Back in 1995, a man died tragically when he was only 42 years old. The official diagnosis was liver failure from alcoholic cirrhosis. No autopsy was done. The body was cremated. No clues remained. End of story. Or was it?

The July 7, 2001 issue of The Lancet chronicles a story of deductive reasoning, genetic medicine, and international cooperation. A physician relative of the deceased kept wondering if the death might have been not due to alcohol but instead from a rare genetic disorder.

The only remaining clue was tiny bits of his skin left in an old electric shaver. These were sent to Semmelweis University in Budapest, Hungary. The genes were analyzed by means of polymerase chain reaction (PCR) amplification in the US.

The result?

The unfortunate man was found to have undiagnosed Wilson disease. This rare genetic condition causes the relentless build-up of copper in the liver, leading to liver failure and brain damage. Effective treatments are available, but Wilson disease is fatal if untreated.

The family learned that alcoholic cirrhosis was not the cause of death. They also learned that his two children (and his father) are carriers of the rare recessive condition. What powerful information was gleaned from nearly-forgotten traces of DNA in that old electric shaver!

If you save a precious lock of your child’s hair, or those tiny baby teeth, or the remnants of her umbilical cord, your memento may prove to have more than just sentimental value as we move through the 21st century.

Dr. Greene’s Answer:

It boggles my mind. The development of a single fertilized egg into the trillion-fold complexities of a crying newborn baby with absolutely unique fingerprints and toeprints amazes me. In a building project of this magnitude, accomplished in only 9 months, it’s a wonder that major things don’t go wrong every time.

The DiGeorge anomaly (formerly DiGeorge syndrome or sequence) is the name given when a particular set of things goes wrong during fetal development. Because this condition usually does not run in families, and because some symptoms look like those of fetal alcohol syndrome, alcohol exposure or other environmental insults during pregnancy used to be blamed for some cases. As you can imagine, this mistake made a tough situation even tougher for parents. Today, more than 95 percent of cases can be traced, not to an exposure, but to a specific genetic problem – a microdeletion of a tiny part of chromosome 22q11.2. Other cases have been traced to deletions on chromosome 10p13. Today, when in vitro fertilization is used, the DiGeorge anomaly can usually be diagnosed even before the embryo is implanted!

This tiny genetic change causesthe lower face and middle of the chest to develop abnormally. Children with DiGeorge anomaly sometimes have rather small mouths, rather widely spaced eyes and low-set ears, but the three classic defects of the DiGeorge anomaly are all focused in the area behind the breastbone. These defects include problems with the large blood vessels leaving the heart, problems with the parathyroid glands, and (most importantly) problems with the thymus.

Congenital heart problems (including interrupted aorta, right aortic arch, truncus arteriosus, and others) can be of immediate, even life-threatening, concern for newborns. Surgical correction or stabilization of these is the first priority. Disasters have occurred, though, when only the cardiac problem was diagnosed and the possibility of the DiGeorge anomaly was not considered. A normal blood transfusion can kill a child with the DiGeorge anomaly– only irradiated, cytomegalovirus (CMV)-negative blood products should be given because of their weakened immune systems.

Seizures are the next concern. The parathyroid glands regulate the amount of calcium in the bloodstream. When they are absent or deficient, calcium can fall to dangerously low levels. This can cause severe seizures or even death, typically in the first or second month of life. If diagnosed, this problem can be prevented with appropriate calcium supplementation and/or the addition of a vitamin D substitute.

If babies survive the heart problems and seizures of the first several months, they begin to display an increased susceptibility to infections such as pneumonia, infectious diarrhea, and severe thrush. This immunodeficiency is the long and difficult battle of the DiGeorge anomaly. It stems from a missing or defective gland that most people haven’t even heard of — the thymus.

Named for its resemblance in shape to a thyme leaf, the thymus is located immediately beneath the breastbone. This organ is relatively huge during the first few years of life (even before the baby is even born). By puberty, it starts to shrink and disappear. If the thymus is found and removed from an adult, there is little or no consequence; however, if the thymus is removed from a newborn, severe immunodeficiency results.

The thymus is like a school for lymphocytes, a type of white blood cell. It is here that they are trained and equipped to fight disease. While the numbers of lymphocytes may be normal in the DiGeorge anomaly, the lymphocytes don’t know how to recognize or respond to infections. In the majority of children with the DiGeorge anomaly, the lymphocytes eventually learn, and these children eventually develop normal immune system functioning, but much slower than in children without the DiGeorge anomaly.

