Abstract
Although muscle diseases occur relatively rarely in cats, a number of congenital feline myopathies have been described over the last 20 years and are reviewed in this paper. Some of them have been reported exclusively in specific breeds, including the hypokalaemic myopathy of Burmese cats, type IV glycogen storage disease in Norwegian Forest cats, or the myopathy of Devon Rex. Other congenital disorders of muscle and neuromuscular junction such as myotonia congenita, dystrophin-deficient hypertrophic feline muscular dystrophy, laminin α2 deficiency, or congenital myasthenia gravis may occur in any cat. A systematic approach is essential in order to efficiently obtain a timely diagnosis in cats showing signs of muscle disease. After a thorough clinical examination, this approach includes blood analyses (eg, serum concentration of muscle enzymes), electrophysiology where available (electromyography, nerve conduction studies), and sampling of muscle biopsies for histological, histochemical and immunohistochemical evaluation. When available, detection of healthy carriers of these genetic disorders is important to eliminate the gene mutations from breeding families. Clinicians regularly receiving feline patients must have a good knowledge of congenital feline myopathies and the features which enable a diagnosis to be made and prognosis given. Besides preserving or restoring the well-being of the myopathic patient, rapid and efficient information and counselling of the breeders are of central importance in order to prevent the recurrence of the problem in specific breeding lines.
Introduction
Diseases of muscle and neuromuscular junction occur infrequently in cats, and congenital myopathies are rare. Muscle weakness is a common clinical sign and may cause a stiff and stilted gait. Weak cats are more prone to show cervical ventroflexion than other species because they lack a nuchal ligament. Other clinical signs may include fatigability, mild lower motor neuron deficits and changes in muscle size (swelling, hypertrophy, atrophy), possibly accompanied by pain (myalgia) in some diseases. As these signs are relatively non-specific, ancillary tests are often needed in order to obtain further diagnostic information. Analyses such as a complete blood count and serum biochemistry profile are useful screening tools. Serum concentrations of specific muscle enzymes such as creatine kinase (CK), electromyography and motor nerve conduction studies, as well as histological analysis of muscle biopsy specimens can all be helpful to confirm muscle involvement and rule out peripheral nerve disorders. In many cases, however, particularly for the diagnostic work-up of congenital myopathies, additional investigations such as immunohistochemical stains of muscle sections are necessary in order to obtain a definitive diagnosis.
After briefly reviewing the diagnostic approach of cats with suspected muscle diseases, this article aims to describe the currently known congenital disorders of feline muscle and the neuromuscular junction.
Diagnostic approach
A complete blood count may identify the presence of inflammation or help identify possible underlying diseases. Besides its general value as a screening tool, the serum biochemistry profile can yield valuable information in feline patients with suspected muscle disease. Typically, increased permeability of the sarcolemma or destruction of muscle fibres will lead to an increase in serum creatine kinase (CK). Although no specific data could be found on the serum half-life of CK in cats, it is generally accepted to be a few hours as it is in other species (Aktas et al., 1993). Thus increased serum activity indicates recent leakage. However, it should be remembered that cats with prolonged anorexia may also have increases in CK (Fascetti et al., 1997). Moreover, as is the case in dogs, intramuscular injections can also lead to increases in CK serum concentrations (Aktas et al., 1995). Serum concentrations of other enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) may also be increased (Gaschen et al., 1992; Gaschen, unpublished data). Moreover, a decrease in serum potassium may be identified and lead to a diagnosis of hypokalaemic myopathy. Serum titres for prevalent infectious diseases such as retroviroses (FeLV, FIV) or protozoal infections (
Electrophysiological investigations are useful to evaluate the concurrent involvement of peripheral nerves. In the presence of a normal motor nerve conduction velocity, it is likely that the signs suggestive of muscle disease are due to a myopathy or a disorder of the neuromuscular junction, and are not neuropathic in origin. Electromyographic changes indicative of primary or secondary muscle involvement are rarely specific for a particular muscle disease. Increased insertional activity, fibrillation potentials, positive sharp waves, myotonic discharges, and complex repetitive discharges can be observed in many myopathies. Their occurrence may depend on the severity of the muscle lesions. It is beyond the scope of this review to discuss electromyographic patterns in detail and the reader is referred to publications specifically focused on this topic (Bowen, 1987; Niederhauser and Holliday, 1989; Cuddon, 2002).
