic diarrhea. Due to the progression of signs and poor quality of life affected dogs are usually euthanized.

Breeds affected: English Springer Spaniel

Reference: Not yet published.

Gene: Not yet published.

Ehlers-Danlos Syndrome (EDS)

Disease description: A group of hereditary connective tissue diseases with similar clinical signs have been classified as forms of Ehlers-Danlos Syndrome. These disorders result from deleterious variants in genes that affect the synthesis of connective tissue proteins such as collagen. In Alapaha Bulldogs Ehlers-Danlos Syndrome results from a mutation in the ADAMTS2 gene that encodes an enzyme required for processing procollagen molecules to collagen. The structure of collagen in the connective tissue of affected dogs is quite abnormal. The disease is characterized by joint hypermobility and loose hyper-elastic skin that is fragile and subject to frequent wounds. Different mutations in the ADAMTS2 gene and other connective tissue genes underlie EDS in other breeds. Please inquire if you have a dog of another breed that you think may be suffering from a form of EDS.

Breeds affected: Alapaha Blue Blood Bulldog

Reference:

Jaffey, J.A.; Bullock, G.; Guo, J.; Mhlanga-Mutangadura, T.; O’Brien, D.P.; Coates, J.R.; Morrissey, R.; Hutchison, R.; Donnelly, K.S.; Cohn, L.A. Katz, M.L.; Johnson, G.S. Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome. Genes 13:2158, 2022.

Gene: ADAMTS2 

Episodic Falling Syndrome

Disease description: Episodic Falling Syndrome (EFS) is characterized by episodes of spastic muscle stiffening triggered by exercise, stress, excitement, or apprehension. Onset of signs can occur between 14 weeks and 4 years of age. Episodes vary in frequency and severity. More severe episodes are characterized by progressive stiffening of all 4 limbs resulting in immobilization and often falling. Other signs may include facial muscle stiffness, stumbling, a “bunny-hopping” gait, arching of the back, or vocalization. Dogs do not lose consciousness during these episodes. Between episodes, dogs appear completely normal. EFS is caused by deficiency of a protein called brevican (BCAN), which plays a role in controlling the functions of specific neurons in the brain and spinal cord. Loss of brevican leads to abnormal bursts of neuronal activity that cause spastic muscle contraction.

Breeds affected: Cavalier King Charles Spaniel, English Toy Spaniel

Reference:

Gill JL, Tsai KL, Krey C, Noorai RE, Vanbellinghen JF, Garosi LS, Shelton GD, Clark LA, Harvey RJ. A canine BCAN microdeletion associated with episodic falling syndrome. Neurobiology of Disease. 45(1):130-6, 2012.

Gene: BCAN

Fanconi Syndrome (FAN1)

Disease description: Fanconi syndrome in dogs is characterized by impaired function of the proximal convoluted tubules of the kidneys resulting in reduced reabsorption of water, nutrients and electrolytes from the tubular fluid and their eventual loss in urine. The clinical consequences of this disease include polyuria and polydipsia, dehydration, weight loss and muscle weakness. Most cases progress to renal failure within a few years of the onset of initial clinical signs.

Breeds affected: Basenji

Reference:

Farias FHG, Mhlanga-Mutangadura T, Guo J, Hansen L, Johnson GS, Katz ML. FAN1 Deletion Variant in Basenji Dogs with Fanconi Syndrome . Genes 15:1469, 2024.

Gene: FAN1

Gangliosidosis, GM2 (GM2A)

Disease description: Japanese Chin dogs with GM2 gangliosidosis presented at 15 and 18 months of age with progressive cerebellar ataxia, spastic, hypermetric postural reactions, obtunded mental status, and visual impairment. Affected dogs are typically humanely euthanized at the owners’ request by about 2 years of age due to progression of the signs.

Breeds affected: Japanese Chin

Reference:

Sanders DN, Zeng R, Wenger DA, Johnson GS, Johnson GC, Decker JE, Katz ML and O’Brien DP. GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay- Sachs disease. Molec Genet Metab 108:70–75, 2013.

Gene: HEXA

Gangliosidosis, GM2 (GM2B)

Disease description: Shiba Inus with GM2 Gangliosidosis exhibit progressive neurologic signs starting with generalized tremors and altered tail carriage (tail down) when approximately12 months of age. The tremors become progressively more severe and marked cerebellar ataxia, spastic tetraparesis, anxiety, decreased appetite, decreased responsiveness to verbal commands, trance-like behavior, loss of ability to climb up and down stairs, and impaired vision develop. Because of the progression of neurologic signs, affected dogs are usually euthanized before 2 years of age.

Breeds affected: Shiba Inu

Reference:

Kolicheski, A, Johnson GS, Villani NA, O’Brien DP, Mhlanga-Mutangadura T, Wenger DA, Mikoloski K, Eagleson JS, Taylor JF, Schnabel RD, Katz ML. GM2 gangliosidosis in Shiba Inu dogs with an inframe deletion in HEXB . J Vet Internal Med 31:1520-1526, 2017.

Gene: HEXB

Glaucoma and Lens Luxation (GLL)

Disease description: As in other breeds, primary lens luxation (PLL) in Chinese Shar-Pei dogs is due to a mutation in the ADAMTS17 gene. PLL is characterized by lens instability in both eyes, although the severity of clinical signs may differ between the 2 eyes. PLL typically goes undetected until the lens becomes severely dislocated in one eye. Dogs typically present with concurrent partial lens displacement of the other eye, which typically progresses into full displacement over a period of weeks to months. The lens often moves anteriorly causing disruption to the pupil and draining mechanism in the eye, which may result in acute glaucoma.

Breeds affected: Chinese Shar-Pei

Reference:

Farias FH, Johnson GS, Taylor JF, Giuliano E, Katz ML, Sanders DN, Schnabel RD, McKay SD, Khan S, Gharahkhani P, O’Leary CA, Pettitt L, Forman OP, Boursnell M, McLaughlin B, Ahonen S, Lohi H, Hernandez-Merino E, Gould DJ, Sargan DR, Mellersh C. An ADAMTS17 splice donor site mutation in dogs with primary lens luxation. Investigative Ophthalmology & Visual Science. 51(9):4716-21, 2010.

