We describe a case of spinal muscular atrophy diagnosed in an infant despite previous parental carrier testing suggesting low risk of the disease. This case report explains how this situation arose and illustrates that clinicians need to perform diagnostic testing in children where clinical suspicion for spinal muscular atrophy is high, regardless of the result of previous parental carrier testing, because of the risk of false negative results.
VerhaartIECRobertsonAWilsonIJ, et al.Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy—a literature review. Orphanet J Rare Dis. 2017;12(1):124.
2.
SugarmanEANaganNZhuH, et al.Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012;20(1):27–32.
3.
MendellJRAl-ZaidySShellR, et al.Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377(18):1713–1722.
4.
MercuriEDarrasBTChiribogaCA, et al.Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625–635.
5.
PriorTW. Spinal muscular atrophy: newborn and carrier screening. Obstet Gynecol Clin North Am. 2010;37(1):23–36.
6.
OginoSWilsonRBGoldB. New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations. Eur J Hum Genet. 2004;12(12):1015–1023.
7.
SmithMCalabroVChongBGardinerNCowieSdu SartD. Population screening and cascade testing for carriers of SMA. Eur J Hum Genet. 2007;15(7):759–766.
8.
WirthBHerzMWetterA, et al.Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Hum Genet. 1999;64(5):1340–1356.
9.
CusinVClermontOGerardBChantereauDElionJ. Prevalence of SMN1 deletion and duplication in carrier and normal populations: implication for genetic counselling. J Med Genet. 2003;40(4):e39.
10.
LuoMLiuLPeterI, et al.An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 2014;16(2):149–156.
11.
ArchibaldADSmithMJBurgessT, et al.Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests. Genet Med. 2018;20(5):513–523.
12.
BoardmanFKYoungPJGriffithsFE. Population screening for spinal muscular atrophy: a mixed methods study of the views of affected families. Am J Med Genet A. 2017;173(2):421–434.
13.
GitlinJMFischbeckKCrawfordTO, et al.Carrier testing for spinal muscular atrophy. Genet Med. 2010;12(10):621–622.
14.
WirthBSchmidtTHahnenE, et al.De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling. Am J Hum Genet. 1997;61(5):1102–1111.
