3.21 Three two one  
3.21 A newsletter that examines the medical aspects of Down syndrome
Vol. 2, No. 4, December 1999
  Reprinted with the permission of Karalee Wetzel

Subscription Time
     It's that time of year again. If you would like to subscribe to the 3rd year of 3.21, please send $16 for 4 issues to the address on the back. This is your last issues of (if I say "the millenium" my spouse will divorce me because he reminds everyone the millenium won't start until 2001) your current subscription.

My School Dilemma
     5 more months and I take my boards. A few months later, I start rotations which means I start touching and treating patients. I hope you are as frightened as I am.
     The school I attend computer matched me to do a 4 month rotation 300 miles away next year. I have 3 kids (one is "a Jenny"), and a spouse who will be in his 3rd year of medical school. The clinical affairs office rejected my appeal to stay in Des Moines, even though my appeal included letters from 2 docs and a principal stating Jenny needs both parents. There are options in Des Moines, but they gave most of them to the single students with no kids.
     A geneticist once told me how the IQ of the mom was the single most important factor in determining the development of a child with special needs. It has nothing to do with passing on the genes, she stated. The smart moms fight harder for their kids, she explained. I may not be the brightest mom, but the fight to stay in Des Moines with my kids has just begun.

How events during pregnancy effect babies with DS
     A study looked at different problems that 219 children with DS were born with. They also surveyed their moms regarding events in the pregnancy, along with demographics of the mom. They found that race was associated with more cardiac problems (they are more common in nonwhite moms), a younger age was associated with cleft palate, and mom having a fever during the pregnancy was associated with the baby having gastrointestinal defects.
     Khoury, MJ and Erickson, JD (1992) Can maternal factors influence the presence of major birth defects in infants with Down syndrome? Am-J-Med-Genet. 43(6), 1016-22

This Issue
Cardiac problems in kids, drug reactions, maternal factors and congenital defects, bone mineral density

Next Issue
Folate and risk of birth defects, kidney transplants in DS

Cardiac Problem in Those With DS
Cardiac malformations represent a significant health risk in those with DS. They are the biggest cause of death, at least in babies born with DS (and perhaps in all ages). Many of the cardiac problems lead to significant respiratory problems such as recurrent pneumonia, which is often the fatal blow.
While pediatricians are certainly aware of the connection between DS and heart disease, many of these problems are very easy to miss. Small holes, for example, may not have any signs or symptoms, and may sound perfectly normal when using a stethoscope.
However, it is important to find even minor problems. Some malformations, for example, increase one's risk for endocarditis (a heart infection) and those kids need to be given antibiotics preventively (prophylactically) when having dental work or minor surgery.
One study looked at 50 kids born with DS. 44% had heart disease, with endocardial cushion defect (ECD) being the most prevalent, followed by VSD. (See the explanation of these starting on page 3) 3 of the children had no signs or symptoms and had normal chest x-rays and EKGs. Their defects were only found by echocardiogram (Bhatia, et al, 1992).
A Japanese study looked the survival in those with DS who had cardiac problems verses those without. They studied 373 children with DS retrospectively from adulthood. The survival rate at age 24 was 92% in those that had no heart disease. In those with cardiac problems, the rate dropped to 75%. How those problems were handled also affected survival. Those that had surgical repairs had an 88% survival at age 24, compared to only 41% in those that were not repaired (Hijii, et al, 1997) With today's technology, and the change in how kids with DS are viewed, however, there should be very few kids who do not get the surgical repair that they need. In addition, better antibiotics and cardiac medications will also increase survival from when these adults were children.

What if your child's echo was normal?
After Jen's last echo showed her ASD had closed, I thought the cardiac worries were over. Not so. Institutionalized adults with DS were given echos. The 30 of them had no signs nor symptoms of any cardiac problems. (Their childhood cardiac problems or repairs were not discussed.). However, echo revealed that 27% had mitral valve prolapse, 17% had mitral valve regurgitation, and 13% had aortic valve regurgitation. The lesson here is to have your older children screened with an echo, even if they were not born with an abnormality. Valve diseases usually develop over time, unlike the malformations such as ECDs and VSDs that children are born with.
     Bhatia, S. et al (1992) Congenital heart disease in Down syndrome: an echocardiographic study. 29(9) 113-6.
     Hamada, T et al (1998) Echocardiographic evaluation of cardiac valvular abnormalities in adults with Down's syndrome. Tohohu-J-Exp-Med 185(1) 31-5.
     Hijii, T. et al (1997) Life expectancy and social adaptation in individuals with Down syndrome with and without surgery for congenital heart disease. Clin-Pediatr-Phila. 36(6) 327-32.