Gene: ADAMTS17

Glycogen Storage Disease/Phosphofructokinase Deficiency

(PFK)

Disease description: English Springer Spaniels with a mutation in the PFKM gene exhibit muscle cramps and exercise intolerance accompanied by a mild increase in blood creatine kinase levels. Affected dogs can also suffer from hemolytic crisis with hemoglobinuria and bilirubinuria after excessive excitement, exercise, or hyperthermia. This can result in severe anemia, icterus, fever, lethargy, and anorexia. This anemia usually resolves within several days. Affected animals have a normal life span, usually but persistent bilirubinuria and reticulocytosis. In some cases dogs may also exhibit muscle wasting, hepatosplenomegaly, and increased total body iron stores.

Breeds affected: English Springer Spaniel

Reference:

Smith BF, Stedman H, Rajpurohit Y, Henthorn PS, Wolfe JH, Patterson DF, Giger U. Molecular basis of canine muscle type phosphofructokinase deficiency. Journal of Biological Chemistry. 271(33):20070-4, 1996.

Gene: PFKM

Intervertebral Disc Disease (IVDD)

Disease description: Intervertebral discs are fibrous tissues between the bones of the spine that provide cushioning when the spine flexes during movements including walking, running and jumping. Intervertebral disc disease (IVDD) is a condition where discs in the spine rupture or herniate, causing severe inflammation extreme pain and sensitivity in the back or neck and reduced mobility. Secondary damage to the spinal cord can occur in dogs with untreated IVDD. IVDD in many breeds results from a DNA sequence variant consisting of the insertion of an insertion of FGF4 retrogene on chromosome 12 (FGF4-12). This variant is also responsible for short leggedness (chondrodystrophy) in many breeds, such as Dachshunds and Corgis, in which the variant is very common. In these breeds, the FGF4-12 variant may not be a good predictor of IVDD risk compared to other genetic or environmental factors. In other breeds that do not typically have short legs, the presence of either one or two copies of the variant will result in shorter than normal legs and a significantly increased risk of developing IVDD.

Breeds affected (excluding those in which the variant is too common to be an indicator of increased risk of developing IVDD): Bassett Hound, Beagle, Bichon Frise, French Bulldog, Cavalier King Charles Spaniel, Chesapeake Bay Retriever, Chihuahua, Chinese Crested, Cocker Spaniel, Coton de Tulear, English Cocker Spaniel, Havanese, Nova Scotia Duck Tolling Retriever, Poodle, Portuguese Water Dog, Russell Terrier group, Scottish Terrier. IVDD associated with the FGF4-12 retrogene insertion may also occur in other breeds, so this test may be warranted for any dog showing signs of IVDD regardless of breed.

References:

Brown EA, Dickinson PJ, Mansour T, Sturges BK, Aguilar M, Young AE, Korff C, Lind J, Ettinger CL, Varon S, Pollard R, Brown CT, Raudsepp T, Bannasch DL. FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proceedings of the National Academy of Sciences of the United States of America. 114(43):11476-11481, 2017.

Batcher K, Dickinson P, Giuffrida M, Sturges B, Vernau K, Knipe M, Rasouliha SH, Drogemuller C, Leeb T, Maciejczyk K, Jenkins CA, Mellersh C, Bannasch D. Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs. Genes (Basel). 10(6), 2019 06 07.

Gene: FGF4 retrogene

Juvenile-onset Laryngeal Paralysis & Polyneuropathy (JLPP)

Disease description: Black Russian Terriers suffering from Polyneuropathy & Juvenile Laryngeal Paralysis present at about 3 months of age with laryngeal paralysis and respiratory distress. Affected dogs also exhibit microphthalmia , cataracts, and miotic pupils. They are typically euthanized by 6 months of age for due to severe dyspnea (shortness of breath).

Breeds affected: Black Russian Terrier

Reference:

Mhlanga-Mutangadura T, Johnson GS, Schnabel RD, Taylor JF, Johnson GC, Katz ML, Shelton GD, Lever TE, Giuliano E, Granger N, Shomper J, O’Brien DP. A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with polyneuropathy and neuronal vacuolation in Black Russian Terrier dogs. Neurobiology of Disease. 86:75-85, 2016.

Gene: RAB3GAP1

L-2-Hydroxyglutaricacidemia (L2HGA) SBT

Disease description: The onset of the disease occurs predominantly at approximately a year of age, although it may not be recognized until affected dogs are older. Typically, the first signs recognized by owners are gait/postural abnormalities. These abnormalities may include a wide-based posture, paresis, hypermetria, kyphosis, ataxia, and most commonly stiffness and muscle cramping of all four limbs. Affected dogs may also suffer from seizures and muscle tremors.

Breeds affected: Staffordshire Bull Terrier

Reference:

Shea A, De Risio L, Carruthers H, Ekiri A, Beltran E. Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. Veterinary Record. 179(21):545, 2016.

Gene: L2HGDH

L-2-Hydroxyglutaricacidemia (L2HGA) YT

Disease description: Yorkshire Terriers with L-2-hydroxyglutaricacidemia present with episodes of hyperactivity and aggressive behavior at 6 to 8 months of age. The episodes may last for about 40 minutes with behavior being normal between episodes. The frequency of the episodes decreased when dogs were placed on a commercial protein restricted diet and phenobarbital was administered.

Breeds affected: Yorkshire Terrier

Reference:

Farias FH, Zeng R, Johnson GS, Shelton GD, Paquette D, O’Brien DP. A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. BMC Veterinary Research [Electronic Resource]. 8:124, 2012.

Gene: L2HGDH

Late Onset (Spinocerebellar) Ataxia (LOA)

Disease description: Dogs in the Russell Terrier group exhibit a disorder characterized by an uncoordinated gait with stilted “toy soldier” leg movements. They can display intention tremors, where an extended limb or head shakes more and more violently as it approaches its target. At rest, dogs sometimes display a truncal sway. The disease is also characterized by involuntary eye movements. Onset of signs typically occurs between six and twelve months of age.

