Advances in the diagnosis and treatment of congenital scoliosis

Abstract

Congenital scoliosis (CS), a severe form of early-onset scoliosis (EOS), arises from vertebral malformations during embryogenesis, driven by complex genetic and environmental interactions. This review synthesizes recent advances in understanding CS etiology, diagnosis, and treatment. Genetically, CS is linked to mutations in TBX6, GDF3, DSTYK, and COL11A2, alongside copy number variations (CNVs) and epigenetic modifications such as allele-specific methylation in SVIL and TNS3. Maternal hypoxia, toxin exposure, and nutritional deficiencies further contribute to pathogenesis. Diagnosis incorporates advanced imaging techniques—such as X-rays, magnetic resonance imaging (MRI), and computed tomography (CT)—as well as genetic testing, with whole-exome sequencing identifying mutations in 18.6% of cases. Conservative management, including casting and bracing (e.g., alternating cast and brace treatment [ARCBT] and 3D-printed orthoses), effectively delays progression in mild-to-moderate cases. Surgical interventions—such as hemivertebra resection, hybrid techniques (HT), and growth-modulating technologies including magnetic controlled growth rods (MCGR) and the Shilla method—have demonstrated improved outcomes in patients with severe deformities. HT combines posterior osteotomy with dual growing rods, achieving significant Cobb angle correction (81.4° to 40.1°) and spinal growth (1.23 cm/year) with fewer complications. MCGR reduces repeated surgeries but shows variable impacts on quality of life. Emerging approaches, including apical control techniques and robotics, highlight the shift toward personalized care. This review underscores the need for multidisciplinary strategies to optimize outcomes, emphasizing early diagnosis, tailored treatments, and long-term monitoring to address CS complexity.

Background

Congenital scoliosis (CS) is a form of early-onset scoliosis (EOS) caused by skeletal abnormalities during gestational weeks 4 to 6, often leading to additional deformities in other systems [1]. Its etiology involves both genetic and environmental factors [2]. Genetic mutations, such as in the TBX6 gene, along with single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), play a significant role [3, 4]. Environmental influences, including prenatal hypoxia, alcohol exposure, and vitamin deficiencies, are also linked to CS development [3, 5, 6]. Diagnosis relies on imaging techniques like X-rays, CT scans, and MRI, while advances in genetic methods, such as whole-exome and whole-genome sequencing, provide more detailed diagnostic insights [7].

Treatment options for CS range from conservative management—such as casting and bracing—for mild-to-moderate cases, to surgical interventions—including in situ fusion, hemivertebra resection, and the use of a vertical expandable prosthetic titanium rib (VEPTR)—for more severe deformities [8–13].

Given its progressive nature, regular follow-up is essential for monitoring and adjusting treatment plans to improve patient outcomes [14–16].

This review discusses recent advancements in the etiology, diagnosis, and treatment of CS, aiming to provide clinicians with the latest insights for personalized care.

Materials and methods

We conducted a narrative literature review in July 2025, adhering to the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines [17].We searched PubMed/MEDLINE, Embase, and Cochrane Library using the terms: “congenital scoliosis” OR “hemivertebra” OR “early-onset scoliosis” OR “growth rod” OR “spinal surgery”. The search spanned January 1955 to July 2025 and was limited to English-language publications. We included clinical studies (prospective cohorts, retrospective series, and randomized trials) on CS etiology, diagnosis, or treatment. We excluded systematic reviews, meta-analyses, and nonclinical biomechanical research. After removing duplicates, two authors independently screened titles and abstracts; relevant full texts were reviewed for inclusion. Discrepancies were resolved by consensus.

Overview of etiology

CS is a type of EOS caused by abnormal spinal development during the embryonic period. It is marked by severe deformities and rapid progression, often accompanied by malformations in other organs [18]. CS is classified into Type I, Type II, and Type III [19], with incidence rates between 0.5‰ and 2‰ [20–23]. Type I defects reflect failure of vertebral formation (for example, a hemivertebra or butterfly vertebra). Type II defects result from failure of segmentation, yielding fused or block vertebrae (such as an unsegmented bar). Type III defects combine both processes (for instance, an anterolateral unsegmented bar on one side with a contralateral hemivertebra) [24]. While typically sporadic, cases among identical twins suggest a complex interaction between genetic and environmental factors. For example, one study documented CS in one twin with Chiari malformation, while the other was unaffected, highlighting this complexity [25]. Family studies further indicate a low recurrence risk, supporting the multifactorial nature of CS [26]. A deeper understanding of how genetic and environmental factors interact is crucial to unraveling the etiology of CS.

