Not everyone will have every symptom.
Problems associated with Dyskeratosis Congenita and Telomere Biology Disorders are listed here:
Mottled pigmentation or depigmentation (darker or lighter patches) of skin.
Dystrophic nails (ridged or thickened nails), loss of nails in severe cases.
Bone marrow/blood
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).
Dyskeratosis congenita can cause problems with production of blood cells.
Bone marrow is the place where blood cells are made.
‘Bone marrow failure’ occurs when the bone marrow doesn’t make enough blood cells to replace those that are used up. Bone marrow failure or insufficiency can occur in dyskeratosis congenita (and other telomere repair disorders).
Blood
Telomeres protect the ends of chromosomes. The name originates from the Greek telos (end) and meros (part).
Telomeres have been likened to the plastic caps that protect the ends of shoelaces to prevent them from fraying. If the telomere caps become too short, the cell dies. The protection provided by telomeres is vital during cell division, a stage of the ongoing process of cell replacement. Mutations in the genes responsible for maintaining healthy telomeres tend to produce more noticeable effects in groups of cells that normally undergo rapid division and replacement. This happens in the bone marrow where cells are constantly dividing to make and replace blood cells.
The effects on bone marrow can be extremely variable but can lead to reductions in the number of red blood cells (responsible for carrying oxygen around the body), white blood cells (important for fighting infection) and platelets (important for blood clotting). Telomeres in affected individuals can also be more sensitive to radiation (X-rays and CT scans), inflammation and some medical treatments.
Dyskeratosis Congenita may be associated with enteropathy (poor function of the intestine causing poor absorption of foods and diarrhoea).
Small abnormal blood vessels called ‘arteriovenous (AV) malformations’ can be problematic and cause bleeding which can be difficult to control. Radiofrequency ablation by endoscopy (tube inserted through the mouth to look at the stomach), oestrogens and VEGF can be helpful. Oesophageal varices (varicose veins in the gullet or stomach) can also occur and are treated by injection/ banding via endoscopy, or by using medication such as beta blockers to reduce the likelihood of bleeding.
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.
Small abnormal blood vessels called ‘arteriovenous (AV) malformations’ can be problematic in several areas of the body. Details can be found in the relevant section (see Gastrointestinal, Lungs, Liver and Eyes).
Cirrhosis of the liver is more common in those affected by dyskeratosis congenita and people who carry DC-associated genes.
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, particularly in patients with DC or DC-associated genes, whose short telomeres cause accelerated aging. Aged liver cells may result in repair with fibrosis (scarring), which if severe, leads to cirrhosis – a condition where scar tissue obstructs and blocks the normal functioning of the liver.
The risk of cirrhosis can be reduced by avoiding alcohol and by avoiding 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 antifibrotic drugs used for lung diseases would be a theoretical option. However, expert care and treatment to prevent complications of cirrhosis is very important.
Small abnormal blood vessels called ‘arteriovenous (AV) malformations’ can also be problematic. They can cause a condition called hepatopulmonary syndrome, which can lead to shortness of breath, low blood oxygen levels, and portal or pulmonary hypertension, where the blood pressure in the arteries leading to the liver or lungs is increased. Portal hypertension can lead to liver and spleen enlargement and oesophageal varices (varicose veins in the gullet or stomach), which can cause bleeding. Varices are treated by injection/ banding via endoscopy (tube inserted through the mouth into the stomach), or by using medication such as beta blockers to reduce the likelihood of bleeding.
* 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.
References and Further Reading:
Pulmonary (lung) 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.
Clubbing of the nails, shown here, can be a sign of pulmonary fibrosis.
Treatment of conditions such as acid reflux (dyspepsia/heartburn) can also improve matters. External factors such as smoking, pollution and exposure to certain medications (busulphan, methotrexate, long term nitrofurantoin) may increase the risk. A full list of medications which should ideally be avoided is available at https://www.pneumotox.com/drug/index/
Guidelines for treating pulmonary fibrosis are available. Although these apply to all forms of pulmonary fibrosis, they are also applicable to those with dyskeratosis congenita.
CT scan showing pulmonary fibrosis.
Small abnormal blood vessels called ‘arteriovenous (AV) malformations’ can also be problematic and cause bleeding or shortness of breath and low blood oxygen. Early treatment with oestrogens, danazol or VEGF may be helpful. AV malformations may also contribute to pulmonary fibrosis. If liver transplant is required, AV malformations in the lungs often improve afterwards.
You can find DC Action’s lungs ‘Cheat Sheet’ here: Respiratory 2025
You may find it useful to take this to your GP or specialist to help explain your symptoms.
References and Further Reading:
https://www.nice.org.uk/guidance/cg163
https://www.actionpf.org/information-support/does-ipf-run-in-the-family
https://bmjopenrespres.bmj.com/content/12/1/e002773
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00170-1/fulltext
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, as seen above, which should be treated to prevent progression to cancer.
Oral leukoplakia is a type of precancer 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 and drinks, and by dental hygiene as above.
Mouth and tongue cancer is prevented by good dental hygiene, avoiding smoking, alcohol and restricting intake of very hot/spicy foods. Sharp teeth which cause irritation to gums or mouth should also be repaired.
Should you need to be referred to an oral medicine consultant, The British and Irish Society for Oral Medicine BISOM has a list of specialist clinics under the Clinical Care tab on its website https://bisom.org.uk/
Mottled pigmentation (brown patches) or depigmentation (white patches) is common, particularly in sun-exposed areas and are characteristic of Dyskeratosis Congenita. Sun exposure also increases the risk of skin cancers (basal cell, squamous cell and melanoma) which are particularly common in Dyskeratosis Congenita. These complications can be minimized by avoiding strong sunshine, using high factor UVA/UVB sunblock and wearing long sleeved garments when in the sun. Any suspicious moles, lumps or bumps should be checked by a doctor.
Ridged or splitting of nails is very common, even in healthy people. However, most people with dyskeratosis congenita have problems with nails, which can sometimes progress to nail dystrophy: thickened small nails which, in extreme cases, may disappear altogether.
Premature greying of hair, loss of hair including eyebrows and eyelashes may occur.
Telomere Biology Disorders affect rapidly proliferating cells – therefore cells such as T and B lymphocytes, important in fighting infections, are particularly vulnerable. The effects can lead to reduced numbers of T and B cells or cells that don’t work properly. Immune problems are common and usually subtle (especially if the condition becomes apparent in later life – adult onset) and may present as CVID (combined variable immunodeficiency) or SCID (severe combined immunodeficiency) predominantly antibody deficiency. Virus susceptibility may be severe especially in early childhood onset which can present as severe combined immune deficiency. There is some evidence that T cell immune deficiency, rather than chromosome instability, may play a role in squamous cell cancer susceptibility.
