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Stone man syndrome

The skeleton is the internal scaffolding of the human body, the structure that supports its movement and guarantees the protections if internal organs.

By Míriam GuaschPublished 6 months ago 8 min read

But precisely this bony scaffolding can become a cage that forces immobility and compresses the very organs that it is supposed to protect. This is the fate of patients suffering from one of the rarest and most devastating genetic diseases known today: Fibrodysplasia Ossificans Progressiva (FOP) or stone man syndrome.

People affected by this syndrome undergo a true metamorphosis, due to the formation of bone tissue in areas of the body where it should not be present. It is estimated that around 2,500 people worldwide are affected by FOP, or one in 2 million.

Harry Raymond Eastlack was the most infamous case of the 20th century stone man syndrome. However, Eastlack is not only remembered as "the man of stone", but also for having contributed significantly to research on this disease.

Harry Raymond Eastlack: FOP's Debut

It was 1933 when Harry Raymond Eastlack was born in Philadelphia. He presents himself to his parents as a child in excellent health, except for a malformation in the big toe of his right foot . Doctors, however, do not attach special importance to it. Harry grew up healthy, spending an active and carefree childhood between a passion for music and football. But at the age of 5, the course of Harry's life changes forever.

On a normal spring afternoon, Harry is playing in the street with his sister Helene, when a car swerves and hits him. Despite the initial shock, the accident turns out to be of limited severity: Harry fractures his left femur , which is then placed in a cast that forces him to temporarily limit his lively vitality.But in reality the trauma has much more serious consequences for Harry. Consequences that, initially silent, begin to manifest once the plaster is removed. His leg actually appears painfully swollen, inflamed and Harry discovers that he is unable to move his hips and knees. In the ER, doctors suspect such unusual symptoms for a bone fracture alone. Harry then undergoes an X-ray examination.

The results from the X-rays are puzzling: the boy's thigh muscle has been partially transformed into bone tissue. It is a discovery so absurd that it leaves doctors baffled, who take a year to formulate a diagnosis . In fact, it was in 1938, a year after the accident, that the Eastlack family first heard of myositis ossificans progressiva, now known as fibrodysplasia ossificans progressiva.

Stone Man Syndrome has been one of medicine's most elusive mysteries for centuries, a disease with no name or explanation. A very rare condition but shocking in its course and severity, the first detailed description of FOP dates back more than 250 years. In a letter to the Royal Society of Medicine dated April 14, 1736, John Freke reports the case of a fourteen-year-old boy who was seeking a cure for a condition that had caused him indescribable suffering for more than three years. From all the vertebrae of her neck and from each rib of his body, large swellings arose that extended to all parts of her back, forming what seemed to be a bony bodice.


Since then, several doctors and scientists have contributed to increase the knowledge about this disease. In the late 19th century, Frankel and Helferich identified one of the features associated with FOP, namely monophalangism and brachydactyly of the great toe . In 1868 von Dusch gave this condition the name myositis ossificans progressiva, believing that the cause of bone formation at the heterotopic site was muscle inflammation . McKusick changed the name of the disease in 1972 after the discovery that the inflammation also affected soft tissues (tendons and ligaments) and only secondarily skeletal muscle tissue.

HR Eastlack: disease progression

Despite the illness, HR Eastlack enjoyed a relatively happy childhood. A movie lover, Harry is said to have had a reserved seat in the center of the seventh row at the Hamilton Theater in Philadelphia, a seat that he could recline to sit comfortably since he could not bend his leg. FOP was at that time a disease shrouded in mystery. In an attempt to understand and treat his condition, Harry underwent multiple biopsies and 11 surgeries . These were not only completely useless but also harmful, as they only stimulated the progression of the disease.

In just a few years, the stiffness had spread from his leg to his back, neck and chest, forcing Harry to live in pain and to rely more and more on his mother's help with daily activities. At the age of 15, his jaw was permanently fused, making it impossible for him to eat solid food. 10 years after the diagnosis, Harry underwent a new examination, which revealed the inexorable progression of the disease: the muscle tissue, ligaments and tendons of his young body were irreversibly transforming into mature bone tissue.

A second skeleton...

Within a few years, HR Eastlack found himself immobilized and forced to sit, unable to move his limbs, head, and pelvis. A second skeleton had been formed from his soft tissue, a bony cage that compressed him into a dead-end rigidity that would lead to his death.

In 1958, Harry entered a nursing home for the incurable patients in Philadelphia. Here he spent the last 15 years of his life, if one can call that an existence deprived of the possibility of movement and speech and characterized exclusively by physical and mental suffering due to the metamorphosis of his own body.

