Ectodermal Dysplasia

Even Before I laid Eyes on Daryn Jordan, I knew something was very wrong. That was five years ago. when Al Reynolds, a pediatric neurologist, called me after admitting the seven-month-old to our hospital. "The kid was doing fine until a month ago," Al had said. "His parents say he smiled, rolled over, sat up, and babbled. But now he's lost all those skills. When I first saw him, he was listless, cranky, and as floppy as a dishrag. Even when he is propped up, he can't sit, and the only sound he makes is this high-pitched cry. "He's degenerating," said. n "Seems like it," Al replied. "We're doing an EEG, an MRI, a spinal tap, and lots of blood work. I'd also like you to evaluate him to see if his problems are genetic."

I promised to see the boy immediately and headed over to the infants' unit. I found Daryn lying on his back, his outstretched limbs flaccid and still. His cry, a constant, high-pitched whine, was one I knew all too well. As a pediatric geneticist, I'd had the misfortune to hear those cries before - and they told me something was wrong with this boy's brain.

Daryn's posture and cry weren't his only troubling features. He had pale skin and dark circles under his eyes, and his head looked too large for his wasted body. I felt sure this baby had a neurodegenerative disease. I prayed that I was wrong.

Neurodegenerative diseases, a group of rare but devastating syndromes, are among the most dreaded disorders of childhood. Flawed genes result in deficiencies in specific enzymes, and the lack of those enzymes allows toxic chemicals to build up in the blood. These substances gradually accumulate in the liver, spleen, bones, and - most disastrously - the brain.

These disorders slowly destroy infants who seemed normal healthy at birth. A fetus with Tay-Sachs disease, for example, seems fine in the womb. Although the fetus lacks an enzyme that breaks down potentially harmful proteins, these proteins are removed from its blood supply through the cleansing action of the mother's normally occurring enzyme, which passes through the placenta. Only after birth, after the umbilical cord has been cut and the placenta no longer nourishes the infant, do these complex proteins slowly accumulate in the child's brain. Around six months after birth, the buildup makes its presence known through a gradual developmental slowdown. First die child stops sitting, then no longer rolls over. Within a few years, the child lapses into a coma and dies. Nothing can done to alter the disease's course.

Like most neurodegenerative diseases, Tay-Sachs occurs in children who have inherited faulty genes from two apparently healthy parents. Each parent bears one working copy of the enzyme-making gene and one defective copy. The amount of enzyme produced by the working gene - about 50 percent of that found in "normal" individuals - is enough to keep the parents in good health. But if a child inherits a flawed gene from each parent and thus cannot make the enzyme, he will have the disease. Such diseases are common in close-knit ethnic groups. Carriers of the Tay-Sachs gene, for example, are 100 times more common among Ashkenazi Jews than in the general population.

Daryn Jordan was not a member of any of the ethnic groups prone to these diseases. He looked African American, though I wasn't yet sure where his family was from. But it was all too clear that something was"' very wrong with him. As I stood over the boy with my eyes closed, I thought about the next step, the step I dreaded most. We would have to tell Daryn's parents that their son had a disease that would probably kill him before he turned five.

I was still standing over the crib with my eyes closed when a heavyset woman appeared at the door.

"What are you doing to my baby?" she asked in a voice that bore more than a hint of a Caribbean accent.

"I'm Dr. Marion. I'm a geneticist, a doctor who specializes in diseases that run in families. Dr. Reynolds asked me to see your son while he was here."

It's not anything that runs in our family that's causing my son to act like this," she replied, seating herself on a chair beside the crib. "He don't like the hot weather, and this room is pretty hot!"

She was right about that. New York City was sweltering in an early-summer heat wave, and the hospital's air-conditioning wasn't helping much.

"Has Dr. Reynolds told you what he's concerned about?" I asked.

"Oh, he told me an right," the woman replied. "He think my baby is storing some stuff in his brain that makes him act like this. Who ever heard of a disease like that?"

He's right," I said, smiling. I liked this woman, and that wasn't good - it would make it harder to tell her that her baby had a terminal disease. "There are diseases that can do that. They're very rare, and they tend to run in families. Is there anyone in either your family or Daryn's father's family who might have had anything like this - where they did okay for a while and then started to lose ground?"

