Felipedia

Muscular dystrophy in cats

Muscular dystrophy-like disorders in cats have been reported in the Netherlands, Germany, and the US. To date, all cats have been male, suggesting an X-linked inheritance. Clinical signs may be first seen in cats about 5 to 6 months of age and include generalized skeletal muscle hypertrophy, excessive salivation, reduced exercise tolerance, stiff gait and bunny-hopping when running, difficulty in jumping, adducted hocks, cervical rigidity, vomiting/regurgitation, and partial protrusion of the tongue. Multifocal lingual calcification (submucosal), hepatosplenomegaly, and megaoesophagus have been noted in some cats. Based on the clinical features, including the extensive muscle hypertrophy, the term "hypertrophic feline muscular dystrophy" has been proposed for this condition. Serum CK levels may be markedly increased, often accompanied by variably elevated levels of aspartate aminotransferase and alanine aminotransferase. Atrial and ventricular dilatation, left ventricular wall thickening, and papillary muscle hypertrophy have been detected in echocardiographic studies. Notching of R waves has been noted with electrocardiographic testing. Electromyographic studies of skeletal muscles reveal bizarre high frequency discharges (also called complex repetitive discharges), sometimes interspersed with positive sharp waves. Motor nerve conduction velocities are normal. Necropsy examination has shown severe hypertrophy of the diaphragmatic musculature, and enlargement of muscles of the tongue and larynx.

Pathological findings are similar to those described for dystrophic dogs and include muscle fibre hypertrophy (involving both type 1 and type 2 fibres), fibre splitting, accumulation of calcium deposits within muscle, myonecrosis and phagocytosis (mononuclear cell infiltrates may be seen), hypercontracted fibres, numerous internalised nuclei, and occasional fibre type grouping. Aging studies have shown a significant decrease in the number of type 2A myofibers and increase in numbers of type 2X fibres in younger dystrophin-deficient cats, with an apparent loss of type 1 fibres in older cats. Endomysial or perimysial fibrosis is not a feature in axial or appendicular muscles. Immunoblotting and immunofluorescent studies have shown marked dystrophin deficiency in skeletal muscles, although, a small percentage of fibres may stain positive. Molecular studies have demonstrated deletion of the dystrophin muscle promoter in affected cats. No histological lesions are seen in carrier females despite presence of a mosaic staining pattern for dystrophin in skeletal muscle (irregular staining in most myofibers or absent staining in rare fibres). Mineralization, fibrosis, and myodegeneration have been seen in cardiac muscle of some affected cats. Ultrastructural changes in skeletal muscle include distension of the sarcoplasmic reticulum and the T system, swollen mitochondria, and Z-band streaming. Prognosis is guarded in cats because of the development of diaphragmatic and lingual hypertrophy which potentially leads to megaoesophagus, insufficient water intake, dehydration, hyperosmolar syndrome (see hypernatremia), and acute renal failure. Another potential complication is rhabdomyolysis, possibly associated with increased sensitivity of the dystrophin-deficient sarcolemmal membrane to volatile anaesthetic agents, stress, or intense muscular activity. In one report, 3 dystrophin-deficient cats developed peracute, lethal rhabdomyolysis following either isoflurane anaesthesia or manual restraint for a procedure). Serum chemistries revealed severe hyperkalemia, hyperphosphatemia, hypocalcemia, massive increases in CK, aspartate aminotransferase, and alanine aminotransferase concentrations, and high ion gap metabolic acidosis. Skeletal muscle changes included severe acute hyaline necrosis and endomysial oedema without infiltration of inflammatory cells.

Congenital Muscular Dystrophy - A novel muscular dystrophy has recently been reported in cats associated with deficiency of merosin (laminin a2). Laminins are large glycoproteins found in the basement membrane of a variety of tissues, including skeletal muscle fibres and Schwann cells of peripheral nerves. Clinical signs in the cats beginning around 6 months of age included progressive muscle weakness, muscle atrophy, and extraordinary muscle contractures resulting in rigidity and extension of the pelvic limbs in one cat. The second cat was non-ambulatory and hypotonic/hyporeflexive in all limbs. Serum CK levels were markedly elevated. Histological muscle changes were characterized by marked endomysial fibrosis, myofiber necrosis, variability of fibre size, and perimysial lipid accumulation. In both cats, immunohistochemical labelling showed complete absence or marked reduction in staining against laminin a2. However, staining for dystrophin and all the components of the dystrophin-associated glycoprotein complex were present and normal. In one cat studied, motor nerve conduction velocity was decreased, and demyelination and vacuolar Schwann cell degeneration were observed in peripheral nerves. No abnormalities were seen in the CNS and there was no evidence of cardiomyopathy. The disease was considered similar to primary or secondary merosin (laminin a 2)-deficient congenital muscular dystrophy in people.