Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

Hypoparathyroidism Associated with Benign Thyroid Nodules in DiGeorge-like Syndrome: A Rare Case Report and Literature Review

Author(s): Claudio Spinelli, Marco Ghionzoli, Carla Guglielmo, Giampiero Baroncelli, Nina Tyutyusheva, Alessia Frega, Armando Patrizio*, Poupak Fallahi, Silvia Martina Ferrari and Alessandro Antonelli

Volume 24, Issue 7, 2024

Published on: 17 November, 2023

Page: [850 - 856] Pages: 7

DOI: 10.2174/0118715303274582231102094440

Price: $65

Abstract

Background: DiGeorge-like syndrome (DGLS) is a rare genetic disorder due to the presence of the same classical clinical manifestations of DiGeorge syndrome (DGS) without its typical deletion. In the DGLS phenotype, hypoparathyroidism seldom occurs and is considered rare. In DGS, hypocalcemia affects up to 70% of patients, and a considerable share often has asymptomatic thyroid abnormalities.

Case Presentation: In this study, we describe an unusual case of a 16-year-old patient with DGLS due to a duplication of 365 kb in the 20p11.22 region, affected by hypoparathyroidism associated with thyroid nodule. The intraoperative parathyroid evaluation ruled out agenesis as a cause of hypoparathyroidism. In addition, we carried out a thorough literature review from 2010 to 2023 of DGLS cases using specific keywords, such as “22q11.2 deletion syndrome”, “Di- George-like Syndrome”, “hypoparathyroidism”, “thyroid”, and “children”, analyzing 119 patients with DGLS.

Conclusion: Interestingly enough, the present case represents, to our knowledge, the first report of a patient with DGLS associated with hypoparathyroidism and the presence of thyroid nodules where an intraoperative observation reported a non-functional parathyroid gland.

