D20: Most important feline genetic diseases

Question 1

what is a genetic disorder?

Answer 1

A genetic disorder is a genetic problem caused by one or more abnormalities formed in the genome.

Genetic disorders may be hereditary, passed down from parental genes.
defects may be caused by new mutations or changes to the DNA.

Question 2

genetic disease of cats involving immune deficiencies:

Answer 2

• Atopy (feline atopy, dermal allergy): inherited predisposition to develop a hypersensitivity to environmental allergens: military dermatitis, alopecia and eosinophilic granuloma complex.
• Chediak-Higashi syndrome: AR, incomplete oculocutaneous albinism, recurrent and severe pyogenic infections, a bleeding tendency. Cats of yellow eye colour and “blue smoke” hair.
• Neonatal isoerythrolysis: life-threatening disorder that affects kittens of blood type A (dominant) that are born to queens of blood type B (recessive), haemolysis in kittens.
• Pemphigus: pemphigus erythematosus usually only affects the head and feet.

Question 3

genetic diseases of cats involving metabolism (lysosomal storage disease)

Answer 3

• Gangliosidosis (GM1, GM2): Siamese, Korat, and Domestic Shorthair cats from 2 to 5 months of age, progressive neurological dysfunction, hepatomegaly, premature death.
• Glycogen storage disease (glycogenosis, GSD) Type IV: Norwegian Forest cats, generalized muscle tremors and weakness progressing to tetraplegia.
• Lipoprotein lipase deficiency - congenital (hyperlipaemia, primary hyperlipoproteinaemia, hyperchylomicronaemia, transient hyperlipidaemia and associated anaemia): fasting hyperlipaemia, lipaemia retinalis, peripheral neuropathies and subcutaneous xanthomata.
• Mannosidosis (alpha-mannosidosis):
• Mucolipidosis type II (facial dysmorphia): abnormal facial features, retarded growth, behavioural dullness, ataxia, cardiac failure.
• Mucopolysaccharidosis (types: MPS I, MPS VI, MPS VII): Siamese and other domestic cats, dwarfism, facial abnormalities, skeletal deformities, ataxia, urine contain high concentrations of mucopolysaccharides.
• Porphyria: Siamese cat, porphyrins in body tissues.
• Pyruvate kinase deficiency: anaemia due to PK deficiency of RBC.

Question 4

genetic disease of cats involving neuromuscular system

Answer 4

• Muscular dystrophy (MD, feline X-linked MD): affects predominantly male cats, deficiency or missing dystrophin, muscular hypertrophy, later muscle atrophy, difficulties swallowing, prognosis is poor.
• Myopathy: in Devon rex cats, weakness, ventroflexion of the neck.
  Other myopathies of cats:
  – Merosin-deficient myopathy,
  – Hypertrophic feline muscular dystrophy (laminin alpha2 deficiency),
  – Hypokalaemic myopathy.
• Myotonia congenita: AR, rare, no breed predisposition, tremor, stiffness.

Question 5

genetic disease of cats involving cardiovascular and blood disorders

Answer 5

• Cardiovascular disorders:
  – Congenital heart defects: atrioventricular defect, malformation of the atrioventricular (mitral and/or tricuspid) valves, endocardial fibroelastosis, patent ductus arteriosis, aortic stenosis, tetralogy of Fallot.
  – Hypertrophic cardiomyopathy (feline HCM).
• Blood disorders:
  –> Coagulopathies: coagulation (bleeding, clotting) disorders (majority: AR, haemophilia: X-LR, males are affected).
• Factor (coagulation) VIII deficiency (Haemophilia A)
• Factor (coagulation) IX deficiency (Haemophilia B)
• Hageman (coagulation factor XII) deficiency
• Pelger-Huet anomaly

Question 6

genetic disease of cats involving bones and cartilage (skeletal)

Answer 6

• Arthritis
• Chondrodysplasia: curled ears, breed standard in Scottish Fold, Curly Eared cats.
• Hip dysplasia.
• Japanese taillessness: shorttailness in Japanese cats, differs from Manx mutation!
• Kinky tail: esthetical problem in Oriental cats.
• Manx taillessness: The gene for taillessness (M) is a dominant mutation of the m gene which stands for
  “normal tail„. homozygous for taillessness (MM) are born dead (lethal factor).
  1. the rumpy, which has absolutely no tail, M.
  2. the riser (or rumpyriser) which has a few vertebrates that can be seen or felt as an upright projection, Mm
  3. the stumpy, which has an extremely short, often kinked tail, also seen in the Japanese Bobtail. mm