Evaluation of muscle biopsy specimens often offers the most specific information required to make a diagnosis. It is usually advisable to sample peripheral nerve and muscle tissue for routine histological analysis. Descriptions of regular and simplified techniques for sampling muscle biopsies have been published (Braund, 1989; Bley et al., 2001). In cases with diffuse involvement, we prefer to biopsy easily accessible muscles such as the vastus lateralis or biceps femoris muscles as cats rarely show any complications after biopsy of these muscles (Braund, 1989). Obviously, in cats with focal myopathies, the involved muscles must be biopsied. Clinicians are strongly advised to contact their reference laboratory before performing the biopsy in order to be clearly informed about the precise requirements regarding sampling, handling and shipping of the specimen. Generally, fresh or flash frozen samples are easiest to analyse if they have been prepared and shipped properly. All histochemical, histological and immunohistochemical investigations can be performed on such samples. Fixation in formaldehyde does not allow a comprehensive analysis of the samples.
Routine analysis of muscle samples should include histochemical stains such as the ATPase stain to evaluate the presence and distribution of the different muscle fibre types. For feline muscle, the ATPase stain at pH 4.45 allows good differentiation between the main fibre types 1, 2A, and 2B (Gaschen and Burgunder, 2001). The classical stains haematoxylin and eosin (HE) or Gomorri trichrome (GT) are used to screen the specimen with respect to muscle fibre size variations, presence of central myonuclei, fibre degeneration and necrosis, regenerative attempts, or infiltrates with inflammatory cells or connective tissue (Banker and Engel, 1994). Specific techniques aimed at staining fibrous tissue, fatty infiltrates and other lesions can then be used as needed.
For cats where a tentative diagnosis of congenital myopathy is made, several antibodies marketed for the diagnosis of human myopathies are available for immunohistochemistry and these antibodies cross-react reasonably well with feline muscle proteins (see paragraphs on specific diseases). Depending on which muscle disease is suspected, molecular testing may be of interest in order to detect healthy carriers in the affected breeding family and exclude them from further breeding to prevent the occurrence of clinical cases (Fyfe, 2002).
Congenital disorders of muscle and neuromuscular junction
A synopsis of congenital myopathies described in cats, including breeds and geographic provenience of reported cases, clinical signs and prognosis is provided in Table 1.
Congenital myopathies in cats
AUS = Australia; B = Belgium; CH = Switzerland; GB = Great Britain; NL = Netherlands; NZ = New Zealand; USA = United States of America.
Congenital myotonia
Myotonia is the continued active contraction of a muscle after the cessation of voluntary effort and is characterised by muscle spasm and stiffness (Braund, 1986). Hereditary myotonia has been reported in a variety of species but only recently in the cat (Hickford et al., 1998; Toll et al., 1998). Myotonia can occur secondary to other disorders; muscular dystrophies and endocrinopathies or as a primary disorder; myotonia congenita. Primary congenital myotonia has been described in the cat.
The clinical features of myotonia in the cats described by Hickford et al. (1998) and Toll et al. (1998) are very similar. The affected cats walk with a stiff awkward gait. The limbs are abducted when walking because of poor flexion of proximal limb joints. There is widespread hypertrophy of muscle groups. The stiffness is worse on awakening and in cold weather, but improves with exercise: a feature of myotonic syndromes in other species (Braund, 1986). When affected kittens are startled, they may stiffen and fall into lateral recumbency with legs extended. Spasm of the eyelids and facial muscles also frequently occur when they are startled (Fig. 1). Their jaws cannot be opened fully and there is sometimes mild dysphagia. Haematology and clinical chemistry are normal including CK, cholesterol and electrolyte values. Hypocholesterolaemia has been associated with myotonia in other species (Farrow and Malik, 1981).
Myotonia congenital: an affected young cat shows flattening of the right ear and retraction of the right lip after receiving a fright (from: Hickford and Jones, 2000 with permission).