Genetic factors

The genetic landscape of CS is increasingly complex, involving a variety of mutations, SNPs, and CNVs. Early studies, such as those by Qiu et al., examined genes like MESP2, HES7, and DUSP6, but found no significant mutations, suggesting these genes may not play a major role in sporadic CS within the Chinese Han population [27]. A 16p11.2 deletion affecting the TBX6 gene has been identified as a key risk factor for CS, particularly in the Han Chinese population, with additional SNPs within TBX6 further elevating risk (rs2289292, rs3809624, rs3809627) when combined with heterozygous deletions [28, 29]. Similarly, CNVs in TBX6, NOTCH2, and other genes have been found to contribute to vertebral malformations [30].

Other genes, including LMX1A and FBN1, also play significant roles in spinal development, with mutations linked to CS [31, 32]. Recent advancements have expanded this genetic framework. For instance, mutations in the GDF3 gene were shown to influence vertebral development, with four variants displaying varying degrees of pathogenicity [33]. Likewise, DSTYK gene mutations in zebrafish models revealed abnormal notochord formation, implicating the mTORC1/TFEB pathway as a key player in scoliosis pathogenesis [34].

Epigenetics has also come to the forefront, with studies like Zhang et al. identifying allele-specific methylation in the SVIL gene, suggesting an interaction between genetic and environmental factors [35]. Similarly, differential methylation in the TNS3 gene promoter region was noted in monozygotic twins discordant for CS, underscoring the role of epigenetic regulation [36].

Recent studies have continued to broaden our understanding of the genetic basis of CS. Novel variants in the FGFR1 and PTK7 genes have been associated with vertebral malformations and scoliosis [37, 38]. Additionally, CNVs identified in Southern Chinese cohorts have provided further insight into the familial genetic patterns of CS [30]. Most recently, Rebello et al. identified COL11A2 as a candidate gene, using CRISPR/Cas9 technology to model CS-like vertebral fusions in zebrafish [39].

Different CS types have distinct etiologies. Type I (formation) anomalies are often driven by genetic disruptions in vertebral development. For example, TBX6 mutations or deletions (at 16p11.2) lead primarily to hemivertebrae or butterfly vertebrae [24]. In contrast, Type II (segmentation) anomalies are mainly linked to defects in somitogenesis signaling. Notch‐pathway genes—such as DLL3, HES7, MESP2 and related factors—when mutated cause segmentation failures like vertebral bars or block vertebrae [40].

In summary, the genetic factors underlying CS are diverse, involving mutations in TBX6, GDF3, DSTYK, and COL11A2, among others, along with CNVs and epigenetic changes. Ongoing research using advanced sequencing technologies and functional assays continues to shed light on this complex disorder, offering potential for more targeted therapeutic approaches.

Environmental factors

Maternal factors during pregnancy play a significant role in the pathogenesis of CS. Hypoxia is considered a primary factor, with studies in mouse models showing that hypoxic conditions disrupt the normal formation of embryonic vertebral cartilage, leading to spinal curvature [5]. Other maternal exposures, such as alcohol consumption, vitamin deficiency, and the use of antiepileptic drugs, also interfere with developmental pathways, affecting spinal development [5, 41–44]. Further evidence suggests that prenatal exposure to nano titanium dioxide may cause skeletal abnormalities, indicating the potential influence of environmental toxins on embryonic development [45]. Additionally, correlations between adrenal hypertrophy, hypoxia, and early scoliosis highlight the need for further research into these mechanisms [46]. In conclusion, maternal health and environmental exposures are key contributors to CS development. Ongoing research is essential for better understanding these influences and developing prevention and treatment strategies.

Treatment options for congenital scoliosis

Treatment for CS includes conservative and surgical approaches. Conservative treatments, such as casts and braces, are generally considered for milder cases, while severe deformities often require surgical intervention.

Conservative treatment

Recent studies on conservative treatment have explored its role in controlling the progression of scoliosis in early-onset cases. Parot et al. observed that chest wall abnormalities and spinal scoliosis could be managed without surgery through braces and regular monitoring, thereby avoiding surgery and highlighting the importance of follow-up care for potential complications [47]. Braces such as the Milwaukee and Boston braces, as demonstrated by Chêneau et al., have shown effectiveness in managing smaller vertebral anomalies in patients with congenital scoliosis [48].

Kawakami et al. demonstrated that ARCBT significantly reduced the progression of EOS compared to brace-only treatment (BT), providing an alternative approach for early intervention [49]. Similarly, Wang et al. confirmed that brace treatment could delay CS progression, preserving growth and postponing surgery [50]. Swain et al. introduced a flexible spinal orthosis for children, offering an innovative and comfortable treatment option [51]. Personalized 3D-printed braces, when combined with traditional physical therapy, were reported by Jin et al. to be 100% effective for adults with newly developed scoliosis [52]. Caredda et al. highlighted the effectiveness of orthotic braces, such as the Milwaukee and Boston braces, in managing CS caused by complete hemivertebra segmentation, advocating for early brace treatment over observation [53].

