Spoan disease: Rare condition in Brazil town popular for cousin marriage

BBC News

11-05-2025

Before Silvana Santos arrived in the little town of Serrinha dos Pintos more than 20 years ago, residents had no idea why so many local children had lost the ability to walk.The remote town in north-eastern Brazil is home to fewer than 5,000 people, and is where biologist and geneticist Santos identified and named a previously unknown condition: Spoan syndrome.Caused by a genetic mutation, the syndrome affects the nervous system, gradually weakening the body. It only appears when the altered gene is inherited from both parents.Santos's research marked the first time the disease had been described anywhere in the world. For this and later work, she was named one of the BBC's 100 most influential women in 2024.Before Santos arrived, families had no explanation for the illness affecting their children. Today, residents talk confidently about Spoan and genetics."She gave us a diagnosis we never had. After the research, help came: people, funding, wheelchairs," says Marquinhos, one of the patients.
Serrinha dos Pintos: a world of its own
Where Santos is from in São Paulo, Brazil's largest and wealthiest city, many of her neighbours were members of the same extended family originally from Serrinha. Many of them were cousins of varying degrees, married to each other.They told Santos that many of people in their hometown couldn't walk, but that no one knew why.One of the neighbours' daughters, Zirlândia, suffered from a debilitating condition: as a child, her eyes moved involuntarily and over time, she lost strength in her limbs and needed to use a wheelchair, requiring help with even the simplest tasks.Years of investigation would lead Santos and a research team to identify these as symptoms of Spoan syndrome.They would go on to find 82 other cases worldwide.
At the invitation of her neighbours, Santos visited Serrinha on holiday. She describes her arrival as stepping into "a world of its own" - not just because of the lush scenery and mountain views, but also due to what seemed to be a notable social coincidence.The more she walked and spoke with locals, the more surprised she was at how common marriages between cousins were.Serrinha's geographical isolation and little inward migration mean that many of the population are related, making marriage between cousins far more likely and more socially acceptable.Worldwide, marriages between relatives were estimated at around 10% in the early 2010s. More recent data shows the rate varies widely, from over 50% in countries like Pakistan, to 1-4% in Brazil and less than 1% in the US and Russia. Most children born to pairs of cousins are healthy, experts say.But these marriages do face a higher risk of a harmful genetic mutation being passed down through the family."If a couple is unrelated, the chance of having a child with a rare genetic disorder or disability is about 2–3%. For cousins, the risk rises to 5–6% per pregnancy," explains geneticist Luzivan Costa Reis from Brazil's Federal University of Rio Grande do Sul.A 2010 study led by Santos showed that more than 30% of couples in Serrinha were related, and a third of them had at least one child with a disability.
Long road to diagnosis
Santos set out to find a diagnosis for the people of Serrinha and she began planning a detailed genetic study, requiring multiple trips and eventually leading to her relocating to the region.She drove the 2,000km to and from São Paulo many times in the early years of her research. She collected DNA samples door-to-door, chatting to locals over coffee and gathering family stories, all the while trying to locate the mutation causing the disease.What was supposed to be three months of fieldwork turned into years of dedication.It all led to the publication in 2005 of the team's study revealing the existence of Spoan in the Brazilian hinterland.Santos's team found that the mutation involves the loss of a small fragment of a chromosome, which causes a gene to overproduce a key protein in brain cells.
"They said it came from Maximiano, a womaniser in our family," recalls farmer Lolô, whose daughter Rejane has Spoan.Lolô, now 83, married his cousin and never left Serrinha. He still tends cattle and relies on family to care for Rejane, who struggles with daily tasks.But the genetic mutation behind Spoan is far older than the legend of Old Maximiano: it likely arrived more than 500 years ago with early European settlers in the north-east of Brazil."Sequencing studies show strong European ancestry in patients, supporting records of Portuguese, Dutch, and Sephardic Jewish presence in the region," says Santos.The theory gained strength after two Spoan cases were found in Egypt, and further studies showed that the Egyptian cases also shared European ancestry, pointing to a common origin in the Iberian Peninsula."It likely came with related Sephardic Jews or Moors fleeing the Inquisition," says Santos. She believes more cases may exist globally, especially in Portugal.
Understanding the risks
Although there's been little progress toward a cure, tracking patients has brought some change. Rejane recalls how people used to be called "cripples". Now, they're simply said to have Spoan.Wheelchairs brought not just independence, but also helped prevent deformities - in the past, many with the condition had been left simply lying in bed or on the floor.As Spoan progresses, physical limitations worsen with age and by 50, nearly all patients become fully dependent on carers.This is the case for Inés's children, who are among the oldest in Serrinha. Chiquinho, 59, can no longer speak, and Marquinhos, 46, has limited communication abilities."It's hard to have a 'special' child. We love them the same, but we suffer for them," says Inés, who is married to a second cousin.
Larissa Queiroz, 25, the niece of Chiquinho and Marquinho, also married a distant relative. She and her husband, Saulo, only discovered their common ancestor after several months of dating."In Serrinha dos Pintos, deep down, we're all cousins. We're related to everyone," she says.Couples like Larissa and Saulo are the focus of a new research project which Santos is also involved in. Backed by Brazil's Ministry of Health, it will screen 5,000 couples for genes linked to serious recessive diseases.
The goal is not to stop cousin marriages, but to help couples understand their genetic risks, says Santos. Now a university professor, she also leads a genetics education centre and works to expand testing in the north-east of Brazil.Though she no longer lives in Serrinha dos Pintos, every visit feels like coming home."It's as if Santos is family," says Inés.