In the meantime, they are susceptible to fatal infections.

Children with poor T and B lymphocyte functioning should be protected by receiving IVIG (intravenous antibodies) every 3 or 4 weeks. Trimethoprim-sulfamethoxazole (Septra, Bactrim, or Sulfatrim) can be used to prevent severe pneumonias. Avoid all live-virus vaccines in these children and their close contacts. When infections are detected, they should be treated promptly.

Basic issues, such as adequate sleep, good nutrition, and frequent hand washing, are of heightened importance to children with the DiGeorge anomaly to give their immune systems the best footing possible. Multivitamins are a good idea, and you may want to consider acidophilus and lactobacillus. I recommend live, active-culture yogurt. By keeping healthy, beneficial bacteria in the gut (especially after all the antibiotics so often required), these children are better able to ward off infection. Herbal supplements, such as echinacea and goldenseal, may be of some benefit, although this remains unproven.

Like most conditions, the DiGeorge anomaly comes in varying degrees of severity. Children who respond well to a test called the phytohemagglutinin stimulation test or who have adequate numbers of CD4+ T lymphocytes are almost certain to develop normal or near-normal immunity in the long run. This includes about 75% of children with the DiGeorge anomaly (Seminars in Hematology 1998; 35(4):282-290).

If the immunodeficiency is severe or not expected to improve, both bone marrow transplant and thymus transplant have shown great success in some children (Immunodeficiency Review 1991; 3(1):1-14). More recently, lymphocyte transplantation has been successful (Lancet 1998; 352(9145):1983-1984). Interestingly, the very defect that renders these children’s lymphocytes ineffective also makes these children less likely to reject a transplant. At the same time, though, it makes them susceptible to something called graft-versus-host disease (GVHD), in which the foreign tissue attacks the child (this is also the earlier-mentioned problem with normal blood transfusions in children with DiGeorge anomaly).

Children with DiGeorge, also have an increased chance of developmental delay, special school needs, and mental health needs (Current opinion in allergy & clinical immunology, 4(6), Dec 2004, 505-512). Parents and doctors should monitor for any signs of developmental or emotional difficulties so that early intervention can be pursued if needed.

Living with the DiGeorge anomaly means facing one ordeal after another. The difficulties of the first few years seem to be never ending. Before the advent of modern medical and surgical techniques, these children had no chance for survival. Today, once children make it through the first 6 years or so, the emerging strength of their immune systems begins to win the day, and the long night watches of early childhood recede into the past as battles well fought and well worth it.

Dr. Greene’s Answer:

Hemihypertrophy, also called hemihyperplasia, is a greater-than-normal asymmetry between the right and left sides of the body. Hemihypertrophy can occur as an independent condition (isolated hemihypertrophy) or as a part of a genetic syndrome (i.e. Beckwith-Wiedemann syndrome). Because hemihypertrophy is a disorder of the body’s normal controls of growth, it is not surprising that people with this condition can also have a higher rate of cancer.

In one study, 168 children with isolated hemihypertrophy were very carefully followed to try to determine the true rate of cancer in children with this condition. Just under 6% developed childhood tumors (American Journal of Medical Genetics, 1998; 79:274–278). The most common cancer is Wilms’ tumor (of the kidney), followed by adrenal carcinoma and liver cancer (hepatoblastoma).

Because most of the cancers occur in the abdomen, the recommendation has been made (by the participants of the First International Conference on Molecular and Clinical Genetics of Childhood Renal Tumors–among others) that children with hemihypertrophy receive a screening abdominal ultrasound every 3 months until age 7 and, at minimum, a careful physical examination every 6 months until growth is completed (I prefer ultrasound). One proposed exception to this recommendation is in hemihypertrophy due to Klippel-Trenaunay Syndrome– the risk of Wilm’s tumor does not appear to be increased in these cases (Pediatrics 2004; 113:326-329).

Some argue that screening for cancer in children with hemihypertrophy is not cost effective because most children do not get these tumors and, even for those who do, these tumors are fairly easy to treat even if caught late. Be that as it may, if it were my child, I would insist on the screening.

Dr. Greene’s Answer:

Vonda, I’m so glad you asked! Most people are not aware of this medical condition. Hemihypertrophy, also called hemihyperplasia, is a greater-than-normal asymmetry between the right and left sides of the body. This difference can be in just one finger; just one limb; just the face; or an entire half of the body, including half the brain, half the tongue and the internal organs, or any variation in between. Someone with hemihypertrophy might have acne on only one side of the face. The skin is often thicker, and there may be more hair on the head, on the larger side. Rarely, children can have crossed hemihypertrophy (one leg and the opposite arm are larger than their partners).

