Genetic Disorder Occurrence

What are genetic disorders?

Genes are the building blocks of heredity which is a small fragment of DNA that are tightly packed in chromosomes. There are 23 pairs of chromosomes in each cell.

DNA carries the genetic information for making a protein. Proteins are responsible for a lot many functions including regulating body processes and transporting materials throughout the body.

Genes are transmitted from parent to a child (A child receives 23 chromosomes from the mother and 23 from the father). Sometimes there occurs a mutation (a change in DNA sequence) in a gene which results in abnormal protein synthesis and leads to a genetic disorder.

There are two main types of genetic disorders

1.   Single gene defects: All human beings have two sets or copies of each gene called “allele”; one copy on each side of the chromosome pair. Recessive diseases are monogenic disorders that occur due to damages in both copies and allele. Dominant diseases are monogenic disorders that involve damage to only one gene copy.

X linked diseases are monogenic disorders that are linked to defective genes on the X chromosome which is the sex chromosome. The X linked alleles can also be dominant or recessive.

2. Chromosomal abnormalities: Disorders resulting from changes in the number or structure of the chromosomes

Common genetic disorders

The following table summarizes the list of most common genetic disorders.

Disorder

Location

Complications

Incidence

Down Syndrome

Chromosome 21 is copied an extra time in all or some cells

Higher disposition for congenital heart defects, low muscle tone, smaller physical stature, and an upward slant to the eyes

1 in 700 babies born in US

Tay Sachs disease

Mutation in HEXA gene, Chromosome 15

Nervous system disorder. The affected baby lacks an enzyme necessary for breaking down certain fatty substances in the brain and nerve cells

One of every 250 members of the general population

Sickle Cell Anemia

In this disease, hemoglobin molecule is defective and red blood cells change from their usual donut shape to a sickle shape.

Infections, organ damage, and acute respiratory syndrome.

Affects approximately 100,000 Americans. 

Cystic Fibrosis

Mutation in CFTR gene

Affects breathing and digestion

In the European Union 1 in 2000-3000 newborns

In the USA, the incidence of CF is reported to be 1 in every 3500 births.

Thalassemia

Absence of or errors in genes responsible for production of haemoglobin.

Chromosome 11 and 16.

The disorder results in large numbers of red blood cells being destroyed, which leads to anemia

In Iran, it is estimated that about 8,000 pregnancies are at risk each year.

Fragile X syndrome

Long arm of the X chromosome (FMR1 gene)

Mental retardation

1 in 3600 males and 1 in 4000 to 6000 females with full mutation worldwide

 How to identify genetic disorder occurrence in pregnancy?

Genetic disorders are more often suspected if there is a family history of a genetic disorder, any abnormalities seen in an ultrasound or any one parent has chromosomal abnormality. Some of the common tests to identify genetic disorder occurrence are discussed here.

Ultrasound

It is a non invasive procedure performed in all pregnant women. It provides a picture of the baby in the uterus. Ultrasound looks at the anatomy of your fetus and also provides information about the position of the baby, the amount of amniotic fluid, the position and structure of the placenta, cord position, length of the cervix and can provide more specialized views of blood flow and velocity within the heart and umbilical cord. Along with other laboratory parameters ultrasound results can be combined to identify the risk of genetic disorder.

First Trimester Screening

Nuchal Translucency:

This test is to identify women who are at an increased risk of having a baby with down syndrome.

This is done after 11th week and before 14 weeks of gestation.

Mother will undergo an ultrasound screening called nuchal translucency and a blood sample is drawn from her to check the levels of serum free β-hCG and PAPP-A.

The nuchal translucency is an ultrasound measurement of the amount of fluid accumulation behind the baby's neck. In case of any chromosomal abnormalities the thickness of the fluid differs.

Maternal age is also included along with ultrasound and lab values and accordingly a mother is graded as “low risk and high risk” group.

Cell free DNA test

Cell-free DNA is the small amount of DNA that is released from the placenta into a pregnant woman’s bloodstream.

This test is to screen for Down syndrome, Patau syndrome (trisomy 13), Edwards syndrome, and problems with the number of sex chromosomes.

This test is done during 10th week of pregnancy.

If this test result is positive other genetic diagnostic tests like amniocentesis or CVS will be performed.

Amniocentesis:

This test is done only if the first trimester screen gives you worrisome results.

It is done between 15 and 20 weeks of gestation.

Amniocentesis is a protocol in which amniotic fluid is removed from a mother’s uterus.

Amniotic fluid surrounds and protects your baby during pregnancy. This fluid has fetal cells and a lot of proteins.

This test will identify any chromosomal abnormalities.

 Chorionic villus sampling

This test is done only if first trimester screen is positive or if you have a family history of a genetic disorder.

Performed at 10-12 weeks of gestation

Chorionic villi are tiny parts of the placenta that are formed from the fertilized egg, so they have the same genes as the baby.

It is an invasive method in which a sample of chorionic villi is removed from the placenta for testing. The sample can be taken through the cervix or the abdominal wall.

This test is to identify genetic disorders like Down syndrome and cystic fibrosis.

Second Trimester Screening

If the first trimester results potentiate any risk of a genetic disorder, second trimester screening is done during 20 weeks of pregnancy. In this test four markers are measured namely alpha fetoprotein, HCG, estriol and inhibin. Neural tube defects and other chromosomal abnormalities are checked here.

Management of the disease

If any of your test results are positive, talk to a genetic counselor. They will explain to you the potential risks of a genetic disorder.

Treatment of the disease depends on the syndrome. Some disorders have very short life expectancy for which treatment would not be beneficial. However, some children with genetic disorders can and do function well with normal life expectancy.

Genetic disorder occurrence is very rare. It is important to screen for the risk of any genetic disorder during your prenatal visits.