A journey to the place with the world’s highest Fragile X syndrome rate: ‘We are not the town of fools’

Patricia Triviño Rodríguez, 53, has spent most of her life caring for family members affected by Fragile X syndrome. Her two sons, Harold and Helmer; two of her sisters, María Julieta and Rosaura; and her nephew Ronald Gabriel all suffer from this genetic mutation, which is the most common inherited cause of intellectual disability in the world.

They live together in a cement house in Ricaurte, Valle del Cauca, a small town in western Colombia that has the highest rate of this condition anywhere on the planet. Globally, it is estimated that the syndrome affects one in every 5,000 men and one in every 8,000 women. In Ricaurte, however, it affects 48 out of every 1,000 men and 20 out of every 1,000 women. Located just a few miles from Cali, the mutation is 343 times more prevalent in men and 226 times more prevalent in women than internationally recognized rates, according to the book Fragile X Syndrome in Ricaurte, Colombia, a compilation of research and scientific articles by Colombian geneticist Dr. Wilmar Saldarriaga. For decades, people in the region have disparagingly referred to Ricaurte as “the little town of fools.”

Of the approximately 1,200 people who live in Ricaurte today, some are healthy, some carry the Fragile X premutation, and others have the full mutation. Saldarriaga, who discovered three decades ago that the disease was the cause of the town’s health problems, explains that the syndrome is caused by an abnormal repetition of the CGG triplet (cytosine-guanine-guanine) in the area of the X chromosome, where the FMR-1 gene is located. A typical person has between 30 and 44 CGG repetitions; those with the premutation have between 55 and 200 repetitions; and individuals with the full mutation have more than 200. The problem, he says, is that when there is an excess of this repetition, a protein essential for brain development is not produced.

Saldarriaga’s doctoral thesis in genetics confirmed the high prevalence of the disease in Ricaurte. After years of collecting and analyzing blood samples from nearly all of the town’s residents, he obtained surprising results: 22 men had the mutation and five the premutation, 11 women had the mutation and 22 the premutation.

Today, this small town nestled between the Western Andes and the Cauca River — surrounded by thousands of acres of sugarcane fields — is the largest geographic and genetic cluster for studying the origin, symptoms, and potential treatment of Fragile X syndrome. Its significance for science is comparable to that of Yarumal, in Antioquia, which has the world’s highest concentration of genetic Alzheimer’s cases.

Elongated faces, large ears

Men with the full mutation can be easily identified by their physical features. Some walk or drag themselves along the few streets of Ricaurte. Many of those affected beg for money outside the church or sell raffle tickets to bring a bit of money home, even if they can’t count or add. Others drink beer and coffee at the establishments surrounding the main square. Sometimes they work in the fields picking fruit.

They have elongated faces, wide foreheads, large hands, and abnormally large ears and testicles. Some also have macrocephaly, scoliosis, loose joints, and flat feet. All have severe intellectual disabilities, struggle to maintain eye contact, and display repetitive behaviors characteristic of the autism spectrum. They have difficulty holding a fluid conversation. They understand what is asked of them and make themselves understood with few words or signs. They often know their name, but can’t remember when they were born, what they did the day before, or what the date is.

In women with the full mutation, the physical features and intellectual disability are less noticeable and less severe, because the other, typically healthy, X chromosome helps to compensate and reduce the effects of the condition. However, they have a higher probability of carrying the premutation and face various related health complications. The most serious include premature ovarian failure, which causes menstruation to stop before age 40, and a kind of tremor in the extremities that prevents them from walking and moving properly.

“The biggest problem is that a woman of reproductive age may not have any symptoms but have the premutation without knowing it,” says Saldarriaga as he drives his pickup on the route from Cali — where he lives and works as a professor and gynecologist — to Ricaurte. He visits the town every last Tuesday of the month to check on all the patients with Fragile X syndrome. He always travels with Dr. Julián Ramírez Cheyne, also a professor at Universidad del Valle and a doctor in genetics.

“The premutation in mothers can be inherited and spread with a high probability to their children, who in most cases are born with the full mutation,” says Ramírez Cheyne.

That’s the case for Patricia Triviño and many other women in Ricaurte who had their children while they were still healthy and unaware that they were carriers of the premutation. Today, their greatest concern is who will care for those now-adult men and women — who have the cognitive abilities of small children — once they’re no longer around.

