Awareness of genetic diseases is significantly increasing

Dr Shailesh Pande, Genetic Counselor Metropolis Healthcare speaks on the trends in genetic diagnostics and the way forward in this field, in an interaction with Raelene Kambli

What are the latest trends in genetic diagnostics?

• Micro array: With an increasing trend for high quality healthcare testing, microarray is the fastest growing segment in diagnostics. Evolution and development of microarrays by biotech companies have dealt with the market requirement of speedy results based not only on high resolution and coverage but by providing an easy and robust data analysis system.

In clinical genetics there has been a transition where chromosomal microarray is the first-tier diagnostic test for individuals with developmental disabilities, multiple congenital anomalies, intellectual disabilities and autism spectrum disorders as per the guidelines by American Society of Clinical Genetics.

Microarray technologies have explored the field of cancer genetics with an aim to give faster cancer diagnosis and management. Treatment decisions in cancer are offered based on cancer profiling and biomarkers.

• Next generation sequencing (NGS): An NGS test gives tremendous throughput and speed and allows researchers to study and analyse at a micro level that was not possible earlier. These tests are rightly filling the void with DNA sequencing tests and are giving answers to many questions. With NGS it has become possible to refine diagnosis, individualise treatment, and prevent drug effects and development of new therapies. NGS will be a very valuable asset in genetic diagnostic in coming years.
• Non-invasive prenatal testing (NIPT): NIPT is a new technology by means of which prenatal screening for common aneuploidies in pregnant women can be done from peripheral blood i.e. by non invasive techniques rather than invasive techniques like CVS and amniocentesis and can be carried out much earlier than invasive techniques. One can overcome the possibility of procedure related miscarriages (though small) associated with invasive methods. Basically it is carried out in circulating cell-free DNA in maternal blood. NIPT falls in between being a screening and a diagnostic test. Abnormal result in NIPT has to be confirmed by invasive test like chorionic villus sampling (CVS) or amniocentesis.

Is genetic diagnostic a booming market in India?

India is experiencing a shift towards prevalence of non – communicable diseases. As per recent studies, India has secured third position in congenital malformations and genetic disorders as the commonest cause for neonatal mortalities in cities.

Awareness of genetic diseases is significantly increasing in India and there is a dire need for adequate and effective genetic testing and genetic counselling services. There are multiple reasons for upsurge in genetic diseases in India; some of them can be summarised as consanguineous marriages, high birth rate, late marriages, and availability of improved diagnostic facilities. Today, very few clinics and labs are providing advanced cytogenetic, biochemical/metabolic, molecular and prenatal diagnosis services and genetic counselling under one roof. There is tremendous scope for genetic testing in India. Metropolis has been at the forefront in adopting global practices and will continue to make the right investments to provide the very best.

What are the opportunities and challenges?

The biggest challenge is in creating awareness of the significance of genetic tests and to make people understand that many of the genetic problems are now treatable. If not treatable they are certainly preventable. Lack of accredited and authorised genetic labs across the nation and counselling services is proving to be a huge impediment to spread the right kind of awareness.

At Metropolis, we have a set protocol that we follow for genetic tests. We send a detailed counselling letter to patients whose samples have come to us for genetic testing if a face to face meeting is not possible. Metropolis is also well positioned with its network of labs across India, collection centres and a seamless logistics team that makes it possible for samples to reach us in the stipulated time. Once the analysis and reporting of the sample is complete, every opportunity is taken to discuss the case with referring clinician and after obtaining detailed medical history, counselling letter addressing to the doctor is issued

What does Metropolis Cytogenetics offer?

We offer the full scope of cytogenetic and Fluorescence In-situ Hybridisation (FISH) tests as well as genetic counselling under one roof.  There is a wide range of cytogenetic and FISH tests for different indication on different tissues like blood, bone marrow, product of conception, prenatal and solid tumours. There are some common conditions and diseases wherein genetic tests are followed or a couple with molecular diagnostic tests.

Metropolis is one of the few labs offering prenatal diagnostic tests. We have also developed Sperm FISH for repeated pregnancy losses with aneuploidies and cases with abnormal semen analysis reports.

