DNA ligase IV deficiency

DNA ligase IV deficiency, also known as LIG4 syndrome, is a rare primary immunodeficiency disorder [1][2]. It is characterized by impaired DNA double-strand break repair mechanisms and is often associated with other systemic features.

The clinical manifestations of DNA ligase IV deficiency can vary widely among affected individuals, but may include:

• Microcephaly (small head size)
• Dysmorphic facial features
• Growth failure
• Pancytopenia (low levels of all blood cells)
• Hypogonadism (underdeveloped sex organs)
• Radiosensitivity (increased sensitivity to radiation)

DNA ligase IV deficiency is a hereditary disorder, meaning it is inherited in an autosomal recessive pattern [5][6]. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

In addition to its primary immunodeficiency features, DNA ligase IV deficiency can also result in a rare form of autosomal recessive radiosensitive SCID (Severe Combined Immunodeficiency), characterized by a TB-NK+ phenotype [8].

Overall, DNA ligase IV deficiency is a complex and rare genetic disorder that requires careful diagnosis and management to ensure optimal outcomes for affected individuals.

References: [1] Altmann et al. (2016) - DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. [2] Altmann et al. (2016) - DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. [3] Staines Boone et al. (2019) - DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, ... [5] Gerasimou et al. (2020) - The DNA ligase IV syndrome is a rare hereditary disorder associated with impaired DNA double-strand break repair mechanisms, associated with combined ... [6] Staines Boone et al. (2019) - LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial. [8] Iyengar et al. (2019) - DNA ligase IV Deficiency is a rare form of autosomal recessive radiosensitive SCID that results in a TB-NK+ phenotype.

DNA ligase IV deficiency, also known as LIG4 syndrome, is a rare genetic disorder characterized by impaired DNA double-strand break repair mechanisms. The condition presents with a wide range of clinical features, including:

• Microcephaly: A significant reduction in head size, which can be associated with growth failure and developmental delays [1][2].
• Primordial growth failure: Failure to thrive from birth, often accompanied by severe microcephaly [3].
• Severe combined immunodeficiency (SCID): A condition where the immune system is severely impaired, making it difficult for the body to fight infections [4].
• Pancytopenia: A reduction in the number of blood cells, including red and white blood cells, which can lead to anemia, infection, and bleeding problems [5][6].
• Radiosensitivity: An increased sensitivity to radiation, which can increase the risk of cancer and other health problems [7].

These symptoms can vary in severity and may be accompanied by other features, such as learning difficulties, developmental delays, and physical abnormalities. DNA ligase IV deficiency is a rare condition, and its diagnosis often requires genetic testing.

References:

[1] T Altmann · 2016 · Cited by 133 — Extreme growth failure is a common presentation of ligase IV deficiency. Hum Mutat. 2014;35(1):76–85.

[2] T Altmann · 2016 · Cited by 133 — Commonly associated features include primordial growth failure with severe microcephaly and a spectrum of learning difficulties, marrow ...

[3] JJ Iyengar · 2019 · Cited by 3 — Key clinical features include microcephaly, severe growth failure, distinctive facial features, severe combined immunodeficiency, and pancytopenia (3,5,6).

[4] P Chadha · 2021 · Cited by 2 — DNA ligase IV deficiency is accompanied with a wide range of phenotypes. Some clinical presentations include pancytopenia, microcephaly, primordial growth ...

[5] LIG4 syndrome is an autosomal recessive severe combined immunodeficiency with features of radiosensitivity, chromosomal instability, pancytopenia, and ...

[6] by K Tilgner · 2013 · Cited by 60 — Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, ...

Diagnostic Tests for DNA Ligase IV Deficiency

DNA ligase IV deficiency, also known as LIG4 syndrome, is a rare genetic disorder that affects the body's

Treatment Options for DNA Ligase IV Deficiency

DNA ligase IV deficiency, also known as LIG4 syndrome, is a rare genetic disorder that affects the body's ability to repair DNA damage. While there is no cure for this condition, various treatment options can help manage its symptoms and improve quality of life.

• Supportive Treatment: The primary goal of supportive treatment is to prevent infections and promote overall health. This includes:
  • Prophylactic antibiotics: To prevent bacterial infections [5].
  • Anti-viral medications: To prevent viral infections [2].
  • Regular monitoring: To detect any potential complications early on.
• Targeted Therapies: Recent studies have explored the use of targeted therapies to treat DNA ligase IV deficiency. These include:
  • DNA-damaging agents: Such as doxorubicin, which can help induce cell death in cancer cells [9].
  • γ-radiation therapy: Which can also be used to target and kill cancer cells.
• Combination Therapy: A study published in 2024 found that combining a DNA ligase IV inhibitor with DNA-damaging agents (doxorubicin and/or γ-radiation) showed therapeutic value for treating this condition [9].

It's essential to note that these treatment options are still being researched, and more studies are needed to fully understand their effectiveness. Patients with DNA ligase IV deficiency should work closely with their healthcare providers to determine the best course of treatment.

References:

[1] by K Felgentreff · 2016 · Cited by 34 [2] by T Altmann · 2016 · Cited by 133 [5] by M Toma · 2018 · Cited by 12 [9] by SN Sriramareddy · 2024 · Cited by 1

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