What causes congenital fiber-type disproportion 1 (CFTD1)?

Updated: Mar 11, 2019
  • Author: Matthew Harmelink, MD; Chief Editor: Amy Kao, MD  more...
  • Print
Answer

Autosomal dominant mutations in ACTA1 are a rare cause of CFTD accounting for fewer than 10% of cases. [55] Mutations in the gene for α-actin are a common cause of nemaline myopathy. It has been shown that CFTD mutant α-actin is unable to properly interact with tropomyosin, leaving tropomyosin in the "switched off" position, thereby not allowing actin to interact with myosin. Furthermore, the sarcomeric disruption common in α-actin mutations that cause severe nemaline myopathy is not seen in patients with severe weakness due to CFTD. These data have lead to the hypothesis that the α-actin mutations that cause CFTD result in disturbed sarcomeric function rather than structure. [56]

Presentation is at birth with severe weakness most prominent in proximal, truncal, facial, and respiratory muscles. Severe feeding difficulties are present, and invasive ventilation is often needed. Most patients die due to progressive respiratory failure before 4 years of age.


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!