X-linked dominant disease

X-linked dominant diseases are a type of genetic disorder that primarily affect females in a family due to their possession of two X chromosomes [1]. These disorders occur when a gene responsible for the condition is located on the X chromosome and only one copy of the mutated gene is necessary to cause the disease [2].

In medicine, X-linked dominant inheritance indicates that a gene responsible for a genetic disorder is located on the X chromosome, and only one copy of the mutated gene is needed to express the condition [3]. This means that females are more likely to be affected by these disorders because they have two X chromosomes, whereas males have only one X chromosome and are less likely to be affected [4].

Examples of X-linked dominant diseases include Rett syndrome, which causes physical and intellectual disability in females, and other conditions that affect both sexes but with a greater incidence in females [5]. These disorders are characterized by expression in both sexes, but with a greater incidence in females due to the greater number of X chromosomes they possess [6].

X-linked dominant disorders are caused by variants in genes on the X chromosome. In males (who have only one X chromosome), a variant in the gene can cause the disease, whereas in females, who have two X chromosomes, a variant in either X chromosome can cause the disease [7].

X-linked dominant diseases are characterized by a range of signs and symptoms that can vary in severity and presentation. Here are some common features associated with these conditions:

• Expression in both sexes: Both males and females can be affected by X-linked dominant diseases, although the incidence is generally higher in females due to their possession of two X chromosomes [6].
• Greater incidence in females: Females tend to have a milder form of the disease compared to males, who often experience more severe symptoms [5].
• Bowed or bent legs: In some cases, individuals with X-linked dominant diseases may exhibit bowed or bent legs, which can be a result of bone deformities [9].
• Short stature: Short stature is another common feature associated with these conditions, particularly in males who are more likely to experience growth retardation [9].
• Bone pain and dental pain: Individuals with X-linked dominant diseases often experience severe bone pain and dental pain, which can significantly impact their quality of life [9].

It's essential to note that the specific signs and symptoms of an X-linked dominant disease can vary depending on the underlying genetic mutation and individual factors. A comprehensive diagnosis by a medical professional is necessary for accurate identification and management of these conditions.

References: [5] - Females tend to have a milder form of the disease compared to males, who often experience more severe symptoms. [6] - X-linked dominant diseases are characterized by: expression in both sexes, but with a greater incidence in females due to the greater number of X chromosomes. [9] - XLH is usually diagnosed in childhood. Features include bowed or bent legs, short stature, bone pain, and severe dental pain.

Diagnostic Tests for X-linked Dominant Diseases

X-linked dominant diseases are rare genetic disorders that primarily affect females due to their possession of two X chromosomes [3]. Diagnostic tests play a crucial role in identifying these conditions, which can be challenging due to the complex inheritance pattern.

• Clinical Evaluation: A thorough clinical evaluation is essential to diagnose X-linked dominant diseases. This involves a detailed medical history, physical examination, and assessment of symptoms [5].
• Biochemical Tests: Biochemical tests can help identify abnormalities in enzyme levels or other biochemical markers associated with these conditions [9]. For example, testing for X-linked adrenoleukodystrophy (X-ALD) may involve measuring very-long-chain fatty acid (VLCFA) levels in the blood.
• Genetic Testing: Genetic testing is a crucial diagnostic tool for X-linked dominant diseases. This can include molecular genetic tests to identify pathogenic variants in genes associated with these conditions [4]. For instance, carrier screening for CDPX2 involves identifying individuals who carry a specific mutation in the PHEX gene.

Other Diagnostic Approaches

• Imaging Studies: Imaging studies such as MRI or CT scans may be used to assess the extent of disease involvement and monitor treatment response.
• Clinical Trials: Participation in clinical trials can provide access to new diagnostic tests and treatments for X-linked dominant diseases [7].

It's essential to note that diagnosis often requires a multidisciplinary approach, involving specialists from various fields such as genetics, endocrinology, and neurology.

