Prenatal malformed lumbar vertebral corpora in trisomies 21, 18 and 13, evaluated radiographically and histologically

Abstract

The aim of the present study was to compare, both radiographically and histologically, malformed vertebral lumbar corpora in trisomies 21, 18 and 13 with earlier reported normal corporal development in the axial lumbar region. Axial skeletons of human fetuses (GA 15-22 wk) derived from therapeutically induced abortion were investigated in connection with requested autopsy. The number of lumbar vertebral corpora examined for each genotype was as follows: 20 from trisomy 21, 10 from trisomy 18, and 10 from trisomy 13. After radiography in frontal, lateral and axial projections, the individual vertebral corpora were decalcified and horizontally embedded in paraffin. The blocks were serially sectioned and stained with toluidine blue and alcian blue/van Gieson. The radiographic characteristics of the vertebral corpora varied from an almost normal appearance of the corporal bone to complete clefting of the bony corpora. Histological examination showed accumulations of cartilage centrally, in some cases associated with amorphous material. Pronounced metachromatic differences were observed in the cartilaginous ground substance. The study showed identical phenotypic characteristics in the corpora from trisomy 21, trisomy 18, and trisomy 13. It is characteristic of all three genotypes that there are central anomalies, corresponding to the location of the notochord in normal corpora, and marked regional differences in metachromasia in the ground substance of the cartilage.

Axial skeletogenesis in human autosomal aneuploidies: A radiographic study of 145 second trimester fetuses

“…radiographic finding in this genotype, as previously demonstrated [Kjaer et al, 1997b;Nolting et al, 2000]. The nature of vertebral clefting in autosomal aneuploidies remains obscure.…”

“…Abnormal ossification patterns at both the radiographic and histological levels were previously documented in 40 fetuses with trisomies 21, 18, and 13 [Nolting et al, 2000], as well as eight fetuses with triploidy [Nolting et al, 2002]. Histologically, marked regional differences in metachromasia in the ground substance of the cartilage with Toluidine blue and Alcian blue/van Gieson stains was documented in all conditions.…”

“…Kjaer et al [1996Kjaer et al [ , 1997a and Keeling et al [1997] first described similarities in distribution of mild vertebral changes among fetuses with the same aneuploidy and traced distinguishing trends among different aneuploidies. Then, further analyses were carried out by the same group on lumbar vertebrae in fetuses with trisomy 13, 18, and 21 [Nolting et al, 2000], vertebral histology in triploidy [Nolting et al, 2002], and of cervical vertebrae, cranial base and mandible in triploidy [Sonnesen et al, 2009]. However, when the rate at conception of human aneuploidies is compared with the number of analyzed fetuses in these studies, the expected variability of costovertebral anomalies in these disorders seems far from be completely understood.…”

Histological examinations of bone and cartilage in the axial skeleton of human triploidy fetuses

“…Histological studies have demonstrated that pathological ossification of the vertebral corpora is associated with changes in metachromasia in ground substance of cartilage in trisomies 21, 18 and 13 (11).…”

Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene

“…Polymorphisms in these genes, however, are not significantly associated with NTDs in all populations, suggesting that polygenic and environmental factors are important. Our groups and others have described NTDs in chromosomal and inherited syndromes, including trisomy 13 (13)(14)(15)(16), trisomy 18 (16 -19), trisomy 21, and 22q11.2 and 13q deletion syndromes (20)(21)(22)(23). In rare cases, syndromes that variably present with NTDs have been associated with a mutation in a single gene (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”