Problems with swallowing seen for SMA children despite early treatment
Development of needed skills lags behind healthy youngsters, study finds
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- Children with SMA, even with early treatment, show delayed swallowing development compared with healthy peers, a study found.
- Swallowing issues were more pronounced in symptomatic SMA children and those with fewer SMN2 gene copies.
- Monitoring swallowing development is essential for SMA patients, alongside motor function, to guide treatment strategies, according to the researchers.
Even when treated early with disease-modifying therapies (DMTs), infants and toddlers with spinal muscular atrophy (SMA) do not develop swallowing skills at the same pace or to the same level as healthy children.
That’s according to a new study from Germany, which tracked more than 30 children with SMA through the age of nearly 3. The researchers found that swallowing development lagged early in life for the SMA children and never fully caught up.
Delays and problems in swallowing occurred even in children treated before SMA symptom onset, and among youngsters with more SMN2 gene copies, who generally have less severe disease, the team noted.
“Our findings underline the necessity of monitoring swallowing development alongside motor function in both clinical practice and research settings,” the researchers wrote. “Additionally, we advise evaluating bulbar outcomes [impaired function in muscles of the face, mouth, and throat] based on SMN2 copy number during the first years of life to enhance understanding and treatment strategies.”
Poor swallowing skills among childeren with SMA can result in problems with feeding, first in an infant’s ability to drink milk at birth, and later with the ability to take food by mouth.
The study, “Swallowing development in infants and toddlers with spinal muscular atrophy following therapy compared to healthy controls: the prospective controlled DySMA trial,” was published in the Orphanet Journal of Rare Diseases.
SMA is chiefly caused by mutations in the SMN1 gene that result in a deficiency of the SMN protein, essential for muscle health. The loss of this protein results in degeneration or death of specialized nerve cells called motor neurons and in SMA symptoms such as muscle weakness and wasting.
Problems with swallowing can hinder feeding for SMA children
Children with SMA may experience swallowing issues due to weakness in the muscles of the tongue, jaw, throat, and neck, which can prevent them from getting adequate nutrition. Swallowing development can be used as an outcome measure for evaluating the effectiveness of DMTs, although “data on this aspect remain limited due to a lack of assessment tools,” the researchers wrote.
To learn more, researchers from the University Medical Center Hamburg-Eppendorf and the University of Luebeck, both in Germany, conducted the observational DySMA study (DRKS00029541), which wrapped up in 2024. The study enrolled 127 infants and toddlers: 35 with SMA and 92 healthy children, who served as controls. The children ranged in age from newborn to 35 months, or nearly 3 years.
About three-quarters of the children with SMA had two copies of the SMN2 gene, a so-called backup gene to SMN1 that produces much less functional SMN. The rest of the youngsters had three copies of the gene.
The most commonly used DMT was the gene therapy Zolgensma (onasemnogene abeparvovec-xioi), used alone. A few patients used Spinraza (nusinersen) or Evrysdi (risdiplam) alone, or one of these medications followed by the gene therapy. The children were divided according to whether they started their first DMT before symptom onset — 18 children in total — or after symptoms started, as was the case for the other 17 youngsters.
The primary goal was to assess swallowing development using DySMA, a score that features two parts — a patient history section reported by parents and a clinician examination — and is defined as the basic ability to drink milk at birth and progression to more advanced skills later in life. Higher scores, in a range of 0 to 35, indicate better swallowing development.
Better progress seen for children treated before symptoms started
The results demonstrated that the median DySMA score was lower in children with SMA than in healthy children (25 vs. 31), with the lowest values seen in symptomatic children and those with two SMN2 gene copies.
Children with SMA also had significantly different swallowing development trajectories than healthy children per month of life, with 0.45 point improvements in the controls in contrast with 0.06 declines in the SMA group. In the healthy group, children achieved the maximum score from 15-17 months onward, while no child with SMA reached that score.
Importantly, according to the researchers, the children with SMA treated before symptom onset demonstrated swallowing progress comparable to that of healthy children through about 15-17 months, but experienced a slight decline thereafter. The group of children with three SMN2 gene copies exhibited similar development to that of healthy children through 2 years of age.
“No significant differences were found for infants with three SMN2 copies, compared to [healthy controls] in any age group, suggesting that while two SMN2 copies correlate with poorer swallowing development, three SMN2 copies appear positively associated, aligning with the development trajectory of [healthy controls] over the first two years,” the investigators wrote.
While presymptomatic initiation of [disease-modifying therapy (DMT)] significantly predicts better swallowing development compared to starting DMT after symptom onset, it becomes evident that even these … children do not reach the same levels of swallowing capability as [healthy children] by 15-17 months.
Children in the presymptomatic and three SMN2 gene copies groups generally had better motor function, defined by higher scores in the CHOP-INTEND tool. That’s short for Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, a widely used measure for assessing children.
“Our findings demonstrate that infants and toddlers with SMA do not develop swallowing skills comparable to their healthy peers, even when they receive early DMT,” the researchers wrote.
The team noted that children with SMA also don’t catch up to their counterparts without the disease.
“While presymptomatic initiation of DMT significantly predicts better swallowing development compared to starting DMT after symptom onset, it becomes evident that even these … children do not reach the same levels of swallowing capability as [healthy children] by 15-17 months,” the team wrote.
The scientists noted that while some SMA children had a follow-up period as long as three years, the controls were followed only through their first two years of life. As such, “further development and the persistence of group differences, deterioration, or improvement remain unclear,” the investigators wrote.