The presence of a dimple on percussion of muscle (tongue or skeletal muscle) and the occurrence of spontaneous high frequency discharges which wax and wane after insertion of a needle electrode are features of all affected cats (Fig. 2). Electromyogram (EMG) amplification produces the ‘dive bomber’ sound (Hickford et al., 1998; Toll et al., 1998). In the absence of CK increase in the serum, these features are confirmatory for myotonia in all species.
Myotonia congenita: electromyographic recording from the triceps muscle of an affected kitten showing waxing and waning high frequency discharges following needle insertion (from Hickford et al., 1998 with permission).
Histological section of muscle shows a variation in fibre size diameter, central nuclei and proliferation of sarcolemmal nuclei (Hickford et al., 1998; Toll et al., 1998). Toll et al. (1998) quantified the increase in the mean fibre area in affected cats, compared with age-matched healthy cats and demonstrated mild dilation of the transverse T tubules by electron microscopy.
The pathophysiology of myotonia has been intensively investigated in other species. The primary defect in chloride conductance in the sarcolemma is the underlying abnormality in most species (Vite et al., 1998). In humans, mice and the Miniature Schnauzer, defects in the chloride channel gene have been proven (Rhodes et al., 1999). The underlying sarcolemmal and genetic defects in the cat have not been investigated. The cats in the report of Hickford et al. (1998) were all related and an autosomal recessive mode of inheritance was suspected.
The reports of myotonia in cats neither described treatment nor emphasised that drug therapy was needed.
Dystrophin-deficient myopathy
Dystrophin-deficient myopathy is a rare disease caused by a nearly total lack in dystrophin, a large protein indirectly connecting the internal cytoskeleton with the extracellular matrix. Dystrophin deficiency is due to a mutation in the dystrophin gene, a very large gene located on the X-chromosome, and is transmitted according to an X-linked recessive inheritance pattern (Engel et al., 1994). Feline dystrophin deficiency is one of three animal models for Duchenne muscular dystrophy (DMD), a crippling hereditary muscular disease causing generalised muscle atrophy and fibrosis in humans (Hoffman and Gorospe, 1991).
Contrary to what is seen in affected humans and dogs, the hallmark of the disease in cats is severe hypertrophy of the axial and proximal appendicular skeletal muscles (Fig. 3). It was therefore given the name hypertrophic feline muscular dystrophy (HFMD). The tongue and diaphragm also show massive hypertrophy in some individuals (Fig. 3). Cats may develop potentially lethal complications due hypertrophy of selected muscles such as oesophageal compression by hypertrophic diaphragmatic pillars, or insufficient water intake and severe hyperosmolality due to dysfunction of the tongue (Gaschen et al., 1992). Moreover, dystrophin-deficient cats may succumb to peracute rhabdomyolysis occurring in association with general anaesthesia, intense physical activity or stress (Gaschen et al., 1998).
Dystrophin-deficient myopathy: a 7-year-old male cat affected with HFMD. The cervical and proximal appendicular musculature is noticeably hypertrophic. The hypertrophic tongue protrudes out of the mouth.
Dystrophic cats cannot be differentiated from normal cats at birth although they consistently show a slower growth curve than their normal littermates. Appendicular muscular hypertrophy is clinically evident starting around 10 weeks of age, and is followed by development of hypertrophy in the axial musculature, especially the cervical muscles. White nodules consisting of dystrophic calcifications may appear on the edges of the enlarged tongue and disappear spontaneously a few weeks later. Functionally, cats with HFMD have a slightly stilted gait, and they tend to ‘bunny hop’ when they want to run. Occasionally, the gait is more abnormal, with marked stiffness and reluctance to move, which may be associated with episodes of increased muscle fibre necrosis.
Dystrophin-deficient cats develop a subclinical cardiomyopathy (Gaschen et al., 1999). Cardiomegaly and changes indicative of progressive concentric myocardial hypertrophy are observed in cats from 6 to 9 months of age. The appearance of the myocardium is abnormal. However, fractional shortening of the left ventricle is usually normal, suggesting normal left ventricular contractility. Although these cats only infrequently develop clinical features of heart failure, some older cats have succumbed to a dilated form of cardiomyopathy (Gaschen, unpublished observations).
EMG findings include a variety of anomalies such as myotonic discharges, fibrillation potentials, prolonged insertional activities, complex repetitive discharges and positive sharp waves.
