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

Abstract

Autosomal aneuploidies associate with multiple minor skeletal defects, which, in fetuses, are best appreciated post-mortem after specific anatomic preparations. The present study was aimed to define patterns of skeletal anomalies in autosomal aneuploidies at standard radiology in second trimester fetuses by comparing findings in and among genotypes and gestational ages. Aneuploid fetuses were selected for availability of radiographs of various axial and non-axial structures, mainly homeotic transformations, vertebral clefts, vertebral segmentation and ossification defects, absent/hypoplastic nasal bone, premature talar calcifications, and selected appendicular anomalies. Eighty six fetuses with trisomy 21, 39 with trisomy 18, eight with trisomy 13, six with triploidy, and six with rare autosomal aneuploidies were identified, 75.2% showing an abnormal costo-vertebral pattern, mostly cervical ribs, absence of the 12th thoracic ribs and posterior homeotic change. Clefting was observed along the entire spine, especially sagittal lumbar clefts, and coronal thoracic clefts. Four different types of vertebral clefting were identified, including type 1 (butterfly), type 2 (incomplete inferior), type 3 (incomplete superior), and type 4 (complete). Attenuation of clefting by gestational age was observed in trisomy 21 and 18. These findings define more clearly the pattern of perturbed morphogenesis in aneuploidy as a type of amplified developmental instability with pleiotropic effects on skeletogenesis.

Increased prevalence of abnormal vertebral patterning in fetuses and neonates with trisomy 21

“…The prevalence of cervical ribs in this study population was only slightly higher (57.4%) and not very different from the study of Castori et al [15], who included the largest study population.…”

“…The prevalence of cervical ribs in cases with trisomy 21 ranged from 12.5 to 57.1% in previously reported studies [14,15,35]. The prevalence of cervical ribs in this study population was only slightly higher (57.4%) and not very different from the study of Castori et al [15], who included the largest study population.…”

“…A high prevalence of vertebral patterning anomalies has also been reported in cases with chromosomal anomalies [8,[11][12][13][14][15]. However, the included study populations were relatively small and in only one of these studies the number of thoracic ribs was compared with a control group [12].…”

Cervical ribs in human early life: morphological variability and first identification as a morbidity criterion in a past population

“…Recent biological and genetic studies, however, indicate that the cervical rib in early childhood is identified, in mice and in humans, as positively and significantly associated with the most frequent congenital anomalies, and several severe medical conditions [Table 5 ( Adson & Coffey 1927;Gladstone and Wakeley, 1932;Bagnall et al 1984;McNally et al 1990;Schumacher et al 1992;Keeling and Kjaer, 1999;Galis et al 2006;Bots et al 2011;Castori et al 2016, Schut et al 2019a2019b)].…”

Paleodysmorphology and paleoteratology: Diagnosing and interpreting congenital conditions of the skeleton in anthropological contexts

“…Although they result from aberrations early in embryonic development, their direct clinical implications seem quite limited, except for cervical ribs, which can occasionally lead to thoracic outlet syndrome. However, they appear to be associated with both malignancies (Merks et al, ) and several congenital malformations, and have a prevalence of 75–80% in stillborn and therapeutically aborted fetuses (Ten Broek et al, ; Castori et al, ). This implies that either the Hox genes themselves—and their targets—or their upstream enhancers are more intricately involved in tissue and organ development and proliferation than has yet been established.…”