References: [3] - X-Linked Dominant Disorders are uncommon mendelian diseases that primarily affect females in a family due to their possession of two X chromosomes. [4] - by AR Gregg · 2021 · Cited by 260 — INTRODUCTION. Carrier screening is used to identify individuals or couples that are at risk to have a child with an autosomal recessive or X-linked genetic ... [5] - Diagnosis of CDPX2 relies on clinical, biochemical and genetic tests. CDP, usually consisting of epiphyseal stippling, is the fundamental radiological finding. [7] - Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [9] - by M Morey · 2011 · Cited by 109 — The non-parametric Mann-Whitney test was used to compare biochemical levels and height SDS with the specific type of PHEX mutation.

Treatment Options for X-linked Dominant Diseases

X-linked dominant diseases are rare genetic disorders that can be passed down through families. While there is no cure for these conditions, various treatment options can help alleviate symptoms and improve quality of life.

• Hydroxylated Vitamin D: Treatment with hydroxylated vitamin D has been shown to help alleviate symptoms in some cases [3].
• Genetic Therapy: Gene therapy using adeno-associated virus (AAV) vectors is being explored as a potential treatment for X-linked dominant diseases, particularly those caused by mutations in the RPGR gene [2].

Other Considerations

It's essential to note that each X-linked dominant disease has its unique characteristics and treatment approaches. A comprehensive diagnosis and consultation with a medical professional are necessary to determine the best course of treatment.

• Renal Phosphate Transport Disorder: This condition, caused by mutations in the SLC34A1 gene, is an example of an X-linked dominant disease that can be treated with hydroxylated vitamin D [3].
• X-Linked Adrenoleukodystrophy: This rare genetic disorder affects the adrenal glands and nervous system. While there is no specific treatment for this condition, researchers are exploring various therapeutic approaches, including gene therapy [4].

References

[1] CMF De La Camara (2022) - X-linked RP caused by mutations in RPGR is an ideal disease to be treated with AAV gene therapy because the size of the coding sequences fits well into AAV vectors. [2] V Baylot (2024) - Table 3 Approved ASO-based therapies for genetic diseases, including those related to X-linked dominant inheritance. [3] Medical Genetics (2024) - Renal phosphate transport disorder is an X-linked dominant disease that can be treated with hydroxylated vitamin D. [4] Drugs.com (2022) - Learn about X-Linked Adrenoleukodystrophy, including symptoms, causes, and treatments.

The differential diagnosis for X-linked dominant diseases involves considering various conditions that can present with similar symptoms and characteristics.

• Autosomal Dominant Hypophosphatemic Rickets: This condition is caused by mutations in the PHEX gene and can present with hypophosphatemia, rickets, and other skeletal abnormalities. It is essential to distinguish this condition from X-linked dominant diseases, as it has a different genetic basis.
• Autosomal Recessive Hypophosphatemic Rickets: This condition is caused by mutations in the DMP1 gene and can present with hypophosphatemia, rickets, and other skeletal abnormalities. It is crucial to differentiate this condition from X-linked dominant diseases, as it has a different genetic basis.
• Hereditary Hypophosphatemic Rickets with Hypercalciuria: This condition is caused by mutations in the CLC5 gene and can present with hypophosphatemia, hypercalciuria, and other skeletal abnormalities. It is essential to distinguish this condition from X-linked dominant diseases, as it has a different genetic basis.
• X-linked Agammaglobulinemia: This condition is caused by mutations in the BTK gene and can present with immunodeficiency, recurrent infections, and other symptoms. It is crucial to differentiate this condition from X-linked dominant diseases, as it has a different genetic basis.

These conditions should be considered in the differential diagnosis of X-linked dominant diseases, as they can present with similar symptoms and characteristics. However, each condition has a distinct genetic basis and clinical presentation, making accurate diagnosis essential for appropriate management and treatment.

References:

• [3] Molecular testing for EBP mutations confirms diagnosis.
• [5] Differential diagnosis includes autosomal dominant and autosomal recessive hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria (...
• [7] Differential diagnosis. X-linked agammaglobulinemia should be distinguished from two other X-linked disorders that result in hypogammaglobulinemia in infant...