Bullitproof Foundation

Supporting Genetic Research to Cure Dyskeratosis Congenita


Dyskeratosis Congenita is an genetic condition causing premature aging. Symptoms can include abnormalities of skin and nails, and in some cases, bone marrow failure, fibrosis of lungs and liver. Dyskeratosis Congenita usually affects children and young people, but can occasionally affect older people. Dyskeratosis Congenita is diagnosed in 1 in a million.

Dyskeratosis Congenita is caused by defective maintenance of telomeres; the genetic material at the end of our chromosomes. Each time a cell divides, its telomeres get a little shorter. With ageing, cells divide many times. After many cell divisions, the telomeres become too short and the cell dies. Depending on the type of cell, this may lead to m
edical problems, such as anaemia (when too many red blood cell producing cells have died) or lung fibrosis (when too many lung cells have died)

Currently, 12 genes are known to be associated with Dyskeratosis Congenita. These are DKC1, TERC, TERT, NOP10, NHP2, WRAP53, CTC1, ST1, RTEL1, ACD, TINF2 and PARN. Being born with a mutation in one of these genes doesn’t necessarily mean that you will get Dyskeratosis Congenita, but you may be at
increased risk. You may be able to minimize this risk by lifestyle modification. Similarly, in some people with Dyskeratosis Congenita, no genetic abnormalities can be found. The DKC1 gene mutations generally only affect males. Females with an abnormal DKC1 gene are healthy carriers, their sons have a 50% chance of being affected and a 50% chance of being healthy/not carrying the gene. Their daughters have a 50% chance of being carriers, but will not have Dyskeratosis Congenita. Males with an abnormal DKC1 gene are likely to be affected with Dyskeratosis Congenita. Their sons will be unaffected/not carry the gene, their daughters will be healthy carriers.


Feed and Play Foundation Symptoms

General Symptoms

Patients diagnosed with Dyskeratosis Congenita may or may not display mottled pigmentation or depigmentation, darker or lighter patches, of skin. Dystrophic nails, ridged or thickened fingernails and toenails, or loss of nails in severe cases. Anaemia (low red cells), causing fatigue and paleness, or if severe, breathlessness. Leucopenia (Low white blood cells). If severely low, infection is more common and more serious. Thrombocytopenia (low platelets). If severe, causes bleeding (purpura/petechiae- red dots or small patches on the skin, or more severely internal bleeding into joints, brain or other organs).


Gastrointestinal TractFeed and Play Foundation Intestines

Dyskeratosis Congenita may be associated with enteropathy, poor function of the intestine causing poor absorption of foods and diarrhea.


Heart and Blood Vessels

Dyskeratosis Congenita may be associated with increased risk of atherosclerosis, especially in older people or those who have had a bone marrow or stem cell transplant. Atherosclerosis causes heart attacks and strokes. Monitoring and if necessary, treatment of high cholesterol and high blood pressure reduces these risks. Avoiding smoking, taking regular exercise and consumption of a healthy diet is also extremely important.


Feed and Play Foundation Liver

Liver

Cirrhosis of the liver is more common in those affected by Dyskeratosis Congenita. The liver filters nutrients and chemicals absorbed from the bowel, often processing or detoxifying them prior to circulation to other parts of the body. For this reason, the liver is subject to continuous stress and potential damage, but has huge capacity to repair and regenerate itself. As the liver cells age, their capacity for recovery is reduced. Aged liver cells may result in repair with fibrosis (scarring), which if severe, leads to cirrhosis. The risk of cirrhosis can be reduced by avoiding alcohol and medications which may cause liver damage, such as long term methotrexate. Vaccinations to prevent hepatitis (infection/inflammation of the liver) should be considered: hepatitis A vaccination for travellers and hepatitis B vaccination for those whose profession or lifestyle entails of risk of exposure to human body fluids (health care workers, law enforcement professionals). Once established, there are no proven treatments to reverse cirrhosis, although anti-fibrotic drugs used for lung diseases would be a theoretical option. However, expert care and treatment to prevent complications of cirrhosis is very important.

Drugs used to treat Dyskeratosis Congenita, such as oxymetholone or danazol have a risk of exacerbating cirrhosis. However this is less than the potential benefit of the treatment in most cases. Many other medications have a lower risk of liver toxicity, and your physician will advise on risk/benefit to you of taking these.


Lungs

Pulmonary Fibrosis is more common in people with Dyskeratosis Congenita, and in some cases can be the first indication of the disease. Pulmonary Fibrosis can be life threatening and is usually looked after by specialist chest physicians. New drugs have shown great promise in treating pulmonary fibrosis; older treatments such as prednisolone are no longer used, since they are unhelpful and could even make things worse. External factors such as smoking, pollution and exposure to certain medications (busulphan, methotrexate, long term nitrofurantoin) may increase the risk.


Feed and Play Foundation Dental

Dental

Dyskeratosis Congenita is associated with increased risk of oral leukoplakia (which can lead to mouth or tongue cancer), periodontitis or tooth decay.

Your dentist should check for leukoplakia, to prevent progression to cancer.

Oral leukoplakia is a type of pre-cancer of the inside of the mouth or tongue and shows up as white patches which cannot be scraped off. Leukoplakia is one of the hallmarks of Dyskeratosis Congenita. Dentists will look for leukoplakia during routine checkups and anyone with leukoplakia will be referred for biopsy and removal of the suspicious area, in order to prevent development of cancer.

Periodontitis is inflammation of the gums and is more common in people with Dyskeratosis Congenita. If untreated, periodontitis can lead to loss of teeth and increase the risk of heart disease, strokes, premature births and cancer. Periodontitis is prevented and treated by regular tooth brushing, regular flossing or interdental cleaning, and regular hygienist treatments. Deep cleansing and extended courses of low dose doxycycline antibiotics are used for treatment in difficult cases. Tooth decay is more common in those with Dyskeratosis Congenita and is prevented by minimizing/avoiding sugary snacks, drinks, and by dental hygiene. Mouth and tongue cancer is prevented by good dental hygiene, avoiding smoking, alcohol and restricting intake of very hot/spicy foods.


 

Treatments

Treating Dyskeratosis Congenita will vary from patient to patient.

Please consult your medical professional before partaking in any treatments.

Prescription Drugs

Diet & Exercise

Transplants

Treating Dyskeratosis Congenita with prescription drugs to improve telomere repair such as ‘Danazol’ is currently under investigation. Increasing Blood Cell Production with EPO (erythropoietin) injections (for anaemia), GCSF injections (for low neutrophil white blood cells), and eltrombopag (for low platelets and sometimes for anaemia) may also be effective alternatives for some patients. It has also been shown that a heathy diet and active lifestyle can have a positive results in overall heath and longevity. In more severe or advanced cases, bone marrow or stem cell transplantation could also be a viable solution, but should be carried out under the guidance of a specialist familiar with the disease.


PLEASE NOTE: The information contained in this website is for information purposes only and should not be deemed as medical advice. Always consult a medical professional before engaging any medical treatments.