|Born||Brooke Megan Greenberg
January 8, 1993
Baltimore, Maryland, United States
|Died||October 24, 2013
Baltimore, Maryland, United States
|Known for||"Syndrome X" disease|
Brooke Megan Greenberg (January 8, 1993 – October 24, 2013) was an American with Syndrome X from Reisterstown, Baltimore County, Maryland, who remained physically and cognitively similar to a toddler, despite her increasing age. She was about 30 inches (76 cm) tall, weighed about 16 pounds (7.3 kg), and had an estimated mental age of nine months to one year. Brooke's doctors termed her condition "Syndrome X".
Birth and early life
Brooke was born on January 8, 1993, to Jewish parents Howard and Melanie Greenberg at Sinai Hospital in Baltimore, Maryland, one month before her due date, weighing just four pounds (1.8 kg). She was born with anterior hip dislocation, a condition that caused her legs to be swiveled upward toward her shoulders; it was corrected surgically. Otherwise, Brooke appeared to be a normal infant.
In her first six years, she went through a series of unexplained medical emergencies from which she recovered. She had seven perforated stomach ulcers. She also suffered a seizure. This was followed by what was later diagnosed as a stroke; weeks later, no damage was detected. At age five, Brooke had a mass in her brain that caused her to go into a deep sleep (after confirmation that it was not a coma) for 14 days. The doctors diagnosed the mass as a brain tumor. She later awoke, and physicians found no tumor present. Brooke's pediatrician, Dr. Lawrence Pakula, states that the source of her sudden illness remains a mystery.
Over several years, the Greenbergs visited many specialists, looking for an explanation for their daughter's strange condition, yet there was no diagnosis of any known genetic syndrome or chromosomal abnormality. In 2001, when Dateline documented Brooke, she was still the size of a six-month-old infant, weighing just 13 lb (5.9 kg) at 30 inches (76 cm) tall. The family still had no explanation. Brooke's mother Melanie said, "They [the specialists] just said she’ll catch up. Then we went to the nutritionist, the endocrinologist. We tried the growth hormone…". The growth hormone treatment had no effect. Howard, Brooke's father, said, "I mean, she did not put on an ounce, or she did not grow an inch... That’s when I knew there was a problem." After the growth hormone administration failed, the doctors, unable to diagnose a known condition, named her condition Syndrome X.
The Greenbergs made many visits to nearby Johns Hopkins Children's Center and even took Brooke to New York’s Mount Sinai Hospital, searching for information about their daughter’s condition. When geneticists sequenced Greenberg's DNA, they found that the genes associated with the premature aging diseases were normal, unlike the mutated versions in patients with Werner syndrome and progeria.
In 2006, Richard Walker, PhD in endocrine physiology of the University of South Florida College of Medicine, said that Brooke's body was not developing as a coordinated unit but as independent parts that were out of synchronization. She was never diagnosed with any known genetic disorder or chromosomal abnormality that would help explain why. Her telomeres seemed to be shortening at the normal rate.
In 2009, Walker said, "There've been very minimal changes in Brooke's brain … Various parts of her body, rather than all being at the same stage, seem to be disconnected." Walker noted that Brooke's brain, for example, was not much more mature than that of a newborn infant. He estimated her mental age at around nine months to a year old. Brooke could make gestures and recognize sounds but could not speak. Her bones were like those of a ten-year-old, and she still had her baby teeth, which had an estimated developmental age of about eight years. Said Walker, "We think that Brooke's condition presents us with a unique opportunity to understand the process of aging." "Different parts of her body are developing at different rates, as if they were not a unit but parts of separate organisms," Walker explained. Dr. Walker did not say whether the genes responsible for development are the same ones responsible for aging.
Brooke Greenberg died on October 24, 2013, at the Herman and Walter Samuelson Children's Hospital at Sinai Medical Center in Baltimore (the same hospital where she had been born in 1993). Her funeral service took place on October 27, 2013, and that same morning, she was buried at Baltimore Hebrew Cemetery - Berrymans Lane, in Reisterstown, Maryland. The cause of her death was bronchomalacia, a medical condition usually occurring in children, which results in difficulty breathing due to weak cartilage in the walls of the bronchial tubes.
Dr. Walker believed that Brooke Greenberg's condition had resulted from a failure of central control genes. He identified two more people with similar developmental issues: Gabrielle Williams of Montana (born in 2004) and Nicky Freeman of Australia (born in 1970), a 44-year-old man who looks like a boy.
Gabrielle Williams's condition has since been determined to have been the result of a genetic mutation. Nicky Freeman has been diagnosed with deformity of the pituitary gland.
María Audenete do Nascimento, a Brazilian woman who lives in the town of Caucaia near Fortaleza in the state of Ceará, Brazil, was once thought to have also been suffering from a condition similar to Greenberg's. She was reportedly born in May 1981 but stopped growing after nine months. She has been diagnosed with severe hypothyroidism.
In May 2015, it was reported that Layla Qualls of Oklahoma looks like she is 9 or 10 months old, but is 3 years old. She is among 7 children worldwide with Syndrome X that are being studied by researchers at the University of California, Los Angeles. In their ongoing research they found that the blood of Syndrome X children appears to age normally.
Blood tissue from five other female syndrome X cases (whose average age was 6.3 years) turned out to be age appropriate  according to a biomarker of aging known as epignetic clock. The mean epigenetic age of the five pure syndrome X subjects was 6.7 years (standard error=1.0) which is not significantly different from the mean chronological age of 6.3 years (standard error=1.8). Notably, the oldest pure syndrome X case had an epigenetic age of 14.5 years which was 3.2 years older than her true chronological age. It is not yet known whether the epigenetic age of other tissues is also age appropriate in these cases.
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