“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, 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 pose challenges such as difficulty breastfeeding, confidence issues due to missing teeth and costly out-of-pocket expenses for dental work.

Graham experienced those challenges firsthand. Correcting his missing teeth required extensive dental implants, procedures that continued well into adulthood. And as a teen active in sports, he frequently required repairs to fix chipped teeth.

The puzzling condition affected five generations of Graham’s family, beginning with his maternal grandfather. Graham’s mother wore false teeth for much of her life, and several of her siblings showed signs of the condition. Two of his three sons were born with natal teeth, and a granddaughter is also affected.   

Graham had a strong hunch that it was an inherited genetic condition. That curiosity ultimately shaped his career. Graham pursued genetics in medical school, driven in part by a desire to understand the condition affecting his family. Years later, he began a formal search for the responsible mutation.

After more than 12 years of research, the mystery has finally been solved.

In a study published in the International Dental Journal, a team of investigators led by Graham and his longtime Cedars-Sinai colleague Pedro Sanchez, MD, identified a mutation in the KDF1 gene as the likely root cause of natal teeth. While natal teeth are relatively common and occur in approximately 1 in every 1,000 newborns, KDF-1-related multiple natal teeth with tooth agenesis is quite rare.

Finding the Gene Mutation

Finding the mutation was not a simple task. For Graham’s first attempt in 2013, he ran tests on DNA samples he collected from affected and unaffected family members. But the genetic testing tools available at the time were not advanced enough to comb through the 20,000 genes in the human genome.

“In order to make a gene discovery, you have to know it's there, and you have to know what it does,” Graham said. “The same gene can give rise to different genetic diagnoses. And how it does that, it's not always clear.”

Years later, as Graham prepared for retirement, Sanchez, Graham’s mentee and director of Pediatric Medical Genetics at Cedars-Sinai Guerin Children’s, encouraged him to revisit the research.

Sanchez credits Graham with inspiring his own path into genetics. Over the years, the two developed a close professional and personal bond, even co-authoring medical textbooks.

“I know him, 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.”

A Detailed Look Into DNA

When Sanchez revisited Graham’s family data with fresh eyes and newer genetic tools, he took a more targeted approach and focused on collecting DNA samples from four family members: Graham and one affected son, as well as Graham’s wife and one unaffected son, who served as controls.

This time, Sanchez deployed whole genome sequencing, a comprehensive test that analyzes a person’s entire DNA sequence.

“I treated them just like a family we see in our clinic,” Sanchez said. “We ended up doing a focused exam, and we sequenced all four of them.”

The strategy worked.

The team pinpointed a mutation in the KDF1 gene, which is known to play a role in epidermal development, including structures like skin and teeth.

The finding doesn’t offer a cure for tooth agenesis, but it opens doors to earlier diagnosis, improved counseling for families and a pathway for research into potential treatments. It may also strengthen advocacy efforts for dental insurance coverage.

For Graham, however, the impact is more than scientific. After decades of questions, the answer is finally in hand, bringing a sense of closure to a family that dealt with this trait for generations. Sanchez said he’s honored to be part of the solution.

“Dr. Graham, as a mentor, taught me to be a physician,” Sanchez said. “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.”

Read more from Cedars-Sinai Stories and Insights: How Do Your Genes Fit? Cracking the Code on Breast Cancer Risk

The prestigious national honor bestowed annually by the medical association recognizes Sanchez’s outstanding contributions to pediatric medicine, his leadership in advancing health equity and his unwavering dedication to the Hispanic community. And Sanchez himself credits his Hispanic cultural roots and values for leading him to a career in medicine.

“It is truly humbling to be recognized by the National Hispanic Medical Association,” said Sanchez, who is also the director of Pediatric Medical Genetics at Guerin Children’s. “Growing up in a Hispanic household, I learned that the foundation of healing is planted at home and nurtured by trust, respect, culture and faith. As a clinical scholar and physician-scientist, I am reminded every day that our work reaches far beyond the clinic.”

Sanchez will be recognized at the association’s 28th annual conference, “Uniendo Voces: Advancing the Future of Latino Health,” on June 7 in Anaheim, California. Established in 1994, the nonprofit organization represents more than 50,000 licensed Hispanic physicians in the United States.

“At Guerin Children’s, ensuring that children and families from California and beyond receive personalized, inclusive care is a top priority,” said Shervin Rabizadeh, MD, MBA, deputy director of Guerin Children’s and chair of the Department of Pediatrics. “Sanchez has played a leading role in developing culturally responsive pediatric genetic services.”

Sanchez said the award highlights the importance of integrating cultural understanding into every aspect of medical care.

“As pediatric geneticists, we care for some of the most vulnerable members of our community— children and families navigating rare and complex conditions,” said Sanchez. “By building trust, improving access and mentoring the next generation of clinicians, we help create a healthcare system that not only treats disease but honors the unique culture, stories and heritage of all patients.”

Sanchez’s leadership roles are wide-reaching. Most recently, he was named as the Advisory Committee Chair for the American College of Medical Genetics and Genomics Engage, Equip, and Empower (E3): Genomics Pathways Program. The program seeks to inspire and prepare the next generation of leaders in genetics and genomics by providing early exposure to the field to high school, community college and undergraduate students from underrepresented backgrounds.

