What We Offer
Enhanced Genetic Screening (EGS) Program
The enhanced genetic screening (EGS) program is often used as the framework in which many of our services are provided, though our services are also offered separately. What to expect in the EGS program:
- The genetic counselor or physician obtains and analyzes a couple's family history, personal history, ethnic groups, medications, and other information, to determine if there are any risk factors for genetic abnormalities above the average 3% population risk of having a baby with a birth defect.
- To identify carrier status for genetic disorders, blood-screening tests are offered as appropriate to the couple's ethnic group or groups. For example, for patients of Ashkenazi Jewish descent, there has been a continually increasing panel of disorders including well-known conditions such as Tay-Sachs diseases and many others just as common but less well known. Patients of African heritage are tested for sickle-cell anemia. Patients of Mediterranean origin are at high risk particularly for β-thalassemia. Patients of Asian descent are at high risk for α-thalassemia. Many other carrier screens are possible but not routinely performed because of low incidence and high expense, but they can be used when suggested because of family history.
- To clarify the risks for Down syndrome and other genetic abnormalities, screening via first-trimester ultrasound, including nuchal translucency measurements, is performed in conjunction with blood tests.
- For those patients found to be at risk sufficient for patient's concern, we perform prenatal diagnostic tests as indicated. Chorionic villus sampling (CVS) in the first trimester, and amniocentesis in the second, are used to determine chromosomal status, such as in Down syndrome. DNA tests are used for disorders such as cystic fibrosis, Tay-Sachs, or sickle-cell anemia.
CHROMOSOMES and SCREENING
- Screening vs. Testing: There are two different types of tests.
- 1. “Diagnostic” tests such as CVS and amniocentesis are meant to give a definitive answer to a specific question. They are generally Yes/No. These tests are sometimes expensive and may also have risks of their being performed. They are commonly only performed on patients known to be at high risk.
- 2. “Screening” tests are those usually offered to everyone and are intended to alter the odds of there being a problem. They do not give a definitive answer but can help patients decide if they wish to pursue diagnostic test to get the definitive answer.
- All pregnancies have a risk of chromosome abnormalities such as Down syndrome (DS). While many patients are most concerned about DS because that is the most commonly discussed condition, the reality is that it is only one of a large number of conditions that are observed. Overall, DS is about half of the chromosomal problems we find with the proportion increasing from about 1/3 at age 20 to 2/3 by age 40.
- For DS screening, low maternal serum alpha-fetoprotein was developed in the 1980’s. Second trimester screening now has evolved into the “Quad” test including AFP, human Chorionic gonadotropin (hCG), estriol (E3), and inhibin. Collectively the detection rate is about 60-65%, i.e. - if there is a DS pregnancy, the test can identify about 65% of them.
- DS screening moved into the first trimester beginning in the 1990’s using both serum (free βhCG and PAPP-A) as well as the ultrasound nuchal translucency (NT) described below. Together 1st trimester screening can identify about 85% of DS cases.
- Non-invasive prenatal testing (NIPT) has been in development for over 20 years – first looking for fetal cells in the maternal blood which did not work satisfactorily and now for free fetal DNA. After many false starts, several papers with in the last year are finally showing very promising results with up to a 99% detection rate for DS. Trisomy 18 and 13 statistics are not quite as good. Clinical introduction in the USA has begun and use is expanding.
- It is very important for everyone to remember for any of the three methods above, that these are SCREENING tests and do not give a definitive answer. For a specific diagnosis they must be followed up by CVS or amniocentesis. Also as a screening test, the chance that a “positive” test really represents an abnormality is directly proportional to the underlying risk. In other words, for younger patients the chance that an abnormal test result actually represents a true abnormality is much lower than for a higher risk patient.
Our geneticists/genetic counselors obtain detailed family histories, analyze inheritance patterns, identify at-risk individuals, and help prospective parents to understand their particular genetic risks, options, and likely outcomes in pregnancy. Working with Dr. Evans, the counselors explain the often complex world of new genetic tests and help patients make important decisions about their pregnancies.
We take a family history to document the issues at hand and ensure that there are no other issues which need evaluation.
Carrier Frequencies of Common Genetic Disorders
Cystic Fibrosis is perhaps the best known Mendellian disorder in the European population. Its incidence and the component markers vary considerably by ethnic group.
Cystic Fibrosis 2012
The "Ashkenazi Jewish Panel"
Recent advances in genetics have led to the expansion of carrier screening for individuals of Ashkenazi Jewish ancestry. For decades screening was available only for Tay-Sachs disease. With advanced capabilities over the past decade, screening is now available for up to 16 conditions. The conditions include:
- Three progressive neurological conditions that begin in infancy: Tay-Sachs disease, Canavan disease, and Niemann-Pick disease,which are all fatal in early childhood
- Gaucher type 1, a chronic blood disorder resulting in anemia with neurological damage
- Fanconi Anemia, is a childhood illness of poor growth and predisposition to some cancers
- Bloom syndrome, a disease that affects the "automatic" and sensory functions of the body
- Familial dysautonomia
- Mucolipidosis Type 4 (ML4)
There are other metabolic disorders such as Maple Syrup Urine Disease (MSUD) - an organic aciduria with severe neurological outcomes and mental retardation, and Usher Syndrome includes profound hearing loss, vestibular abnormalities and retinitis pigmentosa resulting in blindness. Nemaline myopathy is a collection of disorders characterized by severe neuromuscular disease, weakness and hypotonia, and can be associated with early death. Familial Hyperinsulinism causes hypoglycemia which can be lethal or cause irreversible neurological damage. The carrier frequencies and detection rates of these conditions are listed in the following tables.