« Previous Next »
Graphical Abstract

[1]
Cortés-Martín, J.; Peñuela, N.L.; Sánchez-García, J.C.; Montiel-Troya, M.; Díaz-Rodríguez, L.; Rodríguez-Blanque, R. Deletion Syndrome 22q11.2: A Systematic Review. Children (Basel), 2022, 9(8), 1168.
[http://dx.doi.org/10.3390/children9081168] [PMID: 36010058]
[2]
McDonald-McGinn, D.M.; Sullivan, K.E. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/] velocardiofacial syndrome). Medicine (Baltimore), 2011, 90(1), 1-18.
[http://dx.doi.org/10.1097/MD.0b013e3182060469] [PMID: 21200182]
[3]
Cirillo, E.; Prencipe, M.R.; Giardino, G.; Romano, R.; Scalia, G.; Genesio, R.; Nitsch, L.; Pignata, C. Clinical phenotype, immunological abnormalities, and genomic findings in patients with DiGeorge spectrum phenotype without 22q11.2 deletion. J. Allergy Clin. Immunol. Pract., 2020, 8(9), 3112-3120.
[http://dx.doi.org/10.1016/j.jaip.2020.06.051] [PMID: 32668295]
[4]
Alberio, A.M.Q.; Legitimo, A.; Bertini, V.; Baroncelli, G.I.; Costagliola, G.; Valetto, A.; Consolini, R. Clinical, immunological, and genetic findings in a cohort of patients with the DiGeorge phenotype without 22q11.2 deletion. J. Clin. Med., 2022, 11(7), 2025.
[http://dx.doi.org/10.3390/jcm11072025] [PMID: 35407632]
[5]
Koczkowska, M. Wierzba, J.; Śmigiel, R.; Sąsiadek, M.; Cabała, M.; Ślężak, R.; Iliszko, M.; Kardaś, I.; Limon, J.; Lipska-Ziętkiewicz, B.S. Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome. J. Appl. Genet., 2017, 58(1), 93-98.
[http://dx.doi.org/10.1007/s13353-016-0366-1] [PMID: 27629806]
[6]
Rakonjac, M.; Cuturilo, G.; Stevanovic, M.; Jelicic, L.; Subotic, M.; Jovanovic, I.; Drakulic, D. Differences in speech and language abilities between children with 22q11.2 deletion syndrome and children with phenotypic features of 22q11.2 deletion syndrome but without microdeletion. Res. Dev. Disabil., 2016, 55, 322-329.
[http://dx.doi.org/10.1016/j.ridd.2016.05.006] [PMID: 27235769]
[7]
McDonald-McGinn, D.M.; Sullivan, K.E.; Marino, B.; Philip, N.; Swillen, A.; Vorstman, J.A.S.; Zackai, E.H.; Emanuel, B.S.; Vermeesch, J.R.; Morrow, B.E.; Scambler, P.J.; Bassett, A.S. 22q11.2 deletion syndrome. Nat. Rev. Dis. Primers, 2015, 1(1), 15071.
[http://dx.doi.org/10.1038/nrdp.2015.71] [PMID: 27189754]
[8]
Swillen, A.; McDonald-McGinn, D. Developmental trajectories in 22q11.2 deletion syndrome. Am. J. Med. Genet. C. Semin. Med. Genet., 2015, 169(2), 172-181.
[http://dx.doi.org/10.1002/ajmg.c.31435] [PMID: 25989227]
[9]
Levy-Shraga, Y.; Gothelf, D.; Goichberg, Z.; Katz, U.; Somech, R.; Pinhas-Hamiel, O.; Modan-Moses, D. Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome. Am. J. Med. Genet. A., 2017, 173(5), 1301-1308.
[http://dx.doi.org/10.1002/ajmg.a.38175] [PMID: 28421700]
[10]
Ricci, S.; Sarli, W.M.; Lodi, L.; Canessa, C.; Lippi, F.; Azzari, C.; Stagi, S. Characterization of autoimmune thyroid disease in a cohort of 73 paediatric patients affected by 22q11.2 deletion syndrome: Longitudinal single-centre study. Genes (Basel), 2022, 13(9), 1552.
[http://dx.doi.org/10.3390/genes13091552] [PMID: 36140720]
[11]
Torregrossa, L.; Poma, A.M.; Macerola, E.; Rago, T.; Vignali, P.; Romani, R.; Proietti, A.; Di Stefano, I.; Scuotri, G.; Ugolini, C.; Basolo, A.; Antonelli, A.; Materazzi, G.; Santini, F.; Basolo, F. The Italian Consensus for the Classification and Reporting of Thyroid Cytology: Cytohistologic and molecular correlations on 37,371 nodules from a single institution. Cancer Cytopathol., 2022, 130(11), 899-912.
[http://dx.doi.org/10.1002/cncy.22618] [PMID: 35789118]
[12]
Morcel, K.; Watrin, T.; Pasquier, L.; Rochard, L.; Le Caignec, C.; Dubourg, C.; Loget, P.; Paniel, B.J.; Odent, S.; David, V.; Pellerin, I.; Bendavid, C.; Guerrier, D. Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci. Orphanet J. Rare Dis., 2011, 6(1), 9.
[http://dx.doi.org/10.1186/1750-1172-6-9] [PMID: 21406098]
[13]
Bernstock, J.D.; Totten, A.H.; Elkahloun, A.G.; Johnson, K.R.; Hurst, A.C.; Goldman, F.; Groves, A.K.; Mikhail, F.M.; Atkinson, T.P. Recurrent microdeletions at chromosome 2p11.2 are associated with thymic hypoplasia and features resembling DiGeorge syndrome. J. Allergy Clin. Immunol., 2020, 145(1), 358-367.e2.
[http://dx.doi.org/10.1016/j.jaci.2019.09.020] [PMID: 31600545]
[14]
Brunet, A.; Armengol, L.; Heine, D.; Rosell, J.; García-Aragonés, M.; Gabau, E.; Estivill, X.; Guitart, M. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1. BMC Med. Genet., 2009, 10(1), 144.
[http://dx.doi.org/10.1186/1471-2350-10-144] [PMID: 20030804]
[15]
Cuturilo, G.; Menten, B.; Krstic, A.; Drakulic, D.; Jovanovic, I.; Parezanovic, V.; Stevanovic, M. 4q34.1–q35.2 deletion in a boy with phenotype resembling 22q11.2 deletion syndrome. Eur. J. Pediatr., 2011, 170(11), 1465-1470.
