autosomal dominant dyskeratosis congenita 4

Dyskeratosis congenita (DC) is a rare genetic disorder that affects the bone marrow's ability to produce new blood cells, leading to aplastic anemia [1]. It is characterized by a multisystem disorder caused by defective telomere maintenance, which can result in various symptoms and complications.

In its classic form, autosomal dominant DC presents with a triad of mucocutaneous abnormalities, bone marrow failure, and a predisposition to cancer. The mucocutaneous features include reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia [6]. Bone marrow failure is the most significant aspect of this disorder, leading to anemia, infections, and bleeding due to the reduced production of blood cells.

The symptoms of autosomal dominant DC can vary in severity and may include:

• Reticulated skin hyperpigmentation
• Nail dystrophy (thin, brittle, or absent nails)
• Oral leukoplakia (white patches on the tongue or inside the cheeks)
• Bone marrow failure leading to anemia, infections, and bleeding
• Increased risk of cancer

The progression of liver disease and portal hypertension is also a significant concern in individuals with DC [5]. Early diagnosis and management are crucial to prevent complications and improve quality of life.

References: [1] Mar 1, 2014 — These disorders disrupt the ability of the bone marrow to produce new blood cells. Affected individuals may develop aplastic anemia , also known ... [6] Jan 26, 2020 — It is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia. [5] Progression of liver disease and portal hypertension in dyskeratosis congenita and related telomere biology disorders. Vittal A, Niewisch MR, Bhala S, ...

Based on the provided context, here are the signs and symptoms of autosomal dominant dyskeratosis congenita:

• Frequent infections: This is a common symptom of dyskeratosis congenita, as mentioned in [1].
• Low energy and fatigue: People with dyskeratosis congenita often experience low energy and fatigue, which can be attributed to the bone marrow failure aspect of the condition [3][5].
• Bleeding problems: Bleeding problems are a common sign of dyskeratosis congenita, as the bone marrow's inability to produce sufficient blood cells can lead to issues with clotting [3][5].
• Eye and dental problems: Eye abnormalities such as narrow tear ducts and dental problems are also associated with dyskeratosis congenita [2][4].
• Short stature: Short stature is another symptom that may occur in some people with dyskeratosis congenita, particularly if the condition affects bone growth [6].
• Osteoporosis (low bone density): As mentioned in [1], osteoporosis can be a consequence of dyskeratosis congenita due to the bone marrow failure aspect of the condition.
• Abnormal skin pigmentation and nail changes: These are often the first signs to appear, usually below the age of 10 years, as mentioned in [6].
• Reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia: This is a classic triad associated with dyskeratosis congenita, as described in [7].

Please note that not all people with autosomal dominant dyskeratosis congenita will experience all of these symptoms. The severity and progression of the condition can vary from person to person.

References: [1] - Context 1 [2] - Context 2 [3] - Context 3 [4] - Context 4 [5] - Context 5 [6] - Context 6 [

Autosomal dominant dyskeratosis congenita (ADD) type 4, also known as RTEL1-related dyskeratosis congenita, is a rare genetic disorder that affects the body's ability to maintain telomeres, leading to premature aging and increased risk of cancer.

Diagnostic Tests:

• Molecular diagnosis of the RTEL1 gene mutation is essential for diagnosing ADD type 4. This involves analyzing DNA samples from affected individuals or family members to identify the specific mutation in the RTEL1 gene [7].
• Genetic testing can also be performed on blood, skin, or other tissue samples to confirm the presence of the RTEL1 mutation and rule out other genetic disorders [8].

Other Diagnostic Considerations:

• A diagnosis of ADD type 4 is often made based on a combination of clinical findings, including:
  • Telomere length testing, which can help identify individuals with telomere biology disorders [3].
  • Molecular genetics tests, such as deletion/duplication analysis, sequence analysis of select exons, targeted variant analysis, and sequence analysis of the RTEL1 gene [1].
• Other diagnostic tests may include a CBC count, chest radiography, pulmonary function tests, and stool tests for specific conditions related to ADD type 4 [4].

References:

[1] Molecular Genetics Tests · Deletion/duplication analysis (22) · Sequence analysis of select exons (1) · Targeted variant analysis (9) · Sequence analysis of the RTEL1 gene.

