FNMS has initiated and is involved in a genetic research project working to locate the genes responsible for causing Nager and Miller Syndromes through the Johns Hopkins in Baltimore.

Many of you are aware that the rapid advances in Medical Genetics that have been occurring over the past 20 years have been given a dramatic boost by the Human Genome Project. This project is quickening the pace of gene mapping (finding the location of a gene on a chromosome) and sequencing (reading the genetic code). It is now a reality that many disease and malformation causing genes will be mapped in our lifetime. Locating a gene is often the first step in being able to understand the cause of a genetic disorder, improve treatment, develop carrier testing and offer prenatal diagnosis.

Members of the CCDD at Johns Hopkins University in Baltimore, Maryland are working on a number of gene-mapping projects. One of our goals is to map genes causing craniofacial malformation syndromes. An indispensable part of our effort is a partnership with families affected by these disorders. We are interested in finding families with individuals with the Miller Syndrome and other acrofacial dysostoses to help with our gene mapping efforts.

These studies require accurate clinical and family information. We have a genetic counselor involved in this project that will work with interested families during this information-gathering phase of the study. Blood samples will be requested from patients, siblings and parents to perform the DNA studies necessary for gene mapping. We will try to arrange for these samples to be drawn and sent to us so there will be as little inconvenience to the families as possible. Fortunately, we are able to set up long term cell cultures from the blood samples. Therefore, we usually require only one blood sample from each individual that we can continue to test for many years. There will be no cost to the families for the testing that is done and we will keep all the families who participate in this research informed on our progress.

This is slow, time consuming research and it may take years to come up with an answer. But, if we don't start now it will be even longer in coming. If you would like additional information and might be interested in having your family be a partner in this important project, please email us at ph@welch.jhu.edu.

Question:
Is there any new genetic information on Nager syndrome?

Answer: Unfortunately we have no new information about the inheritance of the Nager syndrome. The real difficulty is that the Nager syndrome is "genetically heterogeneous." This is a medical way of saying that there appear to be several different genetic alterations (changes, mutations) that can cause the physical abnormalities (mandibulofacial dysostosis with radial limb anomalies) we call the Nager syndrome. Thus there are really "several" Nager syndromes, each with different recurrence risks. Unfortunately we do not have any way (yet) to tell the different types of Nager syndrome apart. Thus we continue to give empiric risks, based on reported families. The worst case, which has been described in some families, is autosomal dominant inheritance which gives a 50% risk of occurrence in the offspring for an affected parent. Most cases, however, have been sporadic without other affected family members. Unfortunately we cannot separate these two very different risks. This is why we suggest that families try to meet in person with a geneticist familial with this condition, so they will clearly understand this confusing situation. We find most affected individuals overestimate their risk of having affected children so this is usually an encouraging meeting.

People interested in submitting blood samples for Nager and Miller Syndromes mapping research should contact:

Dr. Ethylin Wang Jabs
Phone: 410 955-4160
e-mail: ewjabs@jhmi.edu

For informations on Genetic Research for Nager And Miller Syndromes Mapping the genes for Miller Syndrome, and Nager Syndrome and other Acrofacial Dysostoses:

Eric A. Wulfsberg MD Assistant Professor of Pediatrics
University of Maryland Division of Human Genetics
University of Maryland School of Medicine
22 S. Greene Street, A661 Baltimore, MD 20201-1595
Phone: (410) 328-3335
Fax : (410) 328-3379
e-mail: ewulfsberg@peds.umaryland.edu