It is now possible for physicians to offer preimplantation genetic diagnosis (PGD) for spinal muscular atrophy (SMA) to couples at risk of bearing a child with this disorder. The PGD procedure allows genetic testing to be performed on early embryos before implantation for the purpose of selecting only those embryos that are unaffected by SMA for uterine transfer.
Children’s Hospital of Wisconsin, Froedtert Hospital and the Medical College of Wisconsin offer PGD for SMA.
Spinal Muscular Atrophy and PGDSMA is a motor neuron disease. SMA is divided into 4 types (SMA Type I, II, III, IV) based upon physical milestones achieved. The most severe is SMA type I also called Werdnig-Hoffmann Disease. Diagnosis of children with this type of SMA is usually made before 6 months of age. Affected children are unable to lift their head or accomplish the normal motor skills expected in early infancy. The disorder is characterized by progressive muscular weakness. In the most severe form, affected individuals die within the first few years of life. There is no effective treatment.
SMA is an autosomal recessive genetic disorder. Normally, individuals have two functioning copies of a gene called Survival Motor Neuron 1 (SMN1). In approximately 95 percent of patients with SMA, there is an absence of both copies of the SMN1 gene (known as a gene deletion). In most cases both parents are carriers of the abnormal gene and when both pass this abnormal gene to a pregnancy the child is affected. A DNA test can detect SMA. The DNA test uses polymerase chain reaction (PCR), a process that takes a small amount of DNA and makes many copies of it. This copied DNA can be tested to determine whether the SMN1 genes are present or absent.
Couples who are known to be carriers and/or have had a child with SMA and who are considering a pregnancy face a 1 in 4 (25 percent) chance in each future pregnancy of having a child with the disease. Some couples opt for prenatal diagnosis during pregnancy to determine whether a pregnancy is affected.
An alternative to prenatal testing for SMA is now available using in vitro fertilization (IVF) with PGD to identify an unaffected embryo. In vitro fertilization (IVF) is the process of combining eggs and sperm to form embryos in the laboratory. IVF is often used to help couples with infertility have a child. Preimplantation genetic diagnosis (PGD) is a procedure to analyze the genetic make-up of embryos formed through IVF for determination of disease status. Couples at risk for SMA can use PGD to test for this disease. Based on this analysis embryos that are not affected with SMA can be selected for transfer to the uterus to establish a pregnancy.
PGD Process for the Purpose of SMA TestingParents and their affected child, when possible, will first undergo blood tests to determine whether the PGD process will be feasible. If these tests show that PGD is possible, the parents will undergo an IVF cycle to form embryos.
The embryos created are sampled on the third day of development when they have approximately 6 to 8 cells. One or two cells are taken from each embryo for testing using PCR. The embryo is incubated until testing is complete. Each embryo has a 1 in 4 chance of being affected with SMA. By testing these cells for deletions in the SMN1 gene, only those embryos determined to be unaffected (having one or two working copies of the gene) are selected for transfer back into a woman’s uterus. Thus, the chance to have an unaffected pregnancy is greatly increased.
The biopsy technique required to perform PGD has been in use since 1990. The likelihood of damage to an embryo during the removal of cells is low, but it can occur. This can result in a decreased chance of embryo survival. When compared to IVF without PGD, there is a somewhat decreased chance for embryo survival among embryos that have undergone PGD. IVF with PGD is not known to lead to an increased chance for congenital abnormalities, birth defects, mental retardation, or other abnormal development when compared to natural pregnancies. However, a normal pregnancy outcome is not guaranteed.
Risks of PGD
Preventive Measures During PGD Cycle
It is important for couples undergoing PGD to alter their sexual activity during the PGD cycle. Couples must refrain from intercourse until the cycle is complete.
Cost of PGD
IVF with PGD is expensive. Insurance companies generally do not cover the cost of IVF with or without PGD. We will provide you with a detailed cost analysis for IVF and PGD at your request.
Requests for information regarding the Children’s Hospital of Wisconsin, Froedtert Hospital and the Medical College of Wisconsin PGD program and IVF can be obtained by contacting the Reproductive Medicine Clinic at 414-805-7370 or by using our Contact Us form. Information regarding PGD for the purpose of SMA testing can be discussed in more detail with our geneticist or genetic counselor.