Noncompaction of Left Ventricular Myocardium, Familial Isolated, Autosomal Dominant 1

Alternative Names

  • LVNC1
  • Left Ventricular Noncompaction, Isolated, Autosomal Dominant
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the circulatory system

OMIM Number

604169

Mode of Inheritance

Autosomal Dominant

Gene Map Locus

18q12.1-q12.2

Description

Left Ventricular Noncompaction Cardiomyopathy (LVNC) is a rare condition affecting the cardiac muscles, characterized by a hypertrophic left ventricle with deep trabeculations, and systolic and diastolic dysfunction. The myocardium of the left ventricle appears spongy and non-compacted, and made up of a meshwork of muscle bands. Most affected patients present in infancy or early childhood with tachypnea caused by a low cardiac output. Some may also present with cyanosis, syncope, dysmorphic features, and a failure to thrive. The condition is rare, with an estimated incidence of 0.81 per 100,000 infants.

Diagnosis of LVNC usually relies on ECG, Doppler imaging, and/or cardiac MRI. Diagnostic criteria include the presence of multiple echocardiographic trabeculations, multiple deep intertrabecular recesses communicating with the ventricular cavity, and most importantly, increased non-compacted to compacted ratio, assessed by comparing the size of the muscle bands with the compacted muscles in the heart. The ECG may show evidence of marked biventricular hypertrophy, and features typical of Pompe's disease and Wolf-Parkinson-White syndrome. Differential diagnosis includes hypertrophic or dilated cardiomyopathy. Relevant treatment depends upon the clinical feature of the patient. The most important aspect, however, is the early detection of the abnormality, and prevention of further complications. Regular medications and treatment regimes used in heart failure can be used effectively for the management of LVNC too.

Molecular Genetics

Very little is known about the etiology of LVNC. However, studies seem to indicate that the condition arises from an arrest of myocardial morphogenesis during embryonal development. A genetic basis to this abnormality is indicated by the fact that a number of patients have affected family members. In fact, both autosomal dominant and X-linked forms of this condition have been recognized.

LVNC1, or the major autosomal dominant form of the disease has been found to be due to mutations in the DTNA gene, located on chromosome 18. It is not clear how defects in Dystrobrevin Alpha, the protein product of the DTNA gene, could lead to LVNC1. Researchers suggest that mutations could interfere with the normal binding of the protein to other proteins, such as dystrophin, syntrophin, and proteins of dystrophin-associated glycoprotein complex (DAPC), all of which together play an important role in the stability and maintenance of the plasma membrane during muscle contraction and relaxation.

Epidemiology in the Arab World

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Other Reports

Qatar

Robida and Hajar (1996) described a 9-month-old boy and 4-month-old girl who presented with severe heart failure. Postmortem examination of the heart of the 9-month-old boy showed globular configuration and dilatation of both ventricles. Endocardial fibroclastosis was present in both ventricles. The girl died as well 12 hours after admission. In both infants, the electrocardiogram showed complete and "incomplete" left bundle branch block, respectively. Noncompaction of the ventricular myocardium was also diagnosed with two-dimensional echocardiography. These cases are thought to be the first descriptions of the occurrence of left bundle branch block with noncompaction of the ventricular myocardium.

El-Menyar et al. (2007) studied the prevalence and clinical presentation of non-compaction cardiomyopathy in Qatar, based on hospital records. Only 12 cases of NCCM (8 females, 4 males; mean age at diagnosis: 6.5 years) were diagnosed between the years 2000 and 2004. These patients were then followed upon for 2-5 years. None of these patients had consanguineous parents. However, five patients had a family history of the condition, while one had a family history of dilated cardiomyopathy. All male patients had a family history of cardiomyopathy, and 50% progressed to dilated cardiomyopathy. The most common presentation was shortness of breath (58%), followed by palpitation (17%). Diastolic dysfunction was noted in all patients, whereas systolic dysfunction was subclinical in four, mild to moderate in four, and severe in three patients. Four cases progressed to dilated cardiomyopathy. The left ventricle apex was involved in all 12 cases. Other common sites of non compaction were the inferoposterior wall (11), and the lateral wall (11). Biventricular involvement was the most serious type, with 3 of the 4 affected patients dying. ECG detected left ventricular hypertrophy (6), right ventricular hypertrophy (3), right bundle branch block (3), and left bundle branch block (2) in the patients. Arrythmias noted included sinus tachycardia (2) and supraventricular tachycardia (2). The latter was associated with a poor prognosis, with both patients dying. Other associated congenital anomalies seen in the patients included ventricular septal defect (4), Wolf-Parkinson-White syndrome (1), pulmonary stenosis (1), aortic contraction (1), and Ebstein anomaly (1). This in fact, is the fourth report worldwide of NCCM associated with Ebstein anomaly. A quarter of the patients died (mortality rate-25%); all developing congestive heart failure before death. El-Menyar et al. (2007) stated that the recognition of subclinical systolic dysfunction was important for the diagnosis and proper management of the condition.

Saudi Arabia

Ali (2008) identified 52 patients with non-compaction of the ventricular myocardium (NCVM) between 2000 and 2004 in two hospitals, one each in Saudi Arabia and Sudan. A total of 30 patients, all of them Arabs, were from Saudi Arabia. Of the 22 patients that came from Sudan, two were Arab in origin, while the remaining 17 were Arab/African. Patients were divided to the three following groups: isolated NCVM, NCVM associated with congenital heart disease, and NCVM associated with mitral regurgitation (MR). Within the first group, five patients had a positive family history, including two pairs of female twins. Patients in the second group presented with ventricular septal defects (VSD), pulmonary and tricuspid atresia, and hypoplastic left heart syndrome. In group 3, the female-to-male ratio was 6:1. Seven patients with MR associated with deformity of the anterior mitral leaflet and malcoaptation. All patients with this pathology had myocardial function. Four patients of the whole cohort had clinical as well as echocardiographic improvement. Left ventricular hypertrophy was noted in two patients. A large number of NCVM patients were reported in Saudi Arabia and Sudan during the study period, and Ali (2008) found it to be not as rare as was thought, with females being more affected.

Sudan

[See: Saudi Arabia > Ali et al., 2008].

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