After reading enough articles I have reached the conclusion that there are certain types of mutations that can occur in a family which can cause multiple people in the family to develop extremely tall stature. Whether these mutations means that all families that have the height gene would be something wrong or at least inconclusive. We know that there are people who come from tall families. Their father and mother was tall, so they were tall as well as their siblings. I am not sure if the tallness that they receive can be considered a true mutation. Would Yao Ming be considered a healthy, idiopathically tall individual who does not have any type of genetic mutation to result in his extreme height? I can’t even answer that question. The point is that there are some related people in a family who exhibit height at a level that put them in the upper reach of human height and make them look abnormal.

Some common cases would be the recessive gene that was found in Charles Byrne, the Irish Giant who had distant cousins and relatives who also ended up very tall. I wrote about him and his link to people even today who show extremely tall stature in the post “Genetic Mutation Causes Pituitary Tumor Gigantism, The Interesting Case Of Charles Byrne The Irish Giant”

There is also the curious case where I found an article about this family of extremely tall individuals in Southern Vietnam. The post is “A Family Of Giants Of Extremely Tall Stature In Bac Lieu Southern Vietnam“. This case of extremely tall stature must come from some type of genetic mutation which was passed down to half of the offspring signifying that the mutation is dominant in nature. This situation I would classify as something that is not idiopathic. The extremely tall stature is technically from genetics but is the result idiopathically healthy tall offspring?

The point of this post is to show that unlike the healthy type of genetic cause for extreme height seen in small families, there are some types of genetic mutations that can cause entire families to exhibit tall stature which results in people who are not completely healthy.

So what types of genetic mutation would cause familial gigantism?

Study #1: Familial Gigantism

Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes:

1. multiple endocrine neoplasia type 1 (MEN1) – Autosomal-dominant MEN1 syndrome is associated with a loss of heterozygosity (LOH) on chromosome locus 11q13 (57). The MEN1 gene tumor suppressor gene encodes a 610-amino acid protein known as menin….Pituitary tumors occur in approximately 30–50% of patients with MEN1 (58), but the frequency of GH-producing pituitary tumors in MEN1 patients is only about 10%.
2. Carney complex (CNC) – CNC is associated with a LOH on chromosomal locus 17q22–24. Germline mutations in the protein kinase A (PKA) regulatory subunit 1 (PRKAR1A) gene have been identified…Pituitary adenomas occur in 10–20% of patients with the autosomal-dominant CNC, and these are invariably GH-secreting tumors.
3. familial isolated pituitary adenomas (FIPA) – Inactivating germline mutations in the aryl hydrocarbon receptor that interacts with tumor suppressor protein (AIP) can be found in 40–50% of families that have a case of acromegaly

Study #2: Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene.

1. multiple endocrine neoplasia type I (MEN-1) – Loss of heterozygosity on chromosome 11q13…closely linked to the MEN-1 tumor suppressor gene. 
2. the Carney complex

Study #3: Familial acromegaly

Three distinct syndromes have been recognized to date:

1. multiple endocrine neoplasia, type I (MEN-1),
2. Carney complex (CNC)
3. isolated familial somatotropinomas (IFS)

Study #4: Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12

Isolated familial somatotropinomas can be caused from 1 of three types of genetic mutations. They are…

1. endocrine neoplasia complex that includes multiple endocrine neoplasia type 1 (MEN-1)

2. Carney complex (CNC) – somatotropinomas are the predominant pituitary tumor subtype associated with CNC and arise before 30 yr of age, which is strikingly similar to the age at diagnosis for IFS. CNC has been mapped by linkage analysis to chromosomes 2p15-16 and 17q23-24 in different kindreds

3. isolated familial somatotropinomas (IFS) – defined as the occurrence of at least two cases of acromegaly or gigantism in a family that does not exhibit MEN-1 or CNC. Is associated with loss of heterozygosity (LOH) on chromosome 11q13, the locus of the MEN-1 gene, although the MEN-1 sequence and expression appear normal.

This study was used because it suggests that there is another tumor suppressor gene located at 11q13 that is important in the control of somatotrope proliferation. This report establishes linkage of the tumor suppressor gene involved in the pathogenesis of IFS to chromosome 11q13.1-13.3 and identifies a potential second locus at chromosome 2p16-12.

Study #5: Clues to gigantism provided by family in Borneo Mountains

1. Aryl hydrocarbon receptor interacting protein (AIP) gene. It has been known since 2006 that defects to this gene are associated with a predisposition to development of pituitary tumors

Professor Korbonits was able to identify a specific genetic mutation in Irish patients with a family history of acromegaly

The subsequent complex biostatistical calculations showed that the original mutation developed around 1,500 years ago and has been passed on from generation to generation ever since. It is estimated that around 200 to 300 people still carry the mutation today.

