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Marfan syndrome, also known as “giant killer”.

Patients are generally tall, with long limbs and unusual athletic physiques, but suffer from defects in the skeletal, ocular and cardiovascular systems. Among the most significant hazards are cardiovascular lesions, especially combined heart valve abnormalities and aortic aneurysms, with 95% of patients dying from cardiovascular complications.

In the medical documentary “The World on Earth”, it is called “synonymous with death”, and it is difficult for patients to live beyond the age of 30.

On April 1, a rare third-generation IVF baby with blocked Marfansyndrome (MFS) was born at the Genetics and Infertility Center of Fudan University Obstetrics & Gynecology Hospital, and all the physical indicators of the mother and child are stable at present.

It is reported that there are five Marfans syndrome patients in the family. The birth of this healthy IVF baby not only means that the curse of Marfans syndrome that plagued the family has been completely broken, but also provides a new option for the eugenic fertilization of patients with Marfans syndrome and more single-gene rare disease groups.

“Giant killer": 95% of patients die from cardiovascular complications

This is not the first time that the medical term “Marfan syndrome” has appeared before the public. One of Lang Ping's biggest rivals, Hayman, is best known as the American volleyball player who died suddenly on the court in 1986 from a ruptured aneurysm of the thoracic aortic coarctation - a serious complication of Marfan Syndrome.

In the first season of “The World on Earth,” 23-year-old Marfan Syndrome patient Wang Bin's aorta could tear at any time, hemorrhaging to death, and in order to survive, he needed to have his entire aorta replaced with an artificial blood vessel. After a 16-hour surgery in which his body was nearly split in half and then stitched back together, he eventually died of sudden kidney failure.

People with Marfan syndrome are generally tall, with long limbs and an unusually athletic physique, which is why the disease is also known as the “giant killer”. First proposed by French pediatrician Marfan in 1896, it is an autosomal dominant single gene genetic disease with an incidence of 15,000 to 13,000, most patients have a family history, while 15% to 30% of patients are due to their own mutations, and in 2025 it was included in China's “first batch of rare disease catalog”.

This disease is a lingering nightmare for Ms. Zhou's family. Her mother, aunts, uncles, cousins and Ms. Zhou herself are all living with Marfan Syndrome, and her mother died at the age of 31 from complications of heart surgery. Ms. Zhou developed a strong desire to “have a healthy child, hoping that my children and grandchildren will never have to suffer from Marfan Syndrome again.”

Multi-institutional experts work together to break the spell of high-risk pregnancy

At the age of 28, Ms. Zhou underwent aortic valve replacement surgery to replace her diseased heart valve with an artificial one. After the surgery, she was able to live a normal life, but she needed to take 5 mg of warfarin every day for anticoagulation. Ms. Zhou had experienced an early pregnancy and abortion, and after the heart surgery, she tried to conceive again for two years but nothing happened. After being discouraged from going to many hospitals across the country, she came to the Shanghai JI Ai Genetics and Infertility Clinic at the Obstetrics and Gynecology Hospital Affiliated to Fudan University in 2017, and turned to Professor Sun Xiaoxi's team for help.

Can we break the curse of “Marfan Syndrome” in this family? More than 90% of the disease is caused by mutations in the gene encoding the connective tissue protein fibrinogen-1 (FBN1). After testing, Ms. Zhou herself, her uncle, aunt and cousin were all heterozygous for the c.4469A>C (p.Glu1490A1a) mutation in the FBN1 gene. Although this locus has not been reported in the literature both at home and abroad, Ms. Zhou was able to have it blocked using preimplantation genetic testing (PGT-M), which is commonly known as the third-generation in vitro fertilization (IVF) technique.

“Ms. Zhou can only resort to PGT-M technology if she wants her offspring to be free from Marfan Syndrome, but once a woman with Marfan Syndrome becomes pregnant, she is likely to experience a series of complications and is considered a high-risk pregnancy, so any decision made must be made with caution, caution, and more caution!” Sun Xiaoxi said.