In young and adult cats with HFMD, serum CK activity remains markedly increased. However, serum CK concentrations do not allow a differentiation between dystrophin-deficient kittens and their normal littermates at birth. Serum CK activities are statistically higher in HFMD kittens from 2 weeks of age, and the difference with normal kittens increases dramatically over the following weeks (Gaschen, unpublished data). Serum concentrations of AST and ALT are also severely increased. Although it is known that increases of serum AST concentration can occur following muscle damage, muscle origin of ALT has only been demonstrated in dystrophin-deficient dogs (Valentine et al., 1990).
Histopathological changes observed in dystrophin-deficient feline skeletal muscle cells result from continuous degeneration/regeneration (Fig. 4). There is a wide variation in myofibre diameter, with large myofibres showing splitting, foci of degeneration and regeneration, with minimal mononuclear infiltration. The absence of endomysial or perimysial fibrosis is typical. A unique feature of this model is the frequency and severity of dystrophic calcification foci. A definitive diagnosis can be made when muscle sections immunohistochemically stained for dystrophin show a lack of dystrophin at the sarcolemma.
Dystrophin-deficient myopathy: histological appearance of skeletal muscle in a 6-month-old cat. The wide distribution of myofibre diameters is noticeable. There are two foci of degeneration/regeneration with calcified myofibres, and one focus of regeneration with small myofibres with larger nuclei (arrow). The letter a shows hypertrophic myofibres, ∗ indicates calcified degenerated myofibres. Haematoxylin and eosin, bar = 50 μm.
In our experience, in spite of the absence of specific treatment, the prognosis for HFMD is fair. Most animals can enjoy a nearly normal quality of life with supportive measures only occasionally needed. However, stress, intense physical activity and inhalant anaesthesia should be avoided.
Glycogen storage disease type IV
A myopathy associated with glycogen storage disease type IV has been reported in Norwegian Forest cats (Fyfe et al., 1992). The disease is due to a lack of the glycogen branching enzyme (GBE) and characterised by accumulation of abnormal glycogen in several tissues including skeletal muscle. Hereditary transmission occurs according to an autosomal recessive pattern. Affected cats are homozygous for a deletion in the GBE gene causing instability of mRNA.
Many affected cats are stillborn or die within the first few days of life. The surviving cats are often normal until they reach 5 to 7 months of age. At that time, they show persistently increased body temperature, generalised muscle tremors, intermittent listlessness and ‘bunny hopping’. Muscle weakness and muscle atrophy progress rapidly, resulting in the inability to chew, fibrotic contractures of selected joints, and tetraplegia (Fig. 5). The disease often leads to death of the cats around age 10 to 14 months.
Type IV glycogen storage disease in an 8-month-old male Norwegian Forest cat. The cat is weak. Extensive and severe fibrosis in muscle groups of the front leg caused carpal contracture, preventing a normal stance (courtesy of Dr. J.C. Fyfe, Michigan State University).
Laboratory anomalies include increases in serum CK and ALT. Nerve conduction velocities are normal, but increased fibrillation potentials and bizarre high frequency discharges are present in the EMG. Concentric left ventricular hypertrophy and mild left atrial dilation were seen in one affected cat. Histologically, cytoplasmic inclusions containing Periodic acid-Schiff (PAS) and toluidine blue positive material are present in many organs. Particularly in nervous tissue and in skeletal and cardiac muscle, the disease leads to marked degeneration and atrophy. There is currently no treatment available for this disease.
Diagnosis of the disease in an affected kitten unequivocally identifies the parents as carriers of the mutation, which should have direct implications for their use in any breeding programme. In the USA, the origin of the disease could be likely tracked to a single tom cat imported from Europe in the early 1980s (Fyfe, 1995). However the disease appears to be uncommon in Europe. A DNA-based carrier test is available to screen problem breeding families (http://www.vet.upenn.edu/research/centers/penngen/services/deublerlab/gsd4.html).
Hypokalaemic polymyopathy
There have been numerous reports of polymyopathy in cats associated with a variety of different causes of hypokalaemia (Jones, 2000). Burmese kittens develop hypokalaemia associated with disturbances of the intracellular and extracellular balance of potassium. The syndrome in Burmese kittens bears many similarities to hypokalaemic periodic paralysis of humans, a condition that is thought to be related to a calcium channel disorder. However, sequence data show no evidence for a mutation in the gene for the calcium channel in affected Burmese cats (Gruffydd-Jones, 2000, personal communication). The condition has a familial and inherited basis (putative autosomal recessive) with affected kittens being produced in specific lines of this breed (Mason, 1988; Gruffydd-Jones et al., 1998).
