In real life, it’s impossible to predict which genes will be passed on to which children at each conception. This kind of prediction would be the same as trying to predict the outcome of any particular coin toss. Even though the overall odds are 50 percent heads and 50 percent tails, you can get six heads in a row.
This booklet offers some examples of what could happen in actual situations.
The type of diagram seen on the pages, "What May Happen in a Family with... (DMD, SMA and Myotonic MD)" is called a family tree or pedigree. Geneticists and genetic counselors may construct a pedigree or tree as you give your family history, or you may see these in books or on websites.
This is a question often asked by people who have received a diagnosis of a genetic disorder or who have had a child with such a diagnosis. “But, doctor,” they often say, “There’s no history of anything like this in our family, so how can it be genetic?” This is a very understandable source of confusion.
Very often, a genetic (or hereditary) disorder occurs in a family where no one else has been known to have it.
One way for this to happen is the mechanism of recessive inheritance. In recessive disorders, it takes two mutated genes to cause disease symptoms. A single genetic mutation may have been present and passed down in a family for generations but only now has a child inherited a second mutation from the other side of the family and so developed the disease.
A similar mechanism occurs with X-linked disorders. The family may have carried a mutation on the X chromosome in females for generations, but until someone gives birth to a male child with this mutation, the genetic disorder remains only a potential, not an actual, disease. (Females rarely have significant symptoms in X-linked disorders.)
Another way for a child to develop a dominant or X-linked disease that’s never been seen in the family follows this scenario: One or more of the father’s sperm cells or one or more of the mother’s egg cells develops a mutation. Such a mutation would never be detected by standard medical tests or even by DNA tests, which generally sample the blood cells. However, if this particular sperm or egg is used to conceive a child, he or she will be born with the mutation.
Until recently, when parents who didn’t have a genetic disorder and tested as “noncarriers” gave birth to a child with a genetic disorder, they were reassured that the mutation was a one-time event in a single sperm or egg cell, and that it would be almost impossible for it to happen again.
Unfortunately, especially in the case of Duchenne dystrophy, this proved to be false reassurance. We now know that sometimes more than one egg cell can be affected by a mutation that isn’t in the mother’s blood cells and doesn’t show up on standard carrier tests. Such mothers can give birth to more children with Duchenne dystrophy because subsequent egg cells with the Duchenne mutation can be used to conceive a child.
In a sense, these mothers actually are carriers — but carriers only in some of their cells. They can be thought of as “partial” carriers. Another term is mosaic carrier. It’s very hard to estimate the precise risk of passing on the disorder in these cases.
It’s very likely that this kind of situation occurs in other neuromuscular genetic disorders, although most haven’t been as well studied as Duchenne dystrophy. For example, more than one sperm or egg cell could pass on a dominant mutation to more than one of a parent’s children. Or, in a recessive disorder like spinal muscular atrophy, a child could inherit one mutation from a parent who’s a full carrier, and then acquire a second genetic mutation from the other parent, a mosaic carrier. Standard carrier testing wouldn’t pick up any problem in the latter parent.
In practical terms, the most important message of recent research is that a genetic test that looks only at blood cells and shows that a parent is not a carrier can’t be completely relied upon with regard to the risk of having another affected child. The mutation may be present in cells that weren’t tested, and if those include some of the sperm or egg cells, there’s a risk that more than one affected child could be born.
A geneticist or genetic counselor can help you make informed decisions regarding childbearing if you’ve already had a child with a genetic disorder. The recurrence risk is different in different disorders.