© 2017, GENASSIST, Inc.

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Definitions:

  • HeterotrisomyRepetitive trisomy involving different chromosomes.
  • Homotrisomy – Repetitive Trisomy involving the same chromosome.

Background:

A couple with an unsuccessful pregnancy history including recurrent Trisomy 21 (Down Syndrome) was exploring possible breakthrough technologies for future pregnancies.

Both the wife and husband had normal blood chromosomes.

Possible Breakthrough Technologies:

  • IVF and Preimplantation Genetic Diagnosis hoping that increased number of embryos may allow the replacement and/or retention of normal embryos which can enable this couple to have one or more normal children.
  • Recurrent pregnancy losses with occasional documentation of repetitive trisomy involving the same chromosome (homotrisomy) or different chromosomes (heterotrisomy). Our counseling for homotrisomy usually includes the possibility of gonadal mosaicism with or without a translocation.
  • With more than 1600 genes being described for mitochondrial DNA and the knowledge that mitochondrial DNA plays a role in ATP generation, oxidative stress and cell apoptosis, we might speculate that maternal age and/or mutations in mitochondrial DNA may affect spindle formation and chromosome segregation in families manifesting increased susceptibility to non-dysjunction. Mitochondrial or spindle transplantation may offer these couple additional options in the future.

Recurrence Risks: 

  • In families with recurrent homotrisomy or heterotrisomy the recurrence risks appear to exceed the usually quoted 1% increased risk above the maternal age related risk.
  • The 2004 article by Warburton, et al suggests a greater risk especially for women experiencing repetitive trisomy less than 30 years of age suggesting a relative risk of approximately 8.0 for these women and 2.1 for women who experience homotrisomy at maternal ages greater than or equal to 30 years of age.
  • For heterotrisomy, the relative risk suggested was 2.3 with the risk being the same for women greater than or less than 30 years.

References:

  1. Warburton, D. et al: Trisomy Recurrence: A Reconsideration Based on North American Data
  2. Schon, EA et al: Hum Reprod. 200 July;15 Suppl2:160-172 Chromosomal Non-Dysjunction in Human Oocytes: Is There a Mitochondrial Connection?
  3. Coskun, PE and Busciglio, J. Current Gerontology and Geriatrics Research Volume 2012 (2012) Article ID 383170 from Center for the Neurobiology of Learning and Memory, U of Calif. Irvine, CA 92697. “Oxidative Stress and Mitochondrial Dysfunction in Down’s Syndrome: Relevance to Aging and Dementia.