| Doing 'The Right Thing' |
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The pediatric hematology department referred her to me. I was told that she had severe anemia and needed to be developmentally assessed prior to receiving a bone marrow transplant in a European country. She came with her mother. What was most obvious about her was her short stature and Arachnodactyly (long fingers). This nomenclature is derived from the words arachnoid (any of a class of arthropods comprising chiefly terrestrial invertebrates - including the spiders, scorpions, mites and ticks, and having a segmented body divided into two regions of which the anterior bears four pairs of legs but no antennae) and dactyl (from Latin word dactylus - literally, finger. This comes from the fact that the first of three syllables is the longest, like the joints of the finger). Arachnodactyly is a physical condition in which the fingers are long, slender and curved, resembling a spider's legs. I read about it and saw photos in textbooks, but never observed it close-up. Long, slender fingers can be a normal variation and not associated with any medical problems. However, in some cases, the tendency to develop spider fingers can indicate an underlying hereditary disorder. The inherited Fanconi's Anemia (FA) is one such disorder. FA is an autosomal, recessive disease in more than 99% of patients. In the U.S. the carrier frequency is estimated to be approximately one per 300 people, leading to an expected birth rate of approximately one per 360,000 people. FA has been reported in all races, although "founder" effects exist, which result in higher carrier frequencies in Ashkenazi Jews and Afrikaners. Among Ashkenazi Jews, the carrier frequency is approximately one per 90 people, with a projected birth rate of one per 30,000 people. Internationally, the carrier frequencies are similar to those in the United States, depending on the population. It is classically diagnosed between the ages of two and 15. Mortality/Morbidity: The major cause of death in FA is bone marrow failure, followed by other fatal "situations." Though the mortality rate has been extended in its most severe form (patients do not live beyond the age of 40), many die earlier. Bone marrow failure usually presents itself in childhood, with bruising and hemorrhages, along with pallor and fatigue from the anemia, "punctuating" the young life. Developmental delays, learning disabilities and retardation are among the cognitive problems. Physical: About 75% of patients with FA have birth defects, such as altered skin pigmentation and/or café av-lait spots (50%), short stature (50%), thumb or thumb and radial anomalies (40%), abnormal male gonads (30%), microcephaly/small head (25%), eye anomalies (20%), structural renal defects (20%), low birth weight (10%), developmental delay (10%) and abnormal ears or hearing (10%). FA is distinct from Fanconi's syndrome, a rare kidney disorder in which nutrients are lost through the urine. The disease is caused by a genetic defect that prevents cells from fixing damaged DNA or removing toxic, oxygen free radicals that damage cells. Patients may be suspected of having the disease if they have particular birth defects or develop decreased blood counts. FA is primarily an autosomal recessive genetic condition, as this gene is on the X chromosome. For an autosomal recessive disorder, both parents must be carriers in order for a child to inherit the condition. If both parents are carriers, there is a 25% risk, with each pregnancy for the mother to have an affected child. Genetic counseling and genetic testing is recommended for families that may be carriers of Fanconi anemia. Prognosis: Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer. Treatment: Bone marrow transplantation can cure the blood count problems associated with Fanconi's anemia. An HLA - matched sibling is the best donor source, although umbilical cord blood cells and unrelated bone marrow can also be used. This therapy is very effective, and although there are associated toxicities, there has been improvement in the care of Fanconi patients during the transplant. There is approximately a 70% success rate for those patients fortunate enough to have a well-matched donor. So why am I presenting a modest genetics course? This little eight-year-old girl had been adopted, and when her adoptive parents (who knew she had some physiological problems and was therefore given up for adoption) found out about her disease, they tried to reach the biological parents to have her blood-siblings tested for a match of bone marrow. They were summarily turned down and told that the biological parents did not want their other children to know about this child or her illness because among other things, they didn't want to fashtair, (spoil), their childrens' shidduchim (marriageability). They were insistent on doing "the right thing" for the majority of their children. Their decision of not permitting an ideal biologically-matched donor significantly reduced her chances of long-term survival. I haven't thought about this case in a long time. But recently I came upon an article that discussed an amazing finding that occurred in the past 10 years. The discovery that the Fanconi's Anemia gene and BRCA 1 and BRCA 2 gene for inherited breast cancer are intertwined. So much so, that under the microscope they are hard to tell apart. Women today can be tested for this form of inherited breast cancer, which is more common in Jewish Ashkenazi women. Under the directorship of Dr. Ephrat Levy-Lahad (
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) of the Medical Genetics Unit at Shaare Zedek Medical Center in Jerusalem, is a major site in Israel for this testing (it is a simple blood test), as well as for its cutting-edge research. And here is the connection. The biological parents have unwittingly put their other children at risk. For if these children know that their family genetics include Fanconi's Anemia, they would be able to check for BRCA 1 and BRCA 2. They would then be able to alter their statistical chance of getting this form of breast cancer from 70% down to 30% (which is similar to the general non-inherited statistics). It is important to note that men with an inherited altered BRCA 1 or BRCA 2 gene also have an increased risk of breast cancer (primarily if the alteration is in BRCA 2), and possibly prostate cancer as well. May Hashem grant us the wisdom to "do the right thing." Research for this article included: Evaluation of Fanconi Anemia genes in familial breast cancer predisposition. Seal S, Barfoot R, et al; Breast Cancer Susceptibility Collaboration; Harvard Gazette; Updated 7/29/2005. Updated by William Matsui, M.D., assistant professor of Oncology, Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. Review provided by VeriMed Healthcare NetworkMedline. Originally published in the Jewish Press on October 18, 2006. |
