What Is Camurati-Engelmann Disease

Overview

Camurati-Engelmann disease (CED), also known as Progressive Diaphyseal Dysplasia, is an exceptionally uncommon  hereditary genetic disorder. It has a unique way of affecting the bones, making them thicker than they should be through the process of hyperostosis (excessive bone growth). The bone thickening is most noticeable in the arms, legs, and the bones of the head, particularly the skull. The bones grow extra layers on both the outside and the inside and don't stop when they should. 

Excess bone growth might sound harmless, but it brings along a host of problems, such as causing quite a bit of bone pain and making daily activities uncomfortable. It also weakens the muscles, so one might find it harder to move around and do things previously done with ease. The joints, like those in the knees and ankles, might change shape, causing some odd and uncomfortable movements.¹

But CED doesn't stop at the limbs; it can also affect the head and face. During childhood, CED does not impact much on facial features. However, as one grows, the skull might start to thicken and look unusual. It can make the head appear larger than normal, especially the forehead, and it might push the eyes outward, giving them a bulging appearance. These changes can lead to headaches, vision problems, and other neurological issues because the brain and nerves have less space to work in. 

CED varies from person to person, so while some may experience only mild symptoms and lead relatively normal lives, others may face more severe complications that affect their quality of life. Understanding CED is crucial for proper diagnosis and management, as this rare condition requires specialized care and attention.²

Causes of camurati-engelmann disease

CED is caused by changes in the TGFB1 gene, which makes a protein called transforming growth factor beta-1 that controls cell growth and other body processes. In CED, this gene becomes overly active, leading to thicker bones, reduced fat and muscle, and related symptoms. Most people with CED have these gene changes, and it's usually inherited from a parent with a 50% chance of passing it on. Sometimes, though, CED can start from a random gene change in an egg or sperm cell, even if the parents don't have it. Understanding CED's genetic basis is important for diagnosis and counselling in affected families.³ 

Symptoms and signs of camurati-engelmann disease

CED shows up in different ways and can affect people at different ages. The most common signs are bone pain, weak muscles, and a way of walking that looks like waddling. People with CED might find it hard to stand up from a sitting position, and their joints could change shape, like their knees bending inward or their feet being very flat. Their limbs might swell, turn red, and their spines might curve strangely. 

Besides these limb issues, people with CED might have a thicker skull, which can make their heads and lower jaws look bigger. Their forehead might stick out more, and their eyes might seem like they're bulging. As they get older, these skull changes can lead to problems like headaches, hearing loss, vision trouble, feeling dizzy, and even muscle problems.^4,5

Some other not-so-common signs of CED include having longer arms and legs than usual, having less muscle and body fat, teething late, getting lots of cavities, starting puberty later, having anaemia, having a bigger liver and spleen, thinner skin, and very sweaty hands and feet.⁵

Pathophysiology and genetics of camurati-engelmann disease

CED mainly happen because of changes in a gene called TGFB1. This gene makes a protein called transforming growth factor beta 1, which helps control how bones grow. When there are mutations (changes) in this gene, it makes the bone-making cells too active, causing bones to grow abnormally thick in CED. We're still not completely sure how these mutations lead to all the symptoms of CED.⁴

If someone in a family has CED, there's a 50% chance they could pass it on to their children. But even if CED runs in the family, it might affect people differently, which suggests that other things like genes and the environment could also play a role in how the disease shows up.^5,6

Diagnosis of camurati-engelmann disease

To figure out if someone has CED, doctors usually use a mixture of methods to check the patient.

1. Bone X-rays which could display images as

• in long bones like arms and legs, there's too much bone growth, starting from the middle part and sometimes spreading to the ends
• the outside part of the bone gets thicker unevenly, making the bone wider
• inside the bone, there's extra bone tissue, which can make the hollow part narrower
• this bone growth is usually the same on both sides, but sometimes it can be different
• in the skull, extra bone growth starts at the bottom near the brain and might also affect the forehead
• in some other parts of the spine and flat bones, there's a bit of extra bone too⁶

2. Genetic testing: To find out about the genes causing the condition, doctors can use different tests. These tests can focus on one gene or multiple genes at once (like a group of genes), or they can look at a person's whole genetic code.

Treatment and management of camurati-engelmann disease

Right now, there's no cure for CED. Doctors can help to manage the symptoms and problems of the condition, which can improve the quality of life for those with CED.

• Precision treatment: Some treatments like corticosteroids can ease pain, weakness, and help with how they walk and move. Other medicines have also worked well in reducing pain and improving physical activity for some people with CED
• Palliative care like physical therapy and special tools can help with weak muscles and moving around. Doctors will also keep an eye on bone health, hearing, vision, and how the brain works to catch and deal with any issues that might come up
• Regularly check how kids grow and move, watch for muscle and bone issues, and monitor bone health in those taking corticosteroids. Also, assess brain and nerve function, hearing, growth, and blood pressure⁶

Prognosis and outlook for individuals with camurati-engelmann disease

The prognosis for individuals with CED is highly variable and depends on the severity of the disease and the presence of complications. The condition is typically progressive, with symptoms worsening over time. The degree of disability and its impact on quality of life can also vary among affected individuals. While some individuals may experience relatively mild symptoms and have a normal lifespan, others may develop severe complications and have a significantly reduced life expectancy.

FAQ

How common iscamurati-engelmann disease?

This is a rare condition that is passed down in families and affects people from different ethnic backgrounds. There have been more than 300 reported cases of this condition, but we don't know how common it is overall.⁴

When can you develop camurati-engelmann disease?

Most people with this disease start having problems in their teens, with the first symptoms appearing around age 8.7 on average. In some cases, kids as young as three were affected. Possibly because their unusual way of walking was noticeable early. However, it took about 13 more years, on average, for doctors to diagnose the condition when bone pain or delayed puberty became unbearable.⁵

Differential diagnosis of camurati-engelmann disease

Other conditions make bones thicker too, like craniodiaphyseal dysplasia, Kenny-Caffey syndrome, juvenile Paget disease, Ghosal hematodiaphyseal dysplasia, and osteosclerosis. These conditions can be told apart by looking at their unique symptoms and bone X-ray patterns.

How can I avoid the risk of camurati-engelmann disease?

It's a good idea to check family members who might have the same risk for the condition. This way, we can find out if they have it early, prevent any wrong diagnoses, and give them the right treatment for their limb pain.⁶

Summary

CED is a very uncommon genetic disorder that affects bones in the arms, legs, and head to become thicker than they should be. This can lead to problems like hurting bones, weak muscles, strange joints, and even issues with the shape of the head. CED is caused by changes in the TGFB1 gene, which messes up how bones grow. 

Doctors typically diagnose it by looking at symptoms, taking X-rays, and doing genetic tests. There's no cure for CED, but doctors can help manage the symptoms with medication and, in severe cases, surgery. People with CED often need regular medical check-ups and care to keep their lives as comfortable as possible. Researchers are working to better understand and treat this rare condition.