X-linked severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is the most serious primary or congenital human immunodeficiency disorder. It is a group of congenital disorders in which the immune system does not work properly. Children with SCID are vulnerable to recurrent severe infections, retarded growth, and early death. X-linked SCID occurs primarily in males, who appear normal at birth due to the transfer of maternal antibodies through the placenta before birth. Around 3-6 months of age, as those levels decrease and the infant's body must begin to make its own antibodies, the number of bacterial, viral and fungal infections starts to increase. The severity and length of time for each infection increase as well. Affected infants typically do not grow at normal rates the first year of life and often are missing their tonsils and lymph nodes. Additional symptoms include skin rashes and chronic diarrhea. Without treatment, death typically occurs within the first year of life. Bone marrow or cord blood transplant is the only known cure for X-linked SCID and outcome is better if the transplant happens as soon as a diagnosis is made. X-linked SCID is caused by pathogenic variants in the IL2RG gene.

X-linked SCID is inherited in an X-linked manner. This type of inheritance requires the presence of one copy of a pathogenic variant in the gene located on the X-chromosome for males to be affected. When the pathogenic variant is inherited from the unaffected carrier mother, the male child will have the genetic disease. There is a 50% chance that a baby will inherited the pathogenic variant from the mother; females who inherited the pathogenic variant will be carriers, males who inherited the pathogenic variant will be affected.

There are generally no signs or symptoms associated with being a carrier for X-linked SCID. However, the risk to have a child affected with X-linked SCID is increased for female carriers.

It is unknown exactly how often X-linked SCID is estimated occurs, but it is estimated to occur in 1 in 50,000 to 100,000 newborns worldwide.

The following websites may be informative: Genetic Home Reference: X-linked severe combined immunodeficiency (http://ghr.nlm.nih.gov/)

Gene Reviews: X-linked severe combined immunodeficiency (http://www.ncbi.nlm.nih.gov/books/NBK1116/) OMIM: [300400. SEVERE COMBINED IMMUNODEFICIENCY, X-LINKED] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing