The Impossible Girl
Imagine celebrating your birthday every year, yet physically looking the same without fail. Imagine aging in the present time, but having the mental capacity of an infant. This was the reality for a girl named Brooke Greenberg.1 Despite doctors and scientists working together to solve the problem and analyzing similar cases, her case remains a mystery, and her disease remains named ‘Syndrome X’ as the exact cause of her condition is still unknown.
Brooke Greenberg’s case of Syndrome X is a clear example of a developmental disorder. Developmental disorders are a very common occurrence in today’s day and age. This group of conditions is categorized by impairments regarding physical and behavioural areas. The Centers for Disease Control and Prevention (CDC) estimates that one in six children have one or more developmental disabilities. Developmental disabilities can begin during development in early childhood and are often triggered by stress-related events. Parental health also plays a major role; mothers who smoke or drink alcohol during pregnancy greatly increase their child’s chance of developing a disorder.2 Over decades of research, scientists have begun to understand the complex nature of these conditions. The two major theories within the world of developmental disorders involve genetic differences and chromosomal abnormalities.1 Human cells contain their genetic information within DNA, which is further packaged into chromosomes. This genetic code is a result of a combination of the DNA of the mother and father. When this recombination occurs, problems within the DNA code of an individual can arise; this can lead to errors within the genetic code such as deletions, or whole chromosome errors such as having an extra chromosome or missing a chromosome. A well-known example of a chromosomal abnormality is for the condition of Down Syndrome, in which the individual possesses an extra copy of chromosome 21.3 Although, many such developmental conditions are manageable. For instance, autism spectrum disorder and attention hyperactivity disorder and most children affected by these types of conditions go on to lead a normal life within society.2 This may be through the help of medication or therapy sessions, which teach the individuals how to function within society. However, for individuals such as Brooke Greenberg, leading a normal life is nearly impossible and attest to the difficulty of her disease.
Brooke Greenberg was born with a number of developmental dysfunctions, which included bilateral hip dislocations, abnormal brain development, and other dysmorphic features. However, the most puzzling aspect of her case was the fact that her physical and mental functioning abilities were dangerously delayed, and this continued until her death at 20 years of age in 2013. Despite ‘aging,’ she mentally remained no more than 1 year old, and physically between the ages of 8 and 10 years old, prompting doctors and scientists to term her condition as ‘Syndrome X.’ Though she continued to develop over her 20-year lifespan, she aged incredibly slowly, giving the appearance of not aging at all.1 Due to her strange physical presentation, many tests and treatments were tried to understand and treat her condition. One of the first treatments given was growth hormone at the age of six months; however, Brooke did not respond with weight or height changes. Genetic testing was also completed, and she did not show any genetic disorders or chromosomal abnormalities, which differs from typical developmental disorders as is the case with many other individuals with developmental disorders. One major discovery was that her telomeres were shortening at a normal rate as well. Telomeres are repeated units of nucleic acids at the ends of chromosomes; these begin to shorten when individuals age as nucleic acids are ‘cut’ at the end of each DNA replication cycle. Despite analyzing all of Brooke Greenberg’s physical deformities and mental delays, doctors are still at a loss as to the cause of her condition.
Currently, scientists are trying to understand her condition from an epigenetic perspective, which may be their last hope at solving this mystery.4 A very recent development in the field of epigenetics, which is the study of changing gene expression in an individual despite unaltered DNA sequences, is currently helping scientists work towards understanding Brooke’s condition. The Epigenetic Clock has been developed, and works as a biomarker of aging based on DNA methylation levels; certain levels correlate with chronological age. As such, scientists have the ability to measure methylation levels within an individual’s cells and predict the rate at which their body is growing. A major bonus of using this method is that detecting DNA methylation proves more responsiveness than assessing telomere length, which is futile in the case of Brooke as her telomere lengths are within normal range. By using this method, scientists are currently working towards finding out if Brooke Greenberg’s DNA methylation levels were normal, and if not, may prove to be the basis behind her impossible condition.1
Though Brooke Greenberg’s case is seemingly impossible, there have been comparable cases in the past. Many of these cases have presented in a similar manner to that of Brooke Greenberg - stoppage of growth, short height, and low weight - though most of these cases have been linked to genetic mutations or endocrine malfunctions. For example, Gabrielle William who was born in 2004, has since been diagnosed with a condition related to a genetic mutation.5 Nicky Freeman of Australia is currently 46 years old, but looks like a preteen boy, and has been diagnosed with a deformity of the pituitary gland, which controls the production of growth hormone. This hormone is essential for bone growth and weight gain.6 Though all these cases have similar physical symptoms as Brooke Greenberg, all have been traced back to different causes, and therefore, scientists still have not found the cause of her condition.
Scientists and doctors continue to explore Brooke Greenberg’s condition, even three years after her passing in the hopes that understanding her condition will help others facing similar problems. Apart from epigenetic causes, other theories speculating her case include a hormone deficiency or problem with her endocrine system; although, her hormones continue to test normal. Many hundreds of scientific mysteries such as Brooke’s remain unsolved, despite the thousands of hours and hard work put into solving them. However, it is important to keep working towards understanding these types of conditions and not to lose hope. One day, when the origin of these conditions have been found, and cures start to arise, children like Brooke will be able to lead a normal life.
1. Walker R, Liu J, Peters B et al. Epigenetic age analysis of children who seem to evade aging. Aging. 2015;7(5):334-339. doi:10.18632/aging.100744.
2. About Us | Developmental Disabilities | NCBDDD | CDC. Cdcgov. 2016. Available at: https://www.cdc.gov/ncbddd/developmentaldisabilities/about.html.
3. Chromosome Abnormalities Fact Sheet - National Human Genome Research Institute (NHGRI). Genomegov. 2016. Available at: https://www.genome.gov/11508982/chromosome-abnormalities-fact-sheet/.
4. Walker R, Pakula L, Sutcliffe M, Kruk P, Graakjaer J, Shay J. A case study of “disorganized development” and its possible relevance to genetic determinants of aging. Mechanisms of Ageing and Development. 2009;130(5):350-356. doi:10.1016/j.mad.2009.02.003.
5. Hughes V. Ageing: The girls who never grow older. Bbccom. 2016. Available at: http://www.bbc.com/future/story/20140520-the-girls-who-never-age.
6. CALAUTTI. Forty-year-old trapped in child's body. Aunewsyahoocom. 2015. Available at: https://au.news.yahoo.com/thewest/wa/a/6861274/forty-year-old-trapped-in-childs-body/.
Cite This Article:
Misra A., Zheng K., Chan G., Ho J. The Impossible Girl. Illustrated by H. Zhang. Rare Disease Review. June 2017. DOI:10.13140/RG.2.2.21115.31525.