What is Progeria?
Werner syndrome (WS) is a rare condition that causes premature aging, also known as progeria. This syndrome was first identified by Otto Werner in 1904. It is passed down through families (a trait known as autosomal recessive) and typically begins in late teens or early adulthood. People with Werner syndrome develop physical and metabolic changes that normally occur in older people. These can include severe complications such as diabetes, high blood pressure, weak and brittle bones (osteoporosis), heart attacks, strokes, and cancer.
What Causes Progeria?
Werner syndrome is a condition one can inherit that causes issues with the body’s ability to fix damage in the DNA (the genetic material in all cells). Usually, our body can repair any changes or mutations in the DNA, but in people with Werner syndrome, this ability is compromised.
This means that any mistakes or changes that occur naturally in our DNA as we age can build up in people with Werner syndrome, which may make them seem like they’re aging earlier than they should in certain parts of their body. This early aging doesn’t affect all tissues or organs, which suggests that Werner syndrome doesn’t cause overall quickened aging but rather it affects specific parts of the body or ‘segmental’ aging.
One noteworthy detail is that these individuals typically don’t experience premature neurocognitive deficits, meaning they don’t show early signs of aging related to brain function or mental abilities. This contributes to the argument that Werner syndrome is not necessarily about overall accelerated aging, but rather about specific areas of the body aging prematurely.
Risk Factors and Frequency for Progeria
Werner syndrome is a rare condition. Globally, it’s estimated to affect 1 out of every 100,000 babies. However, it’s more common in Japan, affecting up to 1 in 20,000 to 40,000 babies. In the United States, it’s even rarer, affecting about 1 in 200,000 babies.
Signs and Symptoms of Progeria
People with Werner syndrome generally appear normal until they reach adolescence or their early twenties, when they start to show symptoms that look a lot like rapid aging. Some of the symptoms they may exhibit include skin ulcers, cataracts, graying or loss of hair, and issues with their reproductive systems. On the outside, they might look very thin and have aged-looking skin. Often, they exhibit certain physical traits, like being shorter in stature, having a high-pitched voice, dental abnormalities, and underweight.
The patients also tend to lose muscle mass quickly, especially in their arms and legs, while keeping more mass in their body trunk. This can lead to weakened muscles and a condition called sarcopenia — which is essentially extreme muscle loss — before they even turn 40. Minute mobility, osteoporosis, and soft tissue calcifications, mostly in the Achilles tendon, are common too. Some patients experience flat feet, a misaligned big toe, or muscle contractions in their feet, leading to ulcers, bone inflammation, and infection.
Another issue for people with Werner syndrome is that they have abnormal metabolic activity, which can lead to type 2 diabetes and unusual fat accumulation around their abdomen. They may also present cardiovascular problems, such as artery hardening, heart valve disorder, and aortic opening narrowing.
There is also a heightened risk for these patients to develop tumors. Around 10% of Werner syndrome patients may develop some type of cancer. However, the types of tumors they develop don’t typically correspond to the ones older population tend to develop; half of them are reported to have soft tissue sarcomas, like schwannoma, rhabdomyosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and osteosarcoma of the upper extremities. Other types of cancers reported include brain tumors, skin cancer, and thyroid cancer.
Testing for Progeria
Genetic testing is one of the ways to confirm the diagnosis of Werner syndrome, a disorder that causes rapid aging. Reverse transcription-polymerase chain reaction (PCR) is a method used to copy or produce plenty of a specific gene for study. Combined with a western blot protein analysis, which identifies precise proteins in a sample, these tools can help doctors confirm the diagnosis.
If there’s a high risk of this disorder in an unborn child, prenatal tests such as amniocentesis and chorionic villus sampling can be done. Amniocentesis involves taking a small sample of the amniotic fluid that surrounds the baby in the womb. Meanwhile, chorionic villus sampling involves taking a sample of cells from the placenta, which can provide genetic information about the baby.
Once diagnosed with Werner syndrome, patients must have regular health checks for high cholesterol (hyperlipidemia), diabetes, thyroid problems, and breast and colorectal cancer. Due to the risk of musculoskeletal abnormalities and soft tissue sarcomas (a type of cancer) in people with Werner syndrome, doctors might need to carry out imaging tests like X-ray, CT scan, or MRI. These tests help to evaluate for underlying disorders, infections, or tumors.
DEXA scans, which measure bone density, should also be done regularly. This is to monitor osteoporosis – a condition that weakens bones and makes them more likely to break.
Treatment Options for Progeria
Werner syndrome is treated by focusing on relieving symptoms and managing diseases in other body parts affected by the condition. For conditions like high blood pressure, hardened arteries, diabetes, and other diseases related to Werner syndrome, typical conventional medical treatments and regular monitoring is used; however, the disease keeps progressing.
There have been suggestions that bosentan, which is a type of drug known as an endothelin receptor antagonist, might help treat severe skin ulcers. Sodium etidronate may ease the troublesome calcifications, or build-up of calcium, in soft tissues. To manage the issues with foot deformities, orthotics or shoe inserts can be useful.
Cataracts, a common occurrence in Werner syndrome that cause clouding in the eye leading to blurry vision, are treatable through surgery. Another symptom, sarcopenia, which is the loss of muscle tissue as a part of the aging process, could be managed through diets high in branched amino acids, exercise, vitamin D supplements, and hormone therapy. However, the use of hormone therapy is a debated topic as it might raise the risk of developing cancer.
What else can Progeria be?
When determining a diagnosis, doctors need to rule out several conditions that might have similar symptoms. Here are some conditions that might be considered:
- Systemic sclerosis
- Dermatomyositis
- Hutchinson-Gilford Progeria syndrome (a premature aging disorder)
- Bloom syndrome (a condition that causes many health troubles)
- Cockayne syndrome (a condition that causes premature aging)
- Ataxia telangiectasia (a disorder that affects the nervous system)
- Xeroderma pigmentosum (a condition which makes individuals extremely sensitive to the sun)
- Wiedemann-Rauten-Strauch syndrome (a disorder that leads to premature aging)
It’s crucial for medical professionals to consider all these possibilities to ensure that the diagnosis is accurate.
What to expect with Progeria
People living with Werner syndrome generally live into their 50s. They typically pass away due to cancer or heart disease.
Possible Complications When Diagnosed with Progeria
People with Werner syndrome, a condition linked with symptoms from various affected body systems, have an increased risk of getting cancer. Specifically, they are more likely to develop skin and thyroid cancers. Regretfully, their life expectancy is usually shorter than the average. The prime causes of death in these patients are cancer and heart attacks.
Common Complications:
- Increased probability of developing cancer
- Higher incidence of skin and thyroid cancer
- Shorter life expectancy
- Death most commonly caused by cancer and heart attacks
Preventing Progeria
Doctors often advise patients and their families to see a genetic counselor if they need more information about the condition. Genetic counselors are specialists who can help you understand what your test results mean and what to expect. They might also suggest you join a support group such as the National Organization for Rare Disorders. Support groups offer a community of people who are experiencing similar situations and can share advice and encouragement.