A few blocks from Patricia’s house, up a steep street lined with fruit trees, lives her 88-year-old aunt, Mercedes Triviño. Mercedes has a small cement house with two rooms, where she sleeps alongside her four children with Fragile X syndrome: Jair, 64; Víctor Manuel, 62; Héctor Fabio, 52; and Johana, 42, who, in addition to having Fragile X syndrome, also has Down syndrome. The house has a small kitchen where every morning Mercedes prepares coffee and agua de panela (sugarcane water). They live in poverty, illness, and neglect —like most of the people in Ricaurte — but are thankful for the doctors’ monthly visits. “It’s a blessing from God that you come,” says Mercedes.

Health and medical care brigades

After nearly three hours of driving from Cali, doctors Saldarriaga and Ramírez arrive at the small health center in Ricaurte. It’s an unfinished house with three rooms and very few medical supplies: a couple of examination tables, blood pressure monitors, a stethoscope, a thermometer, and little else. Medical records are handwritten on sheets of paper and in notebooks. Lucy Triviño García, a health promoter and nurse, greets them warmly. A young doctor completing his rural service is also there; he comes a few days a week to handle emergencies in Ricaurte.

Each month follows a similar routine. Lucy gives a brief summary on the health status of Fragile X patients, they identify priority cases, and begin house-to-house visits. This time, Mrs. Aleida Gordillo, over 70 years old and living with Fragile X, beat them to it — she was already waiting at the health center. It’s Tuesday, March 25, and the heat is suffocating for both the doctors and patients.

Aleida doesn’t speak clearly, but she manages to communicate that she has been feeling ill for the past few days. She has lost weight, has difficulty walking, and has experienced dizziness and chills. Saldarriaga reviews her medical history and fears a heart problem. He knows that the only way Aleida can get the tests she needs is for him to take her to the nearest hospital, in the municipality of Bolívar.

Aleida happily climbs into the backseat of Dr. Saldarriaga’s truck. During the ride, she briefly shares that one of her older sisters, who lives in Bolívar and also has Fragile X, is in critical condition. At the hospital, they check Aleida’s vital signs and perform an electrocardiogram.

The doctors also take the opportunity to visit the home of Aleida’s sister and niece. It’s also home to Andrés Felipe Gordillo, one of the youngest Fragile X patients in the area. He’s 16 years old, enjoys drawing with colored pencils, and spends many hours watching videos on his Aunt Milvia’s phone. Milvia has to take care of both her bedridden mother and her sick nephew. The doctors examine them, tend to minor wounds, and provide prescriptions for essential medications.

“Andrés Felipe has a spinal problem, one side is longer than the other — his back is starting to curve,” says his aunt Milvia. The doctors recommend physical therapy and an urgent appointment with an orthopedic specialist, but there are no therapists or orthopedists in any nearby towns. They would have to travel to the city — but they don’t have the money.

The doctors return to Ricaurte, and the house visits continue with several families affected by multiple cases of Fragile X. In every home, there is a small altar dedicated to the Divine Ecce Homo — an image of a seated Jesus that is displayed in the town’s church and draws thousands of tourists seeking miracles. In every home, the two doctors, whose services are unpaid, are welcomed with joy and gratitude. According to Colombian law, Fragile X patients are entitled to special protection by the state as sufferers of an orphan disease, but in reality, they survive on their own and often lack even the basic means to eat three meals a day.

Neither contaminated water nor witchcraft

Before Dr. Saldarriaga discovered Fragile X in Ricaurte, the town had a brief moment of notoriety because the writer Gustavo Álvarez Gardeazábal, in his 1980 novel El Divino, wrote that there were many intellectually disabled people living there. For decades, it was assumed that the high prevalence of intellectual disability was due to environmental factors. Some thought it was caused by drinking magnesium-contaminated water from the mountains. Another theory claimed that women used witchcraft to charm their husbands, accidentally overdosing them with love potions, which supposedly led to children being born with disabilities. A final theory suggested that people in Ricaurte drank milk and ate meat from goats that had fed on a common hallucinogenic plant found in local pastures, and that this caused the disabilities in children. Only a few in town suspected a hereditary issue, noting that many of the sick shared the same last name.

Saldarriaga leaned toward that final explanation. With the guidance of a genetics professor and the reference images in textbooks on genetically inherited intellectual disabilities, he traveled to Ricaurte. It was the late 1990s.

