SNP Shot: Genomic Insights

Dyskeratosis congenita is a condition that can affect various parts of the body. It's typically characterized by three main features: poorly growing or abnormally shaped fingernails and toenails (nail dystrophy), changes in skin pigmentation, often appearing "lacy" on the neck and chest, and white patches in the mouth (oral leukoplakia).

Individuals with dyskeratosis congenita face an elevated risk of developing serious health problems. They are particularly susceptible to conditions affecting bone marrow function, which is critical for producing new blood cells. This can lead to aplastic anemia, also known as bone marrow failure, where the bone marrow doesn't produce enough blood cells. They also have a higher risk of myelodysplastic syndrome, where immature blood cells don't develop properly, potentially progressing to leukemia, a type of blood cancer. Even without developing myelodysplastic syndrome, people with dyskeratosis congenita still have an increased risk of leukemia. Furthermore, they are at a higher risk for other cancers, especially those affecting the head, neck, anus, or genitals.

Individuals with dyskeratosis congenita may also experience pulmonary fibrosis, a condition where scar tissue (fibrosis) accumulates in the lungs, impairing oxygen transfer to the bloodstream. Other possible signs and symptoms include eye problems such as blocked tear ducts leading to eyelid irritation, dental issues, hair loss or premature graying, low bone density (osteoporosis), degeneration (avascular necrosis) of hip and shoulder joints, and liver disease. Some affected males may develop urethral stenosis, a narrowing of the urethra, the tube carrying urine from the bladder, which can cause difficult or painful urination and urinary tract infections.

The severity of dyskeratosis congenita varies significantly from person to person. Some individuals may exhibit only mild physical symptoms and have normal bone marrow function, while others may experience many characteristic features and develop bone marrow failure, cancer, or pulmonary fibrosis at a young age.

While most individuals with dyskeratosis congenita have normal intelligence and motor skill development (standing, walking), some severely affected individuals may experience developmental delays. Hoyeraal Hreidaarsson syndrome, a severe form, involves an unusually small and underdeveloped cerebellum, the brain area responsible for movement coordination. Revesz syndrome, another severe variant, includes abnormalities in the retina (light-sensitive tissue at the back of the eye) in addition to other dyskeratosis congenita symptoms.

Inheritance:

Dyskeratosis congenita can be inherited in different ways. When it's caused by DKC1 gene mutations, it follows an X-linked recessive inheritance pattern. The DKC1 gene is located on the X chromosome, one of the sex chromosomes. Males, with only one X chromosome, are affected if they have one altered copy of the gene in each cell. Females, with two X chromosomes, need mutations in both copies to develop the disorder. Because it's less likely for females to have two altered copies, X-linked recessive disorders are more common in males. A key characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. When dyskeratosis congenita results from mutations in other genes, it can be inherited in an autosomal dominant or autosomal recessive pattern. Autosomal dominant inheritance means only one copy of the altered gene in each cell is enough to cause the condition. Autosomal recessive inheritance requires mutations in both copies of the gene in each cell. Individuals with an autosomal recessive condition inherit one copy of the mutated gene from each parent, who typically do not show signs or symptoms of the condition.