UMC Utrecht discovers genetic cause of disturbed dental development

Utrecht, October 2, 2015 – Researchers at University Medical Center (UMC) Utrecht have identified a gene that may cause oligodontia, the agenesis of six or more teeth. The discovery of the so-called LPR6 gene makes it possible to diagnose patients more effectively, provide them with better information and develop customized treatment. The results were published today in The American Journal of Human Genetics.

Oligodontia is a rare but serious congenital anomaly defined by the absence of six or more permanent teeth. Children usually develop milk teeth at a young age, but when their permanent teeth start to erupt, it becomes clear that something is wrong. In several places, no adult teeth come in. In Europe, this condition affects 14 out of every 10,000 people. There are two types: oligodontia as part of a syndrome and oligodontie as an isolated condition.

Genetic research
We now know that 70 percent of oligodontia patients have mutations in several genes. Further research was recently carried out at UMC Utrecht, led by study leader Dr. Gijs van Haaften. The study involved additional genetic testing in 20 patients with nonsyndromic oligodontia using Whole Exome-Sequencing (WES). WES is a technique for identifying the protein coding regions (exome) of the human genome. The research results showed that, in these patients, the condition is often caused by a mutation in the LPR6 gene. The study also revealed that patients have a 50 percent chance of passing on the mutation to their offspring. Dr. Marie-José van den Boogaard, clinical geneticist at UMC Utrecht explains, “In these patients, the gene is primarily associated with the absence of teeth and, in principle, not with other serious conditions.”

Oligodontia greatly impacts quality of life and may lead to eating and speaking problems, among other things. Dr. Marijn Créton, dentist and maxillofacial prosthetist at the Department of Oral and Maxillofacial Surgery and Special Dental Care at UMC Utrecht, ensures – in consultation with patients – that ultimately they have a good set of teeth both at a young and adult age. This requires a treatment of many years, during which patients are treated by a dentist, oral surgeon and orthodontist. “Moreover, adolescents with oligodontia often have psychosocial issues,” says Créton. “Missing many teeth is conspicuous. Children, teenagers and young adults are sometimes bullied and regularly experience feelings of low self-esteem and shame.”

National Center of Excellence
At the Center of Excellence in Congenital Orofacial and Dental Anomalies, housed at UMC Utrecht, dentists, oral surgeons, plastic surgeons and orthodontists collaborate in a multidisciplinary setting with clinical geneticists of the Department of Medical Genetics. During a single visit, dental problems are assessed, the patient – and/or parents – are given an explanation of DNA research and are presented with the offer to use it. Based on the findings of the dentist and clinical geneticist, specific genetic research is possible. Van den Boogaard adds, “Most patients want to know the cause. Why does it develop? Will my children get it as well? And what is the risk of this happening? This new research provides better insight into the biology of tooth development. The LPR6 gene is now included in the DNA diagnostics of oligodontia, enabling us to give patients a better diagnosis, and to provide better information and to develop customized treatment.”


Massink MPG, Créton MA, Spanevello F, et al. Loss-of-Function Mutations in the WNT co-receptor LRP6 Cause Autosomal-Dominant Oligodontia, The American Journal of Human Genetics, in press 2015.

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About University Medical Center Utrecht
University Medical Center Utrecht (UMC Utrecht) belongs to the largest public healthcare institutions in the Netherlands. It was created in 2000 through the merger of Utrecht Academic Hospital, Wilhelmina Children’s Hospital and the Medical Faculty of Utrecht University. UMC