Haim-Munk syndrome is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
According to the medical literature, parents of many individuals with Haim-Munk syndrome have been closely related by blood (consanguineous). If both parents carry an altered (mutated) gene for the disorder, there is an increased risk that their children may inherit the two genes necessary for the development of the disorder.
Genetic analysis of several affected families (kindreds) suggests that Haim-Munk syndrome may be due to mutations of a gene (known as cathepsin C [CTSC]) located on the long arm (q) of chromosome 11* (11q14.1-q14.3). In addition, such analysis demonstrated that, in affected individuals, a shared, common set of genes (haplotype) surrounded the gene location (locus) and appeared to be transmitted with it as a unit, suggesting that the CTSC gene mutation was inherited from a single common ancestor.
Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered. Therefore, chromosome 11q14.1 refers to band 14.1 on the long arm of chromosome 11.
Researchers also have found that certain mutations of the CTSC gene may cause Papillon-Lefevre syndrome (allelic disorder). (An allele is one of two or more alternative forms of a gene that may occupy a particular chromosomal location.) Papillon-Lefevre syndrome is a rare syndrome characterized by certain features similar to those seen in Haim-Munk syndrome.
The CTSC gene regulates production (encodes for) of an enzyme (i.e., a lysosomal protease) known as cathepsin C that is expressed in various organs and tissues. It is also thought to play a role in the differentiation of certain tightly packed cells (epithelium) that form the protective outer layer of the skin, such as of the palms, soles, and knees, and bind gum tissues of the mouth (gingiva) to the tooth surface. Mutation of the CTSC gene may result in reduced levels of cathepsin C or defective cathepsin C that cannot perform its normal functions in the body.