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Osie
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Introduction:
While many of us have come to understand the hormonal and nutritional necessities for height growth, genetic factors are rarely discussed. Today, with the help of this study, I’ll reveal the more intricate side of height growth and how many of us may have genetic defects we don’t know about!
Genetic Defects:
“Short stature is often seen as a result of a healthy child being naturally short. However, many short children without disorders like GHD or hypothyroidism have genetic defects affecting height growth. These include mutations in genes like SHOX, ACAN, FGFR3, NPR2, or components of the GH/IGF-I axis. These genetic defects often go unnoticed but can impact growth. Early detection can improve treatment approaches and provide more accurate descriptions of different forms of ISS.”“Fake” Short Stature:
Many times, people who are naturally bound to grow later in life are mixed into the “normal” but short-statured population but that isn’t true. These people will eventually reach average height or higher but just takes longer, and most likely have a younger bone age than chronological age. If you notice that you are short, but have premature physical developments (bone age, facial structure, bodily hair) it could just mean that you have delayed growth and will eventually reach average or above-average height.Diagnosis:
The image below provides a good way to analyze your own cause of short stature. If you are pretty confident that your lack of height isn’t caused by endocrine issues, then it most likely needs more specific research done on it (gene testing).
Specific Causes of Short Stature:
GH/IGF-1 Axis
It has been viewed in recent studies that complete mutations to our growth hormone receptor (GHR) cause growth hormone deficiency. Interestingly, less severe to mild mutation of GHR, causes short stature, leading to low IGF-1 levels but won’t lead to a diagnosis of IGF-1 and GH deficiency. It’s believed that 5% of “normal” short-stature cases have mild GHR mutations. Mild mutations of IGF1R also cause short stature in “normal” children. It leads to reduced IGF-1 and IGF-1BP3 levels. In summary, defects in your IGF-1 or GH receptor can lead to growth issues. Discrepancies in the levels of these two hormones could indicate a defect.SHOX Gene
This gene is one of the most important genes for height growth and can also be a potential cause of short stature. When the gene is mutated, it can lead to a gene-dose-dependent effect on height growth. If it’s heavily mutated, it causes extremely short height (Ex: Turner Syndrome) and if slightly mutated, leads to short stature despite “normal health.” Luckily, there are pretty evident signs of a SHOX gene defect like abnormally short forearms, lower legs, high-arched palate, and lack of muscle growth. If experiencing these physical signs, consider genetic testing.ACAN Gene
To preface, this gene is a very important factor for cartilage growth and bone morphogenesis, and a defect of this gene has been shown to be the biggest cause of short stature in “normal” children in comparison to the other genes analyzed. All diseases that involve ACAN mutation lead to compromised adult height. It was revealed in a study that ACAN mutations were responsible for multiple “normal” but short children's lack of height without resulting in skeletal mutations. If you are oddly short despite genetics and showcase no clear skeletal malformations or oddities, it can be possibly caused by an underlying ACAN mutation!NPR2 and CNP Gene
Loss of function mutations to your NPR2 gene disrupts its process with CNP, a process that heavily affects human height growth. It is normally responsible for short stature in “normal” children without unique phenotypes. NPR2 mutations have been found in up to 6% of “normal” children with short stature. While there aren’t any clear physical signs of NPR2 mutations, it’s best characterized by small hands, mild facial abnormalities, and obviously short stature.Chromosomal CNV’s
Chromosomal microarray is a technique that compares a patient’s DNA with a reference DNA to find any imbalances, such as tiny deletions or duplications. These imbalances, known as CNVs, can be inherited or new, and they change the number of copies of one or more genes that are important for growth. CNVs are responsible for 10% of short stature in “normal” children and the rate is increased with more additional deformities. A lower rate of CNV’s has been shown in multiple studies to lead to short stature despite normal health. While having a lower rate of CNV’s aren’t visually apparentDisclaimer:
The studies listed indicate a relatively small amount of “normal” short-stature children having genetic abnormalities, they used a very small sample size of only 30-100 short-statured people, meaning that the total sample size around the world is much larger.Conclusion:
Overall, height growth isn’t as cut and dry as we think. These unseen but highly plausible genetic defects that many of us heightmaxxers may have could be the cause of our short stature or lack of response to hormones. If you believe that you are highly suspicious and have some visible signs that match up with some of the gene defects listed today, consider getting genetic testing done! However, understand that the majority of us aren't short stature cases and have a height that fits into a reasonable prediction possiblity between our mother's and father's height
