Inheritance pattern of Fabry disease in women

A mother with a GLA variant on one of her two X chromosomes has a 50% probability of passing the Fabry disease gene to each of her offspring, regardless of their gender. Under normal circumstances with an x-linked recessive disorder, her sons with the abnormal gene will have Fabry disease, whereas her daughters with the abnormal gene will be carriers. However, although Fabry disease was initially considered to predominantly affect males, studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers and instead suggesting that Fabry disease could be considered X-linked dominant with reduced penetrance. As with many other X chromosome disorders, it has also been argued that Fabry disease should be characterized as inherited in an X-linked manner, without distinction as to being recessive or dominant. (Source: Izhar R, Borriello M, La Russa A, et al. Fabry disease in women: genetic basis, available biomarkers, and clinical manifestations. Genes [Basel] 2023;15[1]:37. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)