Theories abound as to the cause of hemihypertrophy- perhaps it is increased blood flow or decreased lymph drainage, or nerve or hormone abnormalities. To date, not enough research has been conducted to choose between the theories. We don’t know the cause, but we do know that hemihypertrophy is usually not inherited. People with hemihypertrophy can go on to have healthy, normal children (Genetic Counseling, 1993; 4:119–126).

Hemihypertrophy is a key warning to be on the lookout for several kinds of cancers. Sadly, hemihypertrophy is often not looked for and not diagnosed until after the cancer has been discovered.

None of us is exactly symmetric. I recall seeing a series of fascinating magazine photos of famous movie stars. The photos were made by putting together 2 right sides and 2 left sides of their faces. It was surprising how much this changed their appearances. I had not noticed the asymmetry until it was removed.

During World War II, a series of United States Army recruits was carefully measured, and only 23% were found to have legs of equal length. The average difference was a little more than 1/4 inch (American Journal of Roentgenology, 1946; 56:616–623). One of our ears is usually higher than the other. The two eyes are slightly different. Only rarely are two nipples at the same height and the same distance from the midline.

All of us are asymmetric, and where normal variation ends and hemihypertrophy begins is controversial. Nevertheless, the distinction is very important because hemihypertrophy carries real risks. A definition first proposed over 20 years ago still seems to me to be the best general guideline: hemihypertrophy is a 5% or greater difference in size or length between some aspect of the right and left sides of the body (Clinical Orthopedics, 1979; 144:198–211). This translates into a leg-length difference of about 1/2 inch for a 1-year-old, about 1 inch for a 5-year-old, and about 1-1/2 inches for an adult.

As children with hemihypertrophy grow, the discrepancy between the two sides increases, but the relative proportions between the two sides usually remains the same over the long haul. Variations are found among different children, but in most children, the discrepancy about doubles between the first and fifth birthdays, which sounds like what has happened in Jemma.

Hemihypertrophy can occur as an independent condition (isolated hemihypertrophy) or as a part of a genetic syndrome (i.e. Beckwith-Wiedemann syndrome). Isolated hemihypertrophy is thought to occur in about 1 in 86,000 people, but this number may change as there is more agreement on a definition and more people looking for it. Some children with hemihypertrophy also have a genetic syndrome, such as Beckwith-Wiedemann syndrome, neurofibromatosis, Klippel-Trenaunay-Weber syndrome, or Proteus syndrome. Although these occur in the minority of children, each child with hemihypertrophy should be evaluated by a geneticist to look for associated conditions. Inguinal hernias, undescended testicles, and unusual kidneys (renal cysts or horseshoe-shaped kidneys) are more common in children with hemihypertrophy whether or not they have other syndromes.

Because hemihypertrophy is a disorder of the body’s normal controls of growth, it is not surprising that people with this condition can also have a higher rate of cancer. In one study, 168 children with isolated hemihypertrophy were very carefully followed to try to determine the true rate of cancer in children with this condition. Just under 6% developed childhood tumors (American Journal of Medical Genetics, 1998; 79:274–278). The most common cancer is Wilms’ tumor (of the kidney), followed by adrenal carcinoma and liver cancer (hepatoblastoma).

Because most of the cancers occur in the abdomen, the recommendation has been made (by the participants of the First International Conference on Molecular and Clinical Genetics of Childhood Renal Tumors–among others) that children with hemihypertrophy receive a screening abdominal ultrasound every 3 months until age 7 and, at minimum, a careful physical examination every 6 months until growth is completed (I prefer ultrasound). One proposed exception to this recommendation is in hemihypertrophy due to Klippel-Trenaunay Syndrome– the risk of Wilm’s tumor does not appear to be increased in these cases (Pediatrics 2004; 113:326-329).

Some argue that screening for cancer in children with hemihypertrophy is not cost effective because most children do not get these tumors and, even for those who do, these tumors are fairly easy to treat even if caught late. Be that as it may, if it were my child, I would insist on the screening.

The next most immediate concerns are the orthopedic problems that result from any leg-length discrepancy. Over time, scoliosis, or curvature of the spine, commonly develops. This disappears when the leg lengths are equalized, either with surgery or with special shoes or lifts. Close contact with a skilled pediatric orthopedist is a must.

