Facioscapulohumeral muscular dystrophy is an inherited muscle disease in which weakness starts in the face, the shoulder blades and the upper arms, then moves to the lower legs and, later, the hips. GeneReviews puts its prevalence at four to ten per 100,000 people, and reports that around 20% of affected individuals eventually need a wheelchair. Almost every case traces back to the same molecular event: a shortened repeat array on chromosome 4 that allows a gene called DUX4 to switch on in muscle, where it is normally kept off.
No drug is approved to treat it. That fact sits behind an unusual amount of myostatin-pathway research, because FSHD has been a repeated test case for the idea that growing muscle should restore function. So far it has not, and the size of that gap is the most useful thing to understand about the condition.
What the name actually describes
The three roots are anatomical. Facio is the face, scapulo the shoulder blade, humeral the upper arm. GeneReviews describes FSHD as progressive muscle weakness "involving the face, shoulder girdle, upper arm, lower leg (peroneal muscles), and hip girdle in later stages."
In practice that means three signs tend to appear first: weakness of the facial muscles, scapular winging where the shoulder blades stand away from the back wall of the chest, and weakness of the foot dorsiflexors, the muscles that lift the front of the foot when walking. Onset is typically in the teens, though GeneReviews notes significant variability around that.
The condition is progressive but not uniformly disabling. The 20% wheelchair figure means most people never reach that point, and the range of severity within a single family can be wide.
The genetics: two routes to one outcome
FSHD is split into two genetic types that converge on the same result.
FSHD1 accounts for roughly 95% of cases. It results from a heterozygous contraction of the D4Z4 repeat array on chromosome 4q35. A normal allele carries 11 or more repeat units. Contractions of 7 or fewer units are fully penetrant; 8 to 10 units carry reduced penetrance. Crucially, the contraction only causes disease on a permissive chromosome 4 haplotype, typically 4A161. The D4Z4 region itself contains an open reading frame encoding the DUX4 protein, which has two homeoboxes.
FSHD2 covers about 5% of cases and reaches the same endpoint by a different road. Instead of the array being shortened, it is hypomethylated. That hypomethylation is caused by heterozygous variants in SMCHD1 in around 85% of FSHD2 cases, or in DNMT3B, or by biallelic variants in LRIF1. FSHD2 also requires a permissive chromosome 4 haplotype.
Both routes loosen the epigenetic silencing over D4Z4. The consequence is that DUX4, a transcription factor that belongs in early embryonic development and germline tissue, becomes expressible in skeletal muscle. That is why the modern drug pipeline is largely aimed at DUX4 rather than at muscle mass, and it is also why a genetic diagnosis matters: the same clinical picture can come from a contraction, from an SMCHD1 variant, or from both together.
How it is coded and diagnosed
Diagnosis rests on the clinical pattern plus genetic testing, since the repeat contraction and the methylation status are both measurable.
For records and billing, ICD-10-CM assigns facioscapulohumeral muscular dystrophy its own code, G71.02. It sits alongside G71.00 (muscular dystrophy, unspecified), G71.01 (Duchenne or Becker), the G71.03 series for limb girdle subtypes, and G71.09 for other specified muscular dystrophies. A more complete walkthrough of that code family is in our muscular dystrophy ICD-10 guide.
Why myostatin inhibitors keep getting tested in FSHD
The reasoning is straightforward. Myostatin is a negative regulator of skeletal muscle mass. Block it and muscle grows. In a disease defined by muscle loss, more muscle ought to mean more function. FSHD has been an attractive place to test that because the weakness is patchy, leaving some muscles relatively preserved and therefore, in theory, responsive.
Three trials have now put that reasoning to the test in FSHD patients, and the results have been consistent in an uncomfortable way.
MYO-029 (stamulumab), 2008. Wagner and colleagues ran a phase 1/2 trial of a myostatin-neutralizing antibody in 116 adults with Becker muscular dystrophy, FSHD and limb girdle muscular dystrophy, across dose cohorts of 1, 3, 10 and 30 mg/kg. Safety was acceptable apart from cutaneous hypersensitivity at the 10 and 30 mg/kg doses. On efficacy, the paper states plainly that "there were no improvements noted in exploratory end points of muscle strength or function," with only a trend toward increased muscle size in a limited number of subjects. The authors concluded that systemic myostatin inhibition still merited investigation with more potent agents. Background on that drug class is in our page on the anti-myostatin antibody.
ACE-083, 2016 to 2022. Acceleron took a different approach: a locally acting recombinant fusion protein injected directly into a single muscle, either the biceps brachii or the tibialis anterior, rather than dosed systemically. The phase 2 trial (NCT02927080) enrolled 37 participants in an open-label part and 58 in a randomized, double-blind, placebo-controlled part, of whom 55 were evaluable.
It worked on the tissue. Published in Muscle & Nerve in 2022, the results showed total muscle volume up 16.4% versus placebo in the biceps group (P<0.0001) and 9.5% in the tibialis anterior group (P=0.01), with contractile muscle volume also significantly increased in both. And then: "Significant increases in TMV with ACE-083 vs placebo did not result in consistent functional or PRO improvements." The programme was terminated in 2019 to 2020.
