Genetic Cardiac Conditions

and Alwyn Scott2

School of Computer Science, University of Manchester, Manchester, UK

Cardiology High Dependency Unit, Papworth Hospital NHS Foundation Trust, Cambridge, UK




There are many genetically acquired cardiac diseases. To understand the pathology of this group of diseases, a basic knowledge of genetics is required.

Eukaryotic cells contain a nucleus, which stores chromosomes, which in turn contains DNA (deoxyribonucleic acid) (Fig. 8.1). DNA consists of sections called genes that determine various physical traits.


Fig. 8.1
Location of genes within a cell

Germline cells, such as the gametes, which include sperm and ova cells allow genetic material to be passed onto children; as oppose to the somatic cells (all the other cells in the body) whose genetic material is not passed on to children. Each gamete consists of 23 chromosomes, which when combined, make the full complement of 46 chromosomes that most humans posses.

Mutations in genes can lead to various diseases. These mutations can be passed on to children from their parents. If a gene allele has a particular dominant trait it gains precedence over less dominant traits (Fig. 8.2). For example in autosomal dominant inheritance only one of the parents needs to have the mutated gene for it to be passed onto the children. Each child would have a 50 % chance of inheriting the condition. In contrast autosomal recessive inheritance requires both parents to have the genetic defect. This would mean that a child would have a 25 % chance of developing the disease and 50 % chance of inheriting an abnormal gene, which would make the child a carrier of the disease. It is also possible for a new gene mutation to occur in the gametes, termed a ‘de novo’ mutation. In this case the child develops the condition without either parent having the disease, or being a carrier.


Fig. 8.2
Autosomal dominant and recessive inheritance patterns

It is worth noting that there are many other patterns of genetic inheritance, which are beyond the scope of this book (Table 8.1).

Table 8.1
Other inheritance patterns

Autosomal dominant

Autosomal recessive

X-linked dominant

X-linked recessive



Brugada Syndrome

Brugada syndrome is a condition that is associated with a significant increase in the risk of sudden death in young adults and sometimes children. The condition was first accepted as a clinical condition in 1992 based on the work of Pedro and Josep Brugada. Brugada syndrome affects males more than females. Disease prevalence is estimated at 1–5 per 10,000 people and has a high frequency of occurrence in Southeast Asia, especially in Thailand and the Philippines. In contrast there is a lower frequency of cases in western countries.

Brugada has been linked with a mutation in the SCN5A (Fig. 8.3) gene that encodes the α-subunit of the human cardiac sodium channel. Coding is a set of rules that are applied to DNA or mRNA (messenger ribonucleic acid) that translates them into proteins, which in turn consist of chains of amino acids. A mutation in this process can lead to variations that can cause certain positive effects, such as increased resistance to a disease for example; or negative effects, as seen in conditions like cystic fibrosis and Brugada syndrome.


Fig. 8.3
Effects of Brugada syndrome on the sodium channel

Apart from SCN5A, which accounts for around 20 % of cases of Brugada syndrome, several other calcium-channel mutations have been identified i.e. CACNB2, CACNA1C, SCN1B and GDP1L.

The mutation that occurs in brugada leads to ion channel defects, which either: Reduce the sodium or calcium influx into the cell or increase potassium efflux from the cell.

Brugada is an autosomal dominant disease. This means that the abnormal gene can be inherited if only one parent has the condition rather than both. This means that children of a parent with Brugada syndrome have a 50 % chance of inheriting the condition. It is also possible for a spontaneous mutation in either of the parents gametes (sperm or ova) to result in a de novo mutation (a new mutation not seen in either parent) causing Brugada syndrome.

Brugada syndrome is characterised by a Right Bundle Branch Block (RBBB) pattern with persistent ST-elevation in the precordial leads (V1–V3). The ECG is often very dynamic and frequently masks the presence of the syndrome. Brugada can however be revealed by certain physical states, such as hyperthermia and some drugs, for example sodium-channel blockers. Other signs can include a low heart rate at night, which may predispose patients in the group to an increased risk of Ventricular Fibrillation (VF). Brugada patients are also at an increased risk of developing Atrial Fibrillation (AF), which is seen in around 20 % of Brugada syndrome patients. Syncope or Sudden Cardiac Death (SCD) can also be the first clinical manifestation of the condition. Figure 8.4 shows an example of Brugada syndrome.


Fig. 8.4
Brugada syndrome (type 1)

There are three main types of Brugada syndrome, types 1–3. Type 1 is characterised by coved ST-elevation with a negatively deflected T-wave. Type 2 differs in that the ST-elevation is saddle back in appearance and the T-wave is often biphasic or positively deflected. Finally type 3 can have the coved or saddleback appearance of the earlier types but with less ST-elevation (<1 mm). When considering Brugada it is also worth eliminating other causes of the Brugada ECG pattern (Table 8.2).

Table 8.2
Other causes of the Brugada ECG pattern

Abnormal right bundle branch block (RBBB)

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May 29, 2017 | Posted by in CARDIOLOGY | Comments Off on Genetic Cardiac Conditions
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