July 2001 to April 2007 and No One Knows About the Male Biological Clock. Why?

Judy Foreman is a Lecturer on Medicine at Harvard Medical School. Her column appears every other week. Past columns are available on www.myhealthsense.com

07/03/2001

For years, many prospective parents - and doctors as well - have blithely assumed that, if an older couple's baby has birth defects, it's most likely because of the woman's advancing age.



But, increasingly, scientists are discovering that, by focusing almost exclusively on mothers-to-be, they might have been barking up the wrong genome. A man, or more accurately his sperm, also has a biological clock. And it's ticking can be just as spooky as a woman's, perhaps even more so because its virtually impossible to do prenatal tests to pick up all the possible genetic mutations in sperm.

"There's always been this myth that fathers can be fathers until they die, and that would be fine. It's always the mother who had to be young," said Dr. Eric Vilain, a geneticist and pediatrician at the University of California at Los Angeles. But that's because the risks associated with advancing paternal age have been routinely "underestimated."
Over the years, geneticists have linked a number of other diseases to advancing paternal age, including achondroplasia, or dwarfism; Marfan's syndrome, which can lead to the fatal rupture of a major blood vessel; and Apert's syndrome, or the malformation of the skull, hands and feet.

Retinoblastoma, an eye cancer; neurofibromatosis, or fleshy growths of abnormal nerve tissue; and some types of prostate cancer also have been linked with older fathers. And some diseases caused by genes on the X-chromosome, among them hemophilia, Duchenne muscular dystrophy and Hunter syndrome, have been linked to advanced age not of a child's father but of his maternal grandfather. In these cases, an older man passes on a defective gene on the X chromosome to his daughter, who, like Queen Victoria, becomes an unaffected carrier who can pass the disease to her sons.

When certain diseases caused by genetic defects show up in a family for the first time, the odds are seven to 10 times greater that the mutation has occurred in the DNA of the father rather than that of the mother, said Dr. Victor McKusick, professor of%2