X-linked dominant disorders

X-linked dominant disorders are a class of genetic disorders caused by mutations in genes on the X chromosome. These disorders are termed "dominant" because a single copy of the mutated gene (inherited from either parent) is sufficient to cause the disorder. This is in contrast to X-linked recessive disorders, where two copies of the mutation (one from each parent) are typically necessary for the disorder to manifest in females. Due to the nature of X-linked inheritance, these disorders often present differently in males and females.

Causes and Inheritance

X-linked dominant disorders are caused by mutations in genes on the X chromosome. Every individual has two sex chromosomes: females have two X chromosomes (XX), while males have one X and one Y chromosome (XY). Since males have only one X chromosome, a single copy of a mutated gene on the X chromosome will result in the expression of the disorder. Females, having two X chromosomes, can be heterozygous for the mutation (one mutated gene and one normal gene). However, due to a process called X-inactivation, which randomly inactivates one of the X chromosomes in each cell, females may have a milder presentation of the disorder or may be symptomatic if the X chromosome with the normal gene is preferentially inactivated.

Examples of X-linked Dominant Disorders

Some examples of X-linked dominant disorders include:

• Rett Syndrome: A neurodevelopmental disorder affecting mainly females, characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.
• Fragile X Syndrome: A genetic condition causing intellectual disability, behavioral and learning challenges, and various physical characteristics. Though not exclusively inherited in an X-linked dominant manner, it involves the FMR1 gene on the X chromosome.
• Incontinentia Pigmenti: A disorder of skin pigmentation that also affects the teeth, hair, nails, and central nervous system. It is usually lethal in males before birth, thus primarily affecting females.
• Hypophosphatemic Rickets: A condition that affects the bones, leading to soft and weak bones (rickets), due to low levels of phosphate in the blood.

Diagnosis and Management

Diagnosis of X-linked dominant disorders often involves a combination of clinical evaluation, family history, and genetic testing. Management and treatment depend on the specific disorder and may include supportive care, medications, physical therapy, and other interventions aimed at managing symptoms and improving quality of life.

Genetic Counseling

Genetic counseling is recommended for individuals and families affected by X-linked dominant disorders. Counseling can provide information on the nature of the disorder, inheritance patterns, risks to other family members, and the implications for future pregnancies.