Noncompaction of the left ventricular myocardium in a boy with a novel chromosome 8p23.1 deletion

Abstract

Interstitial deletion of chromosome 8p23.1 has been reported in patients with congenital heart defects, including atrial and ventricular septal defects, pulmonary stenosis, and complex cyanotic heart defects. GATA4, a zinc-finger transcription factor gene, has been localized to this region. GATA4 interacts with additional transcription factors in the embryogenesis of the primitive heart tube. Mutations in GATA4 are thought to be responsible for the congenital heart defects reported in association with this chromosomal deletion, and several familial point mutations leading to amino acid substitutions have also been identified. Left ventricular noncompaction (LVNC) is a clinically heterogeneous disorder characterized by LV myocardial trabeculations and intertrabecular recesses that communicate with the LV cavity. Patients may be asymptomatic or may present with evidence of severely depressed LV systolic and diastolic function. The LV may be dilated or hypertrophied, and clinical expression may be undulating. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. A 12-year-old boy with a history of acute lymphoblastic leukemia, dysmorphic features, and LVNC with preserved LV systolic function was referred to the Cardiovascular Genetics Clinic at our institution. The patient was asymptomatic in terms of cardiovascular function. Chromosome microarray testing revealed an interstitial deletion in the region of 8p23.1 containing GATA4. LVNC has not been reported previously in association with this chromosome deletion. Further investigation into the role of GATA4 in patients with LVNC is warranted.

Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association

“…506,514,515 LVNC has also been associated with chromosome 8p23.1 deletion. 516 LVNC can be associated with other syndromes with genetic mutations such as Coffin-Lowry syndrome, Sotos syndrome, Hunter-McAlpine syndrome, [517][518][519] and Charcot-Marie-Tooth disease. 520 Genetic testing in patients with LVNC appears to detect clinically significant variants in 35% to 40% of people, with most-common sarcomere-encoding genes.…”

Left Ventricular Non-compaction: Is It Genetic?

“…Finally, diagnosing the underlying condition enables more accurate genetic counseling for the family. Table 2 Syndromes and copy number variants (CNV) associated with LVNC Syndromes associated with aneuploidies Turner syndrome [1,43] Trisomy 21 [27] Trisomy 18 [5] Trisomy 13 [25] Syndromes associated with copy number variations Velocardiofacial syndrome [21,29] 1p36 deletion syndrome [4] Syndromes associated with neuromuscular diseases Duchenne muscular dystrophy; Becker muscular dystrophy [17,38] Limb girdle muscular dystrophy [20] Multiminicore disease [37] Other syndromes Sotos syndrome [24] Marfan syndrome [18] Noonan syndrome [2] LEOPARD syndrome [19] Cornelia De Lange syndrome [9] Roifman syndrome [22] Hypomelanosis of Ito [8] Nail patella syndrome [12] Other CNV 8p23.1 deletion [6] Trisomic for the 4q31 ? qter region and monosomic for the 1q43 ?…”

Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

“…These gene products have functions related to cytoskeletal and/or mitochondrial function (Tang et al 2010). Another six loci located on chromosomes 1p36 (Thienpont et al 2007), 1q43 (Kanemoto et al 2006), 5q35 (Pauli et al 1999), 8p23 (Blinder et al 2011), and11p15 (Sasse-Klaassen et al 2004) also have been linked to the phenotype of nonsyndromic LVNC. While a number of genes and candidate loci have been reported with LVNC, only a minority of affecteds have been found to harbor causative mutations (Finsterer et al 2004;Ichida 2009;Tang et al 2010;Xing et al 2006).…”