Breeds affected: Jack Russell Terrier, Parson Russell Terrier, Parson Russell Terrier, Russell Terrier

Reference:

Forman OP, De Risio L, Mellersh CS. Missense mutation in CAPN1 is associated with spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS ONE [Electronic Resource]. 8(5):e64627, 2013.

Gene: CAPN1

Leukodystrophy/Lysosomal Storage Disease (LDD)

Disease description: A rare adult-onset disorder in Dalmatians is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Signs first become apparent when dogs are approximately 18 months old and progress slowly. The progression of signs eventually becomes severe enough that euthanasia has been elected when the dogs reach 7 to 8 years of age. The disease is accompanied by accumulation of autofluorescent lysosomal storage bodies similar to those seen in some of the neuronal ceroid lipofuscinoses and by pronounced abnormalities in the myelin surrounding nerves.

Breeds affected: Dalmatian

Reference:

Bullock G, Johnson, GS, Mhlanga-Mutangadura T, Petesch SC, Thompson S, Goebbels S, Katz ML. Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs. Gene 830:146513, 2022.

Gene: CNP

Leukodystrophy/Lysosomal Storage Disease (LDW)

Disease description: A progressive neurological disorder in a Weimaraner was associated with a missense variant in the CNP gene. The disease is characterized by fecal incontinence, lethargy, moderate paraparesis, proprioceptive pelvic limb ataxia, falling, cognitive decline, incoordination, decreased interest in food, changes in posture, and episodes of trance-like behavior. Signs first became apparent at the age of 4 years, 10 months and progressed in severity until euthanasia was elected at 6 years, 7 months of age. Magnetic resonance imaging showed generalized brain atrophy with areas of white matter pathology. The disease was accompanied by pronounced structural abnormalities in myelin throughout the central nervous system and by the intracellular accumulation of autofluorescent lysosomal storage bodies.

Breeds affected: Weimaraner

Reference:

Keller SH, Johnson GS, Bullock G, Mhlanga-Mutangadura T, Schwartz M, Pattridge SG, Guo J, Kortz GD, Katz ML. Homozygous CNP Mutation and Neurodegeneration in Weimaraners: Myelin Abnormalities and Accumulation of Lipofuscin-like Inclusions. Genes 15:246, 2024.

Gene: CNP

Methemoglobinemia (MH)

Disease description: Methemoglobinemia associated with a mutation in the CYB5R3 gene occurs in numerous breeds. Then most recognized sign is exercise intolerance that is accompanied by tachypnea (rapid shallow breathing) and cyanosis (bluish skin coloration due to low blood oxygen levels).

Breeds affected: All breeds tested.

Reference:

Jaffey JA, Reading NS, Abdulmalik O, Kreisler R, Bullock G, Wiest A, Villani NA, Mhlanga-Mutangadura T, Johnson GS, Cohn LA, Isaza N, Harvey JW, Giger U. Clinical, metabolic, and molecular genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in 30 dogs. Scientific Reports. 10(1):21399, 2020.

Gene: CYB5R3

Mucopolysaccharidosis (MPS)

Disease description: Mucopolysaccharidoses type I (MPS I) in Bassett Hounds is a hereditary disease characterized by defective metabolism of glycosaminoglycans (mucopolysaccharides), which accumulate in cells of various tissues. Clinical signs include growth retardation, joint problems, progressive lameness and visual impairment, caused by corneal clouding.

Breeds affected: Bassett Hound

Reference: University of Missouri Canine Genetics Lab discovery, not yet published.

Gene: Not yet published.

Multiple system degeneration (MSD)

Disease description: Multiple System Degeneration in Chinese Crested and Kerry Blue Terrier dogs is a progressive neurological disorder with onset of signs occurring between 9 weeks and 6 months of age. Dogs initially exhibit a mild intention tremor and stiffness in thoracic limb gait, which progresses within 3 to 4 months to severe hypermetric ataxia, spasticity, truncal sway, wide-based stance, delayed postural reactions, and decreased menace response. Dogs eventually become unable to stand and are euthanized by 1 to 2 years of age.

Breeds affected: Chinese Crested, Kerry Blue Terrier

Reference:

Zeng R, Guo J, Bullock G, Johnson GS, Katz ML. Canine Multiple System Degeneration Associated with Sequence Variants in SERAC1. Genes (Basel). 15(11), 2024.

Gene: SERAC1

Neonatal Ataxia (NNA)

Disease description: Disease description: Early-onset cerebellar ataxia (neonatal ataxia) becomes apparent at <2 weeks of age when Russell Group Terrier (Includes Jack Russell and Parson Russell Terriers) puppies begin to walk. Posture evaluation reveals prominent axial musculature, intention tremors, wide-based stance and increased extensor tone in all limbs. Gait evaluation shows severe cerebellar ataxia and dysmetria (hyper- and hypometria). Decreased postural reactions were observed in all limbs. Limb spasticity progressed to a tiptoed stance of the digits. A dancing gait, hypometria in all limbs, decrease in forward ambulation and greater tendency to fall are observed as the disorder progressed. Spinal reflexes remain intact; however, joint flexion of distal limbs decreased as limb spasticity increased in severity. Ocular examination reveals intact vision with absent menace response and persistent, fine, oscillating eye movements with positional slow vertical and rotatory nystagmus. Signs of spasticity in the facial muscles are evident by muscle contracture upon excitement. The genetic inheritance pattern is autosomal recessive. Histopathology shows a cerebellar granuloprival degeneration.

Breeds affected: Russell Terrier group

Reference: Not yet published

Gene: University of Missouri Canine Genetics Lab discovery. Not yet published

Neonatal Cerebellar Ataxia (Bandera’s syndrome) (NCA)

Disease description: Numerous hereditary disorders in dogs are characterized by ataxia (uncoordinated movements). In Coton De Telear’s a variant in the GRM1 gene is associated with a form of ataxia that manifests shortly after birth. Most affected puppies are unable to stand or walk without assistance and use swimming-like movements to propel themselves toward a goal. They may also exhibit fine vertical tremors at rest. Due to the severity of signs, affected puppies usually need to be euthanized.

