Re: NY TImes~ After DNA diagnosis Hello 16p11.2.

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December 28, 2007

The DNA Age

After DNA Diagnosis: ‘Hello, 16p11.2. Are You Just Like Me?’

By _AMY HARMON_

(http://topics.nytimes.com/top/reference/timestopics/people/h/amy_harmon/index.h\

tml?inline=nyt-per)

The girls had never met, but they looked like sisters.

There was no missing the similarities: the flat bridge of their noses, the

thin lips, the fold near the corner of their eyes. And to the families of

14-year-old Napier and 4-year-old Taygen Lane there was something

else,

too. In the likeness was lurking an explanation for the learning

difficulties, the digestion problems, the head-banging that had troubled each

of them,

for so long.

Several of the adults wiped tears from their eyes. “It’s like meeting

family,†said Houk, ’s older sister, who accompanied her and

their mother to a Kentucky amusement park last July to greet Taygen.

But the two families are not related, and would never have met save for an

unusual bond: a few months earlier, a newly available DNA test revealed that

and Taygen share an identical nick in the short arm of their 16th

chromosomes.

With technology that can now scan each of an individual’s 46 chromosomes for

minute aberrations, doctors are providing thousands of children lumped

together as “_autistic_

(http://health.nytimes.com/health/guides/disease/autism/overview.html?inline=nyt\

-classifier) †or “developmentally delayed†with

distinct genetic diagnoses. The symptoms, they are finding, can be traced to

one of

dozens of deletions or duplications of DNA that were previously hard or

impossible to detect.

Some mutations are so rare that they are known only by their chromosomal

address: and Taygen are two of only six children with the diagnosis

“

16p11.2.â€

Few of these mutations were inherited in the traditional sense, and the

affected children are typically the only family member with the disorder. So,

many parents are searching out strangers struck by the same genetic lightning

bolt. They want solace, advice and answers to what the future might hold. From

other families of children with the same chromosomal anomaly, they are seeking

insight into their own. Sometimes what they find is unsettling. But in the

emerging communities of the genetically rare, more often it is sustaining.

For three families, the impulse to find others in the same situation was

immediate.

A few months before the Lanes crossed the state to meet Taygen’s chromosomal

cousin, Jennie Dopp, a mother in Utah, was scouring the Internet for

families with “7q11.23,†the diagnosis that explained her son’s odd

behavior and

halting speech.

“I want someone to say ‘I know what you mean,’†Ms. Dopp told her

husband,

“and really mean it.â€

Noa Ospenson’s parents flew from Boston to South Carolina for a meeting of

100 families with children who, like Noa, are also “22q13.†Hoping for more

information about their daughter’s diagnosis, they emerged as lifetime members

of what they call “Noa’s tribe.â€

For each of them, a genetic mutation became the foundation for a new form of

kinship.

: The Search

If one of his siblings is sitting at his place at the breakfast table,

screams. If a schoolmate gets too close to him, screams. If

someone interrupts him while he is speaking, screams.

“You ruined my talk!†shrieks the sweet-faced boy who must concentrate

intently to string his words together.

has been to so many sleep doctors because of a bone structure that

obstructs his airway that he wants to be one when he grows up. He talks to

himself in church. No matter how many times, or how gently, his father asks him

to play catch in the yard of their home in Layton, Utah, he refuses. He

prefers to play in his tree house, by himself.

“Don’t worry about it,†family members often told and Jennie Dopp

when

they recounted a difficult day with . “My kid is just like that.â€

“Your kids,†Ms. Dopp finally snapped at her sister one afternoon, “are

nothing like this!â€

But for the first seven years of his life, the Dopps could not figure out

what made different. They took him to neurologists and _psychologists_

(http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/psy

chology_and_psychologists/index.html?inline=nyt-classifier) . He had three

brain _M.R.I._

(http://health.nytimes.com/health/guides/test/mri/overview.html?inline=nyt-class\

ifier) ’s. And then there were the annual trips to the

geneticist.

About one in 500 children are born with a chromosomal disorder, the

geneticist, Dr. Alan Rope, told them. Such disorders are responsible for an

unknown

fraction of cases of _mental retardation_

(http://health.nytimes.com/health/guides/disease/mental-retardation/overview.htm\

l?inline=nyt-classifier) and

autism as well as _birth defects_

(http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/bir\

th_defects/index.html?inline=nyt-classifier)

like a cleft palate or heart and kidney defects. _Down syndrome_

(http://health.nytimes.com/health/guides/disease/down-syndrome/overview.html?inl\

ine=nyt-clas

sifier) , which occurs in individuals with an entire extra 21st chromosome

in addition to the usual pair, is the most common, and the easiest to

identify. But there were some 100 known disorders involving subtler

duplications or

deletions of pieces of chromosomes that were considerably harder to detect,

Dr. Rope said. And he could test for only one at a time.

_Fragile X syndrome_

(http://health.nytimes.com/health/guides/disease/fragile-x-syndrome/overview.htm\

l?inline=nyt-classifier) . -Magenis syndrome.

