Dyskeratosis congenita is a group of genetic disease that is characterized by the presence of abnormal growth of the nails (nail dystrophy), pigmentation of the skin, particularly the upper chest and the neck along with white patches within the mouth (oral leukoplakia). The exact prevalence of this condition is not known but is estimated to affect around 1 in a million individuals.
Causes
The genetic mutation in the genes TERT, TERC, DKC1 or TINF2 is estimated to affect around half of the cases. These genes provide instructions to produce proteins that regulate the structures of the chromosomes known as telomeres which protect the chromosomes from degrading. Other genetic mutations have also been identified to cause this disorder and in some cases, the cause remains unknown. The genetic mutation in the gene DKC1 is inherited in an x-linked recessive pattern where the gene is located in one of the sex chromosomes. As males only have one X chromosome, the single altered copy of the gene is sufficient to cause the disorder. The autosomal dominant pattern of inheritance requires a single copy of the defective gene while the autosomal recessive trait requires both the copy to be defective to develop this disorder.
Symptoms
The symptoms of this disorder may vary in different cases depending on the type of gene affected. The classic form of this disorder presents the skin, nail and mouth abnormalities which appear before the age of 10 followed by the bone marrow failure around the age of 20. The skin abnormalities present dark discoloration that usually affects the face, neck and the shoulders. The nail abnormalities include the underdevelopment that can result in the distortion or the loss of the nails. The white thickened patches of the mouth appear on the mucous membranes that progress slowly and can include the mucous membranes of the urethra and the anus in rare cases. The bone marrow failure results in the deficiency of the red, white blood cells and the platelets. The severity of bone marrow failure can vary greatly from very mild to very severe and can present various associated symptoms such as the paleness of the skin, anemia and frequent infections. These individuals are also predisposed to developing leukemia and cancer. Additional abnormalities can include lung disease (pulmonary fibrosis) that presents breathing difficulties and decreased lung function. The less common symptoms include excessive sweating of the palms and the soles of the feet, tooth loss, urinary tract anomalies, excessively watery eyes, short stature, skeletal abnormalities and underdeveloped testes.
Diagnosis
The diagnosis is based on the clinical evaluation and in the identification of features that are characteristic of this condition. The aplastic anemia can also be an initial symptom of this disorder. The bone marrow failure with very short telomeres can also support the diagnosis of dyskeratosis congenita. Molecular genetic testing of the mutation in the genes DKC1, TERC, TERT, TINF2, NHP2 or NOP10 can confirm the diagnosis. However, around 50% of the cases present no mutation although the clinical features of this condition are evident.
Treatment
The treatment may require the coordination of various specialists such as pediatricians, dermatologists, dental specialists, a cancer specialist and other health care professionals to devise an effective treatment plan for the affected individual. Smoking and alcohol should be avoided to prevent lungs and liver complications. Moisturizing creams may be beneficial for the skin condition and good dental care may prevent tooth problems. These individuals require regular monitoring to prevent the onset of infections and in early identification of cancer.
References
https://rarediseases.org/rare-diseases/dyskeratosis-congenita/
https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita#genes
https://www.ncbi.nlm.nih.gov/books/NBK22301/
http://www.dermnetnz.org/topics/dyskeratosis-congenita/
