Left ventricular hypertrabeculation/noncompaction with epilepsy, other heart defects, minor facial anomalies and new copy number variants

BMC Medical Genetics

Josef Finsterer⁵  Eva Klopocki¹  Claudia Stöllberger⁵  Sabine Uhrig²  Ursula Gruber-Sedlmayr³  Bert Nagel⁴ 

[1] Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany;Institute of Human Genetics, Medical University of Graz, Harrachgasse 21/8, A-8010 Graz, Austria;Department of Pediatrics (U. Gruber-Sedlmayr), Medical University Graz, Auenbruggerplatz 30, A-8036 Graz, Austria;Department of Pediatric Cardiology, Medical University Graz, University Children’s Hospital, Auenbruggerplatz 30, A-8036 Graz, Austria;Krankenanstalt Rudolfstiftung, Juchgasse 25, A-1030 Wien, Austria

关键词: Seizures;    Hypertrabeculation;    Array CGH;    Pediatrics;    Neurology;    Congenital heart disease;    Cardiomyopathy;   

Others  :  1177826
DOI  :  10.1186/1471-2350-13-60

 received in 2012-03-06, accepted in 2012-07-25,  发布年份 2012

【 摘 要 】

Background

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism.

Case presentation

A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.5 years old girl. Microarray-based genomic hybridization (array-CGH) detected six previously not described copy number variants (CNVs) inherited from a clinically unaffected father and minimally affected mother, thus, most likely, not clinically significant but rare benign variants.

Conclusions

Despite this complex phenotype de novo microdeletions or microduplications were not detected by array CGH. Further investigations, such as whole exome sequencing, could reveal point mutations and small indels as the possible cause.