Study #6: Genetic Mutation Responsible for ‘Gigantism’ Disease — Or Acromegaly — Identified

Genetic Mutations that would lead to gigantism & acromegaly.

1. a mutation in the AIP gene

Conclusion

So I wanted to try to take all the scientific and genetic information from all 6 studies I read over and summarize them together. There are current three general defined syndromes that cause multiple members in a family to get extremely tall stature. They include

• Multiple Endrocine Neoplasia Type 1 (MEN-1) Syndrome
• Carney Complex (CNC)
• isolated familial somatotropinomas (IFS)

The final result from all of these syndromes is that multiple family members develop pituitary adenomas which can sometimes cause excess growth hormones release when they are in the younger years when the growth plates are still open. This adenoma occurs when the person is young and still growing and when they are adults and have no more growth plates.

As for the cause, the consistent thing that is stated over and over again is that “loss of heterozygosity (LOH) on chromosome locus 11q13” is what seems to cause both the MEN-1 syndrome and the IFS.

I may be wrong but it seems that in the specific chromosome area, there are at least two different ways that mutations can work. Each different mutation leads to either the MEN-1 or the IFS. It seems that maybe MEN-1 is more common than IFS and that the entire term for IFS is referring to a disorder that leads to familial pituitary adenoma and the markers than should indicate it was caused by MEN-1 and CNC don’t show up.

There is actually a fourth syndrom termed called familial isolated pituitary adenomas (FIPA). However I am thinking that FIPA is either just another way to say IFS, or it is an umbrella term to talk about endrocine neoplasia disorders in general. It is said that FIPA is caused from a mutation on the AIP gene, which is defined by the researchers to be “aryl hydrocarbon receptor that interacts with tumor suppressor protein”

While the Carney Complex does have come links in genes to MEN-1 and IFS, its cause seem from be from another area of the genome, specifically chromosomes 2p15-16 and 17q23-24.

I think this idea that I recently discovered called the Somatomedin Hypothesis is going to challenge some of the basic ideas we have been using since the start to explain how the GH and IGF-1 feedback loop really works to control endochondral ossification.

I refer to the 3 studies below as reference to make the point.

• Study #1: The somatomedin hypothesis 2007: 50 years later.
• Study #2: The somatomedin hypothesis: 2001
• Study #3: The somatomedin hypothesis revisited in a transgenic model

Background

GH, or the natural type of human growth hormone found in the human brain’s pituitary gland anterior region was one of the first compounds ever to be discovered and synthesized. Other names for GH, growth hormone are somatropin and somatotropin. Synthetic types of growth hormones have been made for many decades now and the different variations include Syntropin, Nutropin, Humatropin, etc.

After doctors and researchers reached the conclusion that GH is the thing that controls human growth, specifically vertical growth in terms of growing taller, the proposed idea was that there is supposed to be a proxy, an intermediate compound between the actual GH that is made in the pituitary gland and it final target areas, which are the receptors on the chondrocytes in the growth plate.

The old idea proposed was that this intermediate compound is known as somatomedin. Later it seems that Somatomedin was replaced with the now more commonly well known name, IGF-1 after the compound was understood much better through further research.

Somatomedin C = IGF-1 

The idea back then was that somatomedin was produced by the liver in response to the release of GH into the system. Then the somatomedin would be the actual compound that affects the receptors on the chondrocytes in the growth plate by going through the circulatory system.

The reason why it was believed that GH was not the compound that affects the chondrocytes in the growth plate direclty, but required an intermediate was because while injecting the extracted and purified GH into a lab animal did lead to the growth plate getting thicker and expand more, when the growth plate cartilage was extracted out an animal and put in a culture and then had the GH added, there was no increase in thickness. So the scientists believed that there had to be a 2nd compound that the GH caused to initiate. So in vivo, GH worked. In vitro GH didn’t work.

This was the entire premise of the original somatomedin hypothesis.

The picture below as taken from the study “The Somatomedin Hypothesis 2007: 50 Years Later”

Conclusion

The researchers notes that after 50 years, the original somatomedin hypothesis must be changed due to the following 4 reasons…

1. Investigators have shown that, under the proper conditions, GH does indeed exert a direct action on precursor incorporation in the in vitro cartilage system.

2. There is a substantial body of evidence that GH acts directly (and independently of IGF-I) on the growth of bone.

3. Although the liver is the main source of IGF-I in the circulation, IGFs are produced in virtually every tissue of the organism.

4. GH receptors have been shown to be present in virtually every tissue.

They tried to find someone who could come up with a theory to explain for all of the noticed new discoveries for the function of GH and not one theory could explain everything that was going on with GH. So the researcher made their own model or theory to explain how IGF-1 really is connected to GH in function.

