Impact of pathogenic<i>FBN1</i>variant types on the development of severe scoliosis in patients with Marfan syndrome

Taniguchi, Yuki; Takeda, Norifumi; Inuzuka, Ryo; Matsubayashi, Yoshitaka; Kato, So; Doi, Tôru; Yagi, Hiroki; Yamauchi, Haruo; Ando, Masahiko; Oshima, Yasushi; Tanaka, Sakae

doi:10.1136/jmedgenet-2021-108186

Cited by 6 publications

(6 citation statements)

References 42 publications

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“…Because several studies have demonstrated genotype-phenotype correlations in MFS to date, the phenotype of paraspinal muscles may also differ from case to case with different FBN1 variants. [44–48] Fifth, due to the same reason, the relationship between the severity of spinal deformity and the condition of paraspinal muscles was not investigated, which could reinforce our hypothesis.…”

Section: Discussionmentioning

confidence: 85%

Reduced volume and altered composition of paraspinal muscles in Marfan syndrome: A retrospective cohort study

Yoshida,

Doi,

Oka

et al. 2023

Medicine

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Retrospective cohort study. Spinal deformities in patients with Marfan syndrome (MFS) are distinct from those in patients with idiopathic scoliosis (IS). It is more prone to progression and more likely to present with sagittal malalignment than IS. However, the etiology of this characteristic spinal deformity in MFS remains unclear. This study aimed to determine the spinal musculature characteristics in patients with MFS on the hypothesis that the paraspinal muscles of patients with MFS would be qualitatively or quantitatively different from those of patients with IS. Seventeen consecutive patients with MFS aged 25 years or younger undergoing surgery for scoliosis in our hospital were compared with age- and sex-matched patients with IS undergoing surgery for scoliosis. The body size-adjusted relative cross-sectional area (rCSA), fatty infiltration ratio (FI%), and relative functional cross-sectional area (rFCSA) of the psoas muscles (PM) and paravertebral muscles (PVM) at L3/4 and L4/5 were measured using preoperative T2-weighted magnetic resonance imaging. Functional CSA was defined as total CSA minus the fatty infiltration area of each muscle and rFCSA was calculated as the body size-adjusted functional CSA. The rCSA of the PM at L3/4 and L4/5 was significantly smaller in the MFS group than in the IS group (L3/4, P = .021; L4/5, P = .002). The FI% of the PM at L4/5 was significantly higher in the MFS group (P = .044). Consequently, the rFCSA of the PM at L3/4 and L4/5 and the rFCSA of the PVM at L3/4 in the MFS group were significantly smaller than those in the IS group (PM at L3/4, P = .021; PM at L4/5, P = .001; PVM at L3/4, P = .025). Compared with patients with IS, patients with MFS exhibited significantly decreased body-size-adjusted CSA of the PM and reduced body-size-adjusted functional CSA of the PVM and PM. These findings may partially explain the characteristics of distinctive spinal deformities in patients with MFS.

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Section: Discussionmentioning

confidence: 85%

Reduced volume and altered composition of paraspinal muscles in Marfan syndrome: A retrospective cohort study

Yoshida,

Doi,

Oka

et al. 2023

Medicine

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“…Early studies on genotype-phenotype correlation began with the susceptibility to EL and aortic dilatation ( Schrijver et al, 2002 ; Loeys et al, 2004 ). Later studies expanded the studied phenotypes to almost all aspects of the MFS manifestations, including the axial length of the eyeball ( Chen et al, 2021a ), astigmatism of the cornea ( Guo et al, 2021 ), severity of scoliosis ( Taniguchi et al, 2021 ), and incidence of ventricular tachycardia ( Aydin et al, 2013 ). Meanwhile, detailed parameters were applied instead of a broad description of aortic events, such as the aortic root diameters and the aortic stiffness ( Franken et al, 2017 ; Salvi et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Scoliosis is a sideways curvature of the spine if a Cobb’s angle exceeds 20° on radiographs ( Sponseller et al, 1995 ), which is found in 45%–54% of MFS patients ( Faivre et al, 2007 ; Arnaud et al, 2021a ). Taniguchi et al dissect the genotype-phenotype correlations in MFS already having scoliosis and found that HI variants and variants in the neonatal region were associated with severe scoliosis and faster progression ( Taniguchi et al, 2021 ). Higher systematic scores were observed in the HI group than that in the DN group ( Stark et al, 2020 ).…”

