Mitochondrial disorders: Genetics, counseling, prenatal diagnosis and reproductive options

Most patients with mitochondrial disorders are diagnosed by finding a respi ratory chain enzyme defect or a mutation in the mitochondrial DNA (mtDNA). The provision of accurate genetic counseling and reproductive options to th ese families is complicated by the unique genetic features of mtDNA that di stinguish it from Mendelian genetics. These include maternal inheritance, h eteroplasmy, the threshold effect, the mitochondrial bottleneck, tissue var iation, and selection. Although we still have much to learn about mtDNA gen etics, it is now possible to provide useful guidance to families with an mt DNA mutation or a respiratory chain enzyme defect. We describe a range of c urrent reproductive options that may be considered for prevention of transm ission of mtDNA mutations, including the use of donor oocytes, prenatal dia gnosis (by chorionic villus sampling or amniocentesis), and preimplantation genetic diagnosis, plus possible future options such as nuclear transfer a nd cytoplasmic transfer. For common mtDNA mutations associated with mitocho ndrial cytopathies (such as NARP, Leigh Disease, MELAS, MERRF, Leber's Here ditary Optic Neuropathy, CPEO, Kearns-Sayre syndrome, and Pearson syndrome) , we summarize the available data on recurrence risk and discuss the relati ve advantages and disadvantages of reproductive options, (C) 2001 Wiley-Lis s. Inc.