Endocrine system involvement in patients with RASopathies: A case series.
CFC
RASopathies
autoimmunity
bone mineral density
vitamin D
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2022
2022
Historique:
received:
28
08
2022
accepted:
26
10
2022
entrez:
9
12
2022
pubmed:
10
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies. 72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups. The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.
Sections du résumé
Background and Objectives
Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies.
Study Design
72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in
Results
Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups.
Conclusions
The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.
Identifiants
pubmed: 36483002
doi: 10.3389/fendo.2022.1030398
pmc: PMC9724702
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1030398Informations de copyright
Copyright © 2022 Siano, Pivonello, Salerno, Falco, Mauro, De Brasi, Klain, Sestito, De Luca, Pinna, Simeoli, Concolino, Mainolfi, Mannarino, Strisciuglio, Tartaglia and Melis.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Arch Dis Child. 1992 Feb;67(2):178-83
pubmed: 1543375
J Multidiscip Healthc. 2022 Jun 02;15:1277-1296
pubmed: 35677617
Mol Cell Biol. 2010 May;30(10):2498-507
pubmed: 20308328
Endocr Relat Cancer. 2012 Nov 19;19(6):817-25
pubmed: 23089139
Sci Rep. 2022 Mar 14;12(1):4368
pubmed: 35288591
Arch Dis Child. 1982 Jan;57(1):13-7
pubmed: 6121534
J Clin Invest. 2006 Nov;116(11):2880-91
pubmed: 17053831
Mol Genet Metab. 2008 May;94(1):105-11
pubmed: 18289904
J Clin Endocrinol Metab. 2005 Sep;90(9):5377-81
pubmed: 15985475
Pediatr Res. 2008 Jun;63(6):697-701
pubmed: 18317233
Clin Cases Miner Bone Metab. 2012 Sep;9(3):170-8
pubmed: 23289033
Am J Med Genet A. 2017 Mar;173(3):692-698
pubmed: 28211980
Nat Genet. 2009 Sep;41(9):1022-6
pubmed: 19684605
Osteoporos Int. 2005 Aug;16(8):928-36
pubmed: 15551055
Hum Mol Genet. 2018 Jul 1;27(13):2276-2289
pubmed: 29659837
Am J Med Genet A. 2012 May;158A(5):1077-82
pubmed: 22488759
Bone. 2010 Sep;47(3):583-90
pubmed: 20541045
Am J Med Genet A. 2016 Jun;170(6):1525-31
pubmed: 27038324
J Pediatr Endocrinol Metab. 2008 Nov;21(11):1079-84
pubmed: 19189703
Osteoporos Int. 2001;12(10):823-7
pubmed: 11716184
Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):161-79
pubmed: 21396583
Am J Med Genet A. 2013 Nov;161A(11):2756-61
pubmed: 24124081
Curr Opin Endocrinol Diabetes Obes. 2018 Feb;25(1):67-73
pubmed: 29120925
J Clin Endocrinol Metab. 2015 May;100(5):1780-4
pubmed: 25955324
J Adolesc Health. 2003 Jan;32(1):94-7
pubmed: 12507808
Dis Model Mech. 2011 Mar;4(2):228-39
pubmed: 21068439
J Med Genet. 1994 Jun;31(6):468-70
pubmed: 7915331
Nature. 2013 Jul 25;499(7459):491-5
pubmed: 23863940
J Clin Endocrinol Metab. 2006 Jan;91(1):300-6
pubmed: 16263833
Bone. 2005 May;36(5):793-802
pubmed: 15804420
Am J Med Genet A. 2020 Nov;182(11):2797-2799
pubmed: 32845069
Mol Genet Metab. 2012 Jun;106(2):237-40
pubmed: 22551697
Clin Genet. 2011 Dec;80(6):566-73
pubmed: 21204800
J Pediatr Orthop. 2007 Jun;27(4):472-5
pubmed: 17513973
Arch Androl. 1994 Mar-Apr;32(2):135-40
pubmed: 7909426
Eur Urol. 1981;7(5):274-7
pubmed: 6113962
J Pediatr Endocrinol Metab. 2011;24(3-4):169-74
pubmed: 21648285
Am J Hum Genet. 2020 Sep 3;107(3):499-513
pubmed: 32721402
Curr Genet Med Rep. 2016 Sep;4(3):57-64
pubmed: 27942422
Am J Hum Genet. 2006 Feb;78(2):279-90
pubmed: 16358218
World J Urol. 2009 Aug;27(4):513-9
pubmed: 19352683
Orphanet J Rare Dis. 2021 Oct 2;16(1):410
pubmed: 34600590
J Med Genet. 2006 Oct;43(10):810-3
pubmed: 16571643
Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15436-41
pubmed: 19706403
J Pediatr. 2007 Jan;150(1):83-8
pubmed: 17188620
Eur J Endocrinol. 2016 May;174(5):641-50
pubmed: 26903553
Mol Syndromol. 2010 Feb;1(1):2-26
pubmed: 20648242
Int J Behav Nutr Phys Act. 2011 Oct 21;8:115
pubmed: 22018588
Eur J Pediatr. 1988 Dec;148(3):220-7
pubmed: 3215198
Lancet. 2013 Jan 26;381(9863):333-42
pubmed: 23312968
Eur J Endocrinol. 2011 Jul;165(1):137-44
pubmed: 21551165
J Clin Invest. 2011 Mar;121(3):1009-25
pubmed: 21339642
Am J Med Genet A. 2012 Nov;158A(11):2700-6
pubmed: 22887833
J Pediatr Endocrinol Metab. 2003 Feb;16(2):217-8
pubmed: 12713260
J Pediatr. 1973 Aug;83(2):237-40
pubmed: 4123925
J Pediatr. 2016 Mar;170:322-4
pubmed: 26778095
Annu Rev Genomics Hum Genet. 2013;14:355-69
pubmed: 23875798
Pediatr Endocrinol Rev. 2019 May;16(Suppl 2):465-470
pubmed: 31115198
Arch Dis Child. 2007 Feb;92(2):128-32
pubmed: 16990350
Hum Mol Genet. 2019 Jan 1;28(1):74-83
pubmed: 30239744
J Med Genet. 2006 Nov;43(11):833-42
pubmed: 16825433
Mol Genet Metab. 2014 Jan;111(1):41-5
pubmed: 24246682
Eur J Endocrinol. 2018 Dec 1;179(6):409-418
pubmed: 30325180
Sci Rep. 2015 Aug 12;5:12982
pubmed: 26265072
Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4257-62
pubmed: 22371576