Keratitis Ichthyosis Deafness

KID syndrome is a genetic disorder and can be transmitted from a parent to a child in an autosomal dominant fashion. That means that each individual affected with the disease would have one abnormal and one normal copy of the disease gene. When, by chance, the abnormal gene copy is passed on to the offspring, the child will be affected. When the normal gene copy is transmitted, the child will be unaffected. The risk for an individual with KID syndrome to have an affected child is 50% for each pregnancy. Nevertheless, nine out of ten patients carry a new, spontaneously occurring mutation that is not present in either parent.

The research laboratory of Dr. G. Richard at the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA discovered the gene whose mutations cause KID syndrome. It is called gap junction protein beta 2 (GJB2) and located on the long arm of human chromosome 13. This gene encodes the structural protein ‘connexin-26’ (Cx26), which forms gap junction channels that connect neighboring cells and permit the exchange of small molecules and ions. To date is known that about 80% of KID patients carry a common mutation replacing an aspartic acid residue at position 50 of Cx26 with an asparagine. The remainder of patients usually harbors unique mutations. It is thought that the protein made from the abnormal gene copy interferes with the assembly of gap junctions and the function of normal Cx26 in a so-called ‘dominant negative’ manner. Hence the direct cell-cell communication in the skin and other tissues, such as cornea and inner ear, might be impaired. Nevertheless, the exact pathomechanisms leading to KID syndrome are still not fully understood and are subject of current and future research.

Doctors frequently use genetic testing to help define which ichthyosis a person actually has. This may help them to treat and manage the patient. Another reason to have a genetic test is if you or a family member wants to have children. Genetic testing, which would ideally be performed first on the person with ichthyosis, is often helpful in determining a person’s, and their relative’s, chances to have a baby with ichthyosis. Genetic testing may be recommended if the inheritance pattern is unclear or if you or a family member is interested in reproductive options such as genetic diagnosis before implantation or prenatal diagnosis.

Results of genetic tests, even when they identify a specific mutation, can rarely tell you how mild or how severe a condition will be in any particular individual. There may be a general presentation in a family or consistent findings for a particular diagnosis, but it’s important to know that every individual is different. The result of a genetic test may be “negative,” meaning no mutation was identified. This may help the doctor exclude certain diagnoses, although sometimes it can be unsatisfying to the patient. “Inconclusive” results occur occasionally, and this reflects the limitation in our knowledge and techniques for doing the test. But we can be optimistic about understanding more in the future, as science moves quickly and new discoveries are being made all the time. You can participate in research studies and also receive genetic testing through the National Ichthyosis Registry at Yale University or for more information about genetic tests performed you can visit GeneDx, www.genedx.com.