H. R. Eastlack: death and donation of skeletons

Harry Raymond Eastlack died in 1973, at just 39 years old, due to pneumonia developed by physical inactivity. In the last days of his life, Harry expressed to his sister his desire to donate his body to research , so that useful clues could be obtained from the study of his skeleton to advance in the understanding of this terrible disease. The skeleton of HR Eastlack is now on display at the Mutter Museum in Philadelphia, and the city has become one of the main centers for FOP research. The skeleton is also regularly donated to the International FOP Association to be used as a reference for physicians, scientists, and patients during international congresses.

Physical degeneration

This disease has been and continues to be one of the most complex puzzles for medicine to solve, both due to its rarity and the impossibility of carrying out tests and interventions on affected patients so as not to exacerbate their condition. The skeleton of HR Eastlack has thus been revealed as a fundamental tool for the investigation, but above all it is the most direct and tangible proof of the terrible physical degenerationthat afflict patients with FOP. Normal skeletons, once the connective tissue connecting the bones is removed, collapse into a pile of disarticulated bones and must be reassembled with fine wire and glue. Instead, Harry's skeleton is fused into one continuous piece, due to the bridges, plates, and ribbons of bone tissue that have formed in crises of heterotopic ossification.

Observing the skeleton it is possible to notice how ribbons and slabs of bone anchor the vertebral column to the skull and the skull to the mandible. Bands of bone link the spine to the extremities and immobilize the shoulders, elbows, hips and knees, while thin bone bridges connect the arms to the sternum and cross the ribcage.

How does FOP, Stone Man Syndrome, manifest itself?

Eastlack's story is very representative of the typical FOP course. In fact, the disease is characterized by a heterotopic ossification process , that is, in areas of the body where bone tissue should not be present. Children affected by the stone man syndrome do not present the disease from birth but, as the only obvious sign, they present a congenital deformation of the big toe . From childhood, the disease progresses throughout life, the mechanism being inflammation of connective tissue or muscle, which is then destroyed and replaced by bone. This progressively leads to the fusion of the joints of the skeletal system.

That second skeleton, stone man syndrome

Affected patients then experience the excruciating formation of a second skeleton , which progressively traps them in a kind of bony cage. The abnormal ossification process can occur suddenly, often due to trauma, injury, intramuscular injections, and inflammatory processes triggered by infectious diseases.

In addition to blocking joint mobility, FOP can cause speech and nutrition disorders if the bone is in the muscles of the mouth. In addition, the growth of bone tissue around the ribcage can compromise its ability to expand, causing breathing difficulties. Generally life expectancy is about 40 years and death occurs from complications due to thoracic insufficiency syndrome.

The discovery of the gene responsible for FOP, Stone Man Syndrome

A milestone in the history of FOP was the discovery in 2006 of the gene responsible for the disease. In fact, an international group of researchers has identified, through the analysis of a group of subjects affected by FOP, a recurrent heterozygous mutation in the ACVR1 gene. This gene encodes a type 1 bone protein receptor expressed on the surface of stem cells. In particular, this receptor is responsible for the embryonic development of the skeletal system and its repair after birth.

The identified mutation determines in the protein the substitution of a single amino acid in the activation domain of the receptor. This variation is believed to be sufficient to alter the activity of the protein, thus inducing the heterotopic ossification process.

Stone man syndrome has an autosomal dominant pattern of inheritance. It is enough to have a single mutated copy of the gene for the disease to manifest itself. However, in most cases, people with FOP have not inherited the faulty copy of the gene from their parents, but rather the mutation has arisen spontaneously in the individual.

Perspectives for the treatment of FOP, stone man syndrome

To date, the stone man syndrome has no therapy yet. Preventive treatment is limited to reducing the risk of trauma and infectious processes that trigger ossification crises. However, the discovery of the mutation responsible for the disease has allowed the development of cellular and animal models of the disease , useful for improving the understanding of the pathophysiology and studying possible therapeutic approaches. Currently, several drugs have reached the clinical trial phase and promising new therapeutic approaches have emerged in recent years. All therapies developed to date precisely target pathways involved in bone tissue development.

However, there are still many unanswered questions facing the investigation. Therefore, a full understanding of the pathophysiological mechanisms is essential to identify specific and effective therapeutic targets. Furthermore, as with all rare diseases, conducting clinical trials is also difficult. The number of patients that can be enrolled is extremely small and randomized controlled trials are not possible.


About the Creator

Míriam Guasch

Hello, I'm Miriam! Enthusiastic pharmacist passionate about well-being, vegan food, nature, animal lover, avid traveler, ecologist. Excited to learn and share!

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