What causes congenital fiber-type disproportion 4 (CFTD4)?

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

The most common cause is due to autosomal dominant or sporadic (likely de novo autosomal dominant) mutations in the gene for α-tropomyosin 3 (TPM3). This subtype accounts for 25% of call cases of CFTD. [60]  Mutations in TPM3 are a rare cause of nemaline myopathy, but they are a common cause of CFTD. [60]  The reason why certain mutations cause rod formation while others cause CFTD is not known. Biopsy samples showed a predominance of type-1 fibers (83%) that were 72% smaller than type-2 fibers. Some mutations can cause CFTD in some family members and rod formation in others.

The onset of symptoms is usually before 1 year of age but may begin in young adulthood. Typically, hypotonia and delayed major motor milestones are early features, but independent ambulation is always achieved. Weakness of axial, proximal limb, facial, and ankle dorsiflexor muscles is common, as is ptosis, scapular winging, and a thin body habitus. Nearly all patients have respiratory insufficiency with nocturnal noninvasive ventilation needed in 50% of patients between the ages of 3 and 55 years.


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