DOWNS-SYNDROME - ALTERED CHONDROGENESIS IN FETAL RIB

Down's syndrome (DS), a human genetic abnormality usually caused by an extra chromosome 21, presents a wide range of major and minor anomali es, the most significant of which are mental retardation and congenita l heart defects. The anomalous phenotype also includes short stature a nd neck, thin calvaria, and cartilage hypoplasia. The genesis of these skeletal features is unknown. Histopathologic sections of fetal carti lage from skull, vertebra, rib, and femur were studied in 16 fetuses w ith DS (17-22 wk old) and 13 control non-DS fetuses (19-22 wk old) wit h other pathologies not directly affecting skeletal growth. Rib growth cartilage morphology showed a previously unreported structural anomal y in DS, an increase in the hypertrophic portion with a concomitant de crease in proliferative and resting zones. The hypertrophic chondrocyt ic zone was markedly increased in DS compared with non-DS (149 +/- 68 mu m versus 36 +/- 20 mu m, and 26 +/- 12 versus 7 +/- 3 expressed in percent of the total length; p < 0.0001), whereas the proliferative zo ne (114 +/- 58 mu m versus 165 +/- 43 mu m, 20 +/-. 10 versus 33 +/- 4 in percent of the total length; p < 0.001) and the resting zone (53 /- 4 versus 59 +/- 6 in %, p < 0.009) were decreased. These features w ere not found in the femoral epiphyseal growth plate or in cartilage f rom vertebra and skull. Our results demonstrate an imbalance toward th e hypertrophic phenotype. This abnormality, found in DS fetuses 17-22 wk old, may represent an early manifestation of an abnormal growth car tilage maturation pattern, which manifests postnatally in long bones, leading to diminished growth rates.