Plastic surgery for facial discrepancies is sometimes warranted. The best people to contact are a craniofacial team or perhaps the people who repair cleft lip and palate in your area if no one has experience with hemihypertrophy. Computed tomography (CT) scans and computers can now be used to plan the repair for the best outcome (Journal of Oral and Maxillofacial Surgery, 1987; 45:217–222).

These, Vonda are the major issues. I’d be happy to talk with you more about them in chat.

Dr. Greene’s Answer:

Hemihypertrophy, also called hemihyperplasia, is a greater-than-normal asymmetry between the right and left sides of the body. This difference can be in just one finger; just one limb; just the face; or an entire half of the body, including half the brain, half the tongue and the internal organs, or any variation in between. Someone with hemihypertrophy might have acne on only one side of the face. The skin is often thicker, and there may be more hair on the head, on the larger side. Rarely, children can have crossed hemihypertrophy (one leg and the opposite arm are larger than their partners).

Theories abound as to the cause of hemihypertrophy- perhaps it is increased blood flow or decreased lymph drainage, or nerve or hormone abnormalities. To date, not enough research has been conducted to choose between the theories. We don’t know the cause, but we do know that hemihypertrophy is usually not inherited. People with hemihypertrophy can go on to have healthy, normal children (Genetic Counseling, 1993; 4:119–126).

Hemihypertrophy is a key warning to be on the lookout for several kinds of cancers. Sadly, hemihypertrophy is often not looked for and not diagnosed until after the cancer has been discovered.

Dr. Greene’s Answer:

Robi, most parents hold the deep, unquestioned belief that over the next several years we will watch our children grow ever more independent and more mobile as they walk out of our homes into the world beyond. This poignant, long departure that begins at the moment of birth provides a bittersweet backdrop to the many wonderful moments when our children are young.

How jarring, how deeply wrong, it must feel for you to be told that your teenage daughter is going to become progressively less mobile, will soon be wheelchair bound for life, and — at the time she is becoming an adult woman — needs to be cared for at a hospital for crippled children! You are in a discouraging and bewildering situation. Let me tell you what I know of her condition. I’m sorry that you both have to face this, but there is hope with the treatment options now available.

In the palms of our hands and the soles of our feet, we each have a tough fibrous layer called fascia (the palmar fascia and plantar fascia, respectively). In Dupuytren’s contracture (pronounced du-pwe-trahns), one or both of these fibrous layers begins to grow awry. In palmar fibromatosis (“classic” Dupuytren’s contracture) the palmar fascia slowly begins to thicken, and then shorten. The fingers are relentlessly drawn inward into a rigid, misbegotten fist. As flexibility slips away, so does the useful functioning of the hand. In plantar fibromatosis, this same relentless shortening happens in the soles of the feet, drawing the toes downward, folding the feet into a frozen fist, and making it impossible to walk. The foot version is much less common. Either way, untreated Dupuytren’s contracture can be a crippling disease.

Dupuytren’s contracture was first described by Baron Guillaume Dupuytren, a celebrated French surgeon of the early 1800′s who was apparently successful with the surgical treatment of this condition. By carefully cutting the involved fascia he was able to achieve good results — for a while. Whatever had caused the fascia to grow incorrectly before, caused the regrowing fascia to eventually shorten and thicken as well. Thus, for over 100 years the condition was thought to be relentlessly progressive. We now know that it can follow many courses, from quite mild to very severe. There are also more effective treatment options than ever before, and there is real reason to have hope for Jaymie.

Dupuytren’s contracture is a genetic condition that is passed as a dominant trait with “variable penetrance.” This means that, if it runs on your side of the family, it is present in someone in every generation, although it may be so mild as to go unnoticed. Either you or her father must have it, Robi, and one of your parents must have it as well — although neither of you may ever have any symptoms from it at all. Whoever carries this gene will pass it along to about half of his or her offspring.

The real problem in Dupuytren’s contracture is with the DNA in the cells of the fascia. DNA provides the blueprint that instructs the fascia how to grow. Fascial cells with abnormal DNA will eventually produce abnormal fibrous tissue time and time again. Really, then, Dupuytren’s contracture may be classified as a benign tumor of the fascia. I expect that gene therapy will be developed during Jaymie’s lifetime that will correct the root problem and make treatment effective and permanent.