ACE-083 remains the cleanest demonstration in the entire field that muscle volume and muscle function can move independently. That distinction is worth carrying into anything you read about myostatin inhibitors or follistatin based compounds.
The myostatin trials running in FSHD right now
Two programmes are active, and both are worth watching for the endpoint they chose as much as for the drug.
RO7204239 (Roche) is described in its registry entry as "a humanized monoclonal antibody that binds to human latent myostatin," given by subcutaneous injection every four weeks. The phase 2 trial (NCT05548556) randomized 51 ambulant adults with FSHD to drug or placebo for 52 weeks, starting February 2023 with primary completion in May 2025. Its co-primary outcome is percent change from baseline in contractile muscle volume of the quadriceps by MRI, plus adverse events. Note that this is a muscle volume endpoint, the same measure ACE-083 moved without moving function. The trial is listed as active, not recruiting, with final completion in October 2026 and no posted results yet.
Apitegromab (Scholar Rock) entered FSHD in July 2026 with FORGE (NCT07435129), a 52-week phase 2 randomized, double-blind, placebo-controlled trial in 60 adults aged 18 to 60 with genetically confirmed FSHD1 or FSHD2, given intravenously every four weeks. Enrollment requires a clinical severity score of 1.5 to 3.0 and a 10-metre walk or run of five seconds or less, and excludes anyone with previous anti-myostatin treatment. Primary completion is scheduled for June 2028. Apitegromab binds pro and latent myostatin rather than the mature protein; more on the compound is in our apitegromab page. It is not approved for FSHD.
What the non-myostatin pipeline has shown
The most informative recent result in FSHD came from outside the myostatin pathway, and it is a cautionary one.
Fulcrum Therapeutics' losmapimod, an oral drug aimed at reducing DUX4 activity, reached phase 3 in REACH (NCT05397470), which randomized 260 participants to losmapimod 15 mg twice daily or placebo. The primary endpoint was change from baseline at week 48 in total relative surface area over quadrants 1 to 5, with a 500 g wrist weight, averaged over both arms, measured by reachable workspace.
The posted results, first published to the registry in November 2025, show a least squares mean change of 0.013 (SE 0.007) on losmapimod versus 0.010 (SE 0.007) on placebo. The difference was 0.003, 95% CI -0.014 to 0.020, p=0.7501. The trial was terminated by sponsor decision.
Other programmes remain in progress: Avidity Biosciences began a phase 3 trial of del-brax (AOC 1020) in June 2025 (NCT07038200) in 200 participants, with change in a quantitative muscle testing composite at week 78 as the primary endpoint and primary completion in May 2028. Its registry record does not describe the drug's mechanism, so we are not characterising it here. Earlier-stage work includes Sarepta's SRP-1001, Epicrispr's EPI-321, an investigator-led clenbuterol study, and a satralizumab trial.
What treatment looks like today
Care for FSHD is supportive. GeneReviews lists physical therapy, ankle-foot orthoses to help with foot drop and mobility, pain management using NSAIDs, antidepressants or anti-seizure medications, and ventilatory support where breathing muscles are involved.
Nothing sold over the counter has been shown to alter the course of FSHD. Compounds marketed as myostatin inhibitor supplements have not been tested in this population, and the two potent, injectable, clinical-grade myostatin blockers that have been tested here did not improve function. Any decision about drugs, including trial enrollment, belongs with a neuromuscular specialist.
Frequently asked questions
Is there a cure or an approved drug for facioscapulohumeral muscular dystrophy? No. As of August 2026 there is no approved disease-modifying therapy for FSHD, and management is supportive. Several drugs are in phase 2 and phase 3 trials, but the one programme that reached a phase 3 readout, losmapimod, missed its primary endpoint (p=0.7501) and was terminated.
Do myostatin inhibitors work for FSHD? Not on the evidence available. MYO-029 produced no improvement in strength or function in 2008. ACE-083 significantly increased muscle volume, by 16.4% in the biceps and 9.5% in the tibialis anterior versus placebo, and still produced no consistent functional or patient-reported improvement. Two further trials, of RO7204239 and apitegromab, are ongoing and have not reported.
What is the ICD-10 code for facioscapulohumeral muscular dystrophy? G71.02, under the G71.0 muscular dystrophy category in ICD-10-CM.
What is the difference between FSHD1 and FSHD2? FSHD1, about 95% of cases, is caused by a contraction of the D4Z4 repeat array on chromosome 4q35 to 7 or fewer units (or 8 to 10 with reduced penetrance) on a permissive haplotype. FSHD2, about 5%, has a normal-length array that is hypomethylated instead, most often because of an SMCHD1 variant. Both require a permissive chromosome 4 haplotype and both lead to DUX4 expression in muscle.
Can exercise or diet lower myostatin enough to help FSHD? There is no evidence that it can. FSHD is driven by DUX4 expression, not by excess myostatin, and even complete pharmacological myostatin blockade has not improved function in FSHD trials. Exercise has a place in FSHD care through physical therapy, but it should be planned with a specialist rather than pursued as a myostatin strategy.