The disease has been reported in Burmese kittens in the United Kingdom (Blaxter et al., 1986; Gruffydd-Jones et al., 1998), Australia (Mason, 1988; Edwards and Belford, 1995), the Netherlands (Lantinga et al., 1998) and New Zealand (Jones et al., 1988).
The clinical signs are frequently transient with moderate to severe episodes followed by improvement (with or without treatment), but are sometimes persistent. There is generalised muscle weakness with persistent ventroflexion of the neck with the head tucked into the sternum (Fig. 6). The kittens are intolerant of exercise and walk with a stiff, stilted, awkward gait. There may be exertional muscle tremor followed by sudden fatigue and collapse. Severely affected cats are reluctant to move and show pain when their muscles are palpated. Importantly, spinal reflexes and postural reactions are normal.
Hypokalaemic myopathy with ventroflexion of the neck in a 9-month-old Burmese cat (published with permission, Manson Publishing).
The presence of a low serum potassium (<3.0 mmol/l) will confirm a diagnosis of hypokalaemia, although serum potassium concentrations can be normal in some cats which show clinical signs. The low serum potassium concentration is frequently accompanied by increased serum activity of CK which is released only when the concentration of potassium in the muscle is very low. CK concentrations can be very elevated (<100,000 IU/l) (Jones et al., 1988; Gruffydd-Jones et al., 1998). There is no evidence for reduced potassium intake or urinary potassium loss in affected Burmese cats (Jones et al., 1988, Gruffydd-Jones et al., 1998).
Diffuse electromyographic abnormalities are sometimes present (eg, positive sharp waves may be recorded). Muscle biopsy specimens are mostly normal on light microscopy: mild myofibre necrosis is occasionally observed (Jones et al., 1988), however severe rhabdomyolysis is absent.
Clinical signs of muscle weakness are reversible and the response to potassium supplements is rapid. The continued treatment with oral potassium (potassium gluconate; 2–4 mmol/cat per os once to twice daily to effect) is safe and effective. The clinical signs in some kittens resolve without further treatment.
Laminin α2 (merosin) deficiency
In humans, laminin α2 (merosin) deficiency causes congenital muscular dystrophy, a rare congenital disorder. Laminin 2 is a glycoprotein indirectly anchoring the cell membrane and the basal lamina, and is present in skeletal muscle and Schwann cells. Three merosin-deficient cats have been described recently (O'Brien et al., 2001; Poncelet et al., 2003). All animals had shown hindlimb weakness starting as early as 2.5 months of age. When presented at age 12 months, generalised muscle atrophy was noticed. One cat had marked hindlimb extensor muscle contractures and was unable to walk on its hind legs. One cat had a decreased range of motion of the limb joints, and the disease was progressive. Another cat which was hypotonic and hyporeflexive with generalised muscle atrophy was presented recumbent.
Serum CK was markedly increased in all cats, AST and ALT activities were moderately increased in one cat. Electrodiagnostic tests were performed in two cats. Although the EMG was unremarkable, the motor nerve conduction velocity was markedly decreased. Histopathological examination revealed dystrophic changes with marked endomysial fibrosis of all biopsied muscles. Myofibre necrosis, variation in fibre size and lipid accumulation were also present. Additionally, axonal demyelination was present in peripheral nerves. Schwann cell defects were detected by electron microscopy. Immunohistochemical stains revealed a lack or decrease of laminin α2 in skeletal muscle.
No specific therapy is available. The prognosis is grave: one cat died at 13 months of age and the other ones were euthanased before the age of 2 years.
Myopathy of Devon Rex cats
Since 1974 an inherited muscular dystrophy characterised by muscle weakness has been recognised in the Devon Rex breed. The condition has been seen throughout the world and erroneously called ‘spasticity’ by many Devon Rex breeders. There were brief descriptions of the disease in the veterinary literature (Lievesley and Gruffydd-Jones, 1989; Jones, unpublished observations) until Malik et al. (1993) completed a more detailed investigation of affected cats.
