Fukuyama Congenital Muscular Dystrophy: History
Contributors:

Fukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the muscles, brain, and eyes. Congenital muscular dystrophies are a group of genetic conditions that cause muscle weakness and wasting (atrophy) beginning very early in life.

  • genetic conditions

Frequency

Fukuyama congenital muscular dystrophy is seen almost exclusively in Japan, where it is the second most common form of childhood muscular dystrophy (after Duchenne muscular dystrophy). Fukuyama congenital muscular dystrophy has an estimated incidence of 2 to 4 per 100,000 Japanese infants.

Causes

Fukuyama congenital muscular dystrophy is caused by mutations in the FKTN gene. This gene provides instructions for making a protein called fukutin. Although the exact function of fukutin is unclear, researchers predict that it may chemically modify a protein called alpha (α)-dystroglycan. This protein anchors cells to the lattice of proteins and other molecules (the extracellular matrix) that surrounds them. In skeletal muscles, α-dystroglycan helps stabilize and protect muscle fibers. In the brain, this protein helps direct the movement (migration) of nerve cells (neurons) during early development.

The most common mutation in the FKTN gene reduces the amount of fukutin produced within cells. A shortage of fukutin likely prevents the normal modification of α-dystroglycan, which disrupts that protein's normal function. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to progressive weakness and atrophy of the skeletal muscles.

Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes cobblestone lissencephaly in children with Fukuyama congenital muscular dystrophy. Less is known about the effects of FKTN mutations in other parts of the body.

Because Fukuyama congenital muscular dystrophy involves a malfunction of α-dystroglycan, this condition is described as a dystroglycanopathy.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • Cerebromuscular dystrophy, Fukuyama type
  • FCMD
  • Fukuyama CMD
  • Fukuyama muscular dystrophy
  • Fukuyama syndrome
  • Fukuyama type congenital muscular dystrophy
  • Muscular dystrophy, congenital progressive, with mental retardation
  • Muscular dystrophy, congenital, Fukuyama type
  • Muscular dystrophy, congenital, with central nervous system involvement
  • Polymicrogyria with muscular dystrophy

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/fukuyama-congenital-muscular-dystrophy

References

  1. Martin PT. Mechanisms of disease: congenital musculardystrophies-glycosylation takes center stage. Nat Clin Pract Neurol. 2006Apr;2(4):222-30. Review.
  2. Saito K. Fukuyama Congenital Muscular Dystrophy. 2006 Jan 26 [updated 2019 Jul3]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, AmemiyaA, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1206/
  3. Toda T, Kobayashi K, Takeda S, Sasaki J, Kurahashi H, Kano H, Tachikawa M,Wang F, Nagai Y, Taniguchi K, Taniguchi M, Sunada Y, Terashima T, Endo T,Matsumura K. Fukuyama-type congenital muscular dystrophy (FCMD) andalpha-dystroglycanopathy. Congenit Anom (Kyoto). 2003 Jun;43(2):97-104. Review.
  4. Yoshioka M, Higuchi Y, Fujii T, Aiba H, Toda T. Seizure-genotype relationship in Fukuyama-type congenital muscular dystrophy. Brain Dev. 2008 Jan;30(1):59-67.
  5. Yoshioka M, Kuroki S. Clinical spectrum and genetic studies of Fukuyamacongenital muscular dystrophy. Am J Med Genet. 1994 Nov 15;53(3):245-50.
More