Already, today’s surgical techniques provide better treatment than ever before. By means of electron microscopy and DNA analysis, physicians can differentiate between normal fascia and normal-appearing fascia that will one day cause trouble. By carefully removing all of the involved plantar fascia with a wide margin of normal fascia, surgeons at Brown University have had excellent results in treating plantar fibromatosis (Plastic and Reconstructive Surgery, Feb 1989). Since 1989, other surgical techniques have been developed with positive results. If and when Jaymie undergoes surgery, I would insist on a team with experience treating her condition.

The continuous elongation technique, pioneered by Doctors Messina and Messina of Turin, Italy, is a more recent development in the treatment of Dupuytren’s contracture that appears to further enhance both short- and long-term results (Plastic and Reconstructive Surgery, Jul 1993). Here, a device is affixed to a bone in the hand or foot to provide a steady, painless stretching of the contracting fascia. This preparatory step is used in severe Dupuytren’s contracture before excision of the affected fascia (Journal of Hand Surgery, Jun 1996).

A fortuitous observation gave rise to another line of therapy for Dupuytren’s contracture: the contracture tends not to recur beneath a skin graft! (This suggests to me that the DNA of the overlying skin may be involved somehow in the condition). In those patients with a strong inherited tendency to the production of Dupuytren’s contracture, recurrence may occur or even be anticipated, and the placement of a skin graft strategically at a flexion crease is shown to act as a ‘firebreak’ between areas of potential flare-up of recurrent Dupuytren’s disease. These skin grafts (also called ‘Firebreak’ grafts) are now in use as a means of controlling recurrent Dupuytren’s disease (Australia and New Zealand Journal of Surgery, Jun 1984).

The nonsurgical treatments, radiotherapy and injections of superoxide dismutase, have now been shown not to work. But high potency topical steroid ointments may be of some benefit (Lancet, Aug 1993). On the theory that the DNA damage may be the result of an auto-immune problem (i.e. her body’s immune system is attacking her own fascia), clobetasol ointment has been massaged into the skin above contractures, apparently halting, or at least stalling, the progression of the disease. Recent studies using collagenase injections have been promising (Journal of Hand Surgery, July-Aug 2007).

Dupuytren’s contracture is usually thought of as a disease of the elderly. The condition is very rare in children. In fact, the report on largest grouping of these children that I am familiar with appeared in the Journal of Hand Surgery (February 1996). It described only 9 children (all of whom, by the way, were treated with surgery by age 14).

With most of the questions I receive, I have at least some firsthand knowledge of the condition, either from medical school, residency, or pediatric practice. I have never met a child with Dupuytren’s contracture, and my knowledge is limited to what I have read and learned in lectures.

I was able to find in the National Library of Medicine database 199 articles on Dupuytren’s contractures. I reviewed all of these for which abstracts (in English) were available, and have passed along the highlights to you. You can find citations for all of the articles at: http://www.nlm.nih.gov/databases/index.html

It is my hope that physicians with direct knowledge of this condition will share their experience with us, and I will be sure to pass along to you anything I receive.

I also hope that this information at least gets you started on the path out of your bewildering situation. The future is not at all clear. The images of your child, wheelchair bound for life, may well not be real. This will likely be a long battle, but a combination of contracture release surgery, continuous stretching, firebreak grafts, and perhaps some topical medicines, holds some real promise. And over the next decade, genetic treatment of the underlying problem may powerfully and effectively correct Jaymie’s underlying condition.

All the best,

Note: We received a helpful letter from a reader here at drgreene.com who wished to pass on some information about a new minimally invasive surgery for Dupuytren’s Contracture called “needle aponevrotomy” or “needle fasciotomy”. This is not a pediatric surgery, however if you are interested you can learn more about the surgery at www.dupuytrenscenter.com.

Dr. Greene’s Answer:

In the palms of our hands and the soles of our feet, we each have a tough fibrous layer called fascia (the palmar fascia and plantar fascia, respectively). In Dupuytren’s contracture (pronounced du-pwe-trahns), one or both of these fibrous layers begins to grow awry. In palmar fibromatosis (“classic” Dupuytren’s contracture), the palmar fascia slowly begins to thicken, and then shorten. The fingers are relentlessly drawn inward into a rigid, misbegotten fist. As flexibility slips away, so does the useful functioning of the hand. In plantar fibromatosis, this same relentless shortening happens in the soles of the feet, drawing the toes downward, folding the feet into a frozen fist, and making it impossible to walk. The foot version is much less common. Either way, untreated Dupuytren’s contracture can be a crippling disease.