Velocardiofacial syndrome. Negative, negative, negative.

Desperate for a diagnosis, this February, the Dopps took to a

psychiatrist. He told them was autistic.

“Autism covers so much,†Mr. Dopp, a manager at American Express,

complained to his wife. “It doesn’t mean anything.†And did not

quite seem

like the other autistic children they knew.

Finally, at an appointment in March, the geneticist told them that a

technology known as DNA microarray analysis had become available and that it

could

test all known chromosomal disorders at once. At about $3,000, it was

expensive, but one of the major insurers in the state had just agreed to cover

it.

When Dr. Rope called to say that there was an extra stretch of DNA in the

middle of ’s seventh chromosome, the Dopps rejoiced. His oddness was

not

the result of bad parenting. Nor was he just a little “off,†as so many

people had suggested. Perhaps, Ms. Dopp dared to fantasize, there would one day

be a cure for her son. At least now they knew where to look.

But as the Dopps began to tell friends and family members about the source

of ’s disabilities, they grew frustrated.

“You say autism, or Down syndrome, and people know somebody,†said Ms.

Dopp, who stays home with and his three siblings. “When you try to

explain 7q to people and they barely know what a chromosome is, it’s hard.â€

And Dr. Rope had little to offer by way of practical information.

“He said was the only one he had ever seen,†Ms. Dopp told her

husband.

Although they had shied from autism support groups, now they yearned for

somewhere to fit in. Finally, Ms. Dopp called an acquaintance whose child had

Down syndrome. She had heard of an organization in Britain called Unique that

seeks to link families with rare chromosomal disorders.

Ms. Dopp immediately sent away for the registration material. In the packet

she received were the e-mail addresses of six other 7q11.23 families.

, she learned, was one of 11 known children in the world with the DNA

duplication. The Dopps were the only one of those families in Utah. She

wanted to meet them all. But for now, there was e-mail.

“We have seen occupational therapists, physical therapists, geneticists,

speech therapists, neurology, cardiology and eye doctors,†Ms. Dopp wrote.

“

Have you found certain therapies that work better than others? What doctors

have

you seen? Do you have any issues with intestinal problems, behavior, autism?â€

She could not type fast enough.

Taygen: The Meeting

The genetic counselor at the _University of Louisville_

(http://topics.nytimes.com/top/reference/timestopics/organizations/u/university_\

of_louisville/index.

html?inline=nyt-org) Hospital put Gaylene Napier and Lane in touch.

The deletion of DNA on their daughters’ 16th chromosome had never before

been detected.

In the fall, pictures of the girls would appear in a scientific journal: “

Discovery of a previously unrecognized microdeletion syndrome of

16p11.2—p12.2.â€

The first time the mothers spoke, they stayed on the phone for hours.

Taygen was learning to hop, Ms. Lane, an office administrator, told Ms.

Napier. Her occupational therapy was going well. Then Ms. Lane blurted out what

she never said to other mothers.

“I just hate that she has to struggle to do things that we all take for

granted,†she said.

The Lanes live in Benton, in western Kentucky. The Napiers live in Berea, on

the other side of the state. Immediately, they made plans to meet at Beech

Bend, an amusement park in the middle.

Ms. Lane stayed in a hotel room nearby the night before with her husband,

, and her mother, Debbie Duckett.

As Sami and Taygen rode the carousel together, Ms. Duckett peppered Ms.

Napier with questions.

Was Sami sensitive to small noises? Even a _cough_

(http://health.nytimes.com/health/guides/symptoms/cough/overview.html?inline=nyt\

-classifier) or a

sneeze can make Taygen shudder.

Sami, Ms. Napier said, makes her unplug the clock every night because she

cannot stand the ticking.

Taygen is often sweet and then nasty in bewildering succession.

Sami slaps you and then hugs you, Ms. Napier said. You never know what is

coming next.

Taygen does not cry when she is hurt.

Neither does Sami.

They had started trying to potty train Taygen. Sami, Ms. Napier said, had

learned when she was 7.

The head-banging and rocking had tapered off for Sami when she was a few

years older than Taygen, Ms. Napier said. But she still had painful

_constipation_

(http://health.nytimes.com/health/guides/symptoms/constipation/overview.html?inl\

ine=nyt-classifier) .

“Oh,†Ms. Duckett sighed. “I hoped she was going to grow out of that.â€

Ms. Lane could not take her eyes off Sami. She did not want to miss any

detail.

The 14-year-old Sami wore slip-on shoes, because she could not tie laces.

When she was concentrating, she hooked the tip of her index finger onto her

bottom front teeth and kept it there.

After splashing in the kiddie pool, Sami curled up in her mother’s _lap_

(http://health.nytimes.com/health/guides/test/leucine-aminopeptidase-urine/overv\

iew

..html?inline=nyt-classifier) as Ms. Napier wrapped her in a towel. Later,

Ms. Napier wiped her face as ice cream dribbled down her chin.

