Duchenne muscular dystrophy
Muscle cells need a tough but flexible internal scaffold to survive the strain of repeated contraction, the way a tent needs guy-ropes to keep from tearing in the wind. Duchenne muscular dystrophy removes one key rope: a protein called dystrophin. Without it, muscle fibers tear a little with every use and are slowly replaced by scar and fat, causing progressive weakness that usually appears in early childhood and affects walking, then breathing and the heart.
It is X-linked recessive, caused by mutations in the dystrophin gene (DMD), the largest known human gene. Because the gene is on the X chromosome, the disorder appears mainly in boys, who have only one X. Most disease-causing mutations are deletions that shift the reading frame and abolish the protein; milder mutations that keep the reading frame intact cause a related, less severe condition called Becker muscular dystrophy.
The disease often arises from a new mutation, so there may be no family history, and the very large gene mutates relatively often. Care is supportive and steadily improving, with steroids, heart and breathing support, and emerging genetic therapies such as exon-skipping that aim to restore some dystrophin. This entry is educational, not medical advice.
A boy of four has trouble climbing stairs and pushes on his thighs to stand up; testing reveals a deletion of several exons in the dystrophin gene that disrupts the reading frame.
Using the hands to walk up the legs when rising is a well-known early sign.
Whether a DMD deletion preserves or disrupts the reading frame largely determines whether the result is the severe Duchenne or the milder Becker form, a clear illustration of why frameshifts matter.