These findings emphasize that conservative treatments, particularly casting and bracing, can delay surgery and provide personalized care for CS patients. However, further research is necessary to tailor treatment plans based on individual patient needs and ensure long-term success.

Surgical treatment approaches

Surgery for CS is indicated when conservative treatment fails, symptoms are severe, or the curve progresses rapidly. Surgical methods include fusion, non-fusion, hybrid techniques, and growth modulation. Surgery is generally performed when rapid curve progression occurs despite nearing skeletal maturity. Preoperative evaluation and communication about risks, such as infection or nerve injury, are critical, as are postoperative rehabilitation strategies to improve spinal stability and quality of life.

Innovations like robot-assisted surgery and customized graft materials are enhancing surgical outcomes, with ongoing research focusing on more personalized approaches. Interdisciplinary cooperation remains essential for comprehensive CS management [54].

In situ fusion surgery

Historically, in situ fusion surgery has been used to treat CS, particularly in young children. However, its use has decreased due to limitations such as restricted lung development and a high rate of reoperations (25.6%, according to Goldberg) [55–57]. The"Crankshaft Phenomenon", where incomplete fusion leads to worsening scoliosis, is another concern. While effective for minor deformities in younger patients, in situ fusion is now less common, as modern techniques offer more durable results.

Hemivertebra resection short-segment fusion

Hemivertebra resection with short-segment fusion is highly effective for young CS patients (Fig. 1). Studies show that early intervention can reduce the need for long fusions and prevent curve progression [58, 59]. Innovative techniques like the use of titanium cages for anterior support have improved corrective outcomes while minimizing complications [60–62]. Research has demonstrated significant improvements in scoliosis correction without major complications, especially when the surgery is performed early [63–66].

Fig. 1.

Posterior hemivertebra resection and scoliosis correction (T8–T12) in a 3-year-old girl diagnosed with a congenital T10 hemivertebra. a Preoperative anteroposterior (AP) radiograph showing the congenital hemivertebra at T10. b Preoperative lateral radiograph demonstrating sagittal alignment. c Immediate postoperative AP radiograph revealing satisfactory coronal correction. d Immediate postoperative lateral radiograph showing maintained sagittal alignment. e AP radiograph at 2-year follow-up, demonstrating sustained coronal correction. f Lateral radiograph at 2-year follow-up, confirming preserved sagittal alignment

Growth rod technology

Growth rods, including single and dual systems, allow for spinal correction while enabling continued growth (Fig. 2). Dual growth rod (DGR) technology offers improved stability and fewer complications compared to single rods [67]. Studies have shown excellent outcomes with this approach, including curve correction and increased spinal height, particularly with frequent adjustments [68–70].

Fig. 2.

Posterior spinal correction with Isola growth-friendly instrumentation and bone grafting in a 4-year-old girl diagnosed with congenital scoliosis. a Preoperative anteroposterior (AP) radiograph showing congenital spinal curvature. b Preoperative lateral radiograph illustrating sagittal alignment. c Immediate postoperative AP radiograph demonstrating improved coronal correction. d Immediate postoperative lateral radiograph confirming maintained sagittal balance

The Shilla technique focuses on dynamic realignment of the deformity’s apex to reduce corrective loss. It has been compared to traditional growth rod systems for effectiveness [71]. The modified Luque Trolley system is another self-growing rod technique that avoids the need for repeat surgeries [72].

MCGR has transformed EOS treatment, reducing the need for repeated surgeries while maintaining correction [73]. However, some studies show no significant improvement in Health-Related Quality of Life (HRQoL) [74]. Despite this, MCGR remains a promising alternative, offering long-term correction with fewer complications [75–79]. Cost analyses also suggest that MCGR may reduce cumulative healthcare costs compared to traditional methods [80]. While there are varying opinions, MCGR represents a significant advance in EOS management.