The mother shook her head, and I began to take a formal family history. Mr. and Mrs. Jordan were in their early twenties, and Daryn was their first child. Both parents had come from families with eight to ten children. Most of the siblings had children of their own, but Mrs. Jordan said not one of those children had died during childhood, was mentally retarded, or had any problems like Daryn's.

The Jordans Had Been Born, raised, and married in a small town on the coast of Trinidad. Although Mrs. Jordan adamantly denied die possibility that she and her husband were cousins, she did admit that the town was so small and isolated that it was possible that she and her husband might be distantly related.

After I finished the pedigree, I explained to Mrs. Jordan that there was a good chance that Al Reynolds's impression was correct.

"We won't know for sure until we get the tests back," I explained. "Do you have any questions?"

She was silent for a few seconds. "Doctor, is Daryn going to die?" she asked.

I sighed. "I can't be sure. We'll have a much better idea when we get the tests back."

"Is there anything I can do to help him?" she asked, her eyes filling with tears.

"No," I replied. "If he has one of these diseases, nothing' we can do will make him any better." I hesitated, listening to her weep. Then I added, "The only thing you can do is pray that Dr. Reynolds and I are wrong."

I pulled one of my cards out of my pocket, handed it to Mrs. Jordan, and left.

We knew that diagnosing Daryn would not be easy. By the time he was discharged that afternoon, we already had the results of his spinal tap, EEG, and MRI. All were perfectly normal. Our ability to make a more precise diagnosis depended on the results of blood tests that would take weeks to complete. Al promised to schedule a meeting when an abnormal test came back.

Months passed. The torrid summer had turned into a mild autumn, and I'd heard nothing from Al Reynolds about Daryn or his test results. I'd almost forgotten Daryn completely when I received a call from the boy's mother in early November.

"Dr. Marion, I'm calling to tell you that your advice worked - I prayed, and now Daryn is better. My boy is sitting up and taking again. And now he is starting to stand. You and Dr. Reynolds were wrong. It's a miracle!"

"That's very nice," I replied, not believing a word she was saying. Denial is an almost universal stage in the mourning process through which Daryn's mother had to pass before accepting her son's condition. I had no doubt she was going through denial: once children with neurodegenerative diseases begin to lose skills, they never regain them.

Realizing that Mrs. Jordan would sooner or later need our support, I asked her to bring Daryn for a follow-up visit. After hanging up, I called Al Reynolds. "I just got off the phone with Daryn Jordan's mother," I told him. "Have you seen him recently?"

"Not since he left the hospital," he replied. "All the tests came back normal, so I don't really have anything to tell her. But I assume that by now he's probably close to vegetative." He spoke with the fatalism of one who has seen his share of merciless, undiagnosed degenerative illnesses.

"His mom says he's making progress - that he's starting to stand."

"Sure he is," said Al sarcastically. "I wish I knew what was wrong - at least we'd be able to give her a realistic picture of what the future's going to be like. Unfortunately, it looks like this is going to be one of those cases in which the diagnosis isn't made until we get a look at his brain on the autopsy table." "Well, I'm going to see I him in my office next week, just to keep track of him." "Let me know if I can help," he replied.

All Mrs. Jordan's praying must have helped, because Al Reynolds and I were dead wrong about Daryn. Mrs. Jordan wasn't denying her son's condition, nor was she lying about his progress. During the office visit, Daryn was standing, smiling, and holding tight to his mother's knee while she talked.

"Daryn was weak for months. Every morning I went to church and prayed. My husband said, Why you waste your time?' But I kept on. And then one morning, my son smiled at me; the next week, he began rolling over and started to crawl. After that, he was sitting up again. That's when I called you. He doesn't have that disease anymore, does he?"

I had to admit thai Daryn wasn't acting like a child with a neurodegenerative disease. But something still wasn't right. Although Daryn was bigger, stronger, and more alert than the child I'd seen five months before, he didn't look healthy. His skin was sallow and wrinkled, and there were still dark circles under his eyes.

But even more troubling features caught my eye now: Daryn was completely bald and toothless. While that is not unusual in a seven-month-old infant, it is rare in a one-year-old.

At that moment the pieces of the puzzle finally fell into place.

I began questioning Mrs. Jordan. "When exactly did he start to smile at you again? "

She thought for several seconds. "Toward the end of September."

"And he started to roll over and crawl in early October?"

She nodded.

