Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Apr 11;12(1):67.
doi: 10.1186/s13023-017-0613-5.

Cardiac pathology in spinal muscular atrophy: a systematic review

C A Wijngaarde  1 , A C Blank  2 , M Stam  3 , R I Wadman  3 , L H van den Berg  3 , W L van der Pol  4
Affiliations

Cardiac pathology in spinal muscular atrophy: a systematic review

C A Wijngaarde et al. Orphanet J Rare Dis. .

Abstract

Background: Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual levels of the ubiquitously expressed SMN protein. Alpha-motor neurons in the ventral horns of the spinal cord are most vulnerable to reduced SMN concentrations but the development or function of other tissues may also be affected, and cardiovascular abnormalities have frequently been reported both in patients and SMA mouse models.

Methods: We systematically reviewed reported cardiac pathology in relation to SMN deficiency. To investigate the relevance of the possible association in more detail, we used clinical classification systems to characterize structural cardiac defects and arrhythmias.

Conclusions: Seventy-two studies with a total of 264 SMA patients with reported cardiac pathology were identified, along with 14 publications on SMA mouse models with abnormalities of the heart. Structural cardiac pathology, mainly septal defects and abnormalities of the cardiac outflow tract, was reported predominantly in the most severely affected patients (i.e. SMA type 1). Cardiac rhythm disorders were most frequently reported in patients with milder SMA types (e.g. SMA type 3). All included studies lacked control groups and a standardized approach for cardiac evaluation. The convergence to specific abnormalities of cardiac structure and function may indicate vulnerability of specific cell types or developmental processes relevant for cardiogenesis. Future studies would benefit from a controlled and standardized approach for cardiac evaluation in patients with SMA.

Keywords: Cardiac abnormalities; Cardiac pathology; Kugelberg-Welander; SMA; Spinal muscular atrophy; Werdnig-Hoffmann.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flowchart of search and selection process. Summary of search and selection process of eligible articles for inclusion. *: predefined inclusion and exclusion criteria were applied, as shown in Table 2. WoS: ‘Web of Science’
Fig. 2
Fig. 2
Structural cardiac pathology in SMA type 1. Areas of the heart frequently reported to show cardiac defects in patients with SMA type 1 (n = 42) are shown in color. Rarely affected and unaffected areas are shown in shades of grey. Numbers indicate 1: atrial septum; 2: cardiac outflow tract; 3: patent ductus arteriosus; 4: ventricular septum
See this image and copyright information in PMC

References

    1. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371:2120–2133. doi: 10.1016/S0140-6736(08)60921-6. - DOI - PubMed
    1. Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Mol Med. 2013;19:40–50. doi: 10.1016/j.molmed.2012.11.002. - DOI - PubMed
    1. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155–165. doi: 10.1016/0092-8674(95)90460-3. - DOI - PubMed
    1. Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AH. The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet. 1997;6:1205–1214. doi: 10.1093/hmg/6.8.1205. - DOI - PubMed
    1. Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AH, Prior TW. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002;4:20–26. doi: 10.1097/00125817-200201000-00004. - DOI - PubMed

Publication types

MeSH terms

Substances