“One of the children looked exactly like the one in the textbook image that illustrated Fragile X syndrome,” Saldarriaga recalls emotionally. He told his professor what he had seen, and they decided to run serotype tests — which show fragile sites on chromosomes — to confirm whether it was the disease, which no one in Ricaurte had heard of.

“We took samples from five patients who had similar physical features, processed them in the university’s lab, and all tested positive for Fragile X.” The child who made the disease’s identification possible was Ronald Gabriel, Patricia Triviño’s nephew, who still wanders alone down the streets of Ricaurte to this day.

This was followed by numerous investigations, academic awards, and publications in peer-reviewed scientific journals — until, two decades later, Professor Randi J. Hagerman reached out to him. Hagerman is the director of the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at the University of California and the world’s foremost expert on these types of mutations. She invited Saldarriaga to Sacramento, California, and offered him the financial and technological support he needed to continue his research.

“Hagerman has an H-index of 105. A Nobel Prize winner has around 120. I have an H-index of 11. The top researcher in Colombia has 70,” says Saldarriaga, to emphasize the scientific importance of his collaborator, who co-authored the book Fragile X Syndrome in Colombia.

Saldarriaga told her that ideally, they would perform molecular tests on the entire population of Ricaurte to identify carriers and, based on those results, offer genetic and reproductive counseling to prevent new cases. “That’s the real long-term impact we could have.”

Tubal ligation and ancestry studies

Hagerman and her team donated the molecular tests. Saldarriga and other doctors at the Universidad del Valle collected the blood samples and mailed them to the United States. There, they processed them and returned the results. With the information, they conducted a new census in Ricaurte, constructed family heredograms or family trees with information about the disease, and began visiting each home to share the findings.

Saldarriaga visited each person who had the Fragile X mutation or premutation. He provided genetic and reproductive counseling, explaining the risks of having children if the mother or father had the premutation. Ultimately, 12 of the 13 women with the premutation who were of reproductive age decided to have their tubes tied to avoid pregnancy. The hospital and the doctors donated the procedures. The woman who said she didn’t want birth control had a child months later, the youngest case of Fragile X in Ricaurte. “Hopefully it’s the last,” says Saldarriaga.

Dr. Ramírez Cheyne used those results, along with other genetic tests, to conduct a study proving that the syndrome had been present in Ricaurte since the town’s founding — a phenomenon in science known as the founder effect. In 2024, he published a scientific article in the American Journal of Medical Genetics. In the paper, Ramírez confirmed that all the affected individuals in the town shared the same haplotype— meaning a group of genetic variants that tend to be inherited together in a block.

“The human genome is a sequence of letters; they’re like the building blocks of DNA. Our genome has 3 billion of those letters organized in a set way. A mutation occurs when one letter is replaced by another,” Ramírez explains. “The letter that was scrambled is surrounded by a sequence of letters, both forward and backward. That block is the haplotype.” The study found that the Fragile X patients in Ricaurte shared millions of identical letters in both directions, proving they came from the same ancestor. “That’s the founder effect,” says Ramírez.

The scientific investigations were complemented by interviews with many local residents to reconstruct the history of the disease. “We identified three family nuclei that started to merge into a single family going back to the beginning; they had the same lineage.”

Oral traditions were combined with a review of old archives, public deeds, and church-kept birth records. The scientists were able to establish that the town was founded in the late 18th century and that, in the early 19th century, the owner of a large plot of land sold it to 10 families who already lived there. Among those, three families are the most likely to have introduced Fragile X syndrome to Ricaurte. The next step, say Saldarriaga and Ramírez, is to conduct an ancestry study to determine whether the origin of the mutation is Indigenous, African, or Spanish.

“We have indications that it came from Spain, but we need to verify it molecularly,” says Saldarriaga. “If any European researcher wants to help us, they’re welcome,” he adds with a laugh.

Today, after many years of scientific research, the families with members affected by the disease in Ricaurte are calling for a change in the language used to describe them, one that removes the stigma and promotes positive effects in the care and treatment of patients.

“We are not the village of the fools,” says Patricia Triviño before we say our goodbyes. She insists: “Dr. Saldarriaga discovered that we are sick, not fools.”

Patricia knows that her relatives have a disease that reduces their cognitive abilities, causes severe learning limitations, and creates difficulties in interacting with others. But she also knows with absolute certainty that they are not fools. “We need a foundation specialized in Fragile X that helps us, offers physical therapy and speech therapy, teaches young people different activities, and launches productive projects. Today we are alone, abandoned by the state.”

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