Breeds affected: Coton de Tulear

Reference:

Zeng R, Farias FH, Johnson GS, McKay SD, Schnabel RD, Decker JE, Taylor JF, Mann CS, Katz ML, Johnson GC, Coates JR, O’Brien DP. A truncated retrotransposon disrupts the GRM1 coding sequence in Coton de Tulear dogs with Bandera’s neonatal ataxia. Journal of Veterinary Internal Medicine. 25(2):267-72, 2011.

Gene: GRM1

Neonatal Encephalopathy with Seizures (NEWS)

Disease description: Standard Poodle puppies with neonatal encephalopathy and seizures are small at birth and do not develop normally. They initially nurse poorly, but nursing improves over several days after birth. At approximately 3 weeks of age affected puppies exhibit weakness, ataxia, whole-body tremors, wide-based stance with increased extensor tone, and axial muscle weakness with neck ventroflexion. Affected pups do not interact with the dam or littermates and have slow responses to external stimuli. At approximately 3 to 6 weeks of age, affected puppies develop generalized clonic-tonic seizures that quickly become refractory to treatment. They become laterally recumbent with extensor rigidity and opisthotonus, and usually die or are euthanized before 7 weeks of age.

Breeds affected: Standard Poodle

Reference:

Chen X, Johnson GS, Schnabel RD, Taylor JF, Johnson GC, Parker HG, Patterson EE, Katz ML, Awano T, Khan S, O’Brien DP. A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2. Neurogenetics. 9(1):41-9, 2008.

Gene: ATF2

Neuronal Ceroid Lipofuscinosis (CLN1)

Disease description: Cane Corso dogs may suffer from a form of hereditary neuronal ceroid lipofuscinosis (NCL). The NCLs are a group of progressive neurodegenerative disorders with similar signs. The CLN1 form has been identified in Cane Corsos and Dachshunds. In Cane Corsos the onset of signs begins at approximately 8 months of age with progressive visual impairment, ataxia, and lethargy. Due to the progression of sigs, euthanasia has been elected at approximately 10 to 11 months of age.

Breeds affected: Cane Corso

Reference:

Kolicheski A, Barnes Heller HL, Arnold S, Schnabel RD, Taylor JF, Knox CA, Mhlanga-Mutangadura T, O’Brien DP, Johnson GS, Dreyfus J, Katz ML. Homozygous PPT1 splice donor mutation in a Cane Corso Dog with neuronal ceroid lipofuscinosis. J Vet Internal Med 31:149-157, 2017.

Gene: PPT1

Neuronal Ceroid Lipofuscinosis (CLN1)

Disease description: A Miniature Dachshund presented at 9 months of age with disorientation, ataxia, weakness, visual impairment and behavioral changes. These signs progressed over a period of 5 months, at which time the dog was euthanized. Neurons throughout the central nervous system contained autofluorescent lysosomal inclusions with granular osmiophilic deposit (GROD) ultrastructure characteristic of classical infantile NCL (INCL).

Breeds affected: Dachshund

Reference:

Sanders DN, Farias FH, Johnson GS, Chiang V, Cook JR, O’Brien DP, Hofmann SL, Lu J, and Katz ML: A mutation in canine palmitoyl protein thiesterase 1 (PPT1) causes early onset neuronal ceroid lipofuscinosis in a Dachshund . Molec Genet Metab 100:349-356, 2010.

Gene: PPT1

Neuronal Ceroid Lipofuscinosis (CLN2)

Disease description: The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by intracellular accumulation of autofluorescent granules and progressive degeneration of the central nervous system. Multiple forms of NCL occur in dogs, humans, and other species. Among these is CLN2 disease that occurs in Dachshunds. Signs first become apparent at approximately 4 months of age and include visual impairment, head tremors, decreased menace response, myoclonus, ataxia, and cognitive decline. Late in the disease progression, dogs may suffer from grand mal seizures. Due to the progressively increasing severity of signs, most affected dogs are euthanized between 10 and 11 months of age.

Breeds affected: Dachshund

Reference:

Awano T, Katz ML, Sohar I, Lobel P, Sanders DN, Khan S, Johnson GC, Giger U and Johnson GS: A frame shift mutation in the canine ortholog of human CLN2 in a juvenile dachshund with neuronal ceroid lipofuscinosis . Molec Genet Metab 89:254-260, 2006.

Gene: TPP1

Neuronal Ceroid Lipofuscinosis (CLN5)

Disease description: The neuronal ceroid lipofuscinosies (NCLs) are progressive hereditary neurological disorders that occur in humans, dogs, cats and other mammals. A form that occurs in Australian Cattle Dogs, Border Collies, and mixed breed dogs results from a mutation in the CLN5 gene. Subtle changes in stance and balance occur as early as 6 months of age, but typically neurological signs do not become obvious until approximately 10 months of age. These signs include anxiety, loss of housetraining, loss of responsiveness to previously learned commands and verbal prompting, compulsive circling, disruption of previously normal sleep patterns, impaired vocalization, impaired ability to prehend and swallow food, loss of coordination and ability to climb up or down stairs, development of tremors and seizures, exhibition of trance-like behavior, and visual impairment in both dim and bright lighting conditions. These severity of these sings progresses over time so that euthanasia is usually elected before affected dogs reach 2 years of age.

Breeds affected: Australian Cattle Dog

Reference:

Kolicheski A, Johnson GS, O’Brien DP, Mhlanga-Mutangadura T, Gilliam D, Guo J, Anderson-Sieg TD, Schnabel RD, Taylor JF, Lebowitz A, Swanson B, Hicks D, Niman ZE, Winninger FA, Carpentier MC, Katz ML. Australian Cattle Dogs with neuronal ceroid lipofuscinosis are homozygous for a CLN5 nonsense mutation previously identified in Border Collies. J Vet Internal Med 30:1149-1158, 2016.