What are the risks of pregnancy for patients after aortic valve replacement surgery? First, the warfarin that Ms. Zhou takes daily may cause fetal cerebral hemorrhage, raising the probability of fetal arrest and leading to pregnancy failure; second, pregnancy is likely to cause rapid dilation of the aorta, which is potentially risky; and also, the smallest egg retrieval surgery, as well as bleeding during cesarean section, will challenge Ms. Zhou's anticoagulant function.

For this reason, Prof. Sun Xiaoxi's team invited Director Wang Xuefeng, a coagulation expert at Ruijin Hospital, to conduct a consultation to specifically develop a plan for switching between warfarin and heparin before and after the surgery, as well as thoracic surgery and obstetrics specialists to consult with her to develop a treatment plan for the entire pregnancy and delivery process. Ms. Zhou's life came first for both the doctor and the patient. With the risks associated with pregnancy clearly defined and accepted, Ms. Zhou still decided to individualize her medication under multidisciplinary guidance and try to undergo assisted reproductive assisted conception treatment.

The attending doctor, Dr. Chen Hua, used an antagonist regimen to promote ovulation for Ms. Zhou. After weighing the pros and cons of the medication, she stopped taking warfarin 5 days before the egg retrieval surgery and switched to low molecular heparin until the day before the surgery, and then resumed low molecular heparin along with warfarin on the day of the surgery.

After going through the process of egg retrieval, insemination, and sac retention, Ms. Zhou got 7 valid embryos, and the JIU Genetics team conducted pre-implantation genetic testing of the FBN1 gene and 23 pairs of chromosomes of these embryos, and fortunately, two embryos that did not carry the pathogenic mutation of Marfan syndrome and had normal chromosomes were given priority for transfer!

In August 2025, one of the precious embryos was transferred into Ms. Zhou's uterus, and successfully took root and grew, accompanied by internal medicine guidance and obstetrics close monitoring, until “ripe”.

“When the baby is older, we will bring him to Shanghai and tell him that Jie Ai is the place where his life began, and that it was only here that he was born, and that life is so marvelous.” Ms. Zhou said.

Early diagnosis and treatment to prevent the next generation from repeating the same mistakes

Ms. Zhou's encounter is not rare, according to estimates, there are currently 350 million rare disease patients worldwide, China's rare disease patients may be more than 16 million, there are about 7,000 internationally recognized rare genetic diseases, accounting for about 10% of human diseases, is currently one of the biggest problems faced by medical science. At the same time, there is an extreme lack of effective treatments for rare genetic diseases. At this stage, only about 6% of rare diseases have developed treatment strategies, of which less than 1% have the potential to be cured, and the treatment cost is extremely expensive.

In fact, prevention is more important than treatment, and 70% of congenital diseases can be prevented. In recent years, with the popularization of medical knowledge and the public's increased attention, more and more people like Ms. Zhou are using third-generation IVF technology to block hereditary diseases in advance and achieve “primary prevention” of birth defects. As of April this year, JIAC has carried out assisted reproduction treatment for more than 70 kinds of single-gene rare diseases, including progressive muscular dystrophy (DMD), thalassemia, hemophilia, albinism, polycystic kidneys, hereditary deafness, retinitis pigmentosa, spinal muscular atrophy, congenital adrenocortical hyperplasia, hepatic gluconeogenic cumulative disease, citrullinemia, Meckel's syndrome, Waldensburger syndrome, pseudo-chondrodystrophia syndrome, pseudochondrodysplasia, Kennedy's disease, neurofibroma, hepatomegaly, ichthyosis, and other disorders.

“If there is a family history of the disease, but those who have not yet shown symptoms are advised to go to the hospital for family lineage testing to get a diagnosis before the onset of the disease to avoid late detection and poor outcomes.” Sun Xiaoxi said.

Women who, like Ms. Zhou, want their offspring to be exempt from Marfan syndrome, “can first go to a reproductive center for genetic counseling, and before undergoing third-generation IVF-assisted reproduction treatment, the effect of anticoagulant medication as well as the degree of tolerance of cardiac function must be comprehensively assessed to safeguard both the mother's and the fetus's double safety,” Sun Xiaoxi suggests. “Male patients are relatively fortunate in that they are not at risk for pregnancy and can undergo IVF treatment with greater peace of mind.”