Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels

Delagrange, Marine; Rousseau, Vanessa; Cessans, Catie; Pienkowski, Catherine; Oliver, Isabel; Jouret, Béatrice; Cartault, Audrey; Diene, Gwénaëlle; Tauber, Maïthé; Salles, Jean‐Pierre; Yart, Armelle; Edouard, Thomas

doi:10.1016/j.bone.2021.116170

Cited by 14 publications

(27 citation statements)

References 47 publications

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“…There was also a significant positive association ( β =0.3855, P <0.001) between BMD and SMI, suggesting a lower rate of osteoporosis among individuals with higher SMI or lower BFP. This result is consistent with most prior studies ( 16 , 33 , 34 ).…”

Section: Discussionsupporting

confidence: 94%

Retrospective analysis of the relationship between bone mineral density and body composition in a health check-up Chinese population

Huang²,

Gong³

et al. 2022

Front. Endocrinol.

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PurposeThis study was designed to explore the relationship between bone mineral density (BMD) and body composition indicators in Chinese adults (≥50 years) in order to provide a scientific basis for optimal bone health management.MethodIndividuals ≥50 years old who received physical examinations and routine check-ups at the Health Management Research Institute of PLA General Hospital from September 2014 through March 2022 were included as research subjects in this study. Basic clinical and demographic information were recorded for all subjects, along with smoking and drinking status, height and body weight. A panel of routine blood chemistry and metabolite markers were measured, along with lean muscle mass and body fat mass using body composition bioelectrical impedance analysis (BIA). Body mass index (BMI), body fat percentage (BFP), skeletal muscle mass index (SMI), and bone mineral density (BMD) were calculated for all individuals. For comparative analysis, individuals were grouped based on their BMI, BFP, SMI and BMD T-score. Follow-up examinations were performed in a cohort of 1,608 individuals matched for age, sex, smoking and drinking history for ≥5 years,ResultsIn this large cross-sectional study, age, smoking, homocysteine (Hcy) and blood glucose levels were established as independent risk factors for osteoporosis. Multi-factor logistic regression analysis showed that age, sex, BMI, intact parathyroid hormone (iPTH), SMI, BFP, smoking, blood levels of inorganic phosphate (P) and K+ were all significantly associated with osteoporosis risk (P<0.05). A subset of these factors- BMI, SMI, BFP and K+, were determined to be protective. In the cohort followed for ≥5 years, SMI and BMD decreased while BFP and BMI increased significantly (P<0.001) over time.ConclusionRisk of osteoporosis may be reduced by increasing body weight, particularly lean muscle mass, while simultaneously controlling BFP.

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Section: Discussionsupporting

confidence: 94%

Retrospective analysis of the relationship between bone mineral density and body composition in a health check-up Chinese population

Huang²,

Gong³

et al. 2022

Front. Endocrinol.

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“…Physical and radiography examinations of the child showed a short neck, scoliosis, valgus scapula, cubitus valgus and genu valgum, and thorax malformation, all of which were consistent with patients with PTPN11 mutations (15)(16)(17). However, the concurrent SEC24D gene mutation also played a major role in the skeletal development of this patient, such as wormain bones, pelvis malformation and possible low bone mass.…”

Section: Discussionsupporting

confidence: 62%

Case report: Clinical manifestations and genotype analysis of a child with PTPN11 and SEC24D mutations

et al. 2022

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BackgroundThe PTPN11 gene, located at 12q24. 13, encodes protein tyrosine phosphatase 2C. Mutations in the PTPN11 gene can lead to various phenotypes, including Noonan syndrome and LEOPARD syndrome. The SEC24D gene is located at 4q26 and encodes a component of the COPII complex, and is closely related to endoplasmic reticulum protein transport. Mutations in SEC24D can lead to Cole-Carpenter syndrome-2. To date, dual mutations in these two genes have not been reported in the literature.MethodsWe report a patient with short stature and osteogenesis imperfecta as the primary clinical manifestation. Other clinical features were peculiar facial features, deafness, and a history of recurrent fractures. Whole exome sequencing was performed on this patient.ResultsAfter whole-exome sequencing, three mutations in two genes were identified that induced protein alterations associated with the patient's phenotype. One was a de novo variant c.1403C>T (p.Thr468Met) on exon 12 of the PTPN11 gene, and the other was a compound heterozygous mutation in the SEC24D gene, a novel variant c.2609_2610delGA (p.Arg870Thrfs*10) on exon 20 and a reported variant c.938G>A (p.Arg313His) on exon 8.ConclusionsConcurrent mutations in PTPN11 and SEC24D induced a phenotype that was significantly different from individual mutations in either PTPN11 or SEC24D gene. Personalized genetic analysis and interpretation could help us understand the patient's etiology and hence develop treatments and improve the prognosis of these patients.

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“…The exact cause of the reported increased fracture rate in the nondysplastic bones in some individuals with NF1 is not known. There are multiple studies that show reduced bone density in NF1 (Armstrong et al, 2013;Brunetti-Pierri et al, 2008;Caffarelli et al, 2010;Dulai et al, 2007;Heervä, Koffert, et al, 2012;Illés, Halmai, de Jonge, & Dubousset, 2001;Kuorilehto et al, 2005;Lammert et al, 2005;Stevenson et al, 2005;Stevenson et al, 2007;Tucker et al, 2009;Yilmaz, Ozmen, Bora Goksan, & Eskiyurt, 2007), and this is also observed in some of the other RASopathies (Delagrange et al, 2021;Leoni et al, 2014;…”

Section: Neurofibromatosis Typementioning

confidence: 93%

“…Although the musculoskeletal system is affected, bone health in NS has not been adequately investigated. Only a few studies described reduced BMD /bone impairment in NS, and these involved primarily children and hence long-term consequences and risk of fractures during adult age are unknown (Baldassarre, Mussa, Carli, Molinatto, & Ferrero, 2017;Choudhry et al, 2012;Delagrange et al, 2021;Noordam et al, 2002;Stevenson, Schwarz, et al, 2011). concentrations (Camacho et al, 2020).…”

Section: Noonan Syndromementioning

confidence: 99%

Bone health in RASopathies

Stevenson

Viscogliosi

Leoni

2022

American J of Med Genetics Pt C

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The RASopathies are a group of disorders due to pathogenic variants in genes involved in the Ras/MAPK pathway, many of which have overlapping clinical features (e.g., neurofibromatosis type 1, Costello syndrome, cardiofaciocutaneous syndrome and Noonan syndrome) including musculoskeletal manifestations. Osteopenia and osteoporosis are reported in many of the RASopathies suggesting a shared pathogenesis. Even though osteopenia and osteoporosis are often detected and fractures have been reported, the clinical impact of bone mineralization defects on the skeleton of the various syndromes is poorly understood. Further knowledge of the role of the Ras/MAPK pathway on the bone cellular function, and more detailed musculoskeletal phenotyping will be critical in helping to develop therapies to improve bone health in the RASopathies.

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Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels

Cited by 14 publications

References 47 publications

Retrospective analysis of the relationship between bone mineral density and body composition in a health check-up Chinese population

Retrospective analysis of the relationship between bone mineral density and body composition in a health check-up Chinese population

Case report: Clinical manifestations and genotype analysis of a child with PTPN11 and SEC24D mutations

Bone health in RASopathies

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