Gene: CLN5

Neuronal Ceroid Lipofuscinosis (CLN5)

Disease description: The neuronal ceroid lipofuscinoses (NCLs) are progressive neurodegenerative disorders that occur in many dog breeds. There are multiple forms of NCL associated with sequence variants in different genes. A form that occurs in Golden Retrievers results from a mutation in the CLN5 gene. The neurological disease signs first become apparent at approximately 13 months of age, followed by gradual increases in severity. The first sign is loss of coordination causing the dogs to bump into objects and have difficulty climbing stairs. The impairments in coordination are particularly evident when the dogs are excited. The loss of coordination progresses with age and eventually becomes apparent even when the dogs are calm. Also among the early neurological signs are anxiety and agitation, accompanied by long periods of constant pacing and circling starting at approximately 15 months of age. At about the same age the affected dogs lose the ability to recognize or respond to previously learned commands and behaviors and begin to exhibit compulsive behavior such as fixation on a toy. Mild seizure-like activity such as snapping at the air (fly biting) and gum smacking begin as early as 15 months of age. Seizure activity becomes progressively more severe and begins to involve the whole body after about 18 months of age with some episodes lasting for up to an hour. In addition, trance-like behavior starts at approximately 18 months of age. Visual impairment in both bright and dim light become apparent by 18 months of age and worsens over time. In the later stages of the disease the affected dogs may become aggressive toward people. Due to the progression of signs, affected dogs are usually euthanized by 2 years of age.

Breeds affected: Golden Retriever

Reference:

Gilliam D, Kolicheski A, Johnson GS, Mhlanga-Mutangadura T, Taylor JF, Schnabel RD, Katz ML. Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Molec Genet Metabol 115: 101–109, 2015.

Gene: CLN5

Neuronal Ceroid Lipofuscinosis (CLN5)

Disease description:

Breeds affected : Border Collie, Australian Cattle Dog, Mixed breeds.

Reference:

Villani NA, Bullock G, Michaels JR, Yamato O, O’Brien DP, Mhlanga-Mutangadura T, Johnson GS, Katz ML. A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for aCLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Molec Genet Metabol 127:107-115, 2019.

Gene: CLN5

Neuronal Ceroid Lipofuscinosis (CLN6)

Disease description: The neuronal ceroid lipofuscinosies (NCLs) are progressive hereditary neurological disorders that occur in humans, dogs, cats and other mammals. A form that occurs in Australian Shepherds results from a mutation in the CLN6 gene. Disease signs first become apparent after 16 months of age and include progressive vision impairment, anxiety, circling, and loss of coordination. Affected dogs may also exhibit increased sensitivity to touch and sound, cognitive decline, and difficulty eating and drinking. Due to increasing severity of disease signs, affected dogs may have to be euthanized at about 24 months of age.

Breeds affected: Australian Shepherd

Reference:

Katz ML, Farias FH, Sanders DN, Zeng R, Khan S, Johnson GS, and O’Brien DP: A Missense Mutation in Canine CLN6 in an Australian Shepherd with Neuronal Ceroid Lipofuscinosis. J Biomed Biotech, Article ID 198042, 6 pages, DOI:10.1155/2011/198042, 2011.

Gene: CLN6

Neuronal Ceroid Lipofuscinosis (CLN6)

Disease description: A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. An examination of the tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some neuronal ceroid lipofuscinosis (NCL) diseases. The dog also exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband’s DNA revealed a homozygous C to T substitution that altered the intron 3–exon 4 splice site of CLN6. 

Breeds affected: Mixed breeds

Reference:

Mhlanga-Mutangadura T, Bullock G, Cerda-Gonzalez S, Katz ML. Neuronal Ceroid Lipofuscinosis in a Mixed-Breed Dog with a Splice Site Variant in CLN6. Genes 15:661, 2024.

Gene: CLN6

Neuronal Ceroid Lipofuscinosis (CLN7)

Disease description: Chihuahua and Chinese Crested dogs with a mutation in the MFSD8 gene suffer from the CLN7 form of neuronal ceroid lipofuscinosis (NCL). CLN7 disease is a progressive neurodegenerative disorder. Neurological signs typically have an onset of 16 to 18 months and include vision loss, anxiety, ataxia, cognitive impairment, compulsive behaviors, and seizures. These signs are accompanied by diffuse brain atrophy. Due to progression in the severity of signs, affected dogs typically do not survive beyond 24 months of age.

Breeds affected: Chihuahua, Chinese Crested

References:

Ashwini A, D’Angelo A, Yamato O, Giordano C, Cagnotti G, Harcourt-Brown T, Mhlanga-Mutangadura T, Guo J, Johnson GS, Katz ML. Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas. Molec Genet Metabol 118:326-332, 2016.

Guo J, O’Brien DP, Mhlanga-Mutangadura T, Olby NJ, Taylor JF, Schnabel RD, Katz ML, Johnson GS. A rare homozygous MFSD8 single-base-pair deletion and frameshift in the whole genome sequence of a Chinese Crested dog with neuronal ceroid lipofuscinosis. BMC Veterinary Research 2015, 10:960.

Gene: MFSD8 (CLN7)

Neuronal Ceroid Lipofuscinosis (CLN8)

Disease description: English Setters with a progressive neurodegenerative disorder characterized as a form of neuronal ceroid lipofuscinosis (NCL) were discovered by Dr. Nils Koppang in Norway in the late 1950s. The dogs were bred for NCL research for many years and in 2014 the causative variant was identified in the CLN8 gene. Testing since 2014 has not identified any dogs with the risk variant outside of the research colony, which no longer exists. However, this test in still offered for English Setters that present with signs consistent with CLN8 disease. These signs have an onset of 12 to 14 months and include progressive visual impairment, cognitive decline, compulsive circling, ataxia, and limb paralysis. Affected dogs suffer from seizures starting at 17 to 24 months of age that become progressively more severe and frequent. Death or euthanasia due to the severity of signs occurs by 27 months of age.

