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Disease Profile

Dyskeratosis congenita

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Neonatal

ICD-10

Q82.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

DKC; Zinsser-Engman-Cole syndrome; DC

Categories

Blood Diseases; Congenital and Genetic Diseases; Eye diseases;

Summary

Dyskeratosis congenita affects many parts of the body. Three features are especially characteristic of this disorder: (1) fingernails and toenails that grow poorly or are abnormally shaped; (2) changes in skin coloring (pigmentation), especially on the neck and chest, that resembles the appearance of lace; and (3) white patches inside the mouth (oral leukoplakia). People with dyskeratosis congenita also have an increased risk of developing several life-threatening conditions, including pulmonary fibrosis, bone marrow failure, aplastic anemia, myelodysplastic syndrome, leukemia, and other cancers. The severity of dyskeratosis congenita varies widely among affected individuals.[1][2] 

This condition is caused by pathogenic variants (mutations) in a number of different genes known to affect the length of the telomeres.[2] Telomeres are structures found at the ends of chromosomes that protect the chromosomes from sticking together or breaking down. In most cells, the telomeres get shorter over time and eventually tell the cell to stop dividing.[1] The genes known to be involved in dyskeratosis congenita include DKC1, TERC, TERT, TINF2, ACD, CTC1, NHP2, NOP10, PARN, RTEL1, and WRAP53. There is evidence that another gene, NPM1, may also be involved.[3] Approximately 70% of those who meet the clinical diagnostic criteria for dyskeratosis congenita have a mutation in one of these genes.[2] How dyskeratosis congenita is inherited depends on which gene is involved.[1][2] Treatment is aimed at addressing the symptoms present in each individual.[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal blistering of the skin
Blistering, generalized
Blisters

[ more ]

0008066
Abnormal fingernail morphology
Abnormal fingernails
Abnormality of the fingernails

[ more ]

0001231
Abnormality of neutrophils
0001874
Anemia
Low number of red blood cells or hemoglobin
0001903
Hypermelanotic macule
Hyperpigmented spots
0001034
Nail dystrophy
Poor nail formation
0008404
Oral leukoplakia
Oral white patch
0002745
Thrombocytopenia
Low platelet count
0001873
30%-79% of people have these symptoms
Abnormal morphology of female internal genitalia
0000008
Abnormality of coagulation
0001928
Abnormality of the pharynx
0000600
Anorectal anomaly
0012732
Aplasia/Hypoplasia of the skin
Absent/small skin
Absent/underdeveloped skin

[ more ]

0008065
Aplastic/hypoplastic toenail
Absent/small toenails
Absent/underdeveloped toenails

[ more ]

0010624
Bone marrow hypocellularity
Bone marrow failure
0005528
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Cellular immunodeficiency
0005374
Coarse metaphyseal trabecularization
0100670
Esophageal stenosis
Narrowing of the esophagus
0010450
Global developmental delay
0001263
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hypodontia
Failure of development of between one and six teeth
0000668
Hypopigmented skin patches
Patchy loss of skin color
0001053
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Malabsorption
Intestinal malabsorption
0002024
Periodontitis
0000704
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Short stature
Decreased body height
Small stature

[ more ]

0004322
Skin ulcer
Open skin sore
0200042
Sparse hair
0008070
Taurodontia
0000679
Telangiectasia of the skin
0100585
Tracheoesophageal fistula
0002575
Urethral stenosis
Narrowing of the urethra
0008661
5%-29% of people have these symptoms
Abnormal eyebrow morphology
Abnormality of the eyebrow
0000534
Abnormal eyelash morphology
Abnormal eyelashes
Abnormality of the eyelashes
Eyelash abnormality

[ more ]

0000499
Abnormal testis morphology
Abnormality of the testis
0000035
Alopecia
Hair loss
0001596
Avascular necrosis
Death of bone due to decreased blood supply
0010885
Blepharitis
Inflammation of eyelids
0000498
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Diabetes mellitus
0000819
Displacement of the urethral meatus
0100627
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hepatic failure
Liver failure
0001399
Hepatomegaly
Enlarged liver
0002240
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Lymphoma
Cancer of lymphatic system
0002665
Neoplasm of the pancreas
Cancer of the pancreas
Pancreatic tumor

[ more ]

0002894
Osteoporosis
0000939
Palmoplantar keratoderma
Thickening of palms and soles
0000982
Premature graying of hair
Early graying
Premature graying
Premature greying
Premature hair graying

[ more ]

0002216
Scoliosis
0002650
Skin vesicle
0200037
Splenomegaly
Increased spleen size
0001744
White hair

Cause

Dyskeratosis congenita occurs when DNA changes known as pathogenic variants occur in one of the following genes. The genes known to be involved in dyskeratosis congenita include DKC1, TERC, TERT, TINF2, ACD, CTC1, NHP2, NOP10, PARN, RTEL1, and WRAP53. Another gene, NMP1, is also thought to be associated with dyskeratosis congenita. Pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[2][3] The inheritance pattern of dyskeratosis congenita depends on which gene is involved.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • MedlinePlus Genetics contains information on Dyskeratosis congenita. This website is maintained by the National Library of Medicine.
      • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Dyskeratosis congenita in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Dyskeratosis congenita. Click on the link to view a sample search on this topic.

          References

          1. Dyskeratosis congenita. Genetics Home Reference. March 2014; https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita.
          2. Savage SA. Dyskeratosis Congenita. GeneReviews. Updated Nov 21, 2019; https://www.ncbi.nlm.nih.gov/books/NBK22301/.
          3. Nachmani D, Bothmer AH, Grisendi S, Mele A, Bothmer D, et al. Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita. Nat Genet. Oct 2019; 51(10):1518-1529. https://pubmed.ncbi.nlm.nih.gov/31570891/.

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