Dupuytren’s contracture was first described by Baron Guillaume Dupuytren, a celebrated French surgeon of the early 1800′s who was apparently successful with the surgical treatment of this condition. By carefully cutting the involved fascia he was able to achieve good results — for a while. Whatever had caused the fascia to grow incorrectly before, caused the regrowing fascia to eventually shorten and thicken as well. Thus, for over 100 years the condition was thought to be relentlessly progressive. We now know that it can follow many courses, from quite mild to very severe. There are also more effective treatment options than ever before, and there is real reason to have hope.

Dupuytren’s contracture is a genetic condition that is passed as a dominant trait with “variable penetrance.” This means that, if it runs on your side of the family, it is present in someone in every generation, although it may be so mild as to go unnoticed.

Note: We received a helpful letter from a reader here at drgreene.com who wished to pass on some information about a new minimally invasive surgery for Dupuytren’s Contracture. This is not a pediatric surgery, however if you are interested you can learn more about the surgery at www.dupuytrenscenter.com.

Dr. Greene’s Answer:

Pregnancy is one of the most vivid seasons of human life, a time when a woman is sharing an experience with her ancestors all the way back to those before recorded history. In just this last generation, many women have added an intense new moment to the experience of pregnancy — the prenatal ultrasound.

During the prenatal ultrasound, as a mom sees and hears the beating of her baby’s heart, the growing bond with her unborn child is accelerated. For many dads, this is the first moment that they are aware of bonding. It’s powerful to see that your baby is alive and okay. Parents look on with delight as the ultrasonographer points out the head, the hands and the feet. Usually.

For some parents, the ultrasound is the clenching moment when they first discover something is not going right. The mother you describe must have seen a baby with a normal head and face, a normal heart, but no arms and legs. Thus began her long and difficult process of preparing to welcome this particular baby into the world.

Grebe syndrome is a very rare form of short-limbed dwarfism. It is a genetic condition, passed by autosomal recessive inheritance (both parents carry a recessive gene, and 1/4 of their offspring will be affected). The largest cluster of people with Grebe syndrome are in Brazil. The condition was first described in 1952, and initially called achondrogenesis — Brazilian or Grebe type. Today Grebe syndrome bears the name of its discoverer. It is very closely related to a number of other forms of dwarfism, some of which are associated with other major medical problems. Misdiagnosis is common. In one series of three patients with Grebe syndrome (which is a lot for this rare disease), two of them later turned out to have other, more serious types of dwarfism (Journal of Pediatrics, Dec 1977).

Children with Grebe syndrome have normal intelligence, normal emotions, and go through puberty normally. In fact, the only consistent abnormality is missing or greatly shortened limbs. In the most common form, children have extremely short lower legs and arms, with little nubbins of fingers and toes on the ends. Most walk relatively normally.

The situation of the little girl you describe is quite severe. Being born without arms and legs will affect everything that new person does forever. There will be no grabbing a crayon and coloring a picture for Mommy — there will be no grabbing anything. There will be no soccer games, no running in the grass, no climbing a tree.

Raising a child with no arms and legs takes extraordinary care and attention. Most parents are used to the round-the-clock responsibility of having to feed and change a baby, but know that one day the baby will begin to feed herself and go to the bathroom by herself. Kids without arms and legs will always need someone to feed them and change them. Thankfully, there are exciting new devices being developed all the time that can make a tremendous difference in the lives of children. Sophisticated artificial limbs might be an option, depending on the anatomy. A boy I knew who had lost all use of his arms and legs was soaring on cloud nine when he got a new computer/typewriter designed for him. He was able to type simply by looking at the letters on the keyboard.

Working with scientists and physicians (especially physiatrists) at the university, the child you’ve asked about can be fitted with the best devices to help at each stage of growth. It’s possible that creative surgery might also improve her capabilities.

A long road lies ahead. I’m glad that the mother, her family, and the community can begin now to welcome this special child and to help facilitate a unique and rich life. Thanks, Jay, for your vital role in supporting and encouraging the community’s role in the process.

Dr. Greene’s Answer:

Melissa, quite a lot has happened since I wrote you last week. On Wednesday, I drove about an hour and a half to Santa Rosa, California to be present when my sister had a baby. She had had a dream pregnancy, but the baby was in a breech position. A cesarean section was scheduled for 7:45 Wednesday morning, and I was able to schedule to be there — as her brother, not her pediatrician.

As I was driving, Melissa, I remembered your sorrow. I hoped that another child would be able to have you as a mother. I reflected on what a miracle it is whenever a healthy baby is born. Pregnancy and gestation are so complex. Human life is so fragile and strong and beautiful. What a privilege to see a baby come into the world.