Breeds affected: English Setter

Reference:

Katz ML, Khan S, Awano T, Shahid A, Siakotos AN, Johnson GS. A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis. Biochem Biophys Res Commun 327:541-547, 2005.

Gene: CLN8

Neuronal Ceroid Lipofuscinosis (CLN8)

Disease description: In addition to NCL resulting from a mutations in the CLN5 and CLN6 genes, dogs of Australian Shepherd and Australian Cattle Dog ancestry may also suffer from a form of NCL resulting from a mutation in the CLN8 gene. This form of NCL is characterized by progressive vision loss starting at a few months of age. This is accompanied by progressive loss of housetraining, decreased responsiveness to voice commands, increased sensitivity to noises, compulsive circling and pacing behavior, anxiety, and a loss of the ability to navigate stairs. Affected dogs become progressively more ataxic and may exhibit periods of trance-like staring behavior. These signs become prominent by about 20 months of age. By about 21 months of age, the disease is accompanied by severe behavioral changes that include aggression, disorientation and ataxia. Seizures occur at about this age and increase in frequency and severity over time. Due to the severity of signs, euthanasia is usually elected by 22 months of age.

Breeds affected: Australian Shepherd, Australian Cattle Dog

Reference:

Guo J, Johnson GS, Brown HA, Provencher ML, da Costa RC, Mhlanga-Mutangadura T, Taylor JF, Schnabel RD, O’Brien DP, Katz ML. A CLN8 nonsense mutation in the whole genome sequence of a mixed breed dog with neuronal ceroid lipofuscinosis and Australian Shepherd ancestry. Molec Genet Metabol 112:320-309, 2014.

Gene: CLN8

Neuronal Ceroid Lipofuscinosis (CLN8)

Disease description: The CLN8 form of neuronal ceroid lipofuscinosis (NCL) has been identified in German Shorthiared Points. Onset of signs occurs at approximately 11 months of age with loss of coordination that grows progressively worse over time. Affected dogs become clumsy, ataxic, and bump into stationary objects, walls, and people in a familiar environment. By 15 months of age signs include compulsive circling and tongue movements, jaw chattering, and confusion caused by familiar sounds. From that time forward there is a progressive decline in the ability to understand and respond to previously learned commands and other behavioral cues and regression in previously learned housetraining. At 17 months of age visual impairment in both bright and dim light becomes apparent, and by 18 months there is hesitancy to climb up or down stairs. Progressive anxiety develops between 18 and 21 months of age. Due to the increasing severity of signs, affected dogs are euthanized before 24 months of age.

Breeds affected: German Shorthaired Pointer

Reference:

Guo J, Johnson GS, Cook J, Harris OK, Mhlanga-Mutangadura T, Schnabel RD, Jensen CA, Katz ML. Neuronal ceroid lipofuscinosis in a German Shorthaired Pointer associated with a previously reported CLN8 nonsense variant. Molec Genet Metabol Reports 21:100521, 2019.

Gene: CLN8

Neuronal Ceroid Lipofuscinosis (CLN10)

Disease description: Multiple forms of neuronal ceroid lipofuscinosis (NCL) occur in dogs and humans. The NCLs are all progressive neurological disorders. The onset of signs in the form that occurs in American Bulldogs typically occurs between one and two years of age when affected dogs start to exhibit ataxia, hypermetria, and paraparesis. Affected dogs exhibit slowly progressive psychomotor decline and are typically euthanized before 7 years of age due to the severity of signs.

Breeds affected: American Bulldog

Reference:

Awano T, Katz ML, O’Brien DP, Taylor JF, Evans J, Khan S, Lobel P, Sohar I, and Johnson GS. A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid-lipofuscinosis. Molec Genet Metab 87:341-348, 2006.

Gene: CTSD

Neuronal Ceroid Lipofuscinosis (CLN12)

Disease description: Tibetan Terriers can suffer from a late-onset form of neuronal ceroid lipofuscinosis (CLN12 disease) due to a variant in the ATP13A2 gene. Behavioral signs usually appear around 4 to 6 years of age and include cognitive decline, cerebellar ataxia, dementia, seizures, nervousness, aggressiveness, loss of training, hypersensitivity to stimuli, loss of coordination, tremors, and retinal degeneration associated with moderate visual impairment in low light but good visual acuity in bright light.

Breeds affected: Tibetan Terrier

Reference:

Farias FH, Zeng R Johnson GS, Wininger FA, Taylor JF, Schnabel RD, McKay SD, Lohi H, Lindblad-Toh K, Wade CM, O’Brien DP, Katz ML. A truncating mutation in ATP13A2 is responsible for adult-onset neuronal ceroid lipofuscinosis in Tibetan Terriers. Neurobiol Dis 42:468-474, 2011.

Gene: ATP13A2

Neuronal Ceroid Lipofuscinosis (CLN12)

Disease description: The CLN12 disease that occurs in Australian Cattle Dog is a late-onset form of NCL with onset of neurological signs at approximately 6 years of age. Among these related signs are anxiety, impaired ability to recognize and respond to previously learned commands, increased sensitivity to loud or unexpected sounds, sleep disturbances, inappropriate or persistent vocalization, impaired ability to navigate stairs and to jump up or down from furniture, trembling, seizures, stiffness or weakness, loss of coordination, and impaired vision in both bright and dim light. In addition to these signs, neurological examination findings include hypersensitivity to tactile stimuli, clumsiness, a broad-based stance in the pelvic limbs, mild ataxia, unsteady gait on slippery surfaces, intermittent pacing gait, hopping gait in pelvic limbs while trotting, reduced palpebral reflex and reduced menace response in both eyes, normal pupillary light reflexes in response to bright stimuli, and decreased nasal sensation. Due to the progression in severity of signs, affected dogs are typically euthanized at 7 to 8 years of age.

Breeds affected: Australian Cattle Dog

Reference:

Schmutz I, Jagannathana V, Bartenschlager F, Stein VM, Gruber AD, Leeb T, Katz ML. ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis. Molec Genet Metabol, 127:95-106, 2019.