Ashkenazi Panel 2012
Fragile X Syndrome
Fragile X is a leading cause of male mental retardation occurring in about 1/4000 overall but some populations are higher. It is an X- linked dominant disorder which means that the full manifestations of the syndrome are seen in males who inherit the gene from their mothers. Its inheritance is also "imprinted" meaning that it matters from which parent the gene came - in this case the mother. The disease is related to the number of "repeats" of a tri-nucleotide of DNA base pairs - in this case the DNA nucleotides "CGG" at the end ofthe FMR1 gene on the X chromosome. Classically 200 such repeats are needed for the disease, and most normal women have about 30 repeats on each of their X chromosomes. As the number of repeats goes up, infertility increases as does the likelihood of expansion of the number of repeats up to problem levels. Women who carry the gene may have some minor manifestations, but these are commonly unnoticed. In recent years, however, there has been an emerging appreciation of partial effects of Fragile X even with less than the usually required number of repeats needed for the full diagnosis.
Spinal Muscular Atrophy (SMA)
Spinal Muscular Atrophy (SMA), which in older literature was known as Werdnig-Hoffman Disease, is a rare cause of a lethal disorder with an incidence of about 1 in 4000. It is autosomal recessive meaning that both parents need to be carriers, and the age of the parents is irrelevant. Carrier testing for SMA has recently become available but is not yet universally accepted as routine.
First-Trimester Ultrasound, Nuchal Translucency, and First- Trimester Instant Risk Assessment™ Screening
Ultrasound imaging is a noninvasive technique that is used to look at the fetus within the abdomen. First-trimester ultrasound has emerged over the past several years as the most reliable way of establishing the due date of pregnancy; of determining the number of fetuses, and whether multiple fetuses are identical or fraternal; and of screening for elevated risk of genetic abnormalities, including Down syndrome and cardiac, neural, and limb abnormalities.
During ultrasound, the nuchal translucency (NT) can be established; this measurement determines the thickness of the back of the fetal neck. For over nearly 20 years in over 2,000,000 pregnancies NT and blood studies for free ~ hCG and PAPP-A have been shown to be a very reliable indicator of genetic risks. They have a higher yield of detecting problems than do other markers currently being utilized.
First-trimester screening results usually either increase or decrease the age-related risk of the pregnant woman for Trisomy 21 (Down Syndrome), Trisomy 13 and Trisomy 18. For example, the results may describe a 26-year-old woman as having risk of carrying a fetus with Down syndrome equivalent to that of a 40-year old (or vice versa). Research suggests that, by performing first-trimester screening, about 85% of Down Syndrome pregnancies can be identified in the first trimester. Non-invasive prenatal testing for free fetal DNA has finally become available and has a 99% of Down Syndrome but is still a screening test. (The more traditional blood tests in the second trimester can only detect about 60% of cases.) Patients can then use this information to decide whether they wish to have definitive testing such as CVS, to obtain a specific diagnosis in the first trimester.
In general, first-trimester screening is more sensitive than that in the second trimester or than using maternal age alone. Also, early screening allows early diagnosis of fetal abnormalities, giving parents more time to exercise treatment and management options.
The goal of screening is to maximize the chance of finding a problem that might be there while at the same time minimizing the number of women who require diagnostic (definitive) testing to be certain. Patients have a finger stick blood sample taken at 9-11 weeks. Then, at 11-and-a-half to 13 weeks 6 days, we perform the first trimester ultrasound and measure the thickness of the back of the neck - referred to as the Nuchal Translucency (NT) measurement. Accurate measurement of the NT is critical, as its results are used in a formula combined with the gestational age of the fetus (as measured by its length), the age of the mother, and the results of the ~ hCG and PAPP-A blood tests. While the patient is in our office having the US, we can instantly compute the adjusted risk. Low-risk patients can be reassured, and higher risk patients can go on to have a definitive answer by CVS generally performed at the same visit.
Small, normal NT in one twin and enlarged NT in other twin.
Prenatal Diagnosis via Ultrasound
Genetic ultrasound is part of every diagnostic procedure we perform. Assessment of fetal structure and sometimes function allows for the reassurance of normality in the majority of instances. Unfortunately, we also find pregnancies in which there are significant structural abnormalities that can vary from minor to severe to lethal. We use the latest machinery that provides the highest resolution in 2, 3 and 4 dimensions (the 4th dimension is time, i.e. live pictures).
