NF2 Planned Parenthood

Current Prenatal Testing Options, reviewed by Kristinl, June 02, 2008

Neurofibromatosis type 2 (NF2), is a single-gene autosomal dominate genetic disorder, meaning there is a 50/50 chance of passing on the defective gene.

Below are a few planned prenatal options currently available to a person/couple with NF2 who are striving to have children without NF2:

For more information, please consult with a genetic counselor and/or medical professional.

1. The "old-fashioned way" with a regular 50/50 risk of passing on the NF2 mutation, meaning just making babies like any other couple.
   
2. In-vitro Fertilization with Pregestational Diagnosis (IVF with PGD).
   

   Allows you to create multiple embryos and have each one tested to determine if it has inherited the NF2 mutation. Unaffected embryos can be transferred to the uterus of the mother or frozen and stored for future pregnancy attempts.

   PGD has about 95-98% accuracy but requires that the partner with NF2 have a recognizeable genetic mutation, which is only the case for about 60% of people with a clinical diagnosis of NF2. Having the initial genetic testing to determine if the mutation is recognizeable takes aproximately 6 months, and then preparing the probes for the PDG testing takes aproximately another 6 months.

3. Prenatal diagnosis testing - 2 types:
   • Chorionic Villus Sampling (CVS) at about 12 weeks, OR
   • Amniocentesis (at about 18 weeks).

   Even if you do the PGD prior to embryo transfer, it is recommended to have CVS or amniocentesis to confirm the diagnosis. That's because the lab only has one cell per embryo and human error can occur. If a couple would like to decide whether or not to continue the pregnancy with an NF2 diagnosis, these prenatal tests are necessary.

   Also, if a couple has gotten pregnant the old-fashioned way and wishes to see whether the baby inherited the NF2 mutation as early as possible in the pregnancy, this is how it is done.
   Both of these tests have a small risk of miscarriage. These tests can also diagnose other chromosomal disorders like Down's Syndrome.

4. Donor insemination: This makes the pregnancy have all of the same risks as any "normal" couple. A couple can choose either a known donor (sibling, friend, etc.) or an anonymous donor through a sperm bank. If the couple is using donor sperm, they will probably have intrauterine insemination (IUI).

   However, if the couple is using donor eggs, then the donor undergoes ovarian stimulation and embryos are created using IVF. No PGD is necessary unless the couple has some other reason for deciding to do so.

5. Adoption

References:

JPrenatal Diagnosis, 2007 Mar 2;

Preimplantation genetic diagnosis for cancer predisposition syndromes.

Spits C, De Rycke M, Van Ranst N, Verpoest W, Lissens W, Van Steirteghem A, Liebaers I, Sermon K.

Research Centre Genetics and Reproduction, Academisch Ziekenhuis, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.

OBJECTIVES: Mutations in the APC, NF2 and BRCA1 genes cause adult-onset cancer predisposition syndromes.
Prenatal diagnosis (PND) and selective pregnancy termination for adult-onset disorders is emotionally difficult and, in some cases, socially not well accepted. Preimplantation genetic diagnosis (PGD) appears as an attractive alternative to PND, as it ensures the establishment of a pregnancy free of the mutation from the onset, circumventing the potentially difficult decision of termination of pregnancy.

METHODS: Development of single-cell PCRs using Epstein-Barr virus transformed lymphoblasts as single-cell model, followed by clinical application in PGD.

RESULTS: A total of five duplex-PCRs were developed, three for adenomatous polyposis of the colon (APC), one for neurofibromatosis type 2 (NF2) and one for inherited breast and ovarian cancer caused by BRCA1 mutations. Eleven clinical cycles were performed, resulting in the birth of an unaffected girl. For one of the couples undergoing PGD for NF2, a spontaneous pregnancy ensued after five unsuccessful PGD cycles. The couple underwent chorionic villus sampling (CVS) and the application of the same protocol as used during PGD showed an unaffected fetus.

CONCLUSION: In this work, we present the development and clinical application of PGD for three cancer predisposition syndromes. Copyright (c) 2007 John Wiley & Sons, Ltd.

Footnotes:

• PGD with a single-gene disorder
  
• "Helping the Stork: The Choices and Challenges of Donor Insemination", by Carol Frost Vercollone, Heidi Moss, and Robert Moss