“Sanchez’s work reflects Guerin Children’s mission to improve bench-to-bedside healthcare for all communities,” said Ophir Klein, MD, PhD, executive vice dean of Children’s Health and executive director of Guerin Children’s. “This award is a fitting tribute to his compassion, expertise and commitment to care for our youngest patients.”

Read more on the Cedars-Sinai Blog: Do Children Need Genetic Testing?

“They noticed that all the long bones were measuring below the 1 percentile. So, he let us know that he suspected some sort of skeletal dysplasia,” said Gould, 42. “This wasn’t on the radar at all.”

Two weeks later, detailed genetic testing confirmed skeletal dysplasia, specifically achondroplasia.

Skeletal dysplasia, also known as dwarfism, is a group of disorders that affect bone, joint and cartilage growth in a child. Achondroplasia is the most common form. The rare genetic disorder occurs in about 1 in 40,000 births. The condition is characterized by birth complications, shorter bones and limbs and delayed developmental milestones. People with skeletal dysplasia typically require long‑term medical follow-up and monitoring.

Navigating Care

With limited access to specialized care in Nevada, Gould and her husband, John, initially flew to Philadelphia to meet with a team of specialists.

As they processed the shock of the diagnosis and the slew of medical challenges that lay ahead, it quickly became apparent that spending extensive time on the East Coast wouldn’t be ideal due to lack of family support.

The couple, who have five children, contacted Moise Danielpour, MD, a pediatric neurosurgeon highly skilled in pediatric skeletal dysplasia treatments and a medical board member at Little People of America.

To the Goulds’ surprise, within 15 minutes, they got a call from Danielpour, director of the Pediatric Neurosurgery Program at Cedars-Sinai Guerin Children’s.

Danielpour looped in a comprehensive team of specialists, including Pedro Sanchez, MD, director of Pediatric Medical Genetics at Guerin Children’s.

“Dr. Sanchez called me 10 minutes later and we probably talked for 90 minutes,” John Gould said. “It was a really personal conversation. I didn't feel like I was speaking to a doctor.”

For Elliot’s birth and long-term care, the Goulds chose Cedars-Sinai, where, coincidentally, John and his twin sister were born in 1976.

On May 6, 2023, Kelly gave birth to Elliot at 35 weeks via cesarean section with more than 20 medical professionals in the delivery room ready in case of an emergency.

“We were prepared for the worst at birth,” Kelly Gould said. “He came out crying, and that was such a big deal because we weren't sure that might happen due to breathing complications associated with achondroplasia.”

Even though Elliot had respiratory and feeding issues due to his small chest size and required continuous oxygen support, the parents were able to take their newborn home to Las Vegas after spending nearly a month at the Neonatal Intensive Care Unit at Cedars-Sinai Guerin Children’s. Unfortunately, at 8 weeks old, Elliot stopped breathing and had to be airlifted back to Cedars-Sinai from Las Vegas for emergency spinal surgery.

The surgery was necessary to treat Elliot for foramen magnum stenosis (FMS), a potentially life-threatening condition commonly associated with achondroplasia that significantly increases the risk of sudden death.

FMS occurs when the opening at the base of the skull through which the spine passes becomes very narrow or kinked, putting pressure on the junction where the brain and the spinal cord meet. Severe FMS in infants under 2, such as in Elliot’s case, can cause breathing problems and delays in crawling and walking.

“To relieve FMS symptoms, we go in and very carefully expand or increase the size of the foramen magnum by taking out the appropriate bone and making that size more normal so there isn't compression of the brain stem and spinal cord due to narrowness or stenosis at the opening of the skull,” said Danielpour, who performed Elliot’s surgery. “This was not a surprise to the parents, but they hadn’t expected it when Elliot was 60 days old. But we helped them deal with the care he needed afterward and have the best outcome possible.”

A New Path to Growth

About 99% of achondroplasia cases stem from a spontaneous mutation in a gene called FGFR3. This mutation disturbs the average pace of bone growth, resulting in short limbs and dwarfism. Doctors said the mutation is unrelated to the age of the mother.

In 2021, the United States Food and Drug Administration (FDA) approved a growth therapy drug called vosoritide (VOXZOGO). This once-daily drug was approved to boost bone growth and improve muscle tone while stabilizing head growth in children 5 and older.

A few months after Elliot’s birth, in October 2023, the FDA expanded the drug’s usage for newborns and children of all ages with achondroplasia.

As the Goulds came to find out, though, getting their hands on this groundbreaking drug in Las Vegas was both tricky and time-consuming. They waited more than 10 weeks for the medication to arrive. It never did.

So the parents contacted Sanchez for help; he arranged for the medication to arrive.

“Dr. Sanchez is the reason Elliot has the drug,” John Gould said. “And we did the first injection at Cedars-Sinai. They walked us through it with the nursing team, and we knew we had come to the right place.”

Now the Goulds, with Elliot in tow, visit Sanchez’s clinic every three months for regular follow-ups, and Elliot is already showing some improvements. 

“Hopefully, the medication will allow Elliot to get the signal to start growing again. Not only should it affect the long bones, but probably all bones and should also allow the rest of his anatomy to adapt appropriately,” Sanchez said.

As for Elliot, John can’t wait to see what his youngest son will bring to the world.

“I know life is going to be really challenging for Elliot,” John Gould said. “We just want him to be in the best position where he goes through life as anybody else would and has those same opportunities without really thinking about achondroplasia, though it will always be a part of him.”

Read more on the Cedars-Sinai Blog: A High-Risk Pregnancy Lifeline