*3.2.5. Impact on patients and families*

*3.2.3.3. Chromosome microarray*

426 Congenital Anomalies - From the Embryo to the Neonate

such as translocations and triploidies.

tion and CHD [128].

*3.2.3.4. Whole exome sequencing*

tions in these cohort of patient studied [130].

*3.2.4. Preimplantation genetic diagnosis*

Chromosomal microarray (CMA) testing looks for extra (duplicated) or missing (deleted) chromosomal segments, sometimes called copy number variants (CNVs). It refers to a microchip-based testing platform that allows high-volume, automated analysis of many pieces of DNA at once. CMA chips use labels or probes that bond to specific chromosome regions [129]. The resolution of conventional karyotype analysis is limited to 5 Mb or larger genomic imbalances. Chromosome Microarray Analysis (CMA) is a routine technique in clinical molecular testing nowadays, which contains two types of arrays: oligonucleotide arrays and Single Nucleotide Polymorphism arrays (SNP arrays). Computer analysis is used to compare a patient's genetic material to that of a reference sample. A difference between a patient's DNA and the reference sample is called a variant. These include chromosomal microdeletions and micro-duplications that are too small, abnormalities of chromosome number like the trisomies. In addition other variants include unbalanced rearrangements of chromosome structure

Both the arrays could detect genome-wide CNVs. Moreover, SNP arrays can detect mosaicism, triploid, loss of heterozygosity and uniparental disomy. In 2010, the American College of Medical Genetics issued practice guidelines for CMA, and pointed out that CMA was recommended as a first-tier test for postnatal patients with multiple congenital anomalies, intellectual disabilities/developmental delay (ID/DD) and autism spectrum disorders [127, 129]. Recently, CMA has been successfully applied to detect CNVs in patients with CHD, which confirmed the relationship between chromosome microdeletion/microduplica-

Whole exome sequencing is part of next-generation sequencing. With this technology, it is now possible to sequence large amounts of DNA that provide genetic code for making proteins, which are called exons. All the exons in a genome are referred to as the exome, hence this method of sequencing them is known as whole exome sequencing, which allows for the identification of variations in the protein-coding region. It is known that most mutations that cause disease states, occur in these regions. Therefore, the use of this technology allows an efficient way to detect possible disease-causing mutations [130]. Whole exome sequencing has been successfully applied to patients with CHD. Many de novo mutations involved in cardiac related genes to the developing heart have been detected. [22, 130, 131]. This finding helped better elucidate understanding of overall CHD and its developmental pathways. However, more research needs to be done to determine a causal relation and best therapeutic interven-

In the current era of in vitro fertilization, preimplantation genetic diagnosis is possible. PGD provides chromosomal and mutational analysis of blastocyst that results from in vitro fertilization before implantation [22]. In assisted reproductive technology, PGD is becoming a The identification of genetic cause in congenital heart disease can prove to be very beneficial. Firstly is allows for the physician to be confident of the diagnosis and explain the mechanism of disease and other prognostic factors.1 When the cardiac malformation is part of a genetic syndrome, it allows for the care team to look for other associated anomalies in other organ system. A genetic basis for disease may also necessitate evaluation into other family members [22, 117]. This will help further characterize the extent of the disease in the family and monitor risks and assess ability to pass on to future offspring [117]. Patients and families need to be made aware of both the numeric risk, as in Marfan and William Syndrome, an affected person has a 50% risk. However when the cardiac malformation has variable expressivity, predicting severity becomes extremely difficult [118].
