October 18, 1997
Meeting of the National Marfan Foundation
Place: Davis Pubic Library in Bethesda, Maryland
Speaker: Dr. Hal Dietz, member of the NMF Professional
Advisory Board
Forty-two people attended this meeting, including the speaker
Before the presentation a few minutes were taken with questions related to future meetings. It was agreed that we use name tags in future meetings to identify those attending. Betsy asked for suggestions about speakers for future meetings. (Note: Dr. Dietz’s presentation ended before his planned second part because of time constraints and it was agreed that he would continue his presentation at the next meeting.) Betsy announced that she had videos of the Houston conference and offered to have them available for viewing at her home for small groups. She also informed the group about the genetics annual meeting in Baltimore coming up at the end of the month and asked for volunteers to help man the Marfans exhibit booth. Steve Van Reese offered to bring a coffee pot for future meetings. The time and location for the next meeting is yet to be determined but is tentatively set for the same location on April 18.
PRESENTATION.
Dr. Dietz introduced Karen Clarke, a genetics counselor who is the coordinator of the Marfans Clinic at Hopkins in Baltimore. The telephone number for both Ms. Clarke and Dr. Dietz is (410) 955-3122.
Marfans is a dominant disorder, meaning that only one abnormal copy of the gene must be present for the offspring to be affected. (In cases of recessive disorders, it would require both parents to carry the defective gene.) The chance of someone with Marfans having children with Marfans are statistically 50/50. The current best estimate is that one in ten thousand people throughout the world have Marfans. It is estimated that about a quarter of Marfans cases are spontaneous, without a link to a parent who has Marfans. Marfans is characterized by high penetrance. (I.e., if you carry the gene, you will show symptoms. The symptoms do not skip generations.)
Symptoms include:
Early and severe nearsightedness caused by the shape of the
eye which is longer than normal and leads to nearsightedness.
Lens dislocation - The Opthalmologist does a slit lamp exam to determine that the lens has moved. Most people don’t require surgery for lens removal. Surgical correction was used cautiously in the past because of problems such as risk of detached retina. Current techniques have lowered the associated risk and the operation is not considered unnecessarily risky at his point.
Long bone overgrowth wherein the length of arms and legs are longer than normal for the trunk. This characteristic may be seen in arms, legs, or fingers. The finger length can be compared to palm length.
Increased risk of glaucoma and cataracts. Increased risk of glaucoma is present because of the shape of the eye, not simply the dislocated lens.
Indulation of the chest (chest deformity) doesn’t necessarily require surgery to correct.
There can also be combined chest wall abnormalities in which part of the chest can appear pushed in while part is pushed out. Surgery is indicated where the abnormality interferes with breathing.
Curvature of the spine (scoliosis) can cause problems with breathing also. Once the curvature goes beyond 15 degrees, people should be monitored with X-rays.
Increased height which leads some to ask about the possible intervention through use of hormones. There are significant downside risks involved in use of hormones for this purpose and any such treatment should be done under the supervision of a pediatric endocrinologist.
The characteristic high pallet and crowded teeth can mean orthodontic intervention is necessary.
Flat feet - not the ordinary type, but this is where the middle of the foot sinks. Erosion of the skin may result. Supportive inserts may help this condition.
A tendency to have deep-set eyes because there is less fat behind the eye socket.
Cardiovascular implications include Mitral Valve Prolapse, a not unusual condition in the general population. This condition may be characterized by mitral regurgitation or arrhythmia. Valves with this condition are prone to attack by infectious organisms and those with the condition should be premedicated before undergoing treatment that will tend to introduce large amounts of bacteria into the body. Dr. Dietz cautioned that the recent change in recommended premedication guidelines for the general public should not be taken to mean that those with Marfans should follow those guidelines. It is advised that those with Marfans be more cautious because of their abnormal connective tissue which will tend to attract infection. This caution is especially necessary where there has been aortic surgery. The prescription should be from the Cardiologist, not from the dentist, who would be using the general guidelines. The prescription used should reflect the age and condition of the patient. We should not assume a standard dosage for everyone who has MVP. Those who have had aortic surgery are advised to have injected antibiotics to have increased benefit from the antibiotic taken. Premedication is indicated whenever there will be drilling by a dentist or cleaning. In other cases, such as adjustment of braces, one must ask the dentist, or Orthodontist whether the procedure for that day is likely to result in bleeding... and therefore introduction of bacteria into the bloodstream. The other major cardiac implication, aortic root enlargement is a common finding in Marfans. It is now believed that surgery is indicated for more than half of the Marfans population some time during their lives to deal with valves that leak or aorta enlargement. Dr. Dietz cautioned against depending on echocardiograms because they concentrate on the upper part of the Aorta. There is possibility of dilation in other places. To guard against problems in other parts of the circulatory system, he suggests an MRI or CT scan every three or four years. (Those who have metal in their bodies, e.g., pacemakers, cannot have an MRI but can have the CT scan.)