But she was different from Taygen. Sami had been given a diagnosis of mild

retardation. Not Taygen, who had had speech therapy and _physical therapy_

(http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/phy\

sic

altherapy/index.html?inline=nyt-classifier) starting at nine months.

Sami could count only to 14, and was just learning her colors. Taygen knew

all of her colors, though there were certain numbers, like “3,†that she

refused to say.

It got easier, Ms. Napier, a factory inspector, told them. Sami has fewer

tantrums. She had just recently learned her letters, matching each one to a

person she loved. “J†for “,†her sister. “C†for

“Carey,†her cousin.

Ms. Duckett asked Ms. Napier if Sami had started her period. They had

wondered if Taygen would be able to have children.

She had, Ms. Napier said, right on schedule.

But did she think, Ms. Duckett persisted, that Sami would ever grow up and

lead a normal life — have a home, a job, a car? “Or do you think these kids

will always be at home?â€

Ms. Napier looked at her. “I don’t know,†she said.

On the way home, Mr. Lane told his wife that he was sorry for Sami. Later,

he cried. He hated to think, he said, that Taygen would be like her one day.

But they knew so much more than Ms. Napier had, Ms. Lane told him. Who was

to say that Taygen would be just like Sami? “Besides,†she said. “Sami is

happy. She doesn’t know there’s anything wrong.â€

The following week, Mr. Lane moved out. It had nothing to do with the visit,

he said. He said he had been unhappy for years.

“Do you think we scared him?†Ms. Napier asked Ms. Lane when they next

spoke. She herself had been divorced when Sami was about Taygen’s age.

Maybe, Ms. Lane said. But then, weren’t they all scared?

Ms. Napier sent pictures of the girls from that visit. Ms. Lane keeps her

favorite one on her desk.

Noa: The Tribe

The hotel atrium was teeming with 22q13 children. Some were flapping or

crawling on the floor. Some were in wheelchairs or oversize strollers. Others

were in their parents’ arms. They were making sounds like Noa made, a guttural

growl hovering on the edge of language, the kind of sound that made Noa’s

father, Jim Ospenson, yearn all the more to hear her voice.

Noa, now age 4, does not speak.

In the month since Noa had been designated “22q13,†her parents, Mr.

Ospenson and Meryl Perlson, had already found two other children with the same

chromosomal deletion.

They had read the Web site, recently assembled by the 22q13 Deletion

Foundation, whose numbers were growing rapidly along with the accuracy of DNA

diagnoses.

And then they went to the biennial meeting of 22q13 families in July 2006.

But that first day, in Greenville, S.C., they wondered if they had made a

mistake.

Few of the children, even the handful of teenagers, were toilet trained.

Some had never gained the use of their hands, which had stiffened into a

claw-like shape. Many were chewing on rubber tubes or “chew rags,†to keep

them

from shredding their clothes.

Ms. Perlson, a communications consultant, and Mr. Ospenson, a computer

analyst, attended sessions on one of the genes that Noa is missing, which codes

for a protein crucial to neurological development. They learned about the

health problems, like _seizures_

(http://health.nytimes.com/health/guides/symptoms/seizures/overview.html?inline=\

nyt-classifier) and _kidney failure_

(http://health.nytimes.com/health/guides/disease/acute-kidney-failure/overview.h\

tml?inlin

e=nyt-classifier) , that Noa might face in her 20s. The window onto her

future was hard to digest.

But outside the lecture rooms, they found, unexpectedly, that they were

enjoying themselves. Ms. Perlson’s mother, Briller, made friends with

Morton, a chunky 10-year-old who grabbed at passers-by from his wheelchair and

tried to hold their hand. His parents had come from Denmark, and the family

spoke little English. But on a number of occasions, Ms. Briller walked with

Morton through the halls as he held tight to her arm. “I felt attached to him,

like he was the same as Noa ,†she told her daughter.

In the area behind the hotel, Mr. Ospenson watched another father play catch

with his older son as his 22q13 son roamed around the grass. At the bar on

the second evening, Ms. Perlson sat with a group of mothers. One told a story

about being pulled over by a state police officer while speeding. In her car

were several large packages of adult diapers, the size her 22q13 child now

wore. The police officer did not seem to want to contemplate the explanation.

He waved her on.

Everyone laughed. And for the first time that weekend, Ms. Perlson did, too.

“Oh, my God,†she thought, “maybe this is going to be O.K.â€

The next day, Mr. Ospenson and Ms. Perlson watched Noa play on the floor

with several other children. Some of them, because of the low muscle tone

associated with the syndrome, flopped over. They all had the hallmark

appearance of

the syndrome, the flaky toenails, puffy eyes and cheeks, long eyelashes.

Looking at them, Mr. Ospenson said, made him think less about 22q13 for a

moment than about how such a tiny bit of missing DNA could make such a big

difference in how humans work.

He found himself looking forward, he said, “to seeing those kids grow up

alongside my own.â€

E-mails to Amy Harmon about this series may be sent to: dna@nytimes

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