Genetics of non‐isolated hemivertebra: A systematic review of fetal, neonatal, and infant cases

Abstract

Hemivertebra is a congenital vertebral malformation caused by unilateral failure of formation during embryogenesis that may be associated with additional abnormalities.A systematic review was conducted to investigate genetic etiologies of non-isolated hemivertebra identified in the fetal, neonatal, and infant periods using PubMed, Cochrane database, Ovid Medline, and ClinicalTrials.gov from inception through May 2022 (PROSPERO ID CRD42021229576). The Human Phenotype Ontology database was accessed May 2022. Studies were deemed eligible for inclusion if they addressed non-isolated hemivertebra or genetic causes of non-isolated hemivertebra identified in the fetal, neonatal, or infant periods. Cases diagnosed clinically without molecular confirmation were included. Systematic review identified 23 cases of non-isolated hemivertebra with karyotypic abnormalities, 2 cases due to microdeletions, 59 cases attributed to single gene disorders, 18 syndromic cases without known genetic etiology, and 14 cases without a known syndromic association. The Human Phenotype Ontology search identified 49 genes associated with hemivertebra. Non-isolated hemivertebra is associated with a diverse spectrum of cytogenetic abnormalities and single gene disorders. Genetic syndromes were notably common. Frequently affected organ systems include musculoskeletal, cardiovascular, central nervous system, genitourinary, gastrointestinal, and facial dysmorphisms. When non-isolated hemivertebra is identified on prenatal ultrasound, the fetus must be assessed for associated anomalies and genetic counseling is recommended.

Congenital kyphoscoliosis associated with thoracic hemivertebrae in a 9‐month‐old Racking filly

“…Failure of chondrification centres during the formation or the segmentation in the somitogenesis stages and subsequent disruption in ossification during vertebral body formation has been proposed as the pathogenesis of hemivertebrae (Besalti et al, 2005; Goldstein et al, 2005; Johal et al, 2016; Powel et al, 2022; Varras & Akrivis, 2010). Improper formation of the intersegmental arteries of the vertebral column and, therefore, alternation in vascular supply at the developmental stage is postulated as another aetiology for hemivertebrae (Besalti et al, 2005; Goldstein et al, 2005; Johal et al, 2016; Powel et al, 2022; Varras & Akrivis, 2010). Hemivertebrae can result in deviations of the vertebral column in the coronal plane laterally (scoliosis), sagittal plane dorsally (kyphosis) or ventrally (lordosis; Denoix, 2005; Fürst, 2018).…”