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Preimplantation genetic diagnosis for inherited neurological disorders

Nature Reviews Neurology volume 10, pages 417–424 (2014)Cite this article

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Abstract

Preimplantation genetic diagnosis (PGD) is an option for couples at risk of having offspring with an inherited debilitating or fatal neurological disorder who wish to conceive a healthy child. PGD has been carried out for conditions with various modes of inheritance, including spinal muscular atrophy, Huntington disease, fragile X syndrome, and chromosomal or mitochondrial disorders, and for susceptibility genes for cancers with nervous system involvement. Most couples at risk of transmitting a genetic mutation would opt for PGD over prenatal testing and possible termination of a pregnancy. The aim of this Perspectives article is to assist neurologists in counselling and treating patients who wish to explore the option of PGD to enable conception of an unaffected child. PGD can be accomplished for most disorders in which the genetic basis is known, and we argue that it is time for clinicians and neurological societies to consider the evidence and to formulate guidelines for the responsible integration of PGD into modern preventative neurology.

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Figure 1: In vitro fertilization with PGD.
Figure 2: Hypothetical pedigree of a family with an autosomal dominant neurological disorder, such as Huntington disease, myotonic dystrophy, or familial Alzheimer disease.

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Acknowledgements

The authors acknowledge the unique expertise of our co-workers (clinical staff, embryologists and molecular geneticists) involved in in vitro fertilization with preimplantation genetic diagnosis at the Institute for Human Reproduction (IHR) and Reproductive Genetics Institute (RGI), and our co-workers at the Neurocognitive Disorders Program in the Department of Psychiatry at Duke Medicine for their unique patients' care. The authors thank Adi Tur-Kaspa for excellent editorial assistance, and Leeron Tur-Kaspa for the graphic design of Figure 1.

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Authors and Affiliations

  1. Institute for Human Reproduction, 409 West Huron Street, Suite 500, Chicago, 60654, IL, USA

    Ilan Tur-Kaspa

  2. Department of Obstetrics and Gynecology, The University of Chicago, Chicago, 60637, IL, USA

    Ilan Tur-Kaspa

  3. Department of Obstetrics and Gynecology, Wayne State University, 3390 John R. Street, Detroit, 48201, MI, USA

    Roohi Jeelani

  4. Departments of Psychiatry and Medicine, and the Duke Institute for Brain Sciences, DUMC-3018 Duke Medical Center, 1000 Trent Drive, Suite 3550, Durham, 27710, NC, USA

    P. Murali Doraiswamy

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  1. Ilan Tur-Kaspa
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  3. P. Murali Doraiswamy
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Contributions

The abstract outline and references for the proposal were prepared by P.M.D and edited by I.T.-K. I.T.-K. wrote the first draft of the article and I.T.-K. and P.M.D. contributed equally to critical revisions. All authors researched the data and references for the article, and undertook review and/or editing of the manuscript before submission. I.T.-K takes full responsibility for the originality of the manuscript and data accuracy and analysis.

Corresponding authors

Correspondence to Ilan Tur-Kaspa or P. Murali Doraiswamy.

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Competing interests

I.T-K. is the medical director and owner of the Institute for Human Reproduction in Chicago, Illinois, USA, a private fertility centre that offers advanced infertility and in vitro fertilization treatments, with or without preimplantation genetic diagnosis. P.M.D. has received research grants and/or consultation or speaker fees from Abbvie, Accera, Alzheimer's Drug Discovery Foundation, Baxter, Cognoptix, Danone, Eli Lilly, Envivo, Genomind, Grifols, Janssen, Lundbeck, Neurocog Trials, Neuronetrix, Piramal Healthcare, Shire, Sonexa Therapeutics, Takeda Pharmaceutical Company, and Targacept for other projects. He is a shareholder in Sonexa, AdverseEvents, Maxwell Health and Clarimedix the products of which are not discussed here. R.J. declares no competing interests.

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Tur-Kaspa, I., Jeelani, R. & Doraiswamy, P. Preimplantation genetic diagnosis for inherited neurological disorders. Nat Rev Neurol 10, 417–424 (2014). https://doi.org/10.1038/nrneurol.2014.84

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