Spinal Muscular Atrophy During Human Development: Where Are the Early Pathogenic Findings?

  • Eduardo TizzanoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 652)


Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects motor neurons. It is caused by mutations in the survival motor neuron gene 1 (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present in all patients, is unable to prevent the disease. SMA patients can be classified into four groups based on age at onset and acquired milestones (type I or severe acute disease, with onset before 6 months; type II, before 18 months; type III, after 18 months and type IV, in adult life). The human developmental period is believed to play an essential role in SMA pathogenesis. However, the neuropathologic study of SMA comes largely from postnatal necropsy samples, which describe the end-stage of the disease. With the exception of severe congenital SMA (or Type 0 SMA), type I patients tend to present a short but variable presymptomatic period after birth. Our main interest lies in studying SMA during human development so as to gain insight into the mechanism of the disease in the prenatal – presymptomatic stage. In fetuses of 12–15 weeks’ gestational age we systematically studied histology, cell death and gene expression in spinal cord and muscle, the key tissues involved in the disease. Furthermore, ultrasound parameters were investigated at these stages. These studies may help to delineate an early intervention in SMA, in particular during the potential therapeutic window.


Spinal muscular atrophy Prenatal diagnosis Histology Apoptosis Gene and protein expression Fetal movements 



I wish to thank the consenting parents and SMA families who made this study possible and Rebeca Martínez-Hernández, Carolina Soler-Botija, Laura Alias, Sara Bernal, Eva Also, María Jesús Barceló, Juan Parra, Ivón Cuscó, Carolyn Newey and Montserrat Baiget for their invaluable collaboration.


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Genetic and Research Institute Hospital de la Santa Creu i Sant Pau and CIBERERBarcelonaSpain

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