German and Australian researchers report the case of two newborns who tested positive at birth for SMA:
- during the initial routine analysis, a homozygous deletion of the SMN1 gene was identified;
- as the confirmatory test using complementary techniques (ddPCR, MLPA) proved negative, the hypothesis of an unusual genotype was then put forward,
- two distinct rearrangements of 4 base pairs each were subsequently identified on the corresponding alleles and were found not to be pathogenic, as demonstrated by functional studies,
- the children who tested false positive were therefore not treated and are doing well, 24 months on.
This scenario remains extremely rare (a few per cent) but confirms the existence of pitfalls in neonatal screening for SMA.
