Homozygous Pelger-Huët anomaly and chondrodysplasia in a stillborn kitten.

Abstract

Pelger-Huet anomaly is an inherited disorder of leukocyte development characterized by persistent nuclear hyposegmentation of granulocytes and monocytes in the presence of a mature, coarse chromatin pattern. The anomaly has been reported sporadically in humans, but is rare in In humans and animals, Pelger-Huet anomaly usually is encountered in the heterozygous form where most blood granulocytes and monocytes have indented, band-shaped, or bilobed nuclei. In the homozygous form of Pelger-Huet anomaly, however, granulocytes and monocytes generally have round to oval nuclei with a very coarse chromatin pattern.2 The homozygous form of the anomaly is extremely rare, and has only been described in rabbits6 and, presumably, in nine human^.^,^ In a prospective breeding study, a brother-sister test mating of two cats that were heterozygous for the Pelger-Huet trait7 produced a litter of five kittens, three of which were stillborn (Table 1). One stillborn kitten was small and had a domeshaped skull with a flattened face and protruding tongue. The hard palate was intact. All limbs were short, thickened, and had severe medial deviation (Fig. 1). Survey radiographs demonstrated extensive axial and appendicular skeletal changes when compared to the other two stillborn littermates (Fig. 2). A dome-shaped skull and shortenednasal bones were apparent. Vertebral bodies were shortened longitudinally with concave ends, and the ribs also were shortened with flared costochondral junctions. The costochondral cartilage was longer than in the unaffected littermates. Appendicular skeletal abnormalities consisted of shortened long bones with cup-shaped metaphyses. Radiographic skeletal lesions were not seen in the remaining stillborn kittens. One live littermate also had skeletal abnormalities, including pectus excavatum, lordosis, longitudinal compression of the vertebral bodies, and flaring of the distal radial metaphyses. The remaining live kitten had no radiographic abnormalities of the skeletal system. Radiographic findings in both affected kittens were compatible with chondrodysplasia. Examination of Wright-stained smears of umbilical cord blood made at birth revealed that the runted stillborn kitten had a differential leukocyte count of 43% neutrophils, 9% monocytes, 42% lymphocytes, 3% eosinophils, and 3% basophils. The majority of blood granulocytes and monocytes had round to oval nuclei (Fig. 3). All leukocytes, including lymphocytes, had a very coarse, patchy chromatin pattern. Toxic changes of the neutrophil cytoplasm were not observed. Based on the leukocyte phenotype, the hematologic diagnosis was homozygous Pelger-Huet anomaly. In contrast, umbilical cord blood smears from three of the four remaining kittens had band to bilobed leukocyte nuclei which were considered typical of the heterozygous state of PelgerHuet anomaly. In these individuals, the chromatin pattern was less aggregated than in the homozygous kitten. The live chondrodysplastic kitten had a normal leukocyte phenotype, with most neutrophils having three nuclear lobes. Neutrophil mean nuclear scores were calculated, following published guidelines, on blood smears from each kitten.’ The calculated mean nuclear score (1.39) of the homozygous Pelger-Huet kitten was significantly lower than the neutrophil mean nuclear scores of the heterozygous Pelger-Huet (3.13-3.23) and normal phenotype (4.62) littermates (Table 1). The three stillborn kittens were necropsied, and tissues were collected in 10% buffered formalin. Evidence of hydrocephalus in the runted kitten was not found on gross inspection of coronal brain sections. Skeletal tissues were decalcified, and all tissues were processed routinely, embedded in paraffin, sectioned at 5 pm, and stained with hematoxylin and eosin (HE). Microscopic lesions were seen only within the skeletal system of the runted stillborn kitten and involved both the axial and appendicular skeleton and were consistent with chondrodysplasia. Long bones of the limbs were shortened, thickened, and had broad, mushroom-shaped epiphyses (especially noticeable in the distal epiphyses). The physeal zones were incompletely formed with partial or irregular endochondral ossification at the center of the physis and more normal endochondral ossification at the periphery of the physis. Central areas of the physis occasionally were necrotic and associated with a failure of vascular invasion.