Couples Carrying Genetically Inherited Disorders

Preimplantation Genetic Diagnosis (PGD IVF) Preventing Ashkenazi Jewish Genetic Diseases

Very fertile couples can carry genetic inherited disorders that do not impair the ability to have a child. However, genetic inherited disorders significantly increase the chance of having a child born with a debilitating or fatal abnormality.

Single gene abnormalities called mutations are caused by defects in our DNA. DNA resides within the nucleus of our cells, bundled within chromosomes and each cell’s power plant called mitochondria. Although some mutations do not affect our health, others cause errors in how our cells, organs and entire bodies develop and function. Single gene disorders usually show a pattern of inheritance within a family for a specific genetic disease, such as cystic fibrosis, spinal muscular atrophy, Fragile X, Sickle Cell disease and Thalassemia.

Preimplatation Genetic Diagnosis at Michigan Reproductive Medicine, Bloomfield Hills, MI

Genetics 101

Chromosomes

• We all normally have 46 chromosomes that are coupled as 23 pairs. 22 of these pairs are called autosomes and are numbered 1 through 22. The final pair is the sex chromosomes designated as XX for a normal female and XY for a normal male.
• Single gene disorders are determined by whether the disease-causing gene requires one or two autosomes to cause the disease or if the gene is gender-based. When only one autosome with the mutation is required to cause the disease, it is referred to as a dominant mutation. If both of the autosomes with the mutation are required to cause the disease, it is referred to as a recessive mutation. Alternatively, the disease-causing gene may be located on a sex chromosome, and then it is referred to as a sex-linked disease or x-linked disorder.

Dominant Disorders

• For a dominant disorder, a person requires only a mutation on one of the paired chromosomes. If that mutation is passed on to the embryo, the embryo will develop into a child with the affected genetic disease.
• If either parent is a carrier of a dominant mutation, that parent is affected by the mutation and will have the disease, and their child, daughter or son, has a 50% chance of receiving the gene mutation and being affected by the disease.
• Huntington’s Disease and Myotonic Dystrophy are examples of autosomal dominant genetically inherited disorders.

Recessive Disorders

• For a recessive disorder, a person needs to have a mutation on both of the paired chromosomes. This requires both parents to carry the same mutation. This requirement is a higher hurdle to clear than in the case of a dominant mutation where only one parent has the mutation. For this reason, the risk of a child being affected by recessive mutations is less. A carrier of a recessive mutation usually does not experience the disorder.
• If both parents are carriers of a recessive disorder, there is a 25% chance of having an affected child with two mutation copies, one from each parent. There is another 25% chance of having a child free of the disorder because the child received the mutation free chromosomes from both parents. The remaining 50% of children will be unaffected carriers of the mutation like each parent.
• This is the tricky trap of recessive mutations. They can be carried through many generations unnoticed as no one is outwardly affected. Then, when a carrier mates with another carrier, voila! The disease is discovered. For this reason, we refer to some of these disorders as silent assassins.
• Cystic Fibrosis is the most common genetically recessive inherited disorder across all ethnicities, as about 1 in 28 people of Caucasian, European ancestry are carriers. Among families of Ashkenazi Jewish ancestry, who comprise about 80% of the Jewish population in the United States, there is a 1 in 4 chance of a person being a carrier of at least 1 of the 16 most common mutations causing disease. Those of us with ancestors originating from the Mediterranean coast, Pacific Rim of Asia and Africa carry mutations that impair the ability of hemoglobin in our red blood cells to carry oxygen causing Thalassemia and Sickle Cell diseases.
• Our MRM expert doctors recommend preconception testing for common genetically inherited recessive disorders based on your ethnic background. If you are aware of genetic disorders in your family, screening tests may also be available.

X-Linked Disorders

• Mutations act differently on the sex chromosomes. X-linked mutations act like a recessive gene in females and a dominant gene in males. Normal males only have one X-chromosome. Their Y-chromosome is different than the X-chromosome and does not match up gene to gene like teeth of a zipper. (However, this zipper effect does occur with the autosomes or the two X-chromosomes for a normal female. If there is a mutation on the X-chromosome of a male, there is not a second X-chromosome, which might have a normal version of the matched gene, to override the mutation, which would reduce or mask the effects of the mutation on the child as there are in females. Therefore boys who have a mutation on their only X-chromosome will be affected by the mutation whereas girls having a second normal X-chromosome will not be affected by the mutation on the second X-chromosome.
• If a mother is a carrier of an X-linked mutation, her son has a 50% chance of receiving the gene mutation and being affected.
• This is the cause for diseases such as hemophilia, Fragile X syndrome and Duchene Muscular Dystrophy.

There is a solution at Michigan Reproductive Medicine: Genetic Testing with Preimplantation Genetic Diagnosis.

Preimplantation Genetic Testing of Embryos at Michigan Reproductive Medicine

Embryos created from an in vitro fertilization (IVF) cycle can be genetically tested before being implanted in a woman’s uterus. Preimplantation Genetic Diagnosis (PGD), Preimplantation Genetic Screening (PGS), and Comprehensive Chromosomal Screening (CCS) all refer to innovative technologies to biopsy a part of an embryo (trophectoderm) which later becomes the placenta. Genetic testing can be used to select embryos free from specific genetic diseases, such as Cystic Fibrosis. Both single gene mutations (PGD) and the entire DNA complement (PGS/CCS) can be analyzed after embryo trophectoderm biopsy.

Genetic testing aids in selection of a single healthy embryo for transfer, decreasing the risk of multiple births.

If you have genetic inherited disorders, know there is real hope in realizing your dream of having a healthy baby.

Please make an appointment with one of MRM’s fertility expert physicians to learn more about evaluation and treatment to prevent your future children from having genetically inherited disorders.

Please visit our blog entry The Power of Planning Ahead to learn more about the Kaluzny’s journey to becoming parents of children free of Ashkenazi Jewish genetic diseases.