Prenatal Diagnosis via Amniocentesis and Chorionic Villus Sampling (CVS)
Many inherited conditions can be diagnosed prenatally, via CVS or amniocentesis. These procedures have identified chromosomal abnormalities, such as Down syndrome, and neural tube defects, such as spina bifida. Recently, however, explosive growth in DNA testing technology has made it possible to detect literally hundreds of additional genetic disorders, including Tay-Sachs, cystic fibrosis, Duchenne muscular dystrophy, and sickle-cell anemia, to name a few.
We employ molecular technologies that allow us to achieve results for certain conditions such as for Down Syndrome usually within one day after the procedure.
Amniocentesis was the first method developed for prenatal diagnosis. It is usually performed between 15 and 20 weeks from the beginning of the last menstrual period. Under the guidance of ultrasound, a very fine needle is inserted through the woman's abdominal wall and into the uterus. Approximately one ounce of fluid is withdrawn and sent to the laboratory for analysis. In experienced hands, genetic amniocentesis is a very safe test. A limitation of amniocentesis is that reassurance or diagnosis of problems does not occur until the second trimester.
Chorionic Villus Sampling (CVS)
Chorionic villus sampling or CVS is the first-trimester procedure for prenatal diagnosis of fetal chromosomal and genetic disorders, usually performed 11 to 13 weeks from the beginning ofthe last menstrual period. The procedure can be done one of two ways. In singleton pregnancies, most of the time the patient is placed in sturips, and a speculum is inserted just as for a Pap Smear. A small catheter (similar to a straw) is passed painlessly through the cervix and maneuvered into the placental tissue under ultrasound guidance. A syringe is then attached to the end of the catheter, and a very small amount of tissue is aspirated. In some cases (about 30% of the time) depending upon the position of the placenta, a needle may be inserted trans abdominally and maneuvered into the placenta (not the fluid). In either case several milligrams of tissue are sent to the lab. Tests can then be performed for chromosomal (e.g. Down Syndrome) molecular diagnosis (such as cystic fibrosis, or FISH for a quick read of chromosomes such as Down Syndrome), or enzymatic analysis (for some biochemical disorders).
We commonly perform CVS for diagnosis of singleton pregnancies at elevated risk for birth defects; for diagnosis in multiple pregnancies prior to reduction, to help ensure the health of fetuses remaining after the procedure; and for patients who have undergone preimplantation genetic diagnosis (PGD) with in vitro fertilization, who need post-implantation confirmation of the normalcy of the fetus.
Fetal Tissue Sampling
Tests utilizing the DNA in fetal tissues have made possible via CVS the diagnosis of disorders such as Duchenne muscular dystrophy. Sometimes, however, DNA tests cannot give a definitive answer, and the only way to get the answer is by obtaining a piece of fetal muscle, or liver. Over the past 15 years, we have performed more fetal muscle biopsies than anyone else, worldwide.
Similarly, some skin abnormalities and certain chromosomal abnormalities can only be diagnosed by obtaining a piece of fetal skin. Fetal skin biopsy is the optimal way to evaluate ambiguity that occasionally arises in the interpretation of amniocentesis data. These biopsies are performed without a hospital stay, and under ultrasound guidance.
The diagnosis of a serious disorder in a fetus is a devastating event for all involved. In many cases, there may be little that medicine can offer, aside from help in preparing for the birth of child with special needs, or the option to terminate the pregnancy. In some situations, however, there is another alternative: treating the disorder before birth.
We can also provide you with world-class expertise in this area. Dr. Evans, developed:
- the first method for preventing a congenital defect before birth (congenital adrenal hyperplasia);
- performed the first successful stem cell transplant to cure a baby with SCIDS (the "bubble babies");
- was a member ofthe team that did the first successful open fetal surgery (for congenital diaphragmatic hernia); and
- is one of the most-experienced at performing fetal shunt procedures, such as for obstructed fetal bladders. We work with colleagues all over the country to provide cutting-edge therapies in pregnancies with correctable problems.
Multifetal Pregnancy Management
Over the past two decades, the number of twin pregnancies has more than doubled. There has been a 13-fold increase in triplets, the rate of quadruplets has increased 100 times, and there had been a l,OOO-foldincrease in quintuplets. For patients with multiple pregnancies, the risks of loss, prematurity, congenital anomalies, and poor neonatal outcomes are dramatically higher than for singletons. Over the past 30 years, Dr. Evans has been a pioneer in the practice of multifetal pregnancy reduction (MFPR) having performed thousands of such procedures for patients starting with between 2 to as many as 12 fetuses. The procedure has been demonstrated to be a safe way to significantly reduce the risks of multiple pregnancies. Patients with triplets or higher have their risks cut by more than half by reducing to twins. For twins, the risk of pregnancy loss and prematurity can be further cut by reducing to a singleton. We typically see patients for MFPR at about 12 weeks. For the 80% of our patients who are also having CVS, the procedures are done usually on two consecutive days.
Quick Contact Info
Dr. Mark I. Evans (MD PLLC)Phone: 212.288.1422
Email: Evans@CompreGen.com 131 E 65TH ST
NEW YORK NY 10065