Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism

Desirée Deconte; Elisa Pacheco Estima Correia; Géssica Haubert; Vinicius de Souza; Jamile Dutra Correia; Marcia Angelica Peter Maahs; Paulo Ricardo Gazzola Zen; Marilu Fiegenbaum; Rafael Fabiano Machado Rosa

doi:10.1055/s-0040-1705095

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2021; 10(01): 063-069
DOI: 10.1055/s-0040-1705095

Case Report

Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism

Authors

Desirée Deconte

¹Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Elisa Pacheco Estima Correia

²Graduation in Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Géssica Haubert

²Graduation in Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Vinicius de Souza

²Graduation in Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Jamile Dutra Correia

¹Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Marcia Angelica Peter Maahs

³Department of Speech Language Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Paulo Ricardo Gazzola Zen

¹Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

⁴Department of Clinical Medicine, Clinical Genetics, Universidade Federal de Ciências da Saúde de Porto Alegre and Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
Marilu Fiegenbaum

¹Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

⁵Department of Basic Health Sciences, Human Genetics, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
Rafael Fabiano Machado Rosa

¹Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

⁴Department of Clinical Medicine, Clinical Genetics, Universidade Federal de Ciências da Saúde de Porto Alegre and Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil

Abstract

Cherubism is a rare genetic condition characterized by a bone nonneoplastic disease. We aimed to report a 6-year-old girl with cherubism presenting similar cases in the maternal family. However, her mother and grandmother seemed to be asymptomatic. The patient had an enlarged and asymmetric jaw with multiple enlarged cervical lymph nodes that increased in size with time. Sanger sequencing revealed a heterozygous mutation in exon 9 of SH3BP2 not only in the patient but also in her mother. Thus, we observed a variable expression and a probably reduced penetrance within the family, as well as unusual characteristics of the patient (in this case, the asymmetrical involvement of the jaw).