Gene: ATP13A2

Neuronal Ceroid Lipofuscinosis (NCL- ARSG)

Disease description: Many American Staffordshire Terriers and Pitbull Terriers suffer from a late-onset progressive neurological disorder characterized initially by subtle signs of impaired balance and ataxia but progressing slowly to eventually include cognitive decline, generalized motor impairment and seizures. Onset is typically between 3 and 6 years of age, with variable rates of progression. Euthanasia due to the severity of signs has been elected for dogs as young as 7 years, whereas other affected dogs live past 10 years of age. The disease results from a mutation in the ARSG gene that encodes the lysosomal enzyme arylsulfatase G. The canine disease has been classified as a form of neuronal ceroid lipofuscinosis (NCL), although human subjects with ARSG mutations do not develop NCL-like neurological signs. Based on our DNA testing, the disease appears to be quite common in American Staffordshire Terriers and Pitbull Terriers as well as in mixed breed dogs with Pitbull ancestry.

Breeds affected: American Pitbull Terrier, American Staffordshire Terrier

Reference:

Abitbol M, Thibaud JL, Olby NJ, Hitte C, Puech JP, Maurer M, Pilot-Storck F, Hedan B, Dreano S, Brahimi S, Delattre D, Andre C, Gray F, Delisle F, Caillaud C, Bernex F, Panthier JJ, Aubin-Houzelstein G, Blot S, Tiret L. A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proceedings of the National Academy of Sciences of the United States of America. 107(33):14775-80, 2010.

Gen : ARSG

Paroxysmal Dyskinesia (PD)

Disease description: Paroxysmal dyskinesia in Soft Coated Wheaton Terriers is characterized by episodes of involuntary movements. The median reported at onset of these episodes was 2.5 years. Episode frequency ranged from one episode every few days, to greater than 10 per day. Episode duration ranged from several minutes up to greater than 4 hours. No involuntary movements were observed when the dogs were sleeping. In some cases stress, excitement, or loud noises precipitated some episodes, but a clear trigger was not apparent in most instances. The dogs remained alert and responsive during the episodes, but they could not be distracted out of the episode. Typical episodes consist of rapid flexion and extension of one or both pelvic limbs. Most frequently, the flexion alternated irregularly between limbs but sometimes both pelvic limbs were off the ground simultaneously. Episodes often began with one limb or one side was more severely affected. During a mild dyskinesia episode, some dogs repeatedly held one pelvic limb in flexion while walking which resembled a lameness. During more severe episodes, the thoracic limbs also were asymmetrically involved and the dogs appeared anxious and panted. The dogs often developed a kyphotic or less commonly a scoliotic posture, and some episodes consisted of increased extension of the pelvic limbs. Except during the most severe episodes, the dogs are able to stand and walk. Sometimes, however, they have difficulty moving forward and would walk backwards or sideways.

Breeds affected: Soft Coated Wheaton Terrier

Reference:

Kolicheski AL, Johnson GS, Mhlanga-Mutangadura T, Taylor JF, Schnabel RD, Kinoshita T, Murakami Y, O’Brien DP. A homozygous PIGN missense mutation in Soft-Coated Wheaten Terriers with a canine paroxysmal dyskinesia. Neurogenetics. 18(1):39-47, 2017.

Gene: PIGN

Polyneuropathy with Laryngeal Paralysis (PLP)

Disease description: American Staffordshire Terrier and Pitbull Terrier PLP is a fatal neurodegenerative disease that becomes apparent when affected puppies reach 3 or 4 months of age. Typically, the first sign is breathing difficulty which causes choking, aspiration, and possible pneumonia. The signs progress to generalized muscle weakness generally affecting the hindlimbs first, then the forelimbs. The prognosis is poor, often requiring euthanasia. Based on our studies to date, it appears that there are 2 forms of the disease in American Staffordshire Terriers. We offer a test for the more common form. The genetic basis for the other form remains to be determined. Therefore, your dog could still be at risk for PLP even if it does not have the mutation we test for.

Breeds affected: American Pitbull Terrier, American Staffordshire Terrier

Reference: Discovery by the University of Missouri Canine Genetics Lab, not yet published.

Gene: Not yet published.

Primary Lens Luxation (PLL)

Disease description: Primary lens luxation (PLL) occurs in multiple breeds due to a variety of mutations. PLL is characterized by lens instability in both eyes, although the severity of clinical signs may differ between the 2 eyes. PLL typically goes undetected until the lens becomes severely dislocated in one eye. Dogs typically present with concurrent partial lens displacement of the other eye, which typically progresses into full displacement over a period of weeks to months. The lens often moves anteriorly causing disruption to the pupil and draining mechanism in the eye, which may result in acute glaucoma.

Breeds affected: American Eskimo Dog, Australian Cattle Dog, Border Collie, Chihuahua, Chinese Crested, Chinese Foo Dog, Russell Terrier group, Mixed breeds, Pug, Pumi, Tibetan Terrier, Toy Fox Terrier, Volpino Italiano, and others

Reference:

Farias FHG, Johnson GS, Taylor JF, Giuliano E, Katz ML, Sanders DN, Schnabel RD, McKay SD, Khan S, Gharakhani P, O’Leary CA, Pettitt L, Forman OP, Boursnell M, McLaughlin B, Ahonen S, Lohi H, Hernandez-Merino E, Gould DJ, Sargan DR, and Mellersh C: An ADAMTS17 spice donor site mutation in dogs with primary lens luxation. Invest Ophthalmol Vis Sci 51: 4716-4721, 2010.

Gene: ADAMTS17

Progressive Retinal Atrophy (PRA)

Disease description: Basenjis may exhibit a late adult onset form of progressive retinal atrophy (PRA). Initially, affected individuals lose their vision in dim light and their peripheral vision, resulting in tunnel vision. Many individuals can maintain forward day vision for years as disease progresses. Retinal thinning can typically be detected at 5 years old, and by 7 years of age there is usually reduced blood flow through retinal blood vessels.

