A1AD is inherited in an autosomal codominant manner. When both parents are heterozygotes, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. In the rare instance in which one parent is homozygous (PI ZZ) and one parent is heterozygous, the risk for each sib to be affected is 50%.
Unless an individual with A1AD has children with a reproductive partner who is affected or a carrier, his/her offspring will be obligate heterozygotes (carriers) for the disease-causing mutation. Carrier testing is available on a clinical basis by PI typing or mutation analysis for siblings and offspring of affected individuals.
Testing of the siblings of affected individuals is strongly recommended. However, predictive genetic tests should ideally be preceded by genetic counseling, particularly when considering genetic testing of minors. In all cases, the focus should be on the child’s best medical interests. [Genetics in Medicine 2013:15(3): 234-245]
Please consider referring your patients to Alpha-1 Canada.