Role of genetic determinants in the development of congenital scoliosis: a review

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Abstract

BACKGROUND: Congenital scoliosis is a multifactorial disorder resulting from disturbances during vertebral embryogenesis. Defects occurring at any stage of fetal development may lead to congenital scoliosis and progressive spinal deformity. Recent studies highlighted genetic factors as crucial determinants of the development of this condition.

AIM: To review the sources on the genetic basis of congenital scoliosis, focusing on molecular regulatory mechanisms, mutation frequencies, and the contribution of specific genes.

METHODS: Sources were retrieved using keyword searches in PubMed, Google Scholar, Cochrane Library, Web of Science, Lens.org, and eLibrary over the past 25 years. The inclusion criteria were full-text availability, meta-analyses, systematic reviews, cohort studies of patients with congenital scoliosis, experimental animal models, and case–control studies. The exclusion criteria included lack of full-text access, patents, utility models, and studies without clinical data. Finally, 54 publications were selected for detailed analysis.

RESULTS: The identified genes were categorized into four: susceptibility genes (LMX1A, PTK7, SOX9, TBX6, and TBXT); genes wherein mutations directly cause syndromes or monogenic disorders associated with scoliosis (FBN1); genes with copy number variations (DHX40, DSCAM, MYSM1, and NOTCH2); and genes showing abnormal methylation in patients with scoliosis (COL5A1, GRID1, GSE1, RGS3, SORCS2, IGH1, IGH3, IGHM, KAT6B, and TNS3).

CONCLUSION: Analysis of scientific sources revealed the presence of predisposing genetic factors associated with the development of congenital scoliosis in its various phenotypic forms. Data from large-scale studies clarified the etiological factors and were beneficial for predicting the course of congenital scoliosis, and findings from studies with smaller samples may help define future directions for identifying genetic determinants of this disorder.

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About the authors

Sergei V. Vissarionov

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: vissarionovs@gmail.com
ORCID iD: 0000-0003-4235-5048
SPIN-code: 7125-4930

MD, PhD, Dr. Sci. (Medicine), Professor, Corresponding Member of RAS

Russian Federation, Saint Petersburg

Polina А. Pershina

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Author for correspondence.
Email: polinaiva2772@gmail.com
ORCID iD: 0000-0001-5665-3009
SPIN-code: 2484-9463

MD, PhD student

Russian Federation, Saint Petersburg

Sergey E. Khalchitsky

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: s_khalchitski@mail.ru
ORCID iD: 0000-0003-1467-8739
SPIN-code: 2143-7822

PhD, Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Marat S. Asadulaev

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: marat.asadulaev@yandex.ru
ORCID iD: 0000-0002-1768-2402
SPIN-code: 3336-8996
Scopus Author ID: 57191618743

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

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