In the early 1980s, the Howard Hughes Institute of Human Genetics was established at the University of Utah, under the leadership of Raymond L. White. This Utah location was selected due to the availability of extensive world-wide genealogical records as collected by the Church of Jesus Christ of Latter-day Saints. I, Katherine W. Timothy, was employed in 1985 by cardiologist, G. Michael Vincent, to genealogically research a Danish family that was identified to have a little known cardiac disorder known as the Romano-Ward Syndrome, later named the Long QT Syndrome (LQTS). After expanding this family into over 3,000 individuals, we took the family pedigree to Dr. White. Since the pedigree was so expansive in its phenotypic information, research on this family was begun under the investigative leadership of Mark T. Keating. After almost two years of genomic searching, we identified a genetic locus (a gene) for the Long QT disorder. This discovery opened the field of genetics for all known cardiac disorders.
With my knowledge of the families and expertise in reading electrocardiograms, I became the clinical coordinator for the Keating Laboratory in selecting individuals for specific genetic searches. In 1991, G. Michael Vincent, David Salisbury and I organized the Sudden Arrhythmia Death Syndromes, or SADS Foundation, and through this foundation’s awareness program for LQT and sudden unexplained death (SUD), cardiologists began submitting individuals for genetic research to SADS and the Keating Laboratory. Early in 1992, two small children were referred to us as having a very long QT interval and most interestingly, both individuals had syndactyly of their fingers and toes. Within a few years at least five additional children were referred to the Keating Laboratory, and a new and different type of LQT was identified. Meanwhile, the Keating Lab was discovering multiple genes responsible for causing LQT, however none of these LQT genes were associated with the small children who were diagnosed with the LQT-syndactyly disorder. In over 12 years of continuous and diligent genomic searching by Igor Splawski in the Keating Lab, nothing was identified which associated with the disorder. I continued to identify additional LQT-syndactyly children, hoping to learn more about the children and the inheritance pattern of the parents and their families. Unfortunately, at the time, nothing seemed to indicate how this severe disorder was inherited, as all other family members appeared to be completely free of anything related to the disorder. One mother, Christine Badame, became vitally important to the study, and as she and I worked together, a picture of all the symptoms that affected the children became apparent and it was discovered that this cardiac condition included far more health concerns than just the obvious LQT-syndactyly. Finally in the fall of 2003, Dr. Splawski’s passion and patience paid off and his CACNA1C gene discovery answered why this disorder affected multi-systems of the body, as this CACNA1C gene was discovered to express in virtually every body tissue, specifically affecting the brain, lungs, gut, pancreas, muscles, skin, bones, teeth, etc. The scientific paper for this incredible discovery was published in 2004 and in addition to it being a severe cardiac condition, it was the first scientific paper to report a genetic association with autism. To honor my contribution to the identification of this syndrome, the disorder was named Timothy Syndrome (TS). In 2005, because of the importance of the scientific discoveries made in the Keating Laboratory, Drs. Keating and Splawski were propelled into impressive pharmaceutical endeavors. At this time, I retired from clinical genetic research but have continued to follow the TS children. My love of the children and their families has been my passion for over 30 years, and my phenotypic collection and understanding of TS continues to unfold.