The most obvious and consistent clinical sign is passive ventroflexion of the head and neck. Ventroflexion is frequently accentuated when walking, during micturition and defecation. Muscle weakness is particularly evident during exertion, excitement or stress. Typically there is a high stepping forelimb gait, head bobbing and dorsal protrusion of the scapulae due to weakness of the shoulder girdle musculature (Fig. 7). With exertion affected cats tire easily and eventually collapse in sternal recumbency with their head at rest on one side of their front paws.
Devon Rex myopathy in a kitten showing high stepping forelimb gait, dorsally protruded scapulae and cervical ventroflexion.
Affected cats frequently rest in a characteristic ‘dog begging’ position with their front paws resting on a supporting object. This position allows them to maintain normal orientation of their head despite weakness of the cervical muscles.
One of the significant features of the disease is the difficulty affected cats have prehending food and swallowing. They frequently develop upper airway obstruction and ‘choking’ caused by the accumulation of food in the pharynx and occluding the larynx (Malik et al., 1993). Asphyxiation is a common cause of death. Feeding cats from a raised platform minimises the risk of asphyxiation (Malik et al., 1993). The severity of signs often fluctuates from day to day and week to week (Malik et al., 1993; Jones, personal observations). Stress, concurrent illness and cold all tend to accentuate weakness.
The age of onset is variable and less seriously affected kittens may go unnoticed for several months. Breeders normally recognise the affected kittens at about the time they start to walk. The disease is inherited as an autosomal recessive trait (Robinson, 1992).
In the one detailed study by Malik et al. (1993) of four affected cats oesophageal hypomotility and megaoesophagus were identified in all animals. Haematological and serum biochemistry values including electrolytes and CK were within reference ranges (Malik et al., 1993).
Neurophysiological findings are variable. Conduction velocity of motor axons of tibial and ulnar nerves are normal. Sparse fibrillation potentials and positive sharp wave activity may be detected on electrode insertion into cervical and upper limb muscles. Myotonic and bizarre high frequency discharges are not detected (Malik et al., 1993).
Skeletal muscles appear grossly normal but histological changes are best identified in dorsal cervical and proximal forelimb muscles. The severity of the changes correlates with both the severity of signs and the age at the time of biopsy (Malik et al., 1993). The significant lesion in muscle biopsies were variation in cross sectional area, more rounded fibres, occasional degenerating fibres, some fibre segmentation and increased subsarcolemmal nuclei. There is no fibre type distribution of lesions and dystrophin is present.
The above signs are characteristic of a muscular dystrophy. Devon Rex myopathy shares some features with limb-girdle muscle dystrophy (LGMD), a group of disorders with the similar phenotype of a myopathy affecting skeletal muscle of the pelvic and shoulder girdles in humans. A number of types of LGMD have been identified that are due to various genetic defects involving the membrane proteins such as sarcoglycans but also sarcoplasmic proteins (Zatz et al., 2003). However, to date, no published evidence is available to substantiate any relationship between the feline and human diseases. The underlying pathogenesis and the genetic basis of Devon Rex myopathy have not been defined yet.
Nemaline rod myopathy
This condition was described in five related cats (Cooper et al., 1986). The aetiology is unknown. The cats were normal until 6–18 months of age. They then developed weakness, their gait became wobbly and they started to lose weight. They were reluctant to move and showed a fast, jerky and hypermetric gait. They had a crouched stance with an exaggerated hip and tarsus flexion. There was intermittent muscle twitching. The cats were quickly exhausted and started to pant after exertion. Selected muscles became clearly atrophic. The clinical course was slowly progressive. These cats had a modestly increased serum CK activity. There were no changes on EMG examination. Histological examination of muscle biopsies showed severe muscle fibre size variation with many atrophic myofibres, and central migration of myonuclei. Some myofibres contained nemalin rods. No therapy was suggested. The prognosis was poor and all affected cats had to be euthanased for humane reasons.
