Simultaneous presence of Brugada and overgrowth syndromes

Submitted: January 23, 2023
Accepted: April 12, 2023
Published: April 27, 2023
Abstract Views: 537
PDF: 227
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In the present article, we describe the case of a 21-year-old male presenting to the emergency department following a syncopal episode. Physical examination revealed a distinctive facial appearance in the context of an overgrowth syndrome. Also, an ajmaline test was performed because of the evidence of an incomplete right bundle branch block with ST-T segment elevation in the right precordial derivations, revealing a type-1 Brugada electrocardiographic pattern. Considering the high cardiovascular risk phenotype, the patient underwent subcutaneous cardiac defibrillator implantation. The subsequent comprehensive genomic testing analysis led to the diagnosis of a variant of uncertain significance of the nuclear receptor binding SET domain protein 1 (NSD1) gene and a heterozygous mutation of the calsequestrin 2 (CASQ2) gene. NSD1 gene alterations are usually responsible for the Sotos syndrome, characterized by distinctive facial appearance, learning disability, and overgrowth, in addition to cardiac anomalies ranging from single self-limiting alterations to more severe, complex cardiac abnormalities. On the contrary, a compound heterozygous or homozygous alteration of the CASQ2 gene is usually associated with catecholaminergic polymorphic ventricular tachycardia; however, the significance of a merely heterozygous alteration in the CASQ2 gene, as in the present case report, is not yet clear. In conclusion, to the best of our knowledge, this is the first description of the coexisting presence of Brugada and overgrowth syndromes in a single patient.

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Citations

Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391-6.
Brugada J, Campuzano O, Arbelo E, et al. Present status of Brugada syndrome: JACC state-of-the-art review. J Am Coll Cardiol 2018;72:1046-59.
Krahn AD, Behr ER, Hamilton R, et al. Brugada Syndrome. JACC Clin Electrophysiol 2022;8:386-405.
D'Imperio S, Monasky MM, Micaglio E, et al. Brugada syndrome: warning of a systemic condition?. Front Cardiovasc Med 2021;8:771349.
Sotos JF, Dodge PR, Muirhead D, et al. Cerebral gigantism in childhood: a syndrome of excessively rapid growth with acromegalic features and a nonprogressive neurologic disorder. N Eng J Med 1964;271:109-16.
Lapunzina P, Tenorio JA. Sotos syndrome. In: Neri G, Boccuto L, Stevenson RE, eds. Overgrowth syndromes: a clinical guide. Oxford University Press; 2019. pp 73-94.
Tatton-Brown K, Cole TRP, Rahman N. Sotos Syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle: University of Washington; 1993.
Noreau DR, Al-Ata J, Jutras L, Teebi AS. Congenital heart defects in Sotos syndrome. Am J Med Genet 1998;79:327-8.
Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 2022;43:3997-4126.
Rayasam GV, Wendling O, Angrand PO, et al. NSD1 is essential for early post-implantation development and has a catalytically active SET domain. EMBO J 2003;22:3153-63.
Foster A, Zachariou A, Loveday C, et al. The phenotype of Sotos syndrome in adulthood: a review of 44 individuals. Am J Med Genet C Semin Med Genet 2019;181:502-8.
Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet 2005;137C:24-31.
Saccucci P, Papetti F, Martinoli R, et al. Isolated left ventricular noncompaction in a case of Sotos syndrome: a casual or causal link?. Cardiol Res Pract 2011;2011:824095.
Cecconi M, Forzano F, Milani D, et al. Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. Am J Med Genet A 2005;134:247-53.
Wilde AAM, Semsarian C, Márquez MF, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Europace 2022;24:1307-67.
Pagiatakis C, Di Mauro V. The emerging role of epigenetics in therapeutic targeting of cardiomyopathies. Int J Mol Sci 2021;22:8721.
Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet 2012;13:343-57.
Jimenez J, Rentschler SL. Transcriptional and epigenetic regulation of cardiac electrophysiology. Pediatr Cardiol 2019;40:1325-30.
Radford D, Chou OHI, Bazoukis G, et al. Electrocardiographic features in SCN5A mutation-positive patients with Brugada and early repolarization syndromes: a systematic review and meta-analysis. Int J Arrhythmia 2022;23:16.
Allegue C, Coll M, Mates J, et al. Genetic analysis of arrhythmogenic diseases in the era of NGS: the complexity of clinical decision-making in Brugada syndrome. PLoS One 2015;10:e0133037.

How to Cite

Segreti, Andrea, Francesco Piccirillo, Simone Pasquale Crispino, Francesca Cocchia, Arianna Martucciello, Vito Calabrese, Fiorella Gurrieri, and Francesco Grigioni. 2023. “Simultaneous Presence of Brugada and Overgrowth Syndromes”. Monaldi Archives for Chest Disease 94 (1). https://doi.org/10.4081/monaldi.2023.2521.