The Connection Between Multiple Exotoses And Possible Height Increase

Me: I got an email recently from Tyler to do a little research on a condition called Multiple Exotoses to see whether it might have any connection with possible height increase. Wikipedia is always the first link that appears. however, the term that is most cited is NOT multiple exoduses but “hereditary multiple exoduses”.

From this link here

“Extosis – An exostosis is a bone growth that is abnormal or different from the underlying architecture of the bone. These “abnormal growths” are not cancer, They are benign. Sometimes doctors refer to exostoses as “tumors” which like exostose is a general term meaning abnormal growth.”

It seems that Hereditary Multiple Exotoses (aka HME or MHE) is where you get multiple bone spurs and lumps that appear on the bone.  However, for the Hereditary type, HME, this condition only affects children. Hence the hereditary part. From the wikipedia article on HME (HERE)…

“It is characterized by the growth of cartilage-capped benign bone tumours around areas of active bone growth, particularly the metaphysis of the long bones. HME can lead to the shortening and bowing of bones; affected individuals often have a short stature….A person with HME has an increased risk of developing a rare form of bone cancer called chondrosarcoma as an adult. Problems may be had in later life and these could include weak bones and nerve damage.”

It seems the condition can not be cured and that the two most common treatments are surgical methods to  remove the bone spurs/lumps but the osteosarcoma just reappears in the same place later on. The big thing seems to be that the spurs causes a lot of pain. The condition is autosomally dominant and hereditary with a 96% change of a person expressing it if they have the dominant gene. It will be transferred to the children of parent with it. It can also just come about spontaneously. Wikipedia says that “Since the HME genes are involved in the synthesis of a glycan (heparan sulfate), HME may be considered a congenital disorder of glycosylation”. We know that Heparan sulfate is a member of the glycosaminoglycan family of carbohydrates or a proteoglycan. The exact mechanism for how a mutation in the 3 genes associated with HME actually affects bone growth is not known yet. They are…

  • EXT1 which maps to chromosome 8q24.1,  EXT2 which maps to 11p13,  EXT3 which maps to the short arm of Chromosome 19

From the genetics home reference website on the National Institute of Health website located HERE the thing they say about HME is that it only is expressed in children, and by the time the kid is 12, they most likely would have expressed the exoduses. However, when they turn into adults and they stop growing in size, i.e.. their growth plates have fused, the bone growths stop. The thing about multiple exoduses is that when a person gets the disorder, it doesn’t increase bone length but disrupts the growth process leading to short stature, stunting growth ,and limb curvature. The condition is usually non-cancerous. It seems to be a rather rare condition.

From WheelersOnline.com

It is an osteochondroma that results from a dysplasia of peripheral growth plate. Dysplasia is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. It also seems this disorder can be diagnosed rather early, usually around 3.  from the source…

“- cartilaginous exostoses arise from metaphyses, point away from epiphysis, and appear to extend down diaphysis during growth;”

Again it is stated that they increase in size & number w/ growth, but may become latent at maturity. The disorder really only affects people with their growth plates open, children. If the person has stopped increasing in height, they have become the very small minority of people where the exotoses has turned into Chondrosarcoma.


The link between this disorder and longitudinal growth seems to be from the study found below…

Bone. 2005 Mar;36(3):379-86.

EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development.

Hilton MJ, Gutiérrez L, Martinez DA, Wells DE.

Source

Department of Internal Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, MO 63110, USA. mhilton@im.wustl.edu

Abstract

Multiple Hereditary Exostoses (MHE) is an autosomal dominant skeletal disorder most frequently caused by mutations in the EXT1 gene. MHE affects proper development of endochondral bones, such that all affected individuals present with exostoses adjacent to the growth plate of long bones, while some individuals exhibit additional bone deformities. EXT1 functions as a heparan sulfate (HS) co-polymerase, and when defective causes improper elongation of glycosaminoglycan side chains on core proteins of HS proteoglycans. Although analysis of heterozygous EXT1-deficient mice has failed to reveal any significant gross morphological variations in skeletal development, significant alterations in molecular signaling occur in the developing long bones. Our results indicate that defects in EXT1 and the resulting reduction in HS lead to enhanced Indian Hedgehog diffusion causing an increase in chondrocyte proliferation and delayed hypertrophic differentiation.

PMID: 15777636  [PubMed – indexed for MEDLINE]
Me: What we ultimately learn is that this condition which is from a mutation, specifically a truncation of probably the three genes involves causes the chondrocyte proliferation and differentiation of the long bone during endochondral ossification to be disrupted. Of course anything that disrupts this process leads to stunted growth, and short stature. What is critical to realize is that we probably can’t use this research to lead to height increase but we can learn about this pathology to learn more about how height can be decreased. from the study above…
    EXT1 functions as a heparan sulfate (HS) co-polymerase, and when defective causes improper elongation of glycosaminoglycan side chains on core proteins of HS proteoglycans
    defects in EXT1 and the resulting reduction in HS lead to enhanced Indian Hedgehog diffusion causing an increase in chondrocyte proliferation and delayed hypertrophic differentiation.
My issue is that the second statement seems to suggest that we might be able to cause defects in the EXT1 gene for increased chondrocyte proliferation and delayed hypertrophic differentiation but it seems that a very similar type of mutation in the EXT genes could lead to stunted growth. Overall, this is a interesting idea on how gene therapy with vectors could possibly be used to increase height.

One thought on “The Connection Between Multiple Exotoses And Possible Height Increase

  1. Moh

    Hi i am a MHE affected person! My height is the major problem for me
    So far! I am 157 cm tall and now i am 25 age old! As is it a big problem that i face jn my life is the height issue! Any possibility i can grow more taller !

    Reply

Leave a Reply

Your email address will not be published. Required fields are marked *