Congenital Heart Defects
The following is a brief description of some of the more common heart problems that kids (DS or nonDS) are born with. There are many more than the 4 listed here, and some are born with multiple defects. The information presented in this summary is from Pediatric Cardiology for Practitioners, and is in reference to the general population of kids, not just those with DS.

Atrial Septal Defect (ASD) - a hole in the wall between the left and the right atrium.

(*see text for explanation)

Ventricular Septal Defect (VSD) - a hole between the left and right lower two chambers of the heart

Patent Ductus Arteriosis (PDA) - the fetus has a bypass for the blood to avoid the lungs called the ductus arteriosis. When the baby is born and the lungs are functioning, the best scenario would be for that bypass to close and for the blood to enter the lungs. When it does not, some blood gets back into circulation that has not been oxygenated. Endocardial Cushion Defect (ECD) - this is a hole in the wall between an upper and a lower chamber (between an atrium and a ventricle) Valve Problems
Usually valve problem develop over time. It can happen in any of the valves, but the mitral valve and the aortic valves are the ones that will cause the most problems if damaged. Valves openings can become small (stenotic) so that it is hard for the blood to get through, or the valves can get floppy (regurgitation) so that some blood flows backwards. Mitral valve problems, for example, are a big problem in the adult population. One cause is a childhood rheumatic fever which is caused by an untreated strep infection. A regular old sore throat that goes on too long can cause the body to form antibodies against its own mitral valve. This is becoming less of a problem in industrialized countries where antibiotics are available.
Kids with DS really need an echocardiogram (or several of them) since so many of these problems are easy to miss just by listening with a stethescope or looking for signs. (Jenny was born with an ASD which was not diagnosed until she was 9 months old and had an echo). As you will read later, subsequent cardiac testing is needed for those with DS to catch problems that can develop in adulthood.

Medication differences
     It is rare to see any of these differences in reactions to medications between those with DS and normals actually reported in the literature.
     The first drug is theophylline. Theophylline is a drug used to treat asthma. It is one of those drugs that needs to be used cautiously, since it has many (I think 80 known) medications that one cannot take when on theophylline because of nasty drug-drug interactions. It can also reach toxic levels in certain people, so blood levels need monitoring.
     This report was of 6 infants with DS who had a slower than normal clearance of theophylline (Stowe and Phelps, 1999). That means the drug would stay in the body longer, and can easily reach toxic levels. By the way, there are much safer drugs out now to treat asthma (you have probably seen them advertised on television or in magazines). While theophylline is still used, ask your doctor about switching if any of your child takes the drug.
     The other drug with problems in DS is captopril. It is an ACE inhibitor and is frequently used to treat hypertension, but in children with DS its likely use would be to treat congestive heart failure(CHF). (CHF can occur when the heart does not pump hard enough, and blood backflows into the lungs.) This paper reported 2 cases of neutropenia (a decrease in neutrophils). This side effect had not been reported in normals, so it is a problem physicians would not be aware of, but should be if your child has DS and is taking an ACE inhibitor. (Gleason, et al, 1993).
     I also remember a study that showed those with DS metabolize Tylenol faster than normals do. It seems those with DS over produce acetylcystine, which is made in the body but is also used to treat Tylenol overdoses. Therefore, you may have to give Tylenol more frequently in your child with DS when treating for pain or for fever. (Of course, discuss that with your pediatrician first.)
     Gleason, M. et al (1993) Captopril-induced bone marrow suppression in two cardiac patients with trisomy 21. Pediatr-Cardiol. 14(4), 227-9
     Stowe, C and Phelps, S. (1999) Altered clearance of theophylline in children with Down syndrome: a case study. J-Clin-Pharmacol. 39(4), 359-65.

Bone Mineral Density
     Decreased bone mineral density is a problem usually associated with postmenopausal women. It can lead to osteoporosis and more frequent bone fractures. Young adults, both male and female with DS, were found to have significantly lower (about 9%) bone mineral density than their normal peers. The authors did not know if the difference was due to different activity levels, hypotonia, or a biochemical difference.
     Angelopoulou, N. et al (1999) Bone Mineral Density in Adults with Down syndrome. Eur-Radiol. 9(4), 648-51

This newsletter is not associated with any organization.
The information in 3.21 is not intended as medical advice. Discuss any treatments with your physician.

To subscribe to 3.21 for 4 issues, send $16 in US funds to:

Karalee Wetzel
675 35th St
Des Moines IA 50312

Revised: May 9, 2000.