Neonatal hypotonia and neuromuscular weakness — structured clinical encounter

Station brief (candidate)

You are the neonatal registrar. A 3-month-old former term infant is referred with progressive floppiness, symmetric proximal weakness, tongue fasciculations and absent deep tendon reflexes. Between episodes the infant is alert and socially engaged. The creatine kinase is normal. The team asks you to make the bedside diagnosis, arrange the confirming test, and outline the disease-modifying therapy and its timing. You have 12 minutes with the team and 5 minutes for examiner discussion. [10]

Information available on request

• Former term infant, now 3 months; onset of floppiness noted from early infancy, progressive. [10]
• Symmetric proximal weakness greater than distal; tongue fasciculations; absent deep tendon reflexes; alert and socially engaged; no encephalopathy or dysmorphism. [10]
• Capillary glucose normal; creatine kinase normal. No perinatal asphyxia. [3]
• Reduced fetal movements and polyhydramnios were noted antenatally. [9]

Tasks

1. State whether this is a central or a peripheral hypotonia, justifying the call from the clinical features. [10]
2. Give the most likely diagnosis, its genetic basis, and the confirming test. [3]
3. Describe the disease-modifying therapy for which this infant is eligible, the supporting trial evidence, and the principle that governs its timing. [1]
4. Outline the supportive management priorities that run in parallel with disease-specific therapy. [9]

Marking anchors

Must-hit

• Makes the peripheral call: tone down AND true weakness AND absent reflexes AND tongue fasciculations, with preserved alertness and a normal CK — so the motor unit, not the brain, is failing. [10]
• Diagnoses spinal muscular atrophy type 1 from biallelic SMN1 loss with severity set by SMN2 copy number, confirmed by SMN1 deletion testing with SMN2 copy number. [3]
• Names nusinersen (intrathecal antisense that splices SMN2 to make functional SMN protein) and onasemnene abeparvovec (one-time IV AAV9 gene therapy); cites the ENDEAR trial (Finkel 2017, nusinersen motor and survival benefit versus sham) and the SPR1NT trial (Strauss 2022, pre-symptomatic onasemnene-treated infants sitting and walking); states the principle that motor neurons are lost irreversibly so therapy is most effective when started early, ideally pre-symptomatic. [1] [2] [5]

Merit

• Applies the newborn-screening treatment algorithm (Glascock 2018): a screen-positive infant with two SMN2 copies is offered disease-modifying therapy before symptoms, because the treatment bar is the genetic result, not the clinical examination. [5]
• Outlines supportive care in parallel — respiratory support monitoring the CO2 not just saturations, safe feeding to protect against aspiration, and physiotherapy and orthotic management — citing the Mercuri 2018 consensus standard of care. [3]
• Identifies that respiratory failure is the proximate cause of death in untreated motor-unit disease and that the saturations are a late, misleading sign in the hypoventilating infant. [9]

Fail

• Labels the infant as benign congenital hypotonia and defers genetic testing — the treatable, time-critical disease is missed. [1]
• Delays disease-modifying therapy while completing a non-essential work-up, during which motor neurons are lost irreversibly. [5]
• Monitors saturations alone in a weak, hypoventilating infant, so respiratory failure arrives unannounced. [9]