Keywords

cherubism - variable expressivity - asymmetry

Full Text

References

References
1 Dinckan N, Guven Y, Kayserili H, Aktoren O, Uyguner OZ. A novel c.1255G>T (p.D419Y) mutation in SH3BP2 gene causes cherubism in a Turkish family. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114 (05) e42-e46
2 Hershkovitz I, Spigelman M, Sarig R. et al. A possible case of cherubism in a 17th-century Korean mummy. PLoS One 2014; 9 (08) e102441
3 Hyckel P, Berndt A, Schleier P. et al. Cherubism - new hypotheses on pathogenesis and therapeutic consequences. J Craniomaxillofac Surg 2005; 33 (01) 61-68
4 Jones WA. Familial multilocular cystic disease of the jaw. Am J Cancer 1933; 17: 946-950
5 Jones WA. Further observations regarding familial multilocular cystic disease of the jaws. Br J Radiol 1938; 11: 227-241
6 Li CY, Yu SF. A novel mutation in the SH3BP2 gene causes cherubism: case report. BMC Med Genet 2006; 7: 84
7 Papadaki ME, Lietman SA, Levine MA, Olsen BR, Kaban LB, Reichenberger EJ. Cherubism: best clinical practice. Orphanet J Rare Dis 2012; 7 (Suppl 1): S6
8 Von Wowern N. Cherubism: a 36-year long-term follow-up of 2 generations in different families and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 90 (06) 765-772
9 Carvalho VM, Perdigão PF, Pimenta FJ, de Souza PE, Gomez RS, De Marco L. A novel mutation of the SH3BP2 gene in an aggressive case of cherubism. Oral Oncol 2008; 44 (02) 153-155
10 Meng XM, Yu SF, Yu GY. Clinicopathologic study of 24 cases of cherubism. Int J Oral Maxillofac Surg 2005; 34 (04) 350-356
11 Pontes FSC, Ferreira AC, Kato AM. et al. Aggressive case of cherubism: 17-year follow-up. Int J Pediatr Otorhinolaryngol 2007; 71 (05) 831-835
12 Lahiri DK, Nurnberger Jr JI. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 1991; 19 (19) 5444
13 Carvalho Silva E, Carvalho Silva GC, Vieira TC. Cherubism: clinicoradiographic features, treatment, and long-term follow-up of 8 cases. J Oral Maxillofac Surg 2007; 65 (03) 517-522
14 Jain V, Sharma R. Radiographic, CT and MRI features of cherubism. Pediatr Radiol 2006; 36 (10) 1099-1104
15 Misra SR, Mishra L, Mohanty N, Mohanty S. Cherubism with multiple dental abnormalities: a rare presentation. BMJ Case Rep 2014; 2014: 1-5
16 Silva EC, de Souza PE, Barreto DC, Dias RP, Gomez RS. An extreme case of cherubism. Br J Oral Maxillofac Surg 2002; 40 (01) 45-48
17 Muthuraman V, Srinivasan S. Familial case of cherubism from South India: differential diagnosis and report of 2 cases. Case Rep Dent 2014; 2014: 869783
18 Tsodoulos S, Ilia A, Antoniades K, Angelopoulos C. Cherubism: a case report of a three-generation inheritance and literature review. J Oral Maxillofac Surg 2014; 72 (02) 405.e1-405 .e9
19 Roginsky VV, Ivanov AL, Ovtchinnikov IA, Khonsari RH. Familial cherubism: the experience of the Moscow Central Institute for Stomatology and Maxillo-Facial Surgery. Int J Oral Maxillofac Surg 2009; 38 (03) 218-223
20 Kalantar Motamedi MH. Treatment of cherubism with locally aggressive behavior presenting in adulthood: report of four cases and a proposed new grading system. J Oral Maxillofac Surg 1998; 56 (11) 1336-1342
21 Raposo-Amaral CE, de Campos Guidi M, Warren SM. et al. Two-stage surgical treatment of severe cherubism. Ann Plast Surg 2007; 58 (06) 645-651
22 Ueki Y, Tiziani V, Santanna C. et al. Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet 2001; 28 (02) 125-126
23 Reichenberger EJ, Levine MA, Olsen BR, Papadaki ME, Lietman SA. The role of SH3BP2 in the pathophysiology of cherubism. Orphanet J Rare Dis 2012; 7 (Suppl 1): S5
24 Chen G, Dimitriou ID, La Rose J. et al. The 3BP2 adapter protein is required for optimal B-cell activation and thymus-independent type 2 humoral response. Mol Cell Biol 2007; 27 (08) 3109-3122
25 Ueki Y, Lin CY, Senoo M. et al. Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 “cherubism” mice. Cell 2007; 128 (01) 71-83
26 Lietman SA, Kalinchinko N, Deng X, Kohanski R, Levine MA. Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation. Hum Mutat 2006; 27 (07) 717-718
27 Mukai T, Ishida S, Ishikawa R. et al. SH3BP2 cherubism mutation potentiates TNF-α-induced osteoclastogenesis via NFATc1 and TNF-α-mediated inflammatory bone loss. J Bone Miner Res 2014; 29 (12) 2618-2635
28 Carvalho VM, Perdigão PF, Amaral FR, de Souza PE, De Marco L, Gomez RS. Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism. Oral Dis 2009; 15 (01) 106-110
29 Prescott T, Redfors M, Rustad CF. et al. Characterization of a Norwegian cherubism cohort; molecular genetic findings, oral manifestations and quality of life. Eur J Med Genet 2013; 56 (03) 131-137
30 Singh A, Singh K, Goel R, Hu Y, Reichenberger E, Kapoor S. Genetic study of an Indian family with cherubism. Indian J Pediatr 2014; 81 (03) 299-301
31 Levaot N, Voytyuk O, Dimitriou I. et al. Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell 2011; 147 (06) 1324-1339
32 Machado RA, Pontes H, Pires FR. et al. Clinical and genetic analysis of patients with cherubism. Oral Dis 2017; 23 (08) 1109-1115
33 Imai Y, Kanno K, Moriya T. et al. A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism. Cleft Palate Craniofac J 2003; 40 (06) 632-638
34 Lee JY, Jung YS, Kim SA, Lee SH, Ahn SG, Yoon JH. Investigation of the SH3BP2 gene mutation in cherubism. Acta Med Okayama 2008; 62 (03) 209-212
35 de Lange J, van Maarle MC, van den Akker HP, Redeker EJ. A new mutation in the SH3BP2 gene showing reduced penetrance in a family affected with cherubism. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103 (03) 378-381
36 Sekerci AE, Balta B, Dundar M. et al. A c.1244G>A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: report of a family with review of the literature. Med Oral Patol Oral Cir Bucal 2014; 19 (04) e340-e344
37 Ozkan Y, Varol A, Turker N, Aksakalli N, Basa S. Clinical and radiological evaluation of cherubism: a sporadic case report and review of the literature. Int J Pediatr Otorhinolaryngol 2003; 67 (09) 1005-1012
38 Tiziani V, Reichenberger E, Buzzo CL. et al. The gene for cherubism maps to chromosome 4p16. Am J Hum Genet 1999; 65 (01) 158-166
39 Yoshitaka T, Mukai T, Kittaka M. et al. Enhanced TLR-MYD88 signaling stimulates autoinflammation in SH3BP2 cherubism mice and defines the etiology of cherubism. Cell Rep 2014; 8 (06) 1752-1766
40 Hitomi G, Nishide N, Mitsui K. Cherubism: diagnostic imaging and review of the literature in Japan. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996; 81 (05) 623-628
41 Mangion J, Rahman N, Edkins S. et al. The gene for cherubism maps to chromosome 4p16.3. Am J Hum Genet 1999; 65 (01) 151-157
42 Ongole R, Pillai RS, Pai KM. Cherubism in siblings: a case report. J Can Dent Assoc 2003; 69 (03) 150-154
43 Petkovska L, Ramadan S, Aslam MO. Cherubism: review of four affected members in a Kuwaiti family. Australas Radiol 2004; 48 (03) 408-410
44 Mortellaro C, Bello L, Lucchina AG, Pucci A. Diagnosis and treatment of familial cherubism characterized by early onset and rapid development. J Craniofac Surg 2009; 20 (01) 116-120
45 Argyris PP, Gopalakrishnan R, Hu Y, Reichenberger EJ, Koutlas IG. Clinicopathologic and molecular characteristics of familial cherubism with associated odontogenic tumorous proliferations. Head Neck Pathol 2018; 12 (01) 136-144