Genetics of FSHD

Both types of FSHD are autosomal dominant genetic disorders. Each child of a parent with FSHD has a 50% chance of inheriting FSHD. The type of FSHD inherited by the child is always the same as that of the affected parent (i.e. if the parent has FSHD1A, each child is at 50% risk for FSHD1A). The severity of the symptoms may differ from person to person within a family.

Sporadic FSHD cases result from a new mutation. Studies report from 10% to as high as 33% of FSHD cases as sporadic (de novo mutation). Approximately 20% of reported sporadic cases are those inherited from a seemingly unaffected parent who is a “germline mosaic,” meaning that only the mother’s or father’s germ cells (the egg or sperm) is affected. When a germline mosaic is involved, the parent appears unaffected but the children are at risk. In the remaining 80% of sporadic cases, neither parent’s genes are affected; a new spontaneous mutation results in a chromosome 4 deletion that causes FSHD1A. When the 4q35 deletion fragment appears in a sporadic FSHD case, it is transmitted in an autosomal dominant (only one parent needs to be affected) manner to succeeding generations. The probability, then, of passing the disease to an offspring is 50%.