Newborn genetic screening: About the spinal muscular atrophy program (DEPISMA)

Spinal muscular atrophy (SMA) is a neuromuscular genetic disorder characterized by loss of motor neurons from the anterior horn of the spinal cord. Inheritance is autosomal recessive. SMN1 gene is implicated in the survival of the motor neurons. In 95% of cases, there is a biallelic deletion of exon 7 of SMN1. A homologous gene to SMN1, SMN2, is not functional, because of splicing of exon 7 of SMN2, but the severity of the disease is linked to the number of SMN2 copies. There are four clinical types of SMA and 60% of SMA type 1 die at age 18 months. Recently, three drugs have been evaluated in SMA. Nusinersen is an antisense oligonucleotide known to functionalize SMN2 gene. Administration is by regular intrathecal injections. This product has the authorization in France for the treatment of types 1, 2 and 3, and also for presymptomatic use up to three copies of SMN2. A gene therapy (Onasemnogene abeparvovec, Zolgensma (R)) is administered by a single IV injection and has the authorization in France for the same indications. Benefit is better with an early administration of the product, and for this reason, newborn screening has been promoted. A third drug (Risdiplam) is an oral treatment, but has not currently the authorization before the age of 2 months. SMA fulfills the Wilson criteria for newborn screening. Newborn screening is available in many countries, as Belgium, Germany, Taiwan, USA, Japan, Australia & mldr; In France, a pilot project is in process in two areas (Nouvelle-Aquitaine and Grand Est). We will test 2 x 55,000 babies/year, whether 32 children expected to be affected in two years. Newborn screening is effective by molecularely testing SMN1 gene biallelic deletion. Biological confirmation will include the analysis of the copy number of SMN2. When the diagnosis is confirmed, the patient file will be included in a French "RCP" (Multidisciplinary consultation meeting) to discuss the treatment modality.(c) 2023 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.