"And he sat toward the end of October? "

That's right," she said. "And he started to stand last week. He's cured, right? The praying cured him."

"Not exactly cured," I replied, going on with the questions. "I notice he doesn't have any teeth or hair. Did he ever have any teeth or hair?)"

She laughed. "Dr. Marion you think I shaved off my baby's hair or pulled out his teeth? No, this is the way he is, the way he always has been."

"During the summer, did you notice if he ever sweat?"

"No, Daryn never sweats. Even on the hottest day of the year, he stays dry like a bone. Is that bad?"

"Not bad," I replied. It's just Daryn. Mrs. Jordan, do you sweat? "

"No. I'm like Daryn. I'm dry like a bone - and I hate heat. That's why we came to New York. It's not as bad here as it was back home. "

"Does your hair grow fast?"

"Grow fast?" she repeated with a laugh, running her hand through her short, wiry hair. "Dr. Marion, my hair doesn't grow at all. I haven't had it cut in more than a year."

"Do you have any trouble with your teeth? "

She thought for a few seconds. "No trouble. I still have some baby teeth, though. They never fell out. Is that bad? "

"Not bad," I replied. It's just you. You and Daryn. Mrs. Jordan, Daryn doesn't have a disease like the one Dr. Reynolds and I thought. He has a condition called hypohidrotic ectodermal dysplasia, which causes problems in structures that develop from the ectoderm - the outer layer of cells that forms in an embryo. That means Daryn has trouble making teeth and hair. All his life he will have thin hair that grows very slowly, and hell always be missing most of his teeth."

Mrs. Jordan looked shocked.

"People with this condition also lack the holes in the skin that allow them to sweat," I continued. "Without any sweat glands, Daryn can't sweat."

Her look of shock now turned into one of puzzlement. "No sweat glands? I never heard of such a thing."

"No, it's true," I told her, reaching for my genetics handbook and opening it to the section on hypohidrotic ectodermal dysplasia. "See?"

"These pictures do look a little like Daryn," she said. "But did my son catch this from someone?"

"I wouldn't say he caught it," I replied.

It's inherited, passed down from mothers who have mild symptoms to their sons, who are more severely affected. That's why I asked you about your hair and your teeth and your sweating. You have a mild case of it, but Daryn's condition is much worse."

Unlike Tay-Sachs, in which two copies of a flawed gene are inherited, Daryn's condition was sex-linked. That means that the defective gene are lies on one of the sex chromosomes - in this case, the X chromosome. Females are rarely badly affected by sex-linked disorders because one of their two X chromosomes usually carries a working copy of the gene. But males, who carry one Y chromosome and one X chromosome, suffer much more severe consequences if they inherit a defective gene on their lone X chromosome. Color blindness is a common sex-linked disorder. But Daryn's disorder was rare. Like hemophilia, another sex-linked disease, ectodermal dysplasia affects about one in 10,000 people.

Mrs. Jordon Stared At the Photo. "Well, my son does look like this - but Daryn had a brain problem last summer, not a hair or teeth or sweat gland problem."

"Sweat is the body's way of cooling off when it gets overheated," I explained. "If you don't have sweat glands, your temperature keeps going up, and eventually you just can't function anymore. When was it that you first noticed that Daryn was losing his ability to sit up?"

"In the middle of June."

"Just when it got hot. And he started getting better in September-"

When it got cool," Mrs. Jordan interrupted, understanding my point.

"'Right. Daryn's brain never degenerated. Because he can't sweat, his body just doesn't function well in the heat. He wilted like a flower that's been out of water too long, and he didn't come back to life until the weather cooled off."

And like a flower, Daryn Jordan blossomed through the next few years. Soon after that office visit, he was walking. When he was two, he was speaking short sentences, and when he was five, he entered kindergarten right on schedule.

Daryn and his mother have learned to cope with his condition. In the summer Mrs. Jordan carries a spray bottle of ice water and spritzes her son's forehead when he gets too hot. On the hottest days they go to the supermarket; playing in the chilly frozen-food section almost always perks Daryn up.

We take so much for granted. We understand what happens when our heart, lungs, or senses fail, but we rarely consider the importance of our more mundane bodily functions. Daryn Jordan's life will never be easy. He'll have to work much harder than those of us who can make our way through the world by the sweat of our brow.

COPYRIGHT 1995 Discover
COPYRIGHT 2004 Gale Group