[http://dx.doi.org/10.1007/s00431-011-1533-3] [PMID: 21833498]
[16]
Busse, T.; Graham, J.M., Jr; Feldman, G.; Perin, J.; Catherwood, A.; Knowlton, R.; Rappaport, E.F.; Emanuel, B.; Driscoll, D.A.; Saitta, S.C. High-Resolution genomic arrays identify CNVs that phenocopy the chromosome 22q11.2 deletion syndrome. Hum. Mutat., 2011, 32(1), 91-97.
[http://dx.doi.org/10.1002/humu.21395] [PMID: 21120947]
[17]
Tham, E.; Lindstrand, A.; Santani, A.; Malmgren, H.; Nesbitt, A.; Dubbs, H.A.; Zackai, E.H.; Parker, M.J.; Millan, F.; Rosenbaum, K.; Wilson, G.N.; Nordgren, A. Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features. Am. J. Hum. Genet., 2015, 96(3), 507-513.
[http://dx.doi.org/10.1016/j.ajhg.2015.01.016] [PMID: 25728777]
[18]
Cirillo, E.; Giardino, G.; Gallo, V.; Galasso, G.; Romano, R.; D’Assante, R.; Scalia, G.; Del Vecchio, L.; Nitsch, L.; Genesio, R.; Pignata, C. DiGeorge-like syndrome in a child with a 3p12.3 deletion involving MIR4273 gene born to a mother with gestational diabetes mellitus. Am. J. Med. Genet. A., 2017, 173(7), 1913-1918.
[http://dx.doi.org/10.1002/ajmg.a.38242] [PMID: 28436605]
[19]
Hong, N.; Zhang, E.; Wang, Q.; Zhang, X.; Li, F.; Fu, Q.; Xu, R.; Yu, Y.; Chen, S.; Xu, Y.; Sun, K. A loss-of-function mutation p.T52S in RIPPLY3 is a potential predisposing genetic risk factor for Chinese Han conotruncal heart defect patients without the 22q11.2 deletion/duplication. J. Transl. Med., 2018, 16(1), 260.
[http://dx.doi.org/10.1186/s12967-018-1633-1] [PMID: 30241482]
[20]
Wu, W.; Kong, X.; Jia, Y.; Jia, Y.; Ou, W.; Dai, C.; Li, G.; Gao, R. An overview of PAX1: Expression, function and regulation in development and diseases. Front. Cell Dev. Biol., 2022, 101051102
[http://dx.doi.org/10.3389/fcell.2022.1051102] [PMID: 36393845]
[21]
Carter, S.; Fellows, B.J.; Gibson, K.; Bicknell, L.S. Extending the PAX1 spectrum: A dominantly inherited variant causes oculo-auriculo-vertebral syndrome. Eur. J. Hum. Genet., 2022, 30(10), 1178-1181.
[http://dx.doi.org/10.1038/s41431-022-01154-2] [PMID: 35879406]
[22]
Patil, S.J.; Das Bhowmik, A.; Bhat, V.; Satidevi Vineeth, V.; Vasudevamurthy, R.; Dalal, A. Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene. Am. J. Med. Genet. A., 2018, 176(5), 1200-1206.
[http://dx.doi.org/10.1002/ajmg.a.38659] [PMID: 29681087]
[23]
Yamazaki, Y.; Urrutia, R.; Franco, L.M.; Giliani, S.; Zhang, K.; Alazami, A.M.; Dobbs, A.K.; Masneri, S.; Joshi, A.; Otaizo-Carrasquero, F.; Myers, T.G.; Ganesan, S.; Bondioni, M.P.; Ho, M.L.; Marks, C.; Alajlan, H.; Mohammed, R.W.; Zou, F.; Valencia, C.A.; Filipovich, A.H.; Facchetti, F.; Boisson, B.; Azzari, C.; Al-Saud, B.K.; Al-Mousa, H.; Casanova, J.L.; Abraham, R.S.; Notarangelo, L.D. PAX1 is essential for development and function of the human thymus. Sci. Immunol., 2020, 5(44)eaax1036
[http://dx.doi.org/10.1126/sciimmunol.aax1036] [PMID: 32111619]
[24]
McGaughran, J.M.; Oates, A.; Donnai, D.; Read, A.P.; Tassabehji, M. Mutations in PAX1 may be associated with Klippel–Feil syndrome. Eur. J. Hum. Genet., 2003, 11(6), 468-474.
[http://dx.doi.org/10.1038/sj.ejhg.5200987] [PMID: 12774041]
[25]
Wallin, J.; Wilting, J.; Koseki, H.; Fritsch, R.; Christ, B.; Balling, R. The role of Pax-1 in axial skeleton development. Development, 1994, 120(5), 1109-1121.
[http://dx.doi.org/10.1242/dev.120.5.1109] [PMID: 8026324]
[26]
Sivakamasundari, V.; Kraus, P.; Sun, W.; Hu, X.; Lim, S.L.; Prabhakar, S.; Lufkin, T. A developmental transcriptomic analysis of Pax1 and Pax9 in embryonic intervertebral disc development. Biol. Open, 2017, 6(2), 187-199.
[PMID: 28011632]
[27]
Fang, C.; Wang, S.Y.; Liou, Y.L.; Chen, M.H.; Ouyang, W.; Duan, K.M. The promising role of PAX1 (aliases: HUP48, OFC2) gene methylation in cancer screening. Mol. Genet. Genomic Med., 2019, 7(3)e506
[http://dx.doi.org/10.1002/mgg3.506] [PMID: 30636379]
[28]
Sulaiman, L.; Juhlin, C.C.; Nilsson, I.L.; Fotouhi, O.; Larsson, C.; Hashemi, J. Global and gene-specific promoter methylation analysis in primary hyperparathyroidism. Epigenetics, 2013, 8(6), 646-655.
[http://dx.doi.org/10.4161/epi.24823] [PMID: 23764768]
[29]
Singh, P.; Bhadada, S.K.; Arya, A.K.; Saikia, U.N.; Sachdeva, N.; Dahiya, D.; Kaur, J.; Brandi, M.L.; Rao, S.D. Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis. J. Clin. Endocrinol. Metab., 2022, 107(2), e783-e792.
[http://dx.doi.org/10.1210/clinem/dgab626] [PMID: 34453169]
[30]
Kokenge, F. The history of the parathyroid glands - A contribution to the history of the parathyroid glands, their anatomy, function and their diseases. Laryngorhinootologie, 2022, 101(8), 646-651.
[http://dx.doi.org/10.1055/a-1076-9489] [PMID: 35915903]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy