A 15 month old female spayed DSH cat was presented to the Franklin Veterinary Services Referral Centre with a three month history of pelvic limb lameness, intermittent pyrexia and anorexia. The owner reported that the cat
had shown an abnormal pelvic limb gait since acquired as a kitten. The referring veterinarian had noted enlargement of the
popliteal, inguinal and submandibular lymph nodes, and firm swellings in the medial thigh area. Biopsy of the inguinal subcutaneous
swellings supported a diagnosis of steatitis without neoplastic cells or infectious agents. Aspirates from the affected
nodes were reported as reactive lymphoid hyperplasia. Tests for FeLV and FIV were negative. The cat had a partial response
to prednisone at 5 mg daily (improved demeanor and appetite), but not amoxicillin-clavulanic acid or enrofloxacin. The
pelvic limb lameness had progressed to the point where the cat had difficulty walking.
Physical and Neurological Examination
Both stifles were found to be grossly thickened from mid femur to the proximal tibia. The pelvic limbs were "bowed" and the
cat was unable to bear weight normally. The range of motion in the stifles was reduced, with the left extending only to 100°, and the
right to 110°. Both patellas were luxated medially. The thickened soft tissue was firm and non-compressible, and extended into the
inguinal area bilaterally. Both pelvic limbs were painful on palpation and manipulation. The right elbow joint was thickened with a reduced
range of motion, and was painful on palpation. The cat was neurologically normal apart from abnormal pelvic limb reflexes, presumably
due to the restrictive tissue. Voluntary movement and pain perception were present in both pelvic limbs.
Routine laboratory tests
CBC - No abnormalities
Serum biochemistry profile
Calcium and phosphate levels - no abnormalities
Serum Creatine Kinase- 362 IU/L (reference range 0-220 IU/L
Cholesterol - 4.2 mmol/l (reference range 1.9-3.9 mmol/l
Urea - 4.6 mmol/l (reference range 7.1-10.7 mmol/l)
Creatinine - 71 µmol/l (reference range 88-177 µmol/l)
Radiographs showed extensive soft tissue mineralization adjacent to both the right and left proximal tibia (Figures
1 and 2). Opacities in the gastrocnemius and other muscles tended to be ovoid and aligned in the direction of muscle fiber
orientation. There was no evidence of a local periosteal reaction. Similar mineralized densities were seen in the proximal
scapular musculature on both sides, extending towards the dorsal spinous processes of the T2-T5 vertebrae. A mineralized mass
projected medially from the right medial humeral epicondylar periosteum, and there were also small periarticular mineralized
foci adjacent to the left elbow. Patchy areas of mineralization were also seen lateral to the right ilium on a ventrodorsal
view of the pelvis, and to a lesser extent adjacent to the left ilium. Foci of mineralization were identified periarticular
to both stifles, and adjacent to the proximal femurs.
Based on the radiographic findings, a diagnosis of fibrodysplasia ossificans progressiva (generalized myositis ossificans)
was suspected. Due to the extensive nature of the lesions, surgical excision of the affected tissue was not recommended. The
cat responded poorly to further prednisone therapy and pain relief (buprenorphine injections), and was euthanitized for humane
reasons. Samples of affected muscles (left scapula and popliteal regions) were placed in 10% formalin and submitted for histopathologic
Figure 1. Ventrodorsal view of the pelvis, femurs, and proximal tibias showing multifocal mineralized
Figure 2. Lateral view showing similar mineralized densities
Fixed muscle specimens showed collagen proliferation, focal areas of lymphocytic infiltration (Fig 3), and areas of
cartilage and ectopic bone formation within the muscle tissue (Fig 4). The pathological abnormalities appeared to have originated
from the fascial connective tissue. The histologic findings supported the radiographic diagnosis.
Figure 3. H&E stain of muscle specimen showing foci of lymphocytic cellular infiltration and
collagen proliferation |
Figure 4. H&E stain of muscle specimen showing ectopic bone formation surrounded by collagen proliferation
Conclusions and Discussion
The clinical, radiographic and histopathological findings in this case support a diagnosis of fibrodysplasia ossificans progressiva (FOP). FOP is a rare genetic disorder of skeletal malformations and progressive extraskeletal ossification. Unwanted and unneeded bone formation can result in extra-articular ankylosis of all major joints of the axial and appendicular skeleton, rendering movements impossible. This is a rare disorder in humans, and a limited number of feline cases have been previously reported (Norris et al, 1980; Warren and Carpenter, 1984; Waldren et al, 1985; Bradley, 1992; Valentine et al, 1992; Gannon et al, 1998). Although Norris described a similar case as generalized myositis ossificans in 1980, the changes are primarily seen in connective tissue, thus it is more commonly described as a fibrodysplasia. Mutations have been identified in humans in a gene which encodes bone morphogenetic protein which is a likely key regulator of cartilage and bone formation (Shore et al, 2006; Shen et al, 2009).
In humans, treatments including surgical excision of lesions, radiotherapy, corticosteroids, dietary management and diphosphonates
have no proven benefit (Valentine et al, 1992). Although diphosphonate-etidronate disodium inhibits calcification it does not prevent
the formation of ectopic bone matrix which is also disabling. It can also inhibit calcification in normal bone (Bradley, 1992). Progressive
involvement of the respiratory muscles in humans can result in respiratory insufficiency, pneumonia and death (Norris et al, 1980).
Until the mechanisms that regulate osteogenic activity in mesenchymal cells are better understood, the pathogenesis of this disorder
may remain elusive. Genetic studies and biochemical tissue analysis may better define the etiology of this condition in both the cat
The contributors would particularly like to thank C. Honour for supporting the further study of this condition, and Ian Robertson,
Nicola Wilson, Joanne Harrison, Bronwyn Smits, and Noeline Champion for their contributions to this report. The assistance of the Comparative
Neuromuscular Laboratory is gratefully acknowledged.
Bradley WA (1992). Fibrodysplasia ossificans in a Himalayan cat. Aust Vet Pract 22: 154-158.
Gannon FH, Valentine BA, Shore EM et al (1998). Acute lymphocytic infiltration in an extremely early lesion of fibrodysplasia ossificans
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Norris AM, Pallet L, Wilcock B (1980). Generalized myositis ossificans in a cat. J Am Anim Hosp Assoc 16:659-662.
Shen Q et al (2009). The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J Clin Invest 119:3462-3472.
Shore EM et al (2006). A recurrent mutation in the BMP type 1 receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nature Genetics 38:525-537.
Valentine VA, George C, Randolph JE et al (1992). Fibrodysplasia ossificans progressiva in the cat. A case report. J Vet Int Med 6:335-340.
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