Discussion focused on the controversy concerning use of beta
blockers. The doctors at Hopkins are very pro beta blocker for cases of Marfans and will recommend use of
these drugs for all patients with Marfans, including those with low blood pressure and no indication of dilation.
Studies indicate that the beta blockers slow the rate of dilation (rather than stopping the dilation). Dr. Dietz
did not indicate studies focused on overall health or longevity but indicated that side effects that may limit
activity can be avoided by careful use of prescriptions and changing to different types when necessary. Dr.
Dietz sees no problem with learning disabilities linked to beta blockers and suggests use in children as young
as four years old. Use of beta blockers in people who have Asthma is contraindicated. In those cases
calcium channel blockers can be used and should have the same positive impact on lowering the rate of dilation
of the Aorta. However, the long term studies have only been done on the beta
blockers. Dr. Dietz has been using Tinorman as a single dose
in patients and finds that the drug taken at night has enough lasting power for the following day and the negative
possible impact of tiredness is not a problem with that type of dosing. In some cases patients may do better with
split doses. Some patients may find that they have to take the medication with meals to avoid stomach distress.
One member of the group indicated that she had switched to Z Beta and had good results with fewer side effects.
Those who take these medications should be careful to take enough fluids to avoid dehydration. The use of
programed intake of liquids may be necessary.
Discussion of the different types of surgery to repair the damaged valve or aorta followed. Use of animal tissue means that the use of anti coagulants may not be necessary. That is particularly useful in those who are more subject to injuries involving bleeding or those for whom anti coagulants would be contraindicated. But the downside is that these tend to be temporary fixes that may only last for 10 years or so. The more normal procedure, using Dacron grafts and an artificial valve will require use of anti coagulants and particular care about infection. There is a new “valve sparing procedure” that takes the best features of both. This removes the aorta just above the valve and results in not needing anti coagulants because the valve isn’t replaced. This is a relatively new procedure and there is not the 15 to 20-year track record to show efficacy. This procedure, however, is contraindicated only where the valve is a problem such as when it is not closing well.
There is no mechanism at present for artificial valves to fight infection. Infections may require blood cultures. The infections may be present when the patient is experiencing high white cell count, lethargy, fever. The likely site of the infection is the material used in the valve. The recovery rate should be about the same in the valve sparing procedure. Pregnancy is high risk once someone has had surgery to replace the aortic root. During birth and immediately following birth there are rapid fluid losses when the vessels are contracting.
Replacement is generally indicated with dilation of five and one half centimeters. However, family history of early dissection would indicate earlier intervention. Few children actually have dissections, indicating that the problem is one of continued stress over time.
Another problem related to Marfans is dural ectasia. This condition focused on the spinal canal can cause pain in the legs and muscle weakness. It is estimated that about a third of Marfans patients have this condition but symptoms are not necessarily present. The problem occurs in the lower spine. Marfans patients also have a higher incidence of disk problems.
Another characteristic of Marfans, stretch marks that cannot be explained by the normal reasons for stretch marks, may show themselves on shoulders and other places.
The extreme variations in how Marfans manifests are indicated by the fact that many top athletes have been found to have Marfans while others may be disabled by the condition. In severe cases, infants may not survive long after birth.
Exercise is beneficial to those with Marfans but exercise should be noncompetitive and should not involve straining against immovable objects or heavy weight lifting which will tend to cause significant spikes in blood pressure. Running, swimming and dancing can be beneficial to lowering blood pressure in the long run.