© 2018, GENASSIST, Inc.
By Keith S. Wexler, MBA, CFO, Business Development Director, 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
Background: We saw a couple that wanted to have a Level II ultrasound and possible amniocentesis due to a family history Duchenne Muscular Dystrophy (DMD). The patient and maternal grandmother’s carrier X for Duchenne Muscular Dystrophy (DMD) had been identified. Although the family was aware of the possibility of having Preimplantation Genetic Diagnosis (PGD) of the embryos, they chose to achieve pregnancy naturally.
Duchenne Muscular Dystrophy (DMD) is an X-linked disease (50% of males will be affected and 50% of females will be carriers).
Rarely carrier females may manifest symptoms of the disorder but symptoms are usually milder.
Level II ultrasound was performed and the probable sex of the baby on ultrasound was male. Since the couple was concerned about the 50% risk of having a male with Duchenne Muscular Dystrophy (DMD) amniocentesis was performed.
- The amniocentesis returned as 46,XY normal male fetus and the Duchenne Muscular Dystrophy (DMD) gene testing for the Dystrophin gene was negative.
The couple chose to have a second pregnancy and again achieved pregnancy naturally. The couple’s second pregnancy was a probable female at time of Level II ultrasound. They were not concerned about the female carrier risk of for Duchenne Muscular Dystrophy (DMD). At the time of ultrasound three ultrasound markers for a chromosomal abnormality were identified. The couple elected to have an amniocentesis to rule-out a chromosomal abnormality.
- The amniocentesis results returned as 47,XX,+18 – Trisomy 18 female.
The couple was very disappointed to learn that their little girl was diagnosed with a probable fatal chromosomal abnormality.
Three years later the couple was pregnant again and wanted to have a Level II ultrasound to again determine sex. At time of Level II ultrasound the probable sex of the baby was male. Again since the couple was concerned about the 50% risk of having a male with Duchenne Muscular Dystrophy (DMD), amniocentesis was performed.
- The amniocentesis returned as 46,XY normal male fetus and the Duchenne Muscular Dystrophy (DMD) gene testing for the Dystrophin gene was negative.
The couple continues to speak with us annually still perplexed by the dilemma of statistical probability, since the wife was a known carrier of Duchenne Muscular Dystrophy (DMD) and each male had a 50% risk of being affected.
They are still confused why both their males were normal and their one female turned out to have a chromosomal abnormality.
Analysis: The Dilemma of Statistical Probability is a problem that is constantly faced by healthcare providers regardless of the disease or defect the patient is concerned about.
We had a family that both the mother and father were carriers of Sickle Cell Anemia and had 4 sons affected with Sickle Cell Anemia. The father was confused why with Mendelian genetics statistical probability of autosomal recessive disease (25% if both parents are gene carriers) 4 sons should have yielded:
- 1 son – unaffected (25%)
- 2 sons – carriers (50%)
- 1 son – affected (25%)
He and his wife truly did not understand that statistical probability could be any variation on the theme including 4 affected sons.
We have pointed out to families for years that the statistical risk of having a miscarriage following an amniocentesis or having a child with Duchenne Muscular Dystrophy or some other disorder is either 0% or 100% in each pregnancy regardless of the statistical risk.