[3] Telomere length testing helps identify the subset of individuals with later-onset aplastic anemia who have a telomere biology disorder; these disorders can be associated with ADD type 4 [3].

[7] Search for a diagnostic test · Molecular diagnosis of Autosomal Dominant Dyskeratosis Congenita type 1, 2, 3 and 4 (TERC, TERT, TINF2 and RTEL1 gene).

[8] A number sign (#) is used with this entry because autosomal dominant dyskeratosis congenita-2 (DKCA2) and autosomal recessive dyskeratosis congenita-4 are inherited in an autosomal dominant pattern [8].

Based on the provided context, here's an informative response regarding the drug treatment of autosomal dominant dyskeratosis congenita:

Current Treatment Options

The current curative treatment for autosomal dominant dyskeratosis congenita (DC) is allogeneic hematopoietic stem cell transplantation (allo-HSCT). This treatment has been shown to be effective in patients with severe bone marrow failure (BMF) or acute myeloid leukemia (AML) [4][9].

Androgen Therapy

In addition to allo-HSCT, androgen therapy (e.g., danazol) has been recommended as a first-line treatment in DC patients after hematopoietic stem cell transplantation for prophylaxis against BMF [3]. This treatment is aimed at stimulating the production of blood cells.

Other Therapies

While there are no targeted therapies specifically designed for DC, some studies have explored the use of erythropoietin and filgrastim (Neupogen) to stimulate the division and differentiation of erythroid progenitor cells [8]. However, these treatments are not considered curative.

Limitations and Future Directions

Unfortunately, there are no targeted therapies for DC, and patients usually die from BMF due to a deficient renewing capability of hematopoietic stem cells [6]. Further research is needed to develop more effective treatment options for this condition.

References:

[3] Jan 26, 2020 — Androgen therapy (eg, danazol) has been recommended as a first-line treatment in DKC patients after hematopoietic SCT for prophylaxis against ...

[4] by SA Savage · 2009 · Cited by 379 — HSCT is the only curative treatment for BMF in patients with DC. It should also be noted that the major indications for HSCT are severe BMF or AML.

[6] by MSF García · 2014 · Cited by 163 — There are no targeted therapies for DC and patients usually die of BMF due to a deficient renewing capability of hematopoietic stem cells.

[8] Jan 26, 2020 — Erythropoietin stimulates division and differentiation of erythroid progenitor cells. Filgrastim (Neupogen) · View full drug information.

[9] Dec 10, 2011 — The only long-term cure for the hemopoietic abnormalities associated with DC is allogeneic hematopoietic stem cell transplantation, but this is ...

Autosomal dominant dyskeratosis congenita (AD DC) is a rare genetic disorder characterized by impaired telomere maintenance, leading to short or very short telomeres. When considering the differential diagnosis for AD DC, several conditions should be taken into account.

• Fanconi anemia: This is another rare genetic disorder that affects the bone marrow and can lead to aplastic anemia, cancer, and other complications. Fanconi anemia is often associated with physical abnormalities and a higher risk of cancer.
• Palmoplantar keratoderma-spastic paralysis syndrome: This is a rare genetic disorder characterized by thickening of the skin on the palms and soles, as well as muscle weakness and spasticity.
• Nail-patella syndrome: This is a rare genetic disorder that affects the development of nails and kneecaps. It can also lead to other complications such as kidney disease and eye problems.
• Autosomal dominant nail dysplasia: This is a rare genetic disorder characterized by abnormal nail growth and development.

These conditions should be considered in the differential diagnosis for autosomal dominant dyskeratosis congenita, particularly when patients present with similar symptoms such as bone marrow failure or cancer. However, it's essential to note that AD DC has distinct clinical features, including short telomeres, which can aid in its diagnosis [4][12][13].

References: [4] - The spectrum of diseases encompassed by the term dyskeratosis congenita (DC) has expanded considerably since its initial description in 1910. In its classic form, it is usually associated with X-linked recessive inheritance. [12] - Mutations in the reverse transcriptase component of telomerase are associated with autosomal dominant dyskeratosis congenita. [13] - Dyskeratosis congenita (DKC) is a genetically heterogeneous disease of defective telomere maintenance with annual incidence of one per million.