John M. Graham, MD, ScD, experienced a rare dental condition throughout his life—being born with natal teeth that quickly fell out and then not developing some adult teeth. This pattern affected five generations of his family, beginning with his maternal grandfather. The condition is called tooth agenesis.
“The natal teeth were little paper-thin teeth that fell out right away, as they didn’t have well-developed roots. And, where I had natal teeth, I had no secondary teeth later in life,” said Graham, who is a retired professor of Medical Genetics and Pediatrics and former director of the Division of Clinical Genetics and Dysmorphology at Cedars-Sinai. “The condition is called tooth agenesis.”
Tooth agenesis can lead to challenges such as difficulties with breastfeeding for infants, confidence issues due to missing teeth during childhood and adulthood, and high costs for dental care.
Graham’s own experience included extensive dental implants into adulthood and frequent repairs from sports-related chipped teeth during his teenage years. His mother wore false teeth for much of her life; two of his three sons were born with natal teeth; and a granddaughter also shows signs of the condition.
Suspecting a genetic cause shaped Graham’s career in medical genetics. He spent more than 12 years searching for the mutation responsible.
A recent study published in the International Dental Journal has identified a mutation in the KDF1 gene as likely causing this familial pattern of natal teeth with subsequent tooth agenesis. The research was led by Graham along with Pedro Sanchez, MD—a longtime colleague at Cedars-Sinai.
While natal teeth are found in about one in every 1,000 newborns, cases related to mutations in KDF1 are rare.
“In order to make a gene discovery, you have to know it’s there, and you have to know what it does,” Graham explained regarding early unsuccessful efforts using less advanced genetic testing tools available over a decade ago. “The same gene can give rise to different genetic diagnoses. And how it does that, it’s not always clear.”
Sanchez encouraged revisiting the research as more sophisticated methods became available. “I know him [Graham], I know his family, and I’m the same age as his kids,” Sanchez said. “Knowing this condition had affected them for generations without closure, I felt there was a missing piece. The tools had evolved, and I believed we could work together and find an answer.”
Using whole genome sequencing on four family members—two affected (Graham and one son) and two unaffected (his wife and another son)—the team pinpointed the KDF1 mutation involved in epidermal development including skin and teeth structures.
Though identifying this gene mutation does not provide an immediate cure for tooth agenesis, it may help enable earlier diagnosis or counseling for families facing similar issues while supporting advocacy efforts for insurance coverage of related dental treatments.
“Dr. Graham, as a mentor, taught me to be a physician,” Sanchez added. “It’s really nice that he was able to share the findings with his family and finally give the gene variant that has affected them for generations a name.”
Cedars-Sinai Medical Center is located in Los Angeles and has operated since 1902 under its current president Thomas M. Priselac. It serves thousands annually—including pediatric patients—and acts as both treatment center and teaching hospital according to its 2022 annual report (https://www.cedars-sinai.org/about/annual-report.html).
