Carrier Screening Guidelines in India: The Way Forward

Carrier screening is likely to play an increasing and critical role in the prevention and management of genetic disorders. With the technique becoming available through various vendors and laboratories in India and with the considerable load of inherited conditions, the Society for Indian Academy of Medical Genetics (SIAMG) framed guidelines for Carrier Screening in December 2023. These have been endorsed by the Society of Fetal Medicine (SFM) and Federation of Obstetric and Gynecological Societies of India (FOGSI). These recommendations provide a roadmap for universal and expanded carrier screening (ECS), which is tailored to India's diverse genetic landscape.

This work quotes segments of these guidelines and recommends a practical way forward for each scenario.

Routine Universal Screening

Recommendation

In India, β-thalassemia, related hemoglobinopathies, and spinal muscular atrophy (SMA) are the most prevalent conditions warranting universal carrier screening. The high carrier frequency of these disorders necessitates routine screening for all couples, regardless of their perceived risk. Screening can be done sequentially before conception or simultaneously after conception, depending on when the couple presents for care.

The Way Forward

To ensure the program's effectiveness, continuous surveillance of heritable disorders should be conducted at the community and regional levels. Data from this surveillance can help refine screening protocols, especially for ethnic and consanguineous populations where the burden of autosomal recessive disorders is higher. It is also crucial to establish and maintain a national registry, ideally under a public institution like the Indian Council of Medical Research (ICMR), to track incidents and outcomes and guide future policy.

Expanded Carrier Screening

Recommendation

ECS goes beyond the scope of universal screening and should be selectively offered. It is especially relevant for families with a history of suspected genetic disorders where diagnostic testing is not feasible due to the death of the affected individual or the lack of available samples. ECS is also appropriate for consanguineous couples seeking preconception counseling and for those with a history of poor obstetric outcomes such as unexplained stillbirths, second trimester pregnancy losses, or fetal malformations suggestive of monogenic etiology, particularly when fetal samples are unavailable. However, ECS is currently constrained by resource limitations, such as the known mutation spectrum in the Indian population and the complexities associated with variants of uncertain significance.

The Way Forward

To address this, a task force should be constituted to compile condition specific ECS lists tailored to different clinical scenarios.

Technology Selection

Recommendation

Technology selection is a critical component of carrier screening. For β-thalassemia, a combination of red blood cell indices and hemoglobin separation using high performance liquid chromatography or equivalent methods for HbA2, HbS, and HbE is recommended. SMA screening should be performed using multiplex ligation dependent probe amplification or quantitative PCR. For ECS, next generation sequencing is the preferred method, offering broad and sensitive detection of relevant genetic variants. In cases of recurrent pregnancy loss, subfertility, or a family history of chromosomal translocations, karyotyping may also be considered.

Reproductive decision making should be based on the identification of pathogenic or likely pathogenic variants, particularly when both partners are carriers of the same autosomal recessive disorder or when the female partner is a carrier of an X-linked condition. When variants of uncertain significance are detected, couples should be referred to clinical geneticists for expert interpretation and counseling.

The Way Forward

To implement these guidelines effectively, it is essential to invest in the training and certification of genetic counselors. Defined educational pathways, ranging from degrees and diplomas to certification programs, must be developed, with clear curricula, assessment standards, and the inclusion of both public and private training institutions.

When Should Testing Be Offered

Recommendation

Carrier screening is ideally performed during the preconception period, allowing couples the broadest range of reproductive options. If preconception testing is not possible, screening should be offered early in pregnancy. For ECS, the timing and approach depend on when couples seek care. Simultaneous screening of both partners is recommended after conception to avoid delays in decision making. Preconception visits, however, allow for sequential testing. These protocols should be integrated into counselor training to ensure consistent and effective practice.

The Way Forward

Given the widespread use of digital platforms, social media presents a valuable tool for educating the public about carrier screening. A dedicated committee should be tasked with developing and managing content that engages different demographic groups. In parallel, awareness efforts must be extended to school health programs, NGOs, and frontline healthcare providers such as family physicians and obstetricians.

Final Comments

India's approach to carrier screening must be multipronged, encompassing public education, professional training, and technological readiness. Strengthening awareness among healthcare providers and the general population, building partnerships with the private sector, and investing in institutional infrastructure is key to building a sustainable and impactful carrier screening program. With the right strategy, India can take significant strides in reducing the burden of genetic disorders and empowering individuals with informed reproductive choices.