Background: In July 2018, Spinal Muscular Atrophy (SMA) was added to the Recommended Uniform Screening Panel (RUSP) given the ability to screen for SMN1 exon 7 deletions with quantitative PCR and the availability of new gene targeted therapies. SMA was added to the Illinois Newborn Screen (NBS) on June 29th, 2020. The Illinois NBS utilizes a qPCR assay where the Cq value is an indication of what cycle during the PCR assay SMN1 is detected. Cq values between 1 and 35 are the normal range. An assay with Cq = 0 is suggestive of absence of SMN1 and is called out as a positive screen. Cq levels greater than 35 are also called out as positive. Infants with a positive NBS for SMA are referred to specialized centers such Lurie Children’s for follow up diagnostic evaluation.
Objectives: Describe our center’s experience and clinical outcomes to date of infants evaluated for positive NBS for SMA.
Methods: Retrospective study that describes the outcomes (confirmed SMA vs. carrier cases, time to treatment, Cq values, and parental carrier status) of positive SMA NBS referrals seen at our center from June 29th, 2020 to November 30th, 2021.
Results: A total of 15 newborns with a positive NBS were referred to our center for further evaluation of SMA. Two of the 15 newborns were confirmed to have SMA via genetic testing (0 copies of SMN1 detected). Disease-modifying therapies for the two infants were initiated at day 20 and day 28 of life. The remaining 12 infants were found to be carriers of SMA (1 copy of SMN1 present). Of the 12 identified carriers, 5 had Cq levels = 0 and 7 had Cq levels greater than 35.
Conclusion: NBS is essential for early and equitable identification of patients with SMA. With genetic counseling following a positive NBS result, families were able to receive information about the possible follow up test outcomes, including a SMA diagnosis, SMA carrier status, or false positive NBS result. From our observations, providing detailed genetic counseling allows parents to better cope with the emotions that arise from a positive NBS result. To increase efficiency, methods to reduce false positives will need to be explored, without impacting the sensitivity of the assay.