Toulouse-Lautrec syndrome is a genetic disease that is estimated to affect about 1 in 1.7 million people worldwide. There have been just 200 cases described in literature.
Toulouse-Lautrec syndrome is named after the famous 19th century French artist Henri de Toulouse-Lautrec, who is believed to have had the disorder. The syndrome is known clinically as pycnodysostosis (PYCD). PYCD causes brittle bones, as well as abnormalities of the face, hands, and other parts of the body.
What causes it?
A mutation of the gene that codes the enzyme cathepsin K (CTSK) on chromosome 1q21 causes PYCD. Cathepsin K plays a key role in bone remodeling. In particular, it breaks down collagen, a protein that acts as scaffolding to support minerals such as calcium and phosphate in bones. The genetic mutation that causes Toulouse-Lautrec syndrome leads to the buildup of collagen and very dense, but brittle, bones.
PYCD is an autosomal recessive disorder. That means a person must be born with two copies of an abnormal gene for the disease or physical trait to develop. Genes are passed down in pairs. You get one from your father and one from your mother. If both parents have one mutated gene, that makes them carriers. The following scenarios are possible for the biological children of two carriers:
- If a child inherits one mutated gene and one unaffected gene, they would also be a carrier, but wouldn’t develop the disease (50 percent chance).
- If a child inherits the mutated gene from both parents, they’ll have the disease (25 percent chance).
- If a child inherits the unaffected gene from both parents, they’ll be neither a carrier nor will they have the disease (25 percent chance).
What are the symptoms?
Dense, but brittle, bones is the main symptom of PYCD. But there are many more physical features that can develop differently in people with the condition. Among them are:
- high forehead
- abnormal fingernails and short fingers
- narrow roof of mouth
- short toes
- short stature, often with an adult-size trunk and short legs
- abnormal breathing patterns
- enlarged liver
- difficulty with mental processes, though intelligence is not usually affected
Because PYCD is a bone-weakening disease, people with the condition face a much higher risk of falling and fractures. Complications stemming from fractures include reduced mobility. The inability to exercise regularly, due to bone fractures, can then affect weight, cardiovascular fitness, and overall health.
How is it diagnosed?
Diagnosing Toulouse-Lautrec syndrome is often done in infancy. Because the disease is so rare, however, it can sometimes be harder for a physician to make the right diagnosis. A physical exam, medical history, and laboratory tests are all part of the process. Getting a family history is especially helpful, as the presence of PYCD or other inherited conditions can help guide the doctor’s investigation.
X-rays can be particularly revealing with PYCD. These images can show characteristics of the bones that are consistent with PYCD symptoms.
Molecular genetic testing can confirm a diagnosis. However, the doctor needs to know to test for the CTSK gene. Testing for the gene is done at specialized laboratories, because it’s a seldom-performed genetic test.
Usually a team of specialists is involved in PYCD treatment. A child with PYCD will have a healthcare team that includes a pediatrician, an orthopedist (bone specialist), possibly an orthopedic surgeon, and perhaps an endocrinologist who specializes in hormonal disorders. (Although PYCD isn’t specifically a hormonal disorder, certain hormonal treatments, such as growth hormone, can help with symptoms.)
Adults with PYCD will have similar specialists in addition to their primary care physician, who will likely coordinate their care.
PYCD treatment must be designed for your specific symptoms. If the roof of your mouth is narrowed so that the health of your teeth and your bite are affected, then a dentist, orthodontist, and perhaps an oral surgeon would coordinate your dental care. A cosmetic surgeon may be brought in to help with any facial symptoms.
The care of an orthopedist and orthopedic surgeon will be especially important throughout your life. Having Toulouse-Lautrec syndrome means that you’ll likely have multiple bone fractures. These can be standard breaks that occur with a fall or other injury. They can also be stress fractures that develop over time.
A person with multiple fractures in the same area, such as the tibia (shinbone), can sometimes have a harder time being diagnosed with stress fractures because the bone will include several fracture lines from previous breaks. Sometimes a person with PYCD or any other brittle bone condition will need a rod placed in one or both legs.
If the disease is diagnosed in a child, growth hormone therapy may be appropriate. Short stature is a common result of PYCD, but growth hormones carefully supervised by an endocrinologist can be helpful.
Other encouraging research includes the use of enzyme inhibitors, which interfere with the activity of enzymes that could harm bone health.
Promising research also includes the manipulation of a specific gene’s function. One tool for this is known as Clustered Regularly Interspaced Palindromic Repeats (CRISPR). It involves editing the genome of a living cell. CRISPR is new technology and is being studied in the treatment of many inherited conditions. It’s not clear yet whether it can be a safe and effective way of treating PYCD.
What’s the outlook?
Living with pycnodysostosis means making a number of lifestyle adjustments. Children and adults with the condition shouldn’t play contact sports. Swimming or cycling may be better alternatives, because of the lower fracture risk.
If you have pycnodysostosis, you should discuss with a partner the prospects of possibly passing on the gene to your child. Your partner also may want to undergo genetic testing to see if they’re a carrier. If they’re not a carrier, you cannot pass on the condition itself to your biological children. But since you have two copies of the mutated gene, any biological child you have will inherit one of these copies and automatically be a carrier. If your partner is a carrier and you have PYCD, the likelihood of a biological child inheriting two mutated genes and therefore having the condition itself goes up to 50 percent.
Having Toulouse-Lautrec syndrome alone doesn’t necessarily affect life expectancy. If you’re otherwise healthy, you should be able to live a full life, with some precautions and the ongoing involvement of a team of healthcare professionals.