“Abnormal vertebral patterns in genetically heterogeneous deceased fetuses and neonates: evidence of selection against variations”

Abstract

ObjectiveTo assess the vertebral pattern in a cohort of deceased fetuses and neonates, and to study the possible impact of DNA Copy Number Variations (CNVs) in coding regions and/or disturbing enhancers on the development of the vertebral pattern.MethodRadiographs of 445 fetuses and infants, deceased between 2009 and 2015, were assessed. Terminations of pregnancies, stillbirths and neonatal deaths were included. Patients were excluded if the vertebral pattern could not be determined. Copy number profiles of 265 patients were determined using single nucleotide polymorphism array.Results274/374 patients (73.3%) had an abnormal vertebral pattern. Cervical ribs were present in 188/374 (50.3%) and were significantly more common in stillbirths (69/128 (53.9%)) and terminations of pregnancies (101/188 (53.7%)), compared to live births (18/58, 31.0%, p = 0.006). None of the rare CNVs were recurrent or overlapped candidate genes for vertebral patterning.ConclusionThe presence of an abnormal vertebral pattern, particularly in the cervical region, could be a sign of disruption at critical, highly interactive and conserved stages of embryogenesis. The vertebral pattern might provide valuable information regarding fetal and neonatal outcome. CNV analyses did not identify a mutual genetic cause for the occurrence of vertebral patterning abnormalities, indicating genetic heterogeneity.

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)].…”