When I arrived at the hospital, three generations of Greene’s were gathered, tingling with excitement at the magic that was about to happen. We filled the waiting room. My sister and her husband had decided on Brandon Alan if he were a boy, and Brooke Michelle if she were a girl.

When the time came, I went into the operating room with my sister (along with her husband and parents). My job was the video camera, to record memories of one of life’s greatest moments.

Through the lens, I saw her perfect legs and bottom first. “It’s a Brooke Michelle, and she’s beautiful!” I announced. “Congratulations!!!”

Then the obstetrician cautioned, “She has a little cleft lip.” I saw my father’s face fall, and felt a chill in my own heart. Suddenly the moment didn’t seem perfect. I knew that modern cleft lip repair has spectacular results, but it felt as if a bubble had burst.

I rushed to the warming bed where the pediatrician was giving baby Brooke Michelle some oxygen. Was this some kind of nightmare? It looked as if she had trisomy 13!

Arrangements were made to transport Brooke to a university medical center. My sister (as is the standard practice when babies are transported) was left behind, a hollow loneliness replacing a lifetime of hopes and dreams.

As a side note, this practice of separating sick babies from their mothers is wrong. I can understand why insurance companies say that co-transporting the mothers “is not a covered benefit,” but my goal is to overturn this accepted barbarism. In my sister’s case, with much effort we were able to get her transferred an interminable day later. But back to more immediate concerns…

Within hours, the diagnosis was confirmed — trisomy 13. Dreams of her first tentative steps, her first spoken “Mama,” her playing happily in a park, her entire future, all vanished. This was a nightmare from which we would not wake up.

Less than a week ago, I wrote about a mom rocking her baby, knowing that he would die. Today I was in the rocking chair, holding my precious niece. She sucked on my little finger in rhythm with our rocking, cuddling in close. It was a moment that seemed at once endless and slipping away all too fast. The fullness of love and sorrow suffused my heart, and once again I knew that I would never be the same.

Looking at Brooke’s misshapen face, I recalled that all babies’ faces looked like hers early in development. It’s just that most continue to grow and change, and hers didn’t.

My children were introduced to Brooke that first evening, one at a time. Each one’s genuine response was, “She’s beautiful!” I love how they could see her preciousness and not be distracted by her looking different from other babies.

I drove back to see my sister later that first night, and along with everything else, I could see a searching guilt in her eyes. What had she done to make this happen? Was it something she had eaten? A virus she had? Was it the time that she had fainted?

No. No. No. Trisomy 13 is an extra copy of the 13th chromosome that slips in at the moment when the sperm and egg join. Nothing that happens later can change that unalterable fact. Most embryos with trisomy 13 do not survive to be born. Most who are born have mothers, like my sister, who took exquisite care of themselves — not who did something wrong.

Melissa, I am thrilled that your chromosome tests came back normal. This indicates that Quinten’s translocation began with him, a spontaneous event at conception. I do recommend meeting with a geneticist to go over together as much as is known about your family history. The geneticist should be able to give you the risk of recurrence for your specific situation. In all likelihood, the risk of having another baby with trisomy 13 will be extremely low. No other pre-conception testing is available, or necessary. After conception, you can know for certain by 16 weeks, using a combination of ultrasound, CVS, and/or amniocentesis.

When I wrote you last week, I wanted to say something about how trisomy 13 children live on after they die in the way that they change those who love them — but I didn’t want to sound trite, or minimize your loss. Today, though, I’m not afraid to say it. Brooke Michelle and Quinten Gabriel will have a legacy that will ripple through generations to come. Those precious, brief lives have changed us with their searing intensity. I have always loved my sister, but today I love her with a fierceness and tenderness that aches sweetly in my marrow. I feel joined to my brother-in-law as never before. The borders of my heart have been stretched a little wider, to take in more of the beauty and tragedy that surrounds us all. None of us will ever be the same.

Let Quinten Gabriel’s life deepen your capacity for joy and for pain. Let it open you and connect you and make you willing to risk. And thank you, Melissa, for the uncanny way that you and Quinten Gabriel helped prepare me and my family for our little treasure.

N.B. A special fund has been set up in Brooke Michelle’s memory. Contributions can be made to the Brooke Michelle Fund for the Prevention of Birth Defects. This charity will be administered by the University of California San Francisco and will help fund medical research. Checks should be made out to: UC Regents–Brooke Michelle Fund. Mail should be addressed to the Brooke Michelle Fund, c/o Dr. Karin Vargervik, University of California San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0442.

