Spinal muscular atrophy: Case

Summary and immediate impression

This infant presents a textbook case of type 1 spinal muscular atrophy, or Werdnig-Hoffmann disease. The reduced fetal movements, the severe symmetric proximal weakness worse in the legs, the absent deep tendon reflexes, the tongue fasciculations, and the paradoxical breathing with a bell-shaped chest, all in a bright and socially engaged child whose intellect is spared, are the signature picture. The contrast between the alert face and the limp body is the single most valuable bedside clue, and the diagnosis is the homozygous SMN1 deletion test. [1]

The first 24 hours — diagnosis, resuscitation, and the workup

I would confirm the diagnosis urgently with a genetic test for the homozygous deletion of SMN1 exon 7, which is present in over ninety-five percent of affected individuals and confirms the diagnosis in this clinical picture without further testing. I would order the SMN2 copy number together with the deletion test, because it predicts the type and the urgency of treatment, and I would not delay for electromyography or muscle biopsy, which the genetic test makes unnecessary. I would send a creatine kinase to help exclude a muscular dystrophy, a sleep study and pulmonary function testing to quantify the respiratory reserve, and a swallowing assessment to guide nutrition. [1]

My immediate management protects the airway and the breathing while the diagnosis is confirmed. The paradoxical breathing and the weak cough with pooled secretions signal impending ventilatory failure, and I remember that carbon dioxide retention precedes hypoxaemia in neuromuscular respiratory failure, so a normal oxygen saturation does not exclude it. I would involve the paediatric intensive care team early, suction the secretions, position the child, assess the swallow, and introduce cough-assist devices and non-invasive ventilation. I would secure nutrition with a nasogastric tube given the bulbar weakness, and I would contact the paediatric neuromuscular service immediately, because the disease-modifying therapy should begin as soon as the diagnosis is confirmed. [2]

Disease-modifying therapy — choice and evidence

Three disease-modifying therapies are licensed for this infant, and the principle is to start early because motor neurons lost before treatment do not recover. Nusinersen is an intrathecal antisense oligonucleotide that forces SMN2 to include exon 7, given as a loading course on days one, fifteen, twenty-nine, and sixty-four then every four months, and the ENDEAR trial showed it improved motor function and reduced the risk of death or permanent ventilation in type 1 disease. Risdiplam is a daily oral small molecule that stabilises the same splicing step, and the FIREFISH trial showed it improved survival and motor function in type 1 disease. [4][8]

Onasemnogene abeparvovec is a single-infusion AAV9 gene therapy that delivers a working copy of the SMN1 gene, and this infant is under two years of age and meets the criteria. The Mendell 2017 pivotal trial showed dramatic motor gains in type 1 infants, and the STR1VE trial confirmed the benefit in symptomatic infants with two SMN2 copies. The choice between the three therapies turns on the centre, the family, and the local funding, with the shared goal of preserving the surviving motor neurons, and I would make the decision with the paediatric neuromuscular service as soon as the diagnosis is confirmed. [6]

Multidisciplinary care and the long-term course

The drug is only part of the treatment, and the multidisciplinary care is as important as the therapy. The respiratory support runs throughout, with cough-assist and non-invasive ventilation to clear secretions and support the breathing, and the orthopaedic surveillance for scoliosis and contractures begins early because the spine curves with growth and compounds the restrictive lung disease. The swallow is assessed and a gastrostomy secures nutrition when it is unsafe, the physiotherapist and the orthotist address the contractures and the mobility, and the developmental and educational support runs alongside. I would track the motor function with the CHOP-INTEND score to set the baseline and measure the response, because the family and the team need to see the numbers. [2]

Prognosis, counselling, and follow-up

I would tell the family the single most important fact: early treatment changes everything. Untreated type 1 disease was universally fatal before two years of age, and with presymptomatic nusinersen in the NURTURE study the great majority of infants survived without permanent ventilation, most sat, and many walked, outcomes impossible in the natural history. I would be honest that this infant is symptomatic rather than presymptomatic, so the gains are real but less dramatic than in the screen-positive infant, and that the multidisciplinary respiratory, nutritional, and orthopaedic care is as important as the drug. [9][11]

I would explain that spinal muscular atrophy is autosomal recessive, that each future child has a one in four chance of being affected, and that carrier testing and prenatal and preimplantation diagnosis are available. I would emphasise that newborn screening and early treatment now define the standard of care for any future affected child, because the disease does not discriminate and neither should the care. I would arrange genetic counselling, peer support, and social work input, and I would plan a coordinated transition to adult neuromuscular care in the late teenage years as the treated child grows. [1]

Marking domains

• Diagnosis and reasoning: recognises the bright-and-floppy pattern of symmetric proximal weakness with absent reflexes and tongue fasciculations and spared intellect, and confirms the diagnosis by the homozygous SMN1 deletion test. [1]
• Management — resuscitation: protects the airway and breathing, treats the carbon dioxide rather than the oxygen saturation, and introduces cough-assist and non-invasive ventilation early. [2]
• Management — definitive: chooses disease-modifying therapy from the ENDEAR FIREFISH and STR1VE evidence and treats urgently, layered on multidisciplinary care. [4][6][8]
• Communication: counsels the family on the transformed prognosis, the one in four recurrence risk, and the newborn screening pathway for future children. [9]