Inheritance

                   
                    Menkes Disease(MD) is an X-linked recessive syndrome involving the mutation of the ATP7A gene (NIH, 2018). I included this video posted by UCD Medicine (2014) to explain how X-linked recessive inheritance works. I also included links to genetic terminology for further definitions. 
                    MD is inherited from the mother carrier or by a de novo mutation in the ATP7A gene occurring either during fertilization or gametogenesis. One third of MD cases are caused by new mutations, and there is no family history of the disease (NIH, 2018). X-linked recessive disorders are typically only expressed phenotypically in the male offspring (Nussbaum, McInnes, & Willard, 2016). It is unlikely that female offspring are affected by the disorder because she has another X chromosome with the wild-type (or normally functioning) gene from her father. X-inactivation in females silences the mutated ATP7A gene while allowing the wild-type to express normally. In the case of MD, the father is not responsible for passing down the mutation to the affected male offspring because he contributes the Y chromosome. A male with one of the severe forms of MD is not reproductively fit enough to create offspring. However, it is possible that the father of female offspring could contribute a de novo mutated X chromosome to his female offspring, thus creating a carrier of MD. 
                   As of 2012, 16 heterozygous females affected phenotypically by MD have been identified, but the mechanism in which this occurs is still under investigation (Moller et al., 2012). Some of the cases have been explained by faulty X-inactivation where the normal allele is silenced, but the mechanism of some cases have yet to be identified (Moller et al., 2012). I did not find any evidence that uniparental disomy was the cause of MD in any of the cases. I was also unable to find any cases where a female was homozygous for the ATP7A gene.

References

Møller, L.B., Lenartowicz, M., Zabot, M., Josiane, A., Burglen, L…  Jensen, T., (2012, January, 22). Clinical expression of Menkes disease in females with normal karyotype. Orphanet Journal of Rare Diseases, 7(6). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298521/

NIH. National Library of Medicine. (2018, October 16). Menkes syndrome. Genetics Home Reference. Retrieved from https://ghr.nlm.nih.gov/condition/menkes-syndrome#genes

Nussbaum, R. L., McInnes, R. R., & Willard, H. F. (2016). Genetics in medicine. Philadelphia, PA: Elsevier.

UCD Medicine, (2014, September 1). X linked recessive [Video file]. Retrieved from https://www.youtube.com/watch?v=Vdam8pKhRNo