A 3-Month-Old Boy with Generalized Hypotonia, Weakness, Pneumonia and Respiratory Failure

Spinal muscular atrophy (SMA) is an autosomal recessive disease caused in most cases (95%) by a homozygous deletion of exons 7 and 8 of the survival motor neuron gene 1 (SMN1). SMN2 is consider a “back up” gene and the number of SMN2 copies determines the clinical phenotype. It is classified as types 0–4 depending on the age of onset and maximal motor function achieved. Clinically these patients have proximal and distal weakness, as well as areflexia. Diagnosis of SMA consists of molecular genetic testing with targeted mutation analysis of the SMN1 gene and copy number analysis of the SMN2 gene. Muscle biopsy is becoming increasingly uncommon; if done, it shows islands of markedly hypertrophic type 1 fibers floating in a sea of small mixed type 1 and 2 fibers in SMA type 1 and type 2. Management involves a multidisciplinary approach. Currently, Nusinersen is the only treatment approved by FDA for SMA. There are several therapeutic molecules under development, targeting other mechanisms of the disease. The prognosis for these patients is rapidly changing with the new therapy development.