A Simplified Explanation
Jacqueline T. Hecht, Ph.D., Professor
Director, Genetic Counseling Program
Department of Pediatrics
Division of Medical Genetics
University of Texas Houston Medical Center
Hereditary Multiple Exostosis (HME) is caused by a change in either the EXT1 or EXT2 gene. This change is called a mutation and the mutant gene is inherited in an autosomal dominant pattern. Genes are our units of hereditary that instruct our bodies how to grow, develop and function. Genes are carried on structures called chromosomes. There are 30-40,000 genes packaged in 46 chromosomes in every cell of our body except the egg and sperm cells that contain 23 chromosomes. These 46 chromosomes come in 23 pairs, with one of each pair coming from the mother in her egg cell and the other from the father in his sperm cell. Our genes, like our chromosomes, come in pairs; therefore we have two copies of every gene. Individuals who are affected with HME have one copy of the gene that is working correctly and one copy, the mutant gene, which is not working correctly. One "broken" or mutant EXT1 or EXT2 gene causes HME. Persons with two copies of the gene working correctly do not have HME. People with HME have either inherited a mutant gene from one of their parents or they have HME because the change in the gene took place at their conception and was not inherited from either parent. A person who is affected with HME has a 50% chance to have an affected child and a 50% chance (occurs 1 out of 2 times) of having a child that does not have HME everytime they conceive a pregnancy. Unfortunately, chance has no memory, so you do not use up your chances if you have an affected child. The risk remains the same each time a pregnancy is conceived.
The diagnosis of HME is established by clinical and radiographic examinations. In more than 98% of the cases, a diagnosis is established as exostoses can be felt and/or found by x-ray examination. However, a few individuals inherit the gene and do not develop exostoses. This is more often the exception rather than the rule. Mutational examination can be performed on any at-risk person in an HME family to determine whether they have inherited an EXT1 or EXT2 mutation. This is usually done after the mutation is identified in an affected person. Mutational testing provides the most accurate assessment of a person's mutational status. This testing is now available through GeneDX, Inc., www.genedx.com
The ABC's of MHE - Table of Contents
The ABC's of MHE - The Genetics of Hereditary Multiple Exostoses (HME)