Free screening to detect risk of passing down rare disorders

With just a blood test or cheek swab, some 40,000 married couples over the next three years will be able to find out for free if they are at risk of having children with a rare genetic disorder.

The voluntary pilot screening programme is now available to eligible couples at KK Women’s and Children’s Hospital (KKH) till 2027, with hopes that it will be expanded to other public hospitals in the future.

Funded by Temasek Foundation to the tune of $11 million, the Parenthood Genetic Disease Carrier Test, or Predict, will cover 80 severe recessive genetic disorders relevant for Asians. These are disorders that will result in a shortened lifespan and severe intellectual or physical disability, and affect one in 1,000 people locally.

One such disorder is spinal muscular atrophy, which results in progressive muscle weakness and paralysis. As at 2023, nearly 50 people in Singapore are diagnosed with the disease, and the estimated treatment costs per patient can come up to $800,000 a year.

At a briefing held at KKH on Sept 17, Associate Professor Saumya Jamuar, a senior consultant at KKH’s genetics service, said that most commercial screening panels are based on Western data, and not optimal for Singapore’s population.

Studies have found that most genetic test panels miss over 25 per cent of severe recessive disorders among Asians.

KKH worked with Temasek Foundation to design a customised genetic test panel for Singapore, which resulted in a screening panel that includes 20 diseases that are not covered in any such commercial panel currently, said Prof Jamuar.

One example is Shwachman-Diamond syndrome, which has an estimated incidence of one in 76,000 and leads to bone marrow failure.

The Predict screening can be conducted before or during pregnancy, and couples may be referred to the programme during obstetric visits at KKH. To be eligible for the screening, at least one partner needs to be a Singapore citizen or permanent resident.

Currently, carrier screening is conducted for disorders like thalassemia, a condition where sufferers are not able to produce normal haemoglobin and need a blood transfusion every month. Offered for all pregnancies since 1992, carrier screening has reduced the incidence of the disorder by over 90 per cent.

Antenatal screening – during pregnancy – is also extended for common chromosomal disorders like Down syndrome, and high-risk pregnancies where there is known family history of certain disorders.

In Singapore, three in 100 babies born each year have a rare disorder or birth defect, said KKH and the SingHealth Duke-NUS Maternal and Child Health Research Institute. Before Predict, there was no structured screening programme to detect those with rare disorders.

Screening for recessive genetic disorders is important to avoid a situation where parents discover the risk only after an affected child is born, said Prof Jamuar.

In recessive genetic disorders, a child would have inherited two copies of an abnormal recessive gene – one from each parent. Very often, parents with an abnormal recessive gene, who are also known as carriers, may not know that they have such a genetic trait as they have no symptoms.

“Screening of these disorders – all of which have onset in early childhood and can significantly impact a child’s lifespan and cognitive abilities – includes counselling for at-risk couples, to help them better understand the risks of potentially passing an inherited disorder to their child and make informed decisions about family planning,” said Prof Jamuar.

Overall, 99.6 per cent of couples screened are expected to be at low risk of having children with a rare genetic condition.

Only 0.4 per cent are expected to have a high risk as they are carrier couples, where both individuals have a recessive gene for the same genetic disorder. High-risk couples have a 25 per cent chance of conceiving a child with a rare genetic disorder.

“Through this programme, we expect to identify 160 couples who are at increased risk, and 40 babies who will be affected by one of these severe genetic diseases,” said Prof Jamuar.

He added: “This is about empowering couples with information. It’s a choice, and (the screening is) not mandatory. Couples who want to know are being given the opportunity to understand the risk.

“If the couple feel that, from their perspective, that is not something they believe in, we are not going to force them to take the test.”

High-risk couples detected under the programme will be supported by genetic counsellors to help them understand the results of the screening, as well as make informed decisions about the family options available to them, which range from adoption to using a sperm or egg donor.

If couples choose to conceive via in-vitro fertilisation, they can screen their embryos for specific genetic changes before implantation in a process called pre-implantation genetic testing.

For high-risk couples who are detected in the midst of pregnancy, they can choose to do prenatal testing to see if their child is affected. The invasive testing involves carefully removing some placental cells or amniotic fluid via a needle.

Some couples may decide to keep a pregnancy regardless of whether their baby is affected by a rare genetic condition, and may thus decline a prenatal test, Prof Jamuar said.

For couples whose babies are confirmed via prenatal testing to have a rare genetic condition, support is available, said Ms Christina Choi, senior principal genetic counsellor at KKH’s antenatal diagnostic centre.

“Some people choose to stop the pregnancy because they feel they’re not ready to take care of a child with special needs. There are also couples who will continue with the pregnancy regardless... After the baby is born, we optimise the situation by having doctors look at the baby and implement immediate treatment and care,” said Ms Choi.

She added: “I’ve seen couples terminating a much-wanted pregnancy. I’ve seen couples keep pregnancies that are severely affected by birth defects or genetic conditions. It’s hard to decide either way, and none of these decisions are made flippantly.

“At KKH, we have a big team of obstetricians, medical social workers and psychologists to help follow through with these couples, to make sure that they’re okay, not only physically, but mentally and emotionally as well.”

Mr Kee Kirk Chuen, head of health and well-being at Temasek Foundation, said: “This is not about making decisions for them, but about giving them more options – choices that empower them to plan for a future aligned with their values and hopes for the family and child.”

Based on the pilot, KKH will assess how to scale the programme by 2027.

Interested couples can e-mail carrierscreening@singhealth.com.sg, or get in touch via WhatsApp on 6394-3998.

KKH will be offering the test in a phased manner, starting with couples planning to start a family, and then expanding to include couples in the early stages of their pregnancy.