Section: Genotype and Clinical Manifestationsmentioning

confidence: 99%

Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance

2022

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Marfan syndrome (MFS, OMIM: 154700) is a heritable multisystemic disease characterized by a wide range of clinical manifestations. The underlying molecular defect is caused by variants in the FBN1. Meanwhile, FBN1 variants are also detected in a spectrum of connective tissue disorders collectively termed as ‘type I fibrillinopathies’. A multitude of FBN1 variants is reported and most of them are unique in each pedigree. Although MFS is being considered a monogenic disorder, it is speculated that the allelic heterogeneity of FBN1 variants contributes to various manifestations, distinct prognoses, and differential responses to the therapies in affected patients. Significant progress in the genotype–phenotype correlations of MFS have emerged in the last 20 years, though, some of the associations were still in debate. This review aims to update the recent advances in the genotype-phenotype correlations of MFS and related fibrillinopathies. The molecular bases and pathological mechanisms are summarized for better support of the observed correlations. Other factors contributing to the phenotype heterogeneity and future research directions were also discussed. Dissecting the genotype-phenotype correlation of FBN1 variants and related disorders will provide valuable information in risk stratification, prognosis, and choice of therapy.

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“…However, AADA associated with spinal deformity is unusual in MFS patients. Because of pain and restrictive ventilatory disturbance in patients as a result of spinal deformity, patients with MFS may be at an increased risk of additional cardiopulmonary damage while undergoing a thoracotomy or having repeated pneumothoraxes ( 8 ). Moreover, severe spinal deformity affects surgical intervention, aortic surgery in these patients is challenging.…”

Section: Discussionmentioning

confidence: 99%

Successful management of Stanford type A aortic dissection with severe scoliosis in the setting of Marfan syndrome: a case report

Huang¹,

Yang²,

Liu³

et al. 2022

Ann Transl Med

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Background: Marfan syndrome (MFS) is a connective tissue disorder involving multiple organs. The most severe complications include aortic root dilatation and dissection. In the present report, we provide an uncommon case of acute aortic Stanford type A dissection (AADA) repair with severe scoliosis in an MFS patient and it is even more rare for such surgical treatment to be successfully completed along with holistic management that enables the patient to recover successfully. We offer a reference for future surgical therapy since the specific surgical treatment methods in this case have not been reported in the literature.Case Description: A 40-year-old Chinese female with MFS was rushed to our surgical clinic due to the sudden onset of intense chest pain. Physical examination revealed a diastolic murmur at the aortic valve area, increased arm and pectus carinatum deformity, severe scoliosis, acromicria, arachnodactyly, and planovalgus foot. Subsequently, AADA was discovered through computed tomography scan. In addition, echocardiogram revealed moderate aortic regurgitation and hydropericardium in small amount. Based on revised Ghent criteria, the patient was diagnosed with MFS complicated with aortic dissection. Emergency surgery was successfully performed for repair of the patient's aortic dissection and the diseased aortic valve.Postoperatively, the patient presented with a degree of respiratory insufficiency, However, the respiratory function was not greatly impaired, with good early intervention, such as taking deep breaths and coughing fully, active sputum suction, effective analgesia, ambulation and treadmill exercise. The patient finally recovered completely and was discharged 3 weeks later. Conclusions:We reported on a patient with severe scoliosis who successfully underwent surgical repair of AADA. Our report shows that the application of standard median sternotomy for repairing AADA offers the feasibility of implementation, on the basis of effectively solving various practical problems in the surgery brought about by scoliosis. It has been thoroughly assessed and addressed how the postoperative condition of such patients affects subsequent respiratory function and postoperative recovery. This report further provides a successful clinical reference for the implementation of this type of surgery and the postoperative management of respiratory function.

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Impact of pathogenicFBN1variant types on the development of severe scoliosis in patients with Marfan syndrome

Cited by 6 publications

References 42 publications

Reduced volume and altered composition of paraspinal muscles in Marfan syndrome: A retrospective cohort study

Reduced volume and altered composition of paraspinal muscles in Marfan syndrome: A retrospective cohort study

Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance

Successful management of Stanford type A aortic dissection with severe scoliosis in the setting of Marfan syndrome: a case report

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