Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published June 21, 2023


Is there a predictable pattern to the progression of muscle weakness in facioscapulohumeral muscular dystrophy?

Facioscapulohumeral muscular dystrophy (FSHD) is the second most common muscular dystrophy in adults, following myotonic dystrophy type 1. It is caused by dominantly inherited or de novo mutations, and the estimated prevalence is 1 case per 15,000 to 20,000 persons. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: Name a key protein in the pathogenesis of FSHD.

A: There are two types of FSHD, which are phenotypically indistinguishable. FSHD type 1 accounts for 95% of cases of FSHD. The genetic defects associated with both types lead to chromatin relaxation (hypomethylation) of the permissive A allele in the D4Z4 region and result in expression of the double homeobox 4 (DUX4) protein, which is thought to be toxic. DUX4 protein expression is a molecular target for FSHD therapies that are currently being investigated.

Q: What clinical findings are consistent with a diagnosis of FSHD?

A: One can ask a patient with possible FSHD if they have ever kept their eyes partially open during sleep or had difficulty with whistling or drinking through a straw, lifting objects over the shoulders (e.g., reaching top cabinets), or performing abdominal crunches. In addition, one can look for horizontal axillary folds and Beevor’s sign (upward deviation of the umbilicus on truncal flexion while the patient is in a supine position), which are manifestations of weakness in the pectoralis and abdominal muscles, respectively; these findings are not specific for FSHD but are typically seen in patients with this condition.

Morning Report Questions

Q: Is there a predictable pattern to the progression of muscle weakness in FSHD?

A: In patients with FSHD, the progression of muscle weakness usually follows a descending pattern, with weakness starting in facial muscles and then progressing to sequentially involve periscapular muscles, humeral muscles, abdominal and hip-girdle muscles, and finally distal muscles of the anterior compartment of the leg. Facial muscle weakness is often unnoticed, and the most common presenting symptom is difficulty with lifting objects above the shoulder, which usually occurs in the second or third decade of life. However, in some patients who do not have jobs or hobbies that are physically demanding, weakness of the shoulder-girdle muscles is unnoticed, even for decades, because of the absence of symptoms or compensation for symptoms. Such patients present later in life, when weakness of the distal leg muscles develops.

Q: How is FSHD managed?

A: Treatment for FSHD is centered on the management of muscle weakness and extramuscular manifestations of the disease. Aerobic exercises have been shown to be beneficial in patients with FSHD, although not in patients with other myopathic processes. In some patients with relatively preserved deltoid strength, scapular fixation of the dominant side is performed for the temporary improvement of range of motion. Extramuscular manifestations of FSHD that are associated with large D4Z4 repeat deletions include hearing loss and exudative retinopathy (Coats’ disease). Eye taping at night and surgical insertion of lid weights can be performed for the prevention of xerophthalmia and corneal abrasion. Fluorescein angiography can be used for the identification of retinal vasculopathy, and laser photocoagulation may stop progression to full Coats’ disease and vision loss. In addition, if FSHD leads to restrictive lung disease, the use of bilevel positive airway pressure at night may be considered.

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