The DNA is the hereditary material carried by an individual. This DNA resides in every cell of the individual’s body.

A gene is the functional unit of an individual’s DNA. There are about 30,000- 40,000 ‘coding’ genes in the human DNA. These genes ‘code’ for important proteins in our body, which help as building blocks for carrying out various functions like growth, development, reproduction, body metabolism; to name a few. They make up for about 5% of the total DNA. With advances in the branch of genetics, we understand that the rest of the ‘non-coding’ DNA, incorrectly dubbed as ‘junk DNA’, also has important implications in the smooth functioning of the individual.

A Clinical Geneticist (commonly called as a Genetic Specialist) is a trained professional who evaluates patients or their families for possible hereditary diseases. A Clinical Geneticist carefully analyzes the clinical history, elicits a complete three to four generation family tree, carries out detailed physical examination, postulates the possible mode of inheritance of the disease, advices and arranges for the special genetic tests, formulates treatment and surveillance plans, and helps to understand the risk of the other family members to develop a given genetic condition. A Clinical Geneticist is a Clinician along with being a Genetic Counsellor; having an added advantage of Medical training to guide the patients more holistically.

As per definition by the European Union a disease is termed as ‘rare’ when the number of affected subjects is <1:2000. Individually there may be a lot of rare diseases fitting this definition, but taken as a ‘group’, it is estimated that nearly one in every 13 persons will live with a rare disease at some point in their life. This may be a gross understatement given the large proverbial iceberg of undiagnosed and misdiagnosed cases. India shares nearly one-fourth of the rare disease burden of the world. In terms of absolute numbers, the Indian burden of rare diseases is estimated to be between 9-10 crores individuals. Indeed, ‘Rare is Many’; and the challenges posed by ‘Rare’ are in fact far more global than perceived.

Some examples of rare diseases include Duchenne muscular dystrophy, cystic fibrosis, Pompe disease, lysosomal storage disorders, multiple sclerosis, Marfan syndrome, amongst others. Irrespective of whether a disease affects millions of people or just a few, the impact of the disease on the family suffering it can be enormous!

Errors at the level of the gene can occur in different ways, and may be understood easily by comparing with dialling a phone number
If the number one wishes to dial is 9820517545 (correct number)
Or
98205175555 (extra digits)
Or
9920517545 (wrong digits)
I will not be able to connect with the person I intend to.
Similarly, any deletion, duplication or incorrect sequencing of the chemical units in the genes or in the genes themselves, can lead to an error. The nature of the error may be big, or small.
However, I can dial 0-98 205 17 545 and still connect correctly. Not all alterations at the level of the gene cause a disease necessarily.

There is no time frame during which a genetic disorder cannot present. It can present while the baby is growing in the womb, at birth, during the childhood and adolescence. There are many genetic diseases which will present first in adulthood; some when the individual is well in his 40s or 50s or even later.

Though the genes translate the important ‘genetic’ information related to human functioning; the environment also plays an important role in the final expression of this information. The environmental factors which can have an impact on the normal functioning of the genes include tobacco smoke, certain drugs and chemicals, toxins, foods, radiations; to name a few.

The genetic expression can be equated to dialling a phone number from the mobile handset. Whether one can connect correctly to the person one wishes to call depends on whether one has dialled the right number. Whether one can actually talk to the person at the other end, depends on the mobile network signal, the background noise; and other such ‘external’ factors. While environment cannot change the number which is dialled, it can affect the nature of the communication. Similarly, while environment cannot change the sequence of the DNA, it can change the way the genes express themselves.

Yes, it does double the risk of certain types of genetic diseases (autosomal recessive types), from 2.5% in the general population, to 5% in couples who marry amongst first cousins. The risk keeps reducing as the association by blood relation becomes more distant.

Yes, an expert analysis of your family tree with detailed history can help the geneticist to know the possible mode of inheritance of the disorder. Based on that information, the Clinical Geneticist can guide you about the risk of your other family members getting the same disorder.

Is there treatment available for genetic conditions? Genetic disorders result due to changes (mutations) at the level of the gene (which is a functional unit of the DNA and essentially present in every living cell). Thus, with the exception of therapy at the level of the gene (gene therapy) for few disorders; there are not many ‘curative’ options available for genetic diseases.

Certain haematological conditions like sickle cell anemia and thalassemia can be cured by bone marrow transplant. Management strategies can be designed to ameliorate some or most of the symptoms, and ‘support’ the patient. For example, if a child with developmental delay has an associated hearing loss, one can consider the option of hearing aids or cochlear implant (depending on the nature of the hearing loss). Early correction of hearing can facilitate timely development of language milestones and thus ameliorate the overall ‘developmental delay’ in a given child.

In certain disorders (inborn errors of metabolism) involving the ‘metabolism reactions’ in the human body, dietary modifications can be made. Some of these disorders are caused due to a deficiency in the enzyme of a critical metabolic reaction in the body; thereby causing deficiency of the downstream product and accumulation of the upstream reactants. This imbalance can lead to clinical manifestations of the disorder. Some of these patients can be treated special foods devoid of the nutritional elements which are known to accumulate in the disease and cause ‘toxic’ symptoms. Alternatively, the deficient enzyme can be supplemented ‘externally’.

Nearly 50% of the rare diseases affect children, 30% of them will die before 5 years of age. Nearly 80% of the rare disorders have an underlying genetic origin. Rational genetic tests, chosen judiciously can often help these families attain a timely diagnosis. Often confirmed, the accurate diagnosis is the first step towards understanding the depth and the breadth of the disease, exploring ways to minimise the complications, gathering supportive treatment options, and when-available providing curative therapies too. A delayed diagnosis especially for rare disorders of ‘genetic origin’, could mean another child born in the family with the same rare disease, often adding to the financial and emotional woes borne by them.

A rational choice of the genetic test from the many available options, depends on a thorough clinical judgement and patient evaluation. Depending on the test(s) considered most appropriate by your Geneticist, the cost could vary from Rs 3,000 to Rs 1,50,000 or more. These tests are usually not covered under insurance claims, so they could be perceived to be expensive.

If the tests are successful in arriving at a conclusion, the long-term cost of avoiding a ‘delay in diagnosis’, it is said, is in fact, more economical that the short-term cost of the genetic tests.

There is no cure for Down syndrome. In other words, the extra 21st chromosome copy, responsible for the clinical manifestations, cannot be inactivated in these children. However, with regular surveillance, we can keep a close watch for known complications/ associated features, and treat them in a timely manner. This helps to improve the quality and the longevity of lives of individuals with Down Syndrome.

Your physician has sent you to us, in order to evaluate you/ your child/ your family member for a suspected Genetic disorder.

Dual and quadruple marker studies are antenatal screening tools for pregnant women, in order to know if the baby in the womb is carrying any of the common genetic numerical errors (Down syndrome, trisomy 13, trisomy 18). It utilises a first trimester USG marker (nuchal thickness) along with the analysis of the mother’s blood drawn from a vein puncture. If the test results are suspicious or above the cut-off for normal, then the intrauterine baby’s DNA is checked, by a confirmatory test known as karyotype.

However, the combined (dual+quadruple) screening can miss around 5% of the fetuses with trisomy 13, 18, 21.

There are more sophisticated tests, like NIPS (Non-invasive Prenatal Screening), which has a very high sensitivity for these trisomies (nearing 99.9%). It is also carried out by drawing the mother’s blood drawn from a vein puncture. If the NIPT result is suspicious, then the intrauterine baby’s DNA is checked, by a confirmatory test known as karyotype.

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