Who is affected?
Dyskeratosis congenita usually affects children and young people, but can occasionally affect older people. Dyskeratosis Congenita is diagnosed in one in a million. Other Telomere Biology disorders can cause symptoms later in life and affect several organs.
What is the cause?
Dyskeratosis congenita and other Telomere Biology Disorders are the result of mutations in telomere maintenance genes. 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 or functions abnormally. Depending on the type of cell, this may lead to medical problems, such as anaemia (when too many red blood cell producing cells have died) or lung / liver fibrosis (when minor lung or liver damage associated with day to day life heals with scarring) causing shortness of breath or cirrhosis.
Being born with a mutation in one of these genes doesn’t necessarily mean that you will have problems but you may be at increased risk. You may be able to minimize this risk by lifestyle modification.
Similarly, in some people who are diagnosed with with Dyskeratosis Congenita or a Telomere Biology Disorder, no genetic mutations can be found.
What is the cause?
Dyskeratosis Congenita and other Telomere Biology Disorders are the result of alterations in telomere maintenance genes. 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 or functions abnormally. Depending on the type of cell, this may lead to medical problems, such as anaemia (when too many red blood cell producing cells have died) or lung / liver fibrosis (when minor lung or liver damage associated with day to day life heals with scarring) causing shortness of breath or cirrhosis.
Being born with an alteration in one of these genes doesn’t necessarily mean that you will have problems but you may be at increased risk. You may be able to minimise this risk by lifestyle modification.
Similarly, in some people who are diagnosed with Dyskeratosis Congenita or a Telomere Biology Disorder, no genetic changes can be found.
Other related conditions
Coats plus Syndrome
Alterations in the genes encoding CTC1/STN1/TEN1 complex and POT1 lead to Coats Plus Syndrome with similar symptoms to Dyskeratosis Congenita and additional brain calcification and eye complications.
Revesz Syndrome
Revesz syndrome is a rare severe phenotypic variant of dyskeratosis congenita with an onset in early childhood. It is caused by alterations in the TINF2 gene and is characterised by features of Dyskeratosis Congenita including skin, nail and mouth problems, a high risk of bone marrow failure (BMF) and cancer, developmental delay, sparse and fine hair in conjunction with brain and eye complications similar to Coats Plus syndrome.
Hoyeraal-Hreidarsson syndrome
Can be caused by any of the DC genes. This is a severe form of DC with abnormalities developing before birth, which include small brain (microcephaly), small cerebellum (brain balance centre and growth retardation. Affected children are small and have severe learning difficulties in addition to the other features of DC.
How is it inherited?
Currently the following genes are known to be associated with Dyskeratosis Congenita and Telomere Biology Disorders. New genes are being discovered all the time.
TERT, TERC, PARN, RTEL1, NAF1, DKC1, NHP2, TINF2, NOP10, ACD, RPA1, POT1, ZCCHC8 CTC1, DCLRE1B, NPM1, STN1, TCAB1, MDM4, WRAP53 and TYMS-ENOSF1
CTC1 (Coats plus syndrome, DC and additional brain/retina(eye) calcification abnormalities) and TINF2 are associated with more severe disease.
However, some people may have symptoms of Dyskeratosis Congenita or a Telomere Biology Disorder when no genetic alteration can be found.
Types of inheritance:
X-linked: DKC1
DKC1 gene mutations generally only affect males.
Females with an altered DKC1 gene are healthy carriers, their sons have a 50% chance of being affected and a 50% chance of being healthy / not carrying the affected 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.
Autosomal recessive:
TERC (some families), TERT (some families), RTEL 1 (some families), TINF2, PARN (some families), NHP2, NOP10
Two gene mutations (one from each parent) are generally required for dyskeratosis congenita. Parents who carry 1 gene mutation each have a 25% chance that each child will be affected.
Autosomal dominant:
TERT (some families), RTEL1 (some families), PARN (some families).
There is a 50% chance of each child of an affected person carrying the gene. Autosomal dominant genes generally are associated with onset of dyskeratosis congenita at an older age, sometimes in old age, and some people remain healthy.
If you have any questions, please contact our medical advisor, Dr. Hilary Longhurst via info@dcaction.org
You can hear a medical overview of Dyskeratosis Congenita on the Instagram post
Medics for Rare Diseases – an overview of Dyskeratosis Congenita
Disclaimer: The materials contained on this website are provided for general information and guidance purposes only, and do not constitute advice in their own right. For medical advice, please contact your doctor.