Aim 1. To establish the validity of putative physiological SMA biomarkers in the immediate postnatal period. A longitudinal, natural history examination of physiological markers of muscle innervation will be performed in healthy and SMA infants. The first week of life is the ideal first time point, with visits occurring at scheduled visits up to the age two. Compound motor action potential (CMAP) amplitude and electrical impedance myography (EIM) will be examined and will be correlated with motor function. Each of these is associated with muscle innervation and provides information on the number and function of lower motor neurons in the spinal cord, the cellular target of SMA therapeutic interventions. This trial will establish the natural history of these putative SMA biomarkers as the disease evolves in affected infants. Moreover, our approach will allow for measurements in pre-symptomatic and early symptomatic subjects and determine their predictive value. Aim 2. To establish the validity of putative molecular SMA biomarkers in the immediate postnatal period. Survival Motor Neuron (SMN2) copy number is a valid, predictive molecular SMA biomarker; however, it is fixed, and therefore not useful as a biomarker of clinical progression or response to therapy. SMN messenger Ribonucleic acid (mRNA) ( and protein expression is variable in different cell types and, in mice, naturally decreases with age postnatally. In this study, SMN expression levels will be measured longitudinally in SMA patients and controls. Additional putative molecular SMA markers that have been identified to correlate with motor function will be determined in an effort to distinguish between predictive markers that change prior to development of weakness and those that change as a consequence of weakness.
Inclusion Criteria: All infants will be between 0-6 months of age at the time of enrollment. Parents or guardians of the enrolled infants must sign an informed consent form prior to any study procedure being performed. The infants with SMA must have already had a positive DNA test outside of the study to qualify for enrollment. An infant with SMA can have any number of SMN2 gene copies. Knowledge of the number of SMN2 gene copies prior to enrollment is not required. Healthy control infants who meet the following criteria will be enrolled: - Birth between 36 and 42 weeks inclusive of gestation - Siblings of children with SMA must have had prior SMA genetic testing completed con-firming the infant is a healthy control - Principal investigator feels the family/infant is able and willing to comply with study procedures - Parent or guardian able to give informed consent SMA infants who meet the following criteria will be enrolled: - Birth between 36 and 42 weeks inclusive of gestation - Positive SMN1 gene mutation/deletion - Principal investigator feels the family/infant is able and willing to comply with study procedures - Parent or guardian able to give informed consent Exclusion Criteria: - Use of any putative therapy intended to increase the amount of SMN protein in cells - Enrollment in an SMA therapeutic trial at the time of enrollment in the SMA biomarker study - Have a systemic illness requiring ongoing treatment, such as pneumonia - Clinically significant abnormal findings (as determined by the investigator) on the physical examination or medical history (including history of tracheostomy tubes and ventilator-dependency) - Dependency upon non-invasive ventilatory support (ie: BiPAP) for more than 12 hours/day