III. Learning unit: Complex congenital heart defects

Objectives and competencies

This curriculum presents a rare development heart defect the double outlet right ventricle syndrome in multidisciplinary environment. The anatomic and pathological chapter introduces congenital heart defects their morphology and complex circulatory system such as atrial or ventricular septal defect great vessel transposition persisting Botall duct, Fallot tetralogy, or double outlet right ventricle syndrome. Radiology and clinical chapter summarizes imaging modalities required to establish diagnosis, and important aspect of their  treatment in an environment enriched with illustrations photos and tables. 

III./1.Chapter: Disorders of cardiac development

Nándor Nagy

III./1.1.: Introduction

Congenital disorders of the development of the heart constitute nearly 20 % of all developmental malformations observed in infants born alive. However, the percentage of heart disorders is much greater (40-50 %) in those infants which died before birth. Furthermore, certain malformations of the heart manifest themselves only later in adolescence or adulthood under greater physical stress.

Given the diversity of cardiac disorders, both in terms of gravity and complexity, their developmental biological background is only partly known. Disorders of cardiac development may be due either to specific genetic faults (chromosomal aberrations, mutation of a single gene), or to environmental or teratogenic factors. Specific gene mutations have been identified in about 4 % of cardiac malformations (mutations of the transcription factors Tbx5 or GATA4, as well as those of the homeobox gene Nkx-2.5 cause atrial and ventricular septal defects). Chromosomal aberrations typically eliciting disorders of heart development comprise the trisomy of the chromosome 18 or 21 (Down's syndrome) or the DiGeorge syndrome, associated with microdeletion of the chromosome 22.

Malformations of the heart may be due to well known teratogenic factors such as lithium, retinoic acid, alcohol, A and D hypervitaminosis during pregnancy or immunosuppressive and other drugs. In addition, maternal diseases such as rubella contracted in the first trimester of pregnancy, insulin-dependent diabetes or intense smoking may also perturb the normal development of the heart. Rubella causes developmental malformation of the heart in 50 % of cases.

The disorders of cardiac development can be classified according to embryological or functional categories. Dextrocardia may appear in the early phase of development, caused by abnormal looping of the heart tube. In particular, the straight cardiac tube bends to the left, instead of right, as a result of which the heart develops on the right side of thorax. The incidence of this disorder is 1:12 000 cases, and the genetic cause is a mutation of sonic hedgehog, involved in determination of right-left asymmetry, or that of IIa type activin receptor genes.

Another disorder of the early heart tube phase (considered rare) is ectopia cordis, where - due to premature closure of embryonic body wall - the cardiac anlage is situated outside of the thorax. Yet another malformation of the early heart tube phase, truncus arteriosus communis persistens is caused by defective development of aortico-pulmonary septum, resulting in failure of separation of truncus arteriosus into aorta and pulmonary trunk. Truncus arteriosus communis persistens occurs in 1 of every 10 000 infants. In this disease, only a single principal artery arises from the ventricle and, due to a regular defect of interventricular septum, this single vessel receives blood from both sides of the heart.

The next important phase of cardiac development follows the looping of the heart tube, and it lasts until the formation of the septa separating the chambers of the heart. Several malformations belong to this category, e.g. atrial and ventricular septal defects, transposition of principal vessels, stenosis, valvular defects (tricuspidal atresia, aortic stenosis) and a complex developmental disorder termed tetralogy of Fallot

The chapter structure

• III./1.1.: Introduction

• III./1.2.: Atrial septal defect (ASD)

• III./1.3.: Ventricular septal defects (VSD)

• III./1.4.: Transposition of principal vessels

• III./1.5.: Ductus Botalli persistens (patent ductus arteriosus)

• III./1.6.: Tetralogy of Fallot

References

Clark KL, Yutzey KE, Benson DW: Transcription factors and congenital heart defects. Annu Rev Physiol 2006, 68: 97-121.

Lagendijk AK, Smith KA, Bakkers J: Genetics of congenital heart defects: a candidate gene approach. Trends Cardiovasc Med 2010, 20 (4):124-128.

Langman's Medical Embryology, 12th Edition, 2011 ( Lippincott Williams & Wilkins) by Thomas Sadler Thomas W. Sadler PhD , T. W. Sadler , Jill Leland , Susan L. Sadler-Redmond.

Larsen's Human Embryology, 4 Edition, 2008 (Churchill Livingstone) by Gary C. Schoenwolf, Steven B. Bleyl, Philip R. Brauer, Philippa H. Francis-West.

Olson EN: A decade of discoveries in cardiac biology. Nat Med 2004, 10 (5): 467-474.