Dyskeratosis Congenita

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Dyskeratosis congenita is an inherited condition causing premature ageing due to telomere repair abnormalities. Symptoms can include abnormalities of skin and nails, and in some cases, bone marrow failure (anaemia, low white blood count and platelet-blood clotting problems), or fibrosis (scarring) of lungs and liver cirrhosis.

 

 Who is affected?

Dyskeratosis congenita usually affects children and young people, but can occasionally affect older people. Dyskeratosis Congenita is diagnosed in 1 in a million.

 

 What is the cause?

Dyskeratosis congenita is caused by a genetic, inheritable, defect causing 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 medical problems, such as anaemia (when too many red blood cell producing cells have died) or lung fibrosis (when too many lung cells have died).

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.

 

Other types of Dyskeratosis Congenita

Coats Syndrome, Coats plus Syndrome and Revesz Syndrome

CTC1& ST1 (Coats plus syndrome, DC and additional brain/retina(eye) calcification abnormalities) TINF2 (Revesz syndrome, similar to Coats plus, but also growth retardation, affecting babies & children) are associated with more severe disease.

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, 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.

CTC1 (Coats plus syndrome, DC and additional brain/retina(eye) calcification abnormalities) TINF2 (Revesz syndrome, similar to Coats plus, but also growth retardation, affecting babies & children) are associated with more severe disease.

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.

 

Types of inheritance:

X-linked: DKC1

X-linked Recessive

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.

Autosomal recessive: TERC (some families), TERT (some families), RTEL 1 (some families), TINF2, PARN (some families), NHP2, NOP10

Autosomal Recessive

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)

Autosomal Dominant

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.

 

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.