Rare Genetic Disease Didn’t Deter Family

Once Randi Chapnik Myers gave birth to a healthy son in 1996 and a healthy daughter in 1998, she and her husband, Rob, figured that the developmental defect that affected her pregnancy in 1995 was just a fluke. That fetus, a girl, was found to have severe hydrocephalus (water on the brain) at 20-weeks gestation, and the Myerses were told that she stood no chance of surviving beyond birth. They decided to terminate the pregnancy.

But when, in 2000, Chapnik Myers became pregnant with twin girls, and at the 20-week sonogram, the doctor grimly asked what exactly had happened with her first pregnancy, she knew that something was very wrong. One of the fetuses had severe hydrocephalus, while the other appeared to be fine. Rather than carry both babies to term and risk the health of both Chapnik Myers and the healthy twin, the couple opted for selective termination of the sick fetus.

The insertion of a needle into the unhealthy twin came with an attendant 10-percent risk of infection. Unfortunately, Chapnik Myers developed a fever, and she lost the healthy baby, as well.

By now, it was clear to the Myerses and their doctor that this was not just a random genetic misfire, but rather something caused by a recessive genetic mutation that each of them was carrying. The head of genetics at the Hospital for Sick Children in Toronto, where the Myerses live, informed them that two of the daughters they had lost had been afflicted by an extremely rare genetic disease called Walker-Warburg Syndrome.

“It was a pretty big experience to be blindsided with,” said Chapnik Myers of the news.

Walker-Warburg Syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal proteins that are associated with brain malformations and eye anomalies. For this reason, it is also referred to as Muscle-Eye-Brain (MEB) Disease (though WWS is often described as a more severe form of MEB). It is a universally fatal disease, with affected children who survive birth usually living for no more than one to two years.

According to Dr. Wendy Chung, assistant professor of pediatrics and medicine and director of clinical genetics at Columbia University, one in 40,000 Jewish children is affected by WWS, as compared to approximately one in 100,000 children in the general population.

Chung and some colleagues conducted research and discovered that the Fukutin gene, which is most often associated with cases of Fukuyama congenital muscular dystrophy found in Japan, is also the underlying cause for WWS in Ashkenazi Jews. According to their calculations, seven in 1,000 Ashkenazi Jews are carriers for this genetic mutation. This ratio, about one in 143, compares to one in 18 for carriers for Gaucher and one in 31 for Tay Sachs. If two WWS carriers meet and have children, each of their offspring has a 25 percent chance of being affected by the disease.

When the Myerses were having their children, there was no means of screening for the Fukutin gene (identified only later in 2004) either pre-conception or prenatally. All the doctors could tell them was that they had a one in four chance with every subsequent pregnancy of having another child with WWS.

Determined to grow their family, the Myerses tried again. “I knew it was 75 percent probable that I would have a healthy third child,” Chapnik Myers reflected.

Their next pregnancy ended mid-term when the fetus, another girl, suddenly died. It was not definitively determined whether WWS was to blame. Finally, a healthy third child, a son, was born in 2002. “I knew it was just part of my story. I really fought for my kids,” Chapnik Myers mused philosophically of her difficult journey and loss of four out of seven babies.

Today, a genetic screening blood test is available for potential parents. Fetuses can be genetically tested for the disease by amniocentesis or chorionic villus sampling. Pre-implantation diagnosis for IVF embryos is also an option. Parents can be armed with more information now, and clinical practitioners like Chung are better able to help couples think through difficult decisions involved in either terminating an affected pregnancy or carrying it to term.

“Unfortunately, however, most obstetricians are unaware of the available testing,” warned Chung. Only a handful of scientists are conducting WWS-focused research. It is for this very reason that she and her colleagues published their study last year in the Journal of Prenatal Diagnosis and are trying to get the word out that labs such as Athena Diagnostics, Emory Genetics, Prevention Genetics and the University of Iowa have the capacity to run the relevant tests. The labs are working to develop better Ashkenazi genetic screening tests and to include WWS in the standard bundle offered to Ashkenazi patients.

Calls to Dor Yeshorim, a group that does genetic testing in the Jewish community, did not return multiple calls for comment as to whether they were aware of WWS or were advising people to be tested for it.

Another woman interviewed for this article (who wished to remain anonymous) urged fellow parents to be tested for the WWS gene, especially ones that have already given birth to children with the disease. The woman, from the New York City area, has given birth to three children — all of them affected by WWS. Her religious beliefs prohibit elective termination of a pregnancy, and she elected to carry the pregnancies to term despite indications that the fetuses were malformed. The babies lived between three months and three and a half years, all requiring ongoing hospitalization or nursing care. “We cherished every moment we had with them,” their mother said.

It was of paramount importance for the woman and her husband to know what was causing their children to be so ill. The doctors who were treating her did not seem to know what was wrong, and it was due to her own persistent research on the Internet that she, herself, discovered that her children were affected by WWS or MEB. She got in touch with the few doctors who were conducting research into the genetic basis for the disease, and made a considerable financial investment in the genetic testing of tissue samples from both her and her husband, in the U.S. and in Europe.

“I was the pushiest patient,” she declared. Ultimately, the University of Iowa lab was able to confirm that both members of the couple were carriers for the same Fukutin gene mutation found in other Ashkenazi carriers.

Dr. Ching Wang, director of the Pediatric Neuromuscular Clinic at Lucile Packard Children’s Hospital at Stanford University, cited the breakthrough of pre-pregnancy genetic screening and pre-implantation diagnosis. It is extremely rare for him to come across a patient with WWS or MEB. He estimates that only 2 of the 400 patients in his clinic suffer from MEB, and he has made only one WWS diagnosis in his career.

But when Wang does encounter a case of WWS or MEB, “it is important to make an accurate diagnosis. It isn’t hard, but it is important to do so,” he emphasized. “It’s important in terms of caring for the child during his or her short lifespan, and equally important for family planning on the part of the parents going forward.”

Chapnik Myers was thrilled to learn that genetic testing for WWS is now available. She is glad to know that other couples will have more information than she and her husband did to guide them through challenging decisions and experiences.

As for her, those difficult years of “leaking breasts and empty arms,” as she put it, are thankfully behind her. These days she is focusing on happy things, like her oldest two children’s recent b’nai mitzvah ceremonies. In her speech at her son’s bar mitzvah, Chapnik Myers told him that she and his father, given everything they had gone through, consider him to be a miracle child — as they do his younger sister and brother, too.

For a link to a study about Walker-Warburg syndrome, go to:
www.ncbi.nlm.nih.gov/pmc/articles/PMC2735827/