Duchenne, the other disorder waiting for the panel

Duchenne muscular dystrophy was nominated to the Recommended Uniform Screening Panel in 2023 alongside metachromatic leukodystrophy. Both conditions had reached the evidence-review stage of the federal process. Both had foundation coalitions pushing for inclusion. Both were expected to come to a vote. Neither did. The Advisory Committee on Heritable Disorders in Newborns and Children was dissolved in 2025, and the federal infrastructure that would have placed Duchenne on every state's panel went with it.

The screening case for Duchenne is not a hypothetical. The screening test is creatine kinase, elevated in nearly every affected newborn before any clinical sign of muscle weakness has appeared. The intervention window is the years between birth and the onset of fiber damage that puts a child in a wheelchair. What that window is worth depends on what the available drugs do, and that depends on the variant.

What Duchenne is

Duchenne muscular dystrophy is an X-linked recessive disorder caused by loss-of-function variants in DMD on Xp21, the largest gene in the human genome. DMD encodes dystrophin, a structural protein that links the actin cytoskeleton inside muscle cells to the extracellular matrix outside. Without dystrophin, muscle membranes tear during contraction. Calcium leaks in. Fibers die. Muscle is replaced by fat and fibrous tissue. The clinical course follows the histology.

Boys with classic Duchenne typically appear normal at birth. Motor milestones are slightly delayed. Walking is often abnormal by age 3 with the characteristic Gowers sign, the way a boy uses his hands on his thighs to walk himself upright from the floor. Calf pseudohypertrophy is common. Strength declines over the next several years. Most affected boys lose ambulation between ages 9 and 13 in cohorts not on disease-modifying therapy. Cardiomyopathy and respiratory muscle weakness develop in adolescence and become the principal causes of death in the second and third decades. With current cardiorespiratory care, median survival has shifted into the late twenties and thirties; with corticosteroids and the newer modulator therapies, it shifts further.

Becker muscular dystrophy, the milder allelic disorder, results from variants that preserve some functional dystrophin. The clinical course is similar in shape but slower, with later onset and longer ambulation.

Reported live-birth incidence of Duchenne is roughly 1 in 5,000 to 1 in 7,000 boys. Female carriers can have manifesting features, ranging from elevated creatine kinase without weakness to a Becker-like phenotype, depending on X-inactivation patterns.

Detection and the screening case

Creatine kinase, CK, is the laboratory marker. CK is dramatically elevated in newborns with Duchenne, often 50 to 100 times the normal range, and the elevation is detectable on the dried blood spot. Newborn screening protocols use CK as the primary marker, with second-tier DMD gene sequencing on elevated samples to confirm the diagnosis and characterize the variant. The technical performance of the assay is well established. Pilot programs in New York and several international cohorts have run successful screening for years.

The screening case rests on early intervention. Corticosteroids, the longstanding standard of care, prolong ambulation and slow cardiomyopathy when started in early childhood. The exon-skipping antisense oligonucleotides (eteplirsen and others) and the more recent gene therapy delandistrogene moxeparvovec, marketed as Elevidys and approved by the FDA in 2023 for ambulatory boys aged 4 and older with a confirmed DMD variant, target subsets of the variant population and work better when fewer fibers have been lost. Givinostat, an HDAC inhibitor approved by the FDA in 2024 for ambulatory boys aged 6 and older, slows decline by addressing inflammatory and fibrotic processes downstream of dystrophin loss.

The drugs do not restore dystrophin to normal levels. They slow the rate at which the picture deteriorates. The earlier the intervention, the more muscle is preserved. Without screening, most boys are diagnosed at age 4 or 5 after gait abnormalities prompt pediatric referral. Pre-symptomatic identification on a dried blood spot would shift that to within the first weeks of life.

What the federal process would have done

The ACHDNC evidence review process for a candidate condition typically took two to three years. For Duchenne, the review focused on the analytical performance of dried blood spot CK assays, the predictive value of CK-positive screens for confirmed Duchenne (the false-positive rate is non-trivial because CK is also elevated in benign muscle conditions), the natural history baseline against which screen-detected outcomes would be measured, and the availability and cost of disease-modifying therapy. The case was strengthening as gene therapy and exon-skipping data accumulated. A federal recommendation would have followed the same path as every other RUSP addition: HHS Secretary acceptance, then a state-by-state implementation phase across roughly two to four years.

ACHDNC's dissolution stopped that process. Duchenne sits in the same position MLD sits in. State newborn screening programs operate independently. The infrastructure to add a condition state by state, without a federal anchor, is much weaker than the federal process. New York, the program with the most extensive Duchenne pilot history, has the strongest position from which to add the condition formally. Other states await an evidence framework that the federal apparatus is no longer producing.

What this looks like for a family

A boy born today with classic Duchenne, in a state that does not screen, will be brought to a pediatrician somewhere between his second and fourth birthday because his parents notice that he runs differently than his older brother did. CK will be ordered, will return tens of thousands of units per liter, and the diagnosis will follow. He will be started on corticosteroids. Depending on his specific DMD variant, he may or may not be eligible for exon-skipping therapy or for delandistrogene moxeparvovec. The clinical question becomes which combination of available therapies, started at this age, will produce the longest preservation of function.

The same boy born in a state that screens would be identified within the first weeks of life. Cardiac and pulmonary surveillance would begin in toddlerhood. Corticosteroids would be available before any fibers had been lost. Variant-specific therapies would be initiated at the earliest age supported by their respective labels. The trajectory, on the published data so far, would be measurably better.

The screening test costs a few dollars on a multiplexed panel. The treatments cost from thousands per year for steroids to several million for the gene therapy. Whether a boy is offered any of them at the earliest possible point is a question of the panel his state happens to run.