Alpha-thalassemia/mental retardation syndrome, x-linked

Alpha-thalassemia X-linked intellectual disability syndrome is inherited in an X-linked recessive manner. This means that the gene for the disorder, ATRX is located on the X chromosome, and mutations in this gene affect males and females differently. The X chromosome is one of the two chromosomes that determine whether you are male or female. Most females have two X chromosomes and most males have one X chromosome and one Y chromosome. The term recessive means that only one functioning, unchanged copy of the gene is needed for normal development. When a female has a change in the ATRX gene on one of her copies of the X chromosome, her unchanged copy of the gene on her other X chromosome will almost always compensate, leading to her being an unaffected carrier for the condition. Males, on the other hand, have only one X chromosome. If their copy of ATRX is changed, they do not have a backup copy to allow for normal gene function. Therefore, the symptoms of alpha-thalassemia X-linked intellectual disability syndrome are present in all males with ATRX gene changes.

Changes in the ATRX gene in males with alpha-thalassemia X-linked intellectual disability syndrome can be inherited or de novo. When the gene change is inherited, the abnormal ATRX gene is passed down from the patient's mother, who has the gene change in half of the X chromosomes in every cell of her body and is called a "carrier" of the condition. A woman who is a carrier for this condition has a 50% risk with each pregnancy to pass the gene on to her offspring. If the offspring is male, he will be affected. If the offspring is female, she will almost certainly be an unaffected carrier. There has been one report of a female with one changed copy of ATRX having significant symptoms of alpha-thalassemia X-linked intellectual disability disorder; however, this is incredibly rare. When the gene change is de novo, this means that the single egg cell from the mother that was passed on to her son had a spontaneous change in the ATRX gene. In de novo cases, the mother would not be expected to have the abnormal gene in other cells of her body or in other egg cells and would not be expected to have additional affected children. Males with this disorder have not been known to reproduce.