Metropolis is the only lab in India to offer genetic counselling services to its customers. It is an education and training initiative which aims to spread knowledge about genetic aspects of illness in terms of risk analysis, presence of heritable disorder or of chances of passing it to their unborn offspring with following principle elements: diagnostic and clinical aspects, documentation of family and pedigree information, recognition of inheritance patterns risk estimation, scientific communication and empathy in those seen, information on available options and further measures, support in decision making and discussion on cost effectiveness.

Genetic counselling can be offered to large number of genetic disorders for different conditions and different age groups such as:

• Pre-conceptional, prenatal genetic counselling
• Postnatal (paediatric, pubertal, adults) genetic counselling
• Premarital genetic counselling
• Counselling in cancer genetics.

Can you elaborate on some of the studies you are working on?

Currently we are conducting the following studies:

• Prenatal: Karyotyping  and FISH from amniotic fluid
• Postnatal: Karyotyping  and FISH from blood in various paediatric cases, infertility, BOH, products of conception
• Cancer genetics: Karyotyping  and FISH in various blood cancers ,solid tumours like breast cancers
• Sperm FISH: In males with abnormal semen analysis report and repeated pregnancy losses with foetal aneuploidies.

Why is counselling an important aspect of providing genetic diagnostics at Metropolis?

When the doctor suspects some responsible genetic factor then he refers the patient to a genetic counsellor. Genetic counselling is a process of communication and education to increase understanding of genetic disease, discuss disease management options, and explain the risks, benefits and limitations of tests.

After obtaining detailed family, medical, and obstetric history, genetic counselling gives clear, accurate information to make an informed choice of option for the patients, to know what test to be conducted and what is best for them.

In which areas of genetics diagnostics counselling should be offered and why?

Here are some indications  where genetic tests and genetic counselling can be offered. Some of the examples where genetic testing and counselling is offered:

Infants/ Children

• Ambiguous genitalia
• Dysmorphism
• Syndromic appearance
• Congenital abnormalities
• Suspected metabolic disorders
• Growth retardation
• Deaf mutism/ blindness
• Prepupertal/ pubertal

Pubertal disorder

• Underdevelopment of secondary sex character, short height, gynecomastia, hypospadias, genital abnormalities

USG abnormalities

• Absent/ rudimentary UT or absent/streak ovaries
• Primary and secondary amenorrhea
• Mental retardation
• Fragile X syndrome (previous baby)
• Epilepsy, autism, muscular disorders

Preconceptional and prenatal

• Consanguineous marriage
• Members of high risk ethnic group
• Maternal disease (eg. diabetes, Phenylketonuria)
• Single gene disorder (thalassemia, Duchenne muscular dystrophy)
• Infertility or patient on ARTs
• Two or more pregnancy losses
• Previous child or family with H/O genetic/ birth defect.
• Positive Minimum Spanning Tree
• Abnormal ultrasound
• Adverse maternity age

Premarital genetic counselling

• Assist an individual or family to decide whether to proceed and choose appropriate genetic testing.
• Confirmation of clinical diagnoses or rule out a genetic disorder.
• Identify at risk group.
• Support family members and provide information about support groups and local service agencies.

How does accreditation impact the genetic testing labs?

Accreditation is important because these tests are specialised tests and requires the right kind of automation, skilled technicians, trained team and moreover the hands and eyes of an experienced team. It is important that the laboratory adheres to protocols and follows global standards. These tests are important because it could be life changing for the patient and then there is absolutely no room for technical or manual error. Error free diagnosis is critical because doctors depend on diagnostics reports for disease management diseases.

At Metropolis quality is a way of functioning, simply because it guarantees accurate and reliable results. Because we insist on pin-point precision even on routine tests, there is no compromise in upholding highest standards of quality. Every process and every technician in cytogenetic is oriented towards quality. Apart from our stringent internal quality programmes we are following norms of PCPNDT, National Accreditation Board for Testing and Calibration Laboratories (NABL), and College of American Pathologists (CAP).

What is the way forward for genetic diagnostics in India?

• Increased awareness of genetic tests and its applications
• Proving genetic counselling services to tertiary level by building strong network for logistics
• Detailed counselling letters and tele-discussion of reports and assistance can help change the existing situation. It will also help the population choose a proper genetic test
• Reflex strategies and optimisation of test and test panels for benefit of patient
• Mass screening for most common genetic diseases prevalence in certain geographic locations or tribal populations with the help of government bodies and healthcare insitutions E.g. beta thalassemia

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