Three generations of this Italian family have an extremely rare genetic mutation that causes them to feel no pain at all.
The Marsili family in Italy has extremely high tolerance for pain.
Pain is a common reality for most of us. We bump into things, we touch baking trays fresh from the oven without gloves, we get into accidents big or small. For the Marsili family, however, pain is isn’t much of a reality. They reportedly feel very little to no pain at all from things like burns and even broken bones. Sometimes, they don’t even realize that they’ve already been injured because they don’t feel it happening. Thus, the family—78-year-old Maria Domenica, her two daughters Letizia and Maria Elena, and her three grandchildren—lives life perhaps a little differently than the rest of us do.
It’s definitely a mysterious condition, and a baffling one to us who can’t imagine living without the common instances of pain we experience. However, it may not be a mystery for much longer, as scientists start to unravel the genetic tangles that made this condition possible.
Letizia Marsili once went on skiing for an entire afternoon in spite of having broken her shoulder.
The Marsili family is rife with stories of times when they experienced something that would be terribly painful for most of us, but they barely felt a twinge. 52-year-old Letizia, for one, once fractured her right shoulder while skiing. She didn’t notice having done it, and continued to ski for the rest of the afternoon. She only went to get checked out at a hospital the next morning because the fingers on her right hand were tingling. A similar thing happened when she broke a bone in her elbow while playing tennis.
Her 24-year-old son Ludovico, who plays football, has been found to have several microfractures. 21-year-old Bernardo, Letizia’s younger son, has had a calcification of the elbow because he continued cycling for nine miles after breaking his elbow without realizing it.
Maria Domenica, Letizia’s mother, has multiple burns, as well as fractures that never healed properly and have now hardened. Letizia’s sister Maria Elena, meanwhile, oftens burns the top of her mouth because she drinks hot beverages without issue. Maria Elena’s daughter, Virginia, once put her hand in ice for 20 minutes without feeling any discomfort.
The family, while they recognize the risks of feeling no pain, expresses gratitude for being able to avoid what so many others suffer through. "From day to day we live a very normal life, perhaps better than the rest of the population, because we very rarely get unwell and we hardly feel any pain," Letizia says. "However, in truth, we do feel pain, the perception of pain, but this only lasts for a few seconds."
Fractures and broken bones may seem like no big deal for the Marsilis, but their lack of pain can be a problem.
A new study has found that this ability, both a gift and a curse, is rooted in a variant found in the gene ZFHX2. Scientists aren’t sure yet how exactly the mutation works, but they think that that the variant disrupts the way ZFHX2 regulates other genes involved in pain signalling.
Scientists have named the condition after the family—the Marsili pain syndrome. There actually already is a condition called congenital insensitivity to pain, which can describe the Marsilis’ experiences. However, scientists say that they created a sub-type of this condition because the Marsili phenotype is so unique.
Researchers were able to isolate the ZFHX2 variant through exome sequencing. Afterward, the team analyzed how the variant affected mice. They found that mice bred without the gene were sensitive to heat, while mice bred to have the gene had low heat sensitivity like the Marsilis.
It’s possible that with more research into the Marsili pain syndrome, researchers might be able to find a way to discover new drugs for pain relief, which may be vital to those suffering from chronic pain.
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