Breeds affected: Basenji

Reference: Goldstein O, Jordan JA, Aguirre GD, Acland GM. A non-stop S-antigen gene mutation is associated with late onset hereditary retinal degeneration in dogs. Molecular Vision. 19:1871-84, 2013.

Gene: SAG

Progressive Retinal Atrophy (PRA)

Disease description: A number of breeds may suffer from progressive degeneration of the retina with accompanying visual impairment resulting from a mutation in the RPGRIP1 gene. Ophthalmoscopic signs, including changes in the granular appearance of the tapetal fundus followed by generalized tapetal hyperreflectivity and retinal vascular attenuation, can be detected as early as 6 months of age. The electroretinogram amplitudes of affected dogs are initially normal but are greatly diminished or unrecordable extinguished by 9 months of age.

Breeds affected: English Springer Spaniel, Gordon Setter, Irish Setter, Tibetan Terrier

Reference:

Kuznetsova T, Zangerl B, Aguirre GD. RPGRIP1 and cone-rod dystrophy in dogs. Advances in Experimental Medicine & Biology. 723:321-8, 2012.

Gene: RPGRIP1

Progressive Retinal Atrophy (PRA)

Disease description: There are many forms of retinal atrophy in dogs that are characterized by impaired vision. While these diseases may have subtle differences in clinical signs and in the appearance of retinal changes, genetic testing should be performed for confirmation of a diagnosis when possible. A form of hereditary retinal degeneration that occurs in Dachshunds is associated with a variant in the RPGRIP1 gene. This disorder is characterized by changes in the granular appearance of the tapetal fundus followed by generalized tapetal hyperreflectivity and retinal vascular attenuation, starting at approximately 6 months of age. Electroretinogram responses are usually normal until the dogs are at least 10 weeks old, but then decline in amplitude and are usually unrecordable by about 9 months of age.

Breeds affected: Dachshund

Reference:

Mellersh, CS., Boursnell, ME., Pettitt, L., Ryder, EJ., Holmes, NG., Grafham, D., Forman, OP., Sampson, J., Barnett, KC., Blanton, S., Binns, MM., Vaudin, M. Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88:293-301, 2006.

Gene: RPGRIP1

Progressive Retinal Atrophy (PRA)

Disease description: English Springer Spaniels may also suffer from a later-onset form of PRA that causes progressive loss of vision. If your English Springer Spaniel is exhibiting apparent visual impairment, it is advisable to test for both genetic variants associated with PRA in this breed.

Breeds affected: English Springer Spaniel

Reference: Discovery by the University of Missouri Canine Genetics Lab, not yet published.

Gene: Not yet published.

Progressive Retinal Atrophy (PRA-RCD4)

Disease Description: Forms of Progressive Retinal Atrophy (PRA) in many dog breeds. The disorder is characterized by bilateral progressive degeneration of the retina accompanied by progressive vision loss that culminates in blindness. There are no treatments for most forms of canine PRA, each of which is caused by a different mutation in a specific gene, but for some forms, gene therapy has proven effective in preserving vision. The various forms of PRA are typically breed-specific, with affected dogs of the same breed usually sharing an identical mutation. Affected dogs of different breeds, usually have different mutations, although some PRA-mutations have been found to be shared by multiple breeds. In some breeds, there may be more than one form of PRA. Geneticists at the Animal Health Trust (AHT) have identified a recessive mutation that is associated with the development of the RCD4 form of canine for which we offer a test. 

Breeds affected: Australian Cattle Dog, English Setter, Gordon Setter, Irish Red & White Setter, Polish Lowland Sheepdog, Small Musterlander, Tibetan Terrier

Reference: Discovery by the Animal Health Trust, not yet published.

Gene: Not yet published.

Pyruvate dehydrogenase deficiency (PDH)

Disease description: Dogs with hereditary deficiency in the enzyme pyruvate dehydrogenase suffer from exercise intolerance and post-exercise collapse accompanied by a build up of lactic acid during exercise. Management includes exercise restriction and a high-fat diet with thiamine and carnitine supplementation. The disease results from a mutation in the PDP1 gene.

Breeds affected: Clumber Spaniel, Sussex Spaniel

Reference:

Cameron, JM., Maj, MC., Levandovskiy, V., MacKay, N., Shelton, GD., Robinson, BH. Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. Mol Genet Metab 90:15-23, 2007.

Gene: PDP1

Spinocerebellar Ataxia with Myokymia, Seizures or Both

Disease description: A number of genetically distinct forms of hereditary ataxia occur in Russell group terriers. An early onset form is characterized by incoordination and loss of balance with onset between 2 to 6 months of age. The disease is progressive with affected dogs developing a “prancing” gait and frequent falling. Affected dogs may also have episodes of muscle twitching and rigidity that can appear like seizures but dogs are aware of their surroundings during these attacks. The episodes of muscle twitching worsen with age and dogs may overheat. True epileptic seizures may also occur in affected dogs. Dogs with this form of hereditary ataxia are usually euthanized by 2 years of age due to a poor quality of life.

Breeds affected: Russell Terrier group

Reference:

Gilliam D, O’Brien DP, Coates JR, Johnson GS, Johnson GC, Mhlanga-Mutangadura T, Hansen L, Taylor JF, Schnabel RD. A Homozygous KCNJ10 Mutation in Jack Russell Terriers and Related Breeds with Spinocerebellar Ataxia with Myokymia, Seizures, or Both. J Vet Intern Med. 2014.

Gene: KCNJ10

Spongiform-leukoencephalomyelopathy

(Shaking Puppy Syndrome) (SLEM)

Disease description: Border Terriers may suffer from a disorder known as Shaking Puppy Syndrome (SPS) or Spongiform Leukoencephalomyelopathy (SLEM). The disease is characterized by uncontrollable shaking of the hind limbs when puppies begin to stand and try to walk. As the puppies grow, the shaking can progress to affect the entire body. Other signs include incoordination, tremors, and seizures. The clinical signs are accompanied by degeneration of the brain white matter.

Breeds affected: Border Terrier

Reference: Discovery by the University of Missouri Canine Genetics Lab, not yet published.

Gene: Not yet published.