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. 2020;7(1):33-40.
doi: 10.3233/JND-190399.

Spinal Muscular Atrophy (SMA) Subtype Concordance in Siblings: Findings From the Cure SMA Cohort

Cynthia C Jones  1 , Suzanne F Cook  1 , Jill Jarecki  2 , Lisa Belter  2 , Sandra P Reyna  1 , John Staropoli  1 , Wildon Farwell  1 , Kenneth Hobby  2
Affiliations

Spinal Muscular Atrophy (SMA) Subtype Concordance in Siblings: Findings From the Cure SMA Cohort

Cynthia C Jones et al. J Neuromuscul Dis. 2020.

Abstract

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous survival of motor neuron 1 (SMN1) gene disruption. Despite a genetic etiology, little is known about subtype concordance among siblings.

Objective: To investigate subtype concordance among siblings with SMA.

Methods: Cure SMA maintains a database of newly diagnosed patients with SMA, which was utilized for this research.

Results: Among 303 sibships identified between 1996 and 2016, 84.8% were subtype concordant. Of concordant sibships, subtype distribution was as follows: Type I, 54.5%; Type II, 31.9%; Type III, 13.2%; Type IV, 0.4%. Subtype and concordance/discordance association was significant (Fisher's exact test; p < 0.0001). Among discordant sibships (chi-square test, p < 0.0001), Types II/III (52.2%) and Types I/II (28.3%) were the most common pairs. No association was found between sibling sex and concordance. Our findings show that most siblings with SMA shared the same subtype concordance (most commonly Type I).

Conclusions: These data are valuable for understanding familial occurrence of SMA subtypes, enabling better individual treatment and management planning in view of new treatment options and newborn screening initiatives.

Keywords: Child; epidemiology; genetics; growth & development; infant; mutation; neuromuscular disease.

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Conflict of interest statement

CCJ, SPR, JS, and WF are/were employees of and hold stock/stock options in Biogen. SFC was a consultant to Biogen at the time the research was conducted. JJ, LB, and KH are employees of Cure SMA.

Figures

Fig.1
Fig.1
Total sibships in the Cure SMA sibling database from 1996–2016 and number included in this analysis. SMA, spinal muscular atrophy.
Fig.2
Fig.2
Frequency of spinal muscular atrophy subtypes among concordant sibships in the Cure SMA sibling database from 1996–2016 (n = 257 sibships). Chi-square test, 170.72; p < 0.0001.
Fig.3
Fig.3
Spinal muscular atrophy (SMA) subtypes among siblings with SMA subtype discordance in the Cure SMA sibling database from 1996–2016 (n = 46 sibships). Chi-square test, 54.70; p < 0.0001.
Fig.4
Fig.4
Spinal muscular atrophy subtype concordance among same- and different-sex siblings in the Cure SMA sibling database from 1996–2016 (n = 303 sibships). Chi-square test, 0.40; p = 0.5268.
Fig.5
Fig.5
Spinal muscular atrophy subtype concordance among same-sex siblings in the Cure SMA sibling database from 1996–2016 (n = 171 sibships). Chi-square test, 1.09; p = 0.2963.
See this image and copyright information in PMC

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