Question 7

genetic disease of cats involving disorders of the eye

Answer 7

• Cataracts
• Entropion
• Glaucoma
• Progressive retinal atrophy, dysplasia (PRA): AR, Abyssinian and Persian cats, early-onset (more prevalent) and a late-onset retinal degeneration, blindness.
• Retinal dysrophy: rod cone degeneration/rod cone dysplasia (rcd): progressive rod cone degeneration and rod-cone dysplasia, a photoreceptor dysplasia of Abyssinian cats until the age of 1.5-2 years.

Question 8

genetic disease of cats involving urogenital disorders

Answer 8

• Cryptorchidism.
• Disorders of sexual development (intersexuality, hermaphoditism):
  – sexual reversal (SRY-gene),
  – tfm (testicular feminization, missing androgen receptors) syndrome,
  – Klinefelter’s syndrome (XXY males).
• Polycystic kidney disease (PKD): AD, mainly Persian and Himalayan cats.
  -> Autosomal DOMINANT Polycystic Kidney Disease (PKD) is a progressive, inherited disease which causes multiple fluid filled cysts on the kidneys of Persians/Exotic cats & breeds.
  -> Cysts are present from birth.
  -> Cysts can range from very small to several centimetres in diameter - causing kidney failure.
  -> Ultrasound: Ultrasound diagnosis is 98% accurate after approximately 10 months of age.
  -> DNA test.

Question 9

genetic disease of cats involving the endocrine system

Answer 9

• Hypothyroidism (congenital hypothyroidism): rare in cats.
• Diabetes mellitus: rae, Burmese and domestic cats, type-2 diabetes, characterised by inadequate insulin secretion and impaired insulin action.
• Pituitary (proportional) dwarfism (hypopituitarism): disorder of growth hormone secretion or its receptor, rare.

Question 10

genetic disease of cats involving the skin and integument

Answer 10

• Albinism: tyrosinase (TYR gene) mutation corresponds to the colour locus (C) in cats and its polymorphic alleles, from dominant to recessive, are as follows: C (full colour) > c^b (burmese) ≥ c^s (siamese) > c (albino).
• Basal cell tumour: timorous skin disease in older
  Siamese and Oriental cats.
• Cutaneous asthenia (Ehlers-Danlos syndrome,
  dermatosparaxis): AR, rare in cats.
• Epidermolysis bullosa, junctionalis: separation of the nails from the corium (dermis).
• Hairlessness (hypotrichosis, alopecia): AR or AD
  (homozygotes are lethal) inheritance, breed standard in Sphinx, Don-Sphinx and Peterbald cats.
• Rex coat: AR or AD, breed standard.
• White colour and deafness: linkage.
• White colour and squamous cell carcinoma (SCC): This type of tumour is associated with increased exposure to ultraviolet radiation (UVA and UVB) from sunlight.
• Wire hair: AD, breed standard.

Question 11

what feline genetic DNA tests are available?

Answer 11

• Glycogenosis (glycogen storage disease GSD) Type IV: Norwegian Forest Cat (PennGen, Dr. John Fyfe, Laboratory of Comparative Medical Genetics, Michigan State University, USA).
• Pyruvate Kinase Deficiency (PK): Abyssinian cats, Somali (PennGen).
• Hypertrophic Cardiomyopathy (HCM): Maine Coon Cat, Ragdoll (Washington State U., Meurs Lab).
• Polycystic Kidney Disease (PKD): American Shorthair Himalayan, Persian, Scottish Fold (UC-Davis – Lyons Lab, Animal Health Trust).
• PRA (rdAC-PRA defect): Siamese-related cats included Siamese, Colourpoint Shorthair, Oriental Shorthair, Balinese, Javanese and Ocicat
  breeds (UC Davis (USA) or Laboklin - Germany).
• Severe Spinal Muscular Atrophy: Maine Coon Cat (Michigan State U –Fyfe Lab).

Question 12

how can genetic diseases be prevented?

Answer 12

• Careful selection: between high performance and gene defects might be association (CSS!).
• Heterozygote screening and selection (DNA-test).
• Using disease-free sires in breeding (all offspring are healthy!).
• Avoid close inbreeding (except test mating).
• Breeding for disease-resistance (MHC haplotypes).