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Facioscapulohumeral muscular dystrophy (FSHD)

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A 20-year-old has difficulty whistling and raising his arms above his head. He has scapular winging and facial weakness.

AD

  • FSHD1: D4Z4 repeat contraction on 4q35 (1-10 repeats vs normal 11-100)
  • FSHD2: SMCHD1 variants + permissive 4qA haplotype
  • Facial weakness (difficulty whistling, closing eyes)
  • Scapular winging, shoulder weakness
  • Asymmetric
  • Onset usually adolescence/young adult
  • Slow progression
  • Clinical recognition: descending, often asymmetric facial, scapular, and humeral weakness
  • Serum creatine kinase normal to mildly elevated; muscle biopsy/EMG nonspecific (genetic testing has largely replaced them)
  • Confirm with specialized testing for FSHD1, a contracted D4Z4 repeat (1-10 units) on a permissive 4qA allele at 4q35; if negative, test SMCHD1 for FSHD2. Standard multigene myopathy panels do not detect the repeat contraction
  • No disease-modifying therapy; supportive multidisciplinary care
  • Physical therapy, low-impact exercise, ankle-foot orthoses for foot drop, and scapular fixation surgery in selected patients
  • Screen for and treat retinal vasculopathy (Coats-like) and sensorineural hearing loss (especially infantile-onset); monitor respiratory function in those with severe or axial involvement

"FSHD = Face, Shoulder, Humerus, Down (foot drop)": The name tells you the muscles affected: facial weakness, scapular (shoulder) winging, and humeral (upper arm) weakness. Foot dorsiflexor weakness is also common.

"DUX4 is the culprit in both types": Both FSHD1 (D4Z4 repeat contraction) and FSHD2 (SMCHD1/DNMT3B variants) lead to inappropriate reactivation of the DUX4 gene, which is normally silent in adult skeletal muscle.

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