Malignant hyperthermia
This is a very rare disease in cats. An exaggerated sensitivity to various anaesthetic gases (eg, halothane) is suspected as is the case in other species. Primary malignant hyperthermia was described in two apparently healthy cats that were anaesthetised with halothane (De Jong et al., 1974; Bellah et al., 1989). Cats with dystrophin deficiency developed rhabdomyolysis during halothane anaesthesia (Gaschen et al., 1998). All these cats died during or immediately after a general anaesthetic.
Myasthenia gravis
Myasthenia gravis (MG) is a condition in which the neuromuscular transmission is impaired due to deficiency of acetylcholine receptors (AChRs) in the postsynaptic neuromuscular junctions (Shelton, 2002). Depletion of postsynaptic membrane AChRs results in failure of neuromuscular transmission. Striated muscle weakness is the main clinical symptom (Shelton, 2002). Congenital MG was described in two cats (Indrieri et al., 1983; Joseph et al., 1988). It is probably caused by inherited reduction of AchRs and is an extremely rare condition. It is seen in young animals around 4–5 months of age without breed or sex predisposition (Indrieri et al., 1983; Joseph et al., 1988). Clinically, weakness that is exacerbated by exercise and improved by rest is characteristic for MG. Stiff, choppy movements of all limbs followed by episode of rest in sternal recumbency, changes in voice, head ventroflexion and dysphagia and/or regurgitation are usually noticed (Indrieri et al., 1983; Joseph et al., 1988). Other clinical tests like positive endrophonium (Tensilon) test and decrement of the evoked muscle action potential during repetitive nerve stimulation support the diagnosis of MG. Additionally, normal blood biochemistry profile and complete blood cell count, physiological electromyographical examination and nerve conduction velocities as well as negative routine muscle and nerve biopsy help to exclude other generalised muscle and nerve disorders (Indrieri et al., 1983; Joseph et al., 1988). In cases of confirmed myasthenia gravis, oral anticholinesterase therapy should be attempted. Optimal dosage of pyridostigmine bromide should be individually established and ranges between 0.25 and 3 mg/kg body weight bid. Appropriate therapy led to resolution of neuromuscular weakness in the two cats with congenital MG reported in the literature (Indrieri et al., 1983; Joseph et al., 1988).
Other diseases
Several congenital diseases that affect skeletal muscle only secondarily may cause clinical signs suggestive of myopathy. Fibrodysplasia ossificans progressiva (also improperly called myositis ossificans) is a congenital disease resulting in proliferation and ossification of skeletal muscle-associated connective tissue (Valentine et al., 1992). Affected cats were presented between 10 months and 6 years of age with an abnormal gait, muscle enlargement with myalgia in some cases. Nerve entrapment was observed. Areas of soft tissue mineralisation within muscles were visible on radiographs. Histological analysis of muscle biopsies revealed marked epimysial proliferation of fibrovascular connective tissue. The disease is rapidly progressive and leads to euthanasia of all affected cats.
Motor neuron disease (MND) describes a group of diseases associated with degeneration of motor neurons. Adult-onset MND was recently reported in three cats (Shelton et al., 1998). The animals were all older than 5 years, and showed progressive weakness of the pelvic limbs, crouched gait, and muscle fasciculations or tremors. The disease was slowly progressive and led to muscle atrophy and extreme weakness. All cats were eventually euthanased. Lesions of the ventral horn neurons were detected. These findings confirmed that muscle weakness and atrophy were neurogenic in origin. Based on a report posted on the internet (http://medicine.ucsd.edu/vet_neuromuscular/cases/2003/sep03.html), spinal muscular atrophy, a juvenile-onset MND with autosomal recessive inheritance has been detected in Maine Coon cats. It results in weakness and severe muscle atrophy first evident around 4 months of age. Affected kittens may go on to walk with a pelvic limb sway by 5–12 months of age.
In spite of the relative rarity of congenital muscle diseases in cats, it is important for clinicians who regularly examine feline patients to recognise and correctly identify these important conditions. This can only occur with full knowledge of these diseases and the features that enable a diagnosis to be made and prognosis given. Treatment of individual cats and the delivery of advice to breeders to help them to eliminate the hereditary trait from their breeding lines depend on accurate diagnosis.
Footnotes
Acknowledgments
We are indebted to Dr. J.C. Fyfe, Comparative Medical Genetics, Michigan State University for the information and illustrations on glycogen storage disease type IV in Norwegian Forest cats he kindly provided.