Genetic testing and counselling

Spinal muscular atrophy (SMA) is a genetic condition. It is one of the commonest inherited neuromuscular disorder.

Understanding underlying genetics and inheritance

• SMA is inherited as an autosomal recessive condition, which implies that, in most instances an affected child is born since he/ she inherits both mutated copies of the SMN1 gene from the carrier parents, who are unaffected, but has mutation in one of the two copies of the SMN1 gene.
• The carrier frequency is fairly high in the population and an affected child is born due chance marriage of two carriers.
• Testing for the carrier status is not widely available. Paucity of testing facilities compounded with lack of awareness makes it almost impossible to screen and detect carrier status before an affected child is born.
• Moreover, the risk of having an affected child is 25% when both partners are carriers, so many a times, many such families never come to medical attention.

• Even during the pandemic, genetic testing needs to be carried out for all suspected children with this disorder.
• Testing in children is done in blood and there is very little chance of transmission of the virus to the child during sampling and to the lab personnel if standard precautions are taken. Blood is collected in EDTA vials/ vacutainer tubes.
• DNA is extracted and molecular testing is done by MLPA technique. .
• In 95% to 98% instances, there is deletion of Exon 7 (and most of the times with Exon 8) detected in both copies of the SMN1 gene; for which MLPA is the right technique.
  Detection of SMN2 copy number by MLPA is important as it has implications in the clinical outcome and therapeutic strategies.
• Carrier status in parents can also be detected by MLPA. In 2% conditions, deletion in the other copy can be denovo. In 5% to 8% carrier individuals, both the normal Exon 7 can be in one copy of the gene and the other copy has deletion, which complicates the genetic testing for carrier status and its interpretation.
• Rarely other molecular techniques are required to confirm SMA.

Genetic testing to prevent recurrence of SMA

• Any form of medical intervention or procedure carries the risk of viral transmission to the patient and the health care providers. It is recommended that standard precautions should be taken to prevent pregnancy during the pandemic.
• In case there is a pregnancy in a couple who has a child with SMA (confirmed by molecular test), the risk of having another affected child is 25%.
• Chorionic villus sampling (CVS) is recommended at 11 to 12 weeks of pregnancy to know the status of the unborn baby. In case the fetus is found to be affected, the couple can opt for MTP (Medical termination of pregnancy).
• During the pandemic, centres to undergo procedure and testing centres may be difficult to reach. There are very few centres, like SGPGIMS Lucknow, AIIMS New Delhi and Sir Gangaram Hospital, where procedure and testing is done at the same centre.
• Travel restrictions mandates to search for a local centre for procedure and counselling and the transport of sample for testing to a reliable centre. Stepwise, it can be achieved in the following way:
  • Pregnancy confirmed by urine pregnancy test/ USG.
  • Helpline at CureSMA India and/ or E-OPD facilities/ Teleconsultation at reliable centres (SGPGIMS Lucknow, AIIMS New Delhi, Sir Gangaram Hospital, CMC Vellore, NIMS Hyderabad etc.).
  • Local centres offering CVS/ antenatal procedures helps in doing the procedure Transport of samples to reliable centres/ reliable private labs (Preferably the centre/ lab that did testing in the affected child in the same family).
  • Return back of results to the centre/ doctor who did the procedure for counselling and further action. Opinion through teleconsultation from the testing centre can also be sought in addition to counselling in case of any doubts.

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6. Personal opinion and literature search by Dr Kausik Mandal.