This is what they proposed…

We propose that the IGFs, rather than effectors of GH action, are augmentative hormones that amplify the anabolic actions of GH while countering its potentially deleterious effects. Because the IGFs are counteractive for some but not all the effects of GH, their insulin-like effects may act to negate GH-stimulated gluconeogenesis and enhanced lipolysis.

Analysis

This means that the IGF-1 are not the type of hormone that only increase when GH increases and only helps out the function of GH. There are some functions where the IGF-1 negates the effects of GH, and that means that our original idea that IGF-1 is the main type of hormone/protein that can get to the growth plate cartilage is wrong. GH can directly interact with the growth plates.

The exact way that IGF-1 contributes to the function and effects of GH is by helping GH in anabolic activities and somatic growth. When it counteracts the effects of GH, it is to prevent the GH from causing diseases like hyperglycemia and loss of lipid stores. So the lipid and carbohydrate metabolism effects of the IGF-1 and GH in action concurrently are exactly the opposite.

The main thing is to show that the old somatomedin hypothesis is not completely right and needs to be modified. The four reasons are…

1. GH does indeed exert a direct action on precursor incorporation in the in vitro cartilage system.
2. There is a substantial body of evidence that GH acts directly (and independently of IGF-I) on the growth of bone.
3. Although the liver is the main source of IGF-I in the circulation, IGFs are produced in virtually every tissue of the organism.
4. GH receptors have been shown to be present in virtually every tissue

The GH themselves have a much more direct affect on chondrocytes that previously expected.

The idea of doing what are known as the supine flexion exercise to increase spinal disk height and relieve lower back from disk decompression is an idea which I actually forgot about which would definitely work.

From WikiAnswers the Supine Flexion exercise is defined as “supine flexion is lying in supine (on your back) while “flexing” (bending) your knees into your stomach and keeping your head off the floor“. Refer to the picture to the right.

From the Clinical Study “Interventional Study of Effects on Spine Height With Two Unloading Positions” we see that these researchers were actually testing to see how useful it is to do this exercise to restore spinal torso height and decrease lower back pain and other pains which might be in the upper leg area, probably due to either bulging disks, herniated disks, or sciatica.

The way the subjects did the exercise was by….

“…lying on their back with hip and knees flexed to a 90 degree angle. The height of each person will be measured before and after completion of each intervention using a specially designed measuring tool…”

“…The subject will lay supine with the legs supported by a foam wedge with hips flexed to 90 degrees and knees flexed to 65 degrees. They will maintain this unloaded position for 15 minutes.”

From the same PubMed study cited in the previous post about Aquatic Vertical Suspension, Immediate changes in spinal height and pain after aquatic vertical traction in patients with persistent low back symptoms: a crossover clinical trial, the result was that after going through with this specific exercise where the lower vertebrate bones are completely unloaded, the height increase is 4.21 ± 2.53 mm.

Analysis:

Supine Flexion is a good land based stretching exercise to gain temporary height. It however is not as good in getting temporary height as using the Aquatic Vertical Suspension technique, which is only slightly better by providing about 1-2 extra millimeters. In addition, the water way of unloading the body seems to show better results on reducing pain and reducing the compression of nerve endings. I would guess that the smartest way to get as much height increase as possible is to do BOTH types of exercises, to unload the lower back region on land and in water.

So to get some noticeable height increase very quickly, like Tyler said, do both the Supine Flexion stretching when you are on land and when you decide to go swimming or to the pool, carry some weights with you to try out the Aquatic Vertical Suspension.

This idea that I just read about is actually one of the only ideas that I have seen which have a really good chance of working in at least restoring the lost height in the lower back of the torso from diurnal variation of height throughout the day.

Of all the stretching exercises that I have looked at, this is one of the most creative and smartest. I am actually rather surprised that I did not consider this idea since it has many of the elements to at least temporarily increased height in a person from spinal disk decompression.

I was reading this Clinical Study entitled “Interventional Study of Effects on Spine Height With Two Unloading Positions” from the Clinical Studies government website where these researchers wanted to see if a person who suffers from lower back pain and upper leg pain can find pain relief from doing certain exercises which will restore their height back. ClinicalTrials.gov Identifier:NCT01048749. It is sponsored by the Texas Tech University Health Sciences Center.

“This study will compare two such positions; 1) floating in deep warm water with weights attached to the ankles, to take the load off of the spine…”

“Experimental hypothesis:

1. Subjects with low back and leg pain suggestive of nerve root compression syndrome will experience increase in spinal height when completing aquatic vertical suspension and/or land-based supine flexion.”

Other: aquatic vertical suspension.

1. Subject is suspended in a warm water deep pool with two pool noodles around the subject and directly under the axilla. Five pound weights are placed on the ankle and the subject maintains this unloaded position for 15 minutes.

Other Name: Physical Therapy Treatment

Detailed Description: