| The science of prenatal diagnosis has undergone major advances over the previous two decades. Currently, there are two general approaches to prenatal diagnosis: (1) ultrasound imaging, and (b) tissue analysis. Improvements in ultrasound technology provide better image quality with greater morphologic detail so as to allow diagnosis of physical abnormalities which were previously never visualized. Similarly, ultrasound provides a window to the fetus in utero, allowing the diagnostician an opportunity to obtain samples of a variety of fetal tissues for genetic diagnosis. In the contest of the Rubinstein-Taybi syndrome, the following prenatal diagnostic techniques may be of use:(1) Ultrasound Imaging or Prenatal Sonography:Prenatal sonography is useful in the detection of physical fetal anomalies. Individuals who have the Rubinstein-Taybi syndrome, however, do not have a characteristic physical abnormality which can always be visualized on ultrasound to make an absolute diagnosis with 100% accuracy. The physical characteristics that are associated with Rubinstein-Taybi syndrome include: short stature, retarded osseous maturation, slanting palpable fissures, broad thumbs, and broad toes. None of these can be visualized sonographically with any significant degree of accuracy. With the knowledge that a given individual or family was at risk, occasional malformations such as polydactyly ventricular septal defect, prominent forehead, micrognathia, etc., might be suggestive of Rubinstein-Taybi syndrome. Therefore, ultrasound alone cannot be used for prenatal diagnosis of Rubinstein-Taybi syndrome.(2) Tissue Analysis:There are several approaches to obtaining embryonic or fetal tissue for genetic analysis. These are:(a) CVS (Chorionic Villi Sampling)This particular technique, using direct ultrasound guidance, allows the operator to obtain tissue from the developing placenta with either a transabdominal or a transcervical approach. In the transabdominal approach, using direct ultrasound guidance and sterile technique, a 20-gauge needle is inserted into the developing placenta through the maternal abdomen and 10 to 15 mg. of chorionic villi are obtained by aspiration. Similarly, in the transcervical technique, direct ultrasound guidance is used to thread a catheter through the cervix into the base of the developing placenta with aspiration of 15 to 30 mg. of chorionic villi. These villi may then be examined directly or cultured for genetic diagnosis. Both the transabdominal and transcervical CVS techniques add a 1% risk of pregnancy loss over and above the background pregnancy loss rate.(b) Amniocentesis:Using direct ultrasound guidance and sterile technique, a 22-gauge needle is inserted into the amniotic cavity through the maternal abdomen and 15 to 20 ccs. of amniotic fluid surrounding the baby is aspirated. This fluid is then centrigued and cells that have been shed from the fetal skin, as well as those expelled from the fetal lungs, are collected. These cells are then cultured and analyzed for genetic abnormalities. Genetic amniocentesis is usually performed at 13 or more weeks gestation and adds a 0.25% risk of pregnancy loss over and above the background pregnancy loss rate.(c) PUBS (Percutaneous Umbilical Blood Sampling):In this technique, a transabdominal approach is used to obtain fetal blood from the umbilical vein again under ultrasound visualization. Fetal blood may then be used for culture of fetal lymphocytes and genetic diagnosis. PUBS places a 1% rate of pregnancy loss over background loss rates and is usually possible after 16 weeks gestation. The advantage of PUBS is the rapid rate at which lymphocytes grow allowing rapid genetic diagnosis.In addition to the above techniques, other experimental techniques for visualizing the embryo or fetus in utero include the following:(1) Embryoscopy:Embryoscopy is performed in the first trimester (up to 12 weeks gestation) and is an experimental technique in which an endoscopic instrument is inserted through the cervix into the space between the amnion and the chorion using sterile technique and ultrasound guidance. The embryo is visible and individual antomic features may be studied in detail. This technique is not currently available for ongoing pregnancies and is only used in individuals who plan to have a termination of pregnancy. As this technique develops, it may prove very useful for the prenatal diagnosis of Rubinstein-Taybi syndrome.(2) Fetoscopy:Fetoscopy is similar to embryoscopy except that it is usually performed after 16 weeks gestation. An endoscopic instrument, using sterile technique and ultrasound guidance, is inserted into the amniotic cavity through a small maternal abdominal incisioin and the mebryo and its different parts are visualized. The view through the fetoscope is extremely limited so that ultrasound guidance is required to help the operator view different aspects of the fetus. The fetoscope may be used to obtain a sample of fetal blood as well as a skin biopsy.In summary, current prenatal diagnostic techniques using ultrasound alone may not be able to provide a definite diagnosis of Rubinstein-Taybi syndrome. In those instances where a gene defect is present and detectable by current molecular biology techniques, a chorionic or fetal tissue sample may be obtained for confirmation of Rubinstein-Taybi syndrome. |