Hybrid technique

The HT is an advanced surgical method developed to overcome limitations of traditional dual growing rods (TDGR) in treating severe, long-segment congenital early-onset scoliosis (CEOS). Key issues with TDGR, such as insufficient main curve correction, persistent apical deformities, inadequate sagittal plane control, and frequent implant failures due to asymmetric growth forces, are mitigated by HT. Combining posterior osteotomy or vertebrectomy with short fusion and dual growing rods, HT improves deformity correction, especially at the apex, while reducing mechanical complications and preserving spinal growth. Initially proposed by Wang et al., HT demonstrated significant improvements in scoliosis correction (from 81.4° to 40.1°) and spinal growth (T1–S1 length increased by 1.23 cm/year), with a low complication rate over a 53.3-month follow-up [9]. Sun et al. further confirmed its success, reporting a major curve correction from 86.4° to 37.3° and consistent growth (1.31 cm/year), with fewer complications in dual GR cases [81]. Another study by Sun et al. comparing HT to TDGR showed superior Cobb angle correction, thoracic kyphosis improvement, and fewer complications such as rod breakage in the HT group [82]. Most recently, Wang et al. affirmed HT’s superior apical control and deformity correction, though noting a slightly higher risk of dural and neurological complications compared to TDGR [83]. Overall, HT has been proven effective for severe CEOS, offering enhanced deformity correction and fewer mechanical complications while maintaining spinal growth.

Apical control techniques

The TDGR technique, combined with apical control techniques (ACTs), has been utilized to improve deformity correction in EOS by addressing apical vertebral rotation and enhancing curve control. Kamaci et al. demonstrated the efficacy of the TDGR in controlling both coronal and sagittal plane deformities while improving apical vertebral rotation [84]. Building on this, Zhao et al. explored the combination of TDGR and Apical Convex Control Pedicle Screws (ACPS), showing superior correction of apex deformity with fewer complications compared to TDGR alone [85]. Wang et al. confirmed that ACT, including hybrid techniques, could significantly enhance curve correction without hindering spinal growth, while maintaining lower complication rates [86]. Yang et al. further supported the combined approach, showing that TDGR with apical pedicle screws improved primary curve correction and spinal growth in EOS patients [87]. Wang et al. expanded on this by comparing outcomes of CEOS patients treated with TDGR and ACT, finding better deformity correction and fewer mechanical complications [88]. Li et al. confirmed these findings, demonstrating that TDGR with ACT provided better apical control and reduced complications, leading to fewer revision surgeries and avoidance of final fusion [89].

Conclusions

CS is a multifactorial disorder rooted in disrupted vertebral development during embryogenesis. Genetic studies implicate mutations in TBX6, GDF3, DSTYK, and COL11A2, alongside CNVs and epigenetic dysregulation, while environmental triggers such as maternal hypoxia and toxin exposure exacerbate risk. Diagnosis leverages advanced imaging and genetic sequencing, with MRI critical for detecting spinal cord anomalies. Conservative therapies, including innovative bracing (e.g., ARCBT, 3D-printed orthoses), effectively manage mild cases, delaying surgical needs. For severe deformities, surgical advancements like HT and MCGR offer superior correction and growth preservation. HT, combining osteotomy with growth rods, achieves 50% Cobb angle reduction and 1.23 cm/year spinal growth, outperforming traditional methods. MCGR minimizes repeat surgeries but requires further quality-of-life assessments. Apical control strategies and robotics enhance precision, reducing complications. Future research must address gene–environment interactions, and long-term outcomes of emerging therapies. A multidisciplinary approach—integrating genetics, imaging, and personalized interventions—is vital to improving prognosis for CS patients. Clinicians should prioritize early diagnosis, tailored treatment algorithms, and lifelong surveillance to mitigate progression and associated comorbidities.

Abbreviations

ACPS

Apical convex control pedicle screws

ACTs

Apical control techniques

ARCBT

Alternating cast and brace treatment

BT

Brace-only treatment

CEOS

Congenital early-onset scoliosis

CS

Congenital scoliosis

CT

Computed tomography

CNVs

Copy number variations

DGR

Dual growth rod

EOS

Early-onset scoliosis

HRQoL

Health-related quality of life

HT

Hybrid techniques

MCGR

Magnetic controlled growth rods

MRI

Magnetic resonance imaging

SNPs

Single nucleotide polymorphisms

TDGR

Traditional dual growing rods

VEPTR

Vertical expandable prosthetic titanium rib

Author contributions

Z.P. developed the research concept and drafted the initial version of the manuscript. H.Z. was in charge of collecting and organizing the figures. S.W. and J.Z. reviewed and approved the final manuscript for submission.

Funding

National Key Research and Development Program of China, 2023YFC2507700; National High Level Hospital Clinical Research Funding, 2022-PUMCH-D-004; CAMS Innovation Fund for Medical Sciences (CIFMS), 2021-I2M-1–051.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study received approval from the Institutional Review Board of Peking Union Medical College Hospital. Written informed consent was provided by the legal guardians of all participating patients. The research was conducted in accordance with the ethical principles outlined in the 1964 Declaration of Helsinki and its later revisions.

Consent for publication

Written consent from the patients’ legal guardians was obtained for the publication of any images included in this study.

Competing interests

The authors declare no competing interests.