Truncated FAM8A1 in Russian Blue encephalopathy
REM sleep behaviour disorder (RBD) is a disease characterised by the loss of lower motor neuron inhibition responsible for skeletal muscle atonia during REM sleep. It has been reported in humans, dogs and cats, and can be idiopathic or secondary to a neurodegenerative disease. Five young adult Russian Blue cats from 2 related families were presented for progressively worsening RBD episodes frequently associated with urinary loss. Three of these cats also suffered urinary retention with overflow incontinence between RBD episodes. Clinical examination revealed a large bladder in 3 cats, and neurological examination a bilateral mydriasis with absent pupillary light reflexes (PLRs) in 2 cats. Complete blood count and serum biochemistry, magnetic resonance imaging of the brain and cerebrospinal fluid analysis in 2 cats were unremarkable. Treatment attempts were unsatisfactory, wherefore 3 cats were euthanised. Histopathology of the brain did not reveal any abnormalities. A disease-associated FAM8A1 variant was identified by WGS. The variant segregated in the affected family with a recessive mode of inheritance, but was not present in 264 cats belonging to 32 breeds. The variant FAM8A1 isoform is predicted to affect the assembly and activity of the endoplasmic-reticulum-associated protein degradation (ERAD) pathway, which plays an important role in cell homeostasis. RBD and urinary retention syndrome is a hereditary encephalopathy affecting Russian Blue cats. A genetic test now allows diagnosis and prevention of this debilitating disease.