Dr. Anya Kleinman
Two-month-old male presented with unknown duration of respiratory distress. He had been “breathing fast since birth” with no acute fevers, vomiting, or sick contacts. Review of systems is notable for diffuse muscle weakness and chronic coughing with feeds. Developmental history is significant for lifelong decreased movement and inability to lift head when prone. No family history of motor delay or decreased tone.
Vitals: afebrile, HR 163, RR 68, PO2 92%. Patient is ill-appearing with minimal response to tactile stimuli. The evident tachypnea is associated with increased abdominal muscle use with retractions and grunting. Neurological exam has open, flat, anterior fontanelle with profound head lag and “frog-legging” of lower extremities. Deep tendon reflexes cannot be elicited. Skin exam is negative for rashes or hematomas.
After further evaluation and management, he was diagnosed with spinal muscular atrophy (SMA).
Initial management of hypotonic infant is multi-faceted given the broad differential that includes suspicion for congenital pathologies and acute ingestion, as well as sepsis and non-accidental trauma. Thorough history-taking and physical exam are essential to distinguishing between the various causes. SMA and infantile botulism especially should be considered in the setting of diffuse hypotonia on exam and appropriate supportive care initiated pending confirmatory testing. Other sources of “floppy baby” include genetic causes of weakness such as Prader-Willi syndrome, glycogen storage diseases, and metabolic disorders.
Acute management includes pan-cultures and broad-spectrum antibiotics given the potential for sepsis with this clinical presentation. Screening labs also help to distinguish infectious from non-infectious etiology. Oral gastric tube for abdominal decompression is helpful when there is significant distension with tachypnea and concern for impending respiratory failure; abdominal distension in the neonate can impair already weak diaphragmatic and intercostal muscles further increasing the work of breathing. Caution should be exercised before intubating patients with suspected SMA given the minimal reserve and predisposition for muscular deconditioning following intubation.
In our patient, WBC was normal with lymphocytic predominance; serum ammonia and CRP were without elevation. Toxicology screen was negative with normal newborn screen at birth. Head CT to evaluate for NAT was negative for intracranial pathology. Chest Xray (figure 1) was characteristic of the suspected diagnosis of SMA; it demonstrated greater impairment of the intercostal muscles than the diaphragm with the development of the classic, bell-shaped chest deformity. The noted paradoxical breathing—with inspiratory effort causing inward movement of the rib cage and outward movement of the abdomen—was also attributable to this discrepancy in muscle involvement.
Spinal Muscular Atrophy:
Spinal muscular atrophy is an autosomal recessive, hereditary neuromuscular disorder; it is characterized by progressive proximal muscle weakness from degeneration of the anterior horn cells of the spinal cord. It is the most common genetic cause of infant mortality. SMA type 1—also called Werdnig-Hoffmann disease—presents prior to 6 months of age. Though symptoms can be retrospectively noted from the newborn period, the diagnosis of SMA is often precipitated by an acute presentation of decompensated, respiratory distress.
All traditional therapies are currently supportive and aimed at nutritional and respiratory sufficiency. For our patient, SMA type 1 was diagnosed by emergent EMG and confirmed with genetic testing. A gastric tube was placed along with Nissen fundoplication when recurrent aspiration with all liquids was noted on modified barium swallow. The family choose supportive, home BiPAP as needed with close pulmonology and comprehensive care follow-up outpatient.
In December 2016, The FDA approved the first curative therapy for SMA- Sprinaza: an antisense oligonucleotide that modulates splicing and survival of the impaired protein’s mRNA.
– Leyenaar J, Camfield P, et al. A schematic approach to hypotonia in infancy. Paediatrics & Child Health. 2005;10(7):397-400.
– Prior, T, Russman, B. Spinal Muscular Atrophy. Gene Reviews. 2013- updated 2016.