Dr. Greene’s Answer:

Melissa, one of my most vivid memories from my pediatric residency was sitting with a mom while she rocked her son who was born with trisomy 13. We were in the Intensive Care Nursery at Children’s Hospital Oakland, surrounded by tiny premature babies in incubators. This boy was full term and normal size. While the other babies were all hooked up to mechanical ventilators, IV pumps, or other high tech equipment, this child was simply wrapped in a receiving blanket, cradled in his mother’s arms. As she gently rocked back and forth in the plain wooden chair, she knew that he would die within a day.

The fullness of motherhood was compressed into that day. A mother’s deep love for her son, her tender concern, her exquisite pain of separation, her comforting touch for a lifetime’s scraped knees, her worry for a lifetime’s dangers, her peace in their inseparable bond, all came together in that rich moment as she gazed upon her precious little boy.

Even when our children have normal life-spans, their childhoods vanish oh so quickly. When childhood is cut short, it is a gut-wrenching shock. Trisomy 13 (also called Patau Syndrome) occurs in up to 1 out of 5,000 newborns (Smith’s Recognizable Patterns of Human Malformation, Saunders 1988). Even the mildest forms of this syndrome can be devastating.

The 13th chromosome contains blueprints that direct a baby’s development in the early weeks following conception. When a child has an extra 13th chromosome (three copies, instead of two), as is the case in trisomy 13, the genetic messages are confused and contradictory – there’s just too much to juggle. This results in multiple significant defects in major organ systems. The brain is often the most severely affected. Children with trisomy 13 may also have abnormalities in the shape of their lips, eyes, ears, fingers, toes, and bones. It’s also common for these children to be born blind, deaf, and with no sense of smell. Taste and touch become the limited means by which a mother can convey an ocean of feeling.

Most children with trisomy 13 have some kind of heart defect, but a double-outlet right ventricle is not common. A normal heart has four chambers. Blood from the body enters the right atrium. From there, it flows into the right ventricle, whose strong muscular wall sends the blood out of the heart to the lungs (via the pulmonary artery). In the lungs, the blood is supplied with oxygen before it returns to the heart, entering the left atrium. From there, it flows into the left ventricle, whose mighty walls propel the blood out of the heart (via the aorta) to supply the rest of the body with oxygen.

In double-outlet right ventricle, the pulmonary artery and aorta both exit from the right ventricle. Thus, poorly oxygenated blood is used for the body’s main supply. The only exit from the left ventricle is a hole in the wall (called a ventricular septal defect) through which the oxygenated blood from the lungs can at least enter the right ventricle to blend with the depleted blood from the body before it leaves. In your son, a hole in the wall between the two atria (an atrial septal defect) also allowed mixing of the blood entering the heart. Double-outlet right ventricle occurs in less than 1 percent of children with congenital heart disease.

Trisomy 13 was first described in 1657, but four hundred fifty years of medical knowledge have not improved the outlook for children born with this syndrome. Most babies who are conceived with trisomy 13 die early in gestation. Of the babies who live to be born, about 44% die within the first month and 69% die by six months. Only 18 percent reach their first birthdays — and these have severe mental defects and seizures (Smith’s Recognizable Patterns of Human Malformation, Saunders 1988).

While we cannot cure trisomy 13, we have started to find ways to detect it early. Sometimes, a blood test, called the AFP (alphafetoprotein) or triple screen, may help a pregnant woman find out her baby’s risk of several diseases, including Trisomy 13. Trisomy 13 is often detectable on prenatal ultrasound as early as 10 weeks of pregnancy. Chorionic villous sampling can detect trisomy 13 by 12 weeks. Amniocentesis, usually performed after 16 weeks gestation, can give a definite answer if any question still remains.

Often, trisomy 13 is associated with older mothers. Even so, the risk of having another baby with trisomy 13 is usually very low — unless, as with your son, the trisomy 13 is a translocation. A translocation is not associated with mom’s age, but is a hereditary chromosome problem. The risk of recurrence in some types of (balanced) translocations can be quite high. The inheritance of trisomy 13 is very complex. By testing your blood and that of the baby’s father, a geneticist can give you the best available information for your situation.

Trisomy 13 is a desolate and difficult challenge that I wish you didn’t have to face. Melissa, your mother’s heart comes through in your search for information about your son. You are a mother in the fullest sense of the word.