【 授权许可】

   
2012 Nagel et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Battaglia A, Hoyme HE, Dallapiccola B, Zackai E, Hudgins L, McDonald-McGinn D, Bahi-Buisson N, Romano C, Williams CA, Brailey LL, Zuberi SM, Carey JC: Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation. Pediatrics 2008, 121:404-410.
• [2]Budde BS, Binner P, Waldmüller S, Höhne W, Blankenfeldt W, Hassfeld S, Brömsen J, Dermintzoglou A, Wieczorek M, May E, Kirst E, Selignow C, Rackebrandt K, Müller M, Goody RS, Vosberg HP, Nürnberg P, Scheffold T: Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene. PLoS One 2007, 2:e1362.
• [3]Fazio G, Pipitone S, Iacona MA, Marchi S, Mongiovi M, Zito R, Sutera L, Novo S: The noncompaction of the left ventricular myocardium: our paediatric experience. J Cardiovasc Med 2007, 8:904-908.
• [4]Kanemoto N, Horigome H, Nakayama J, Ichida F, Xing Y, Buonadonna AL, Kanemoto K, Gentile M: Interstitial 1q43-q43 deletion with left ventricular noncompaction myocardium. Eur J Med Genet 2006, 49:247-253.
• [5]Monserrat L, Hermida-Prieto M, Fernandez X, Rodríguez I, Dumont C, Cazón L, Cuesta MG, Gonzalez-Juanatey C, Peteiro J, Alvarez N, Penas-Lado M, Castro-Beiras A: Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects. Eur Heart J 2007, 28:1953-1961.
• [6]Profitlich LE, Kirmse B, Wasserstein MP, Diaz GA, Srivastava S: High prevalence of structural heart disease in children with cb1C-type methylmalonic aciduria and homocystinuria. Mol Genet Metab 2009, 98:344-348.
• [7]Tsai SF, Ebenroth ES, Hurwitz RA, Cordes TM, Schamberger MS, Batra AS: Is left ventricular noncompaction in children truly an isolated lesion? Pediatr Cardiol 2009, 30:597-602.
• [8]Wessels MW, De Graaf BM, Cohen-Overbeek TE, Spitaels SE, de Groot-de Laat LE, Ten Cate FJ, Frohn-Mulder IF, de Krijger R, Bartelings MM, Essed N, Wladimiroff JW, Niermeijer MF, Heutink P, Oostra BA, Dooijes D, Bertoli-Avella AM, Willems PJ: A new syndrome with noncompaction cardiomyopathy, bradycardia, pulmonary stenosis, atrial septal defect and heterotaxy with suggestive linkage to chromosome 6p. Hum Genet 2008, 122:595-603.
• [9]De Pasquale Meyer G, Kretschmar O, Valsangiacomo Buechel ER, Kellenberger C, Bauersfeld U, Attenhofer Jost CH: Rare combination of congenital aplasia of the right pulmonary veins, left ventricular noncompaction, partial membranous obstruction of left-sided pulmonary veins and secundum atrial septal defect. Int J Cardiol 2011, 152:e49-51.
• [10]Ouyang P, Saarel E, Bai Y, Luo C, Lv Q, Xu Y, Wang F, Fan C, Younoszai A, Chen Q, Tu X, Wang QK: A de novo mutation in NKX2.5 associated with atrial septal defects, ventricular noncompaction, syncope and sudden death. Clin Chim Acta 2011, 412:170-175.
• [11]Sakan H, Okayama S, Uemura S, Somekawa S, Ishigami K, Takeda Y, Kawata H, Horii M, Fujimoto S, Saito Y: Atrial right-to-left shunt without pulmonary hypertension in a patient with biventricular non-compaction cardiomyopathy accompanied by ventricular and atrial septal defects. Intern Med 2011, 50:1747-1751.
• [12]Blinder JJ, Martinez HR, Craigen WJ, Belmont J, Pignatelli RH, Jefferies JL: Noncompaction of the left ventricular myocardium in a boy with a novel chromosome 8p23.1 deletion. Am J Med Genet A 2011, 155:2215-2220.
• [13]Hussein A, Schmaltz AA, Trowitzsch E: Isolierte Fehlentwicklung (“Noncompaction“) des Myokards bei drei Kindern. Klin Pädiatr 1999, 211:175-178.
• [14]Finsterer J, Stöllberger C, Gelpi E: Successful heart failure therapy in mitochondrial disorder with noncompaction cardiomyopathy. Int J Cardiovasc Imaging 2006, 22:393-398.
• [15]Saito S, Kawamura R, Kosho T, Shimizu T, Aoyama K, Koike K, Wada T, Matsumoto N, Kato M, Wakui K, Fukushima Y: Bilateral perisylvian polymicrogyria, periventricular nodular heterotopia, and left ventricular noncompaction in a girl with 10.5–11.1 Mb terminal deletion of 1p36. Am J Med Genet A 2008, 146A:2891-2897.
• [16]Thienpont B, Mertens L, Buyse G, Vermeesch JR, Devriendt K: Left-ventricular non-compaction in a patient with monosomy 1p36. Eur J Med Genet 2007, 50:233-236.
• [17]Martinez HR, Belmont JW, Craigen WJ, Taylor MD, Jefferies JL: Left ventricular noncompaction in Sotos syndrome. Am J Med Genet A 2011, 155A:1115-1118.
• [18]Altenberger H, Stöllberger C, Finsterer J: Isolated left ventricular hypertrabeculation /noncompaction in a Turner mosaic with male phenotype. Acta Cardiol 2009, 64:99-103.
• [19]Klopocki E, Ott CE, Benatar N, Ullmann R, Mundlos S, Lehmann K: A microduplication of the long range SHH limb regulator (ZRS) is associated with triphalangeal thumb-polysyndactyly syndrome. Med Genet 2008, 45:370-375.
• [20]Klopocki E, Mundlos S: Copy-number variations, noncoding sequences, and human phenotypes. Annu Rev Genomics Hum Genet 2011, 12:53-72.
• [21]Finsterer J: Cardiogenetics, neurogenetics, and pathogenetics of left ventricular hypertrabeculation/ noncompaction. Pediatr Cardiol 2009, 30:659-681.
• [22]Lorenz S, Heils A, Kasper JM, Sander T: Allelic association of a truncation mutation of the KCNMB3 gene with idiopathic generalized epilepsy. Am J Med Genet B Neuropsychiatr Genet 2007, 144B:10-13.
• [23]Varadkar P, Kraman M, Despres D, Ma G, Lozier J, McCright B: Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells. Dev Dyn 2008, 237:1144-1152.
• [24]Kamath BM, Bauer RC, Loomes KM, Chao G, Gerfen J, Hutchinson A, Hardikar W, Hirschfield G, Jara P, Krantz ID, Lapunzina P, Leonard L, Ling S, Ng VL, Hoang PL, Piccoli DA, Spinner NB: NOTCH2 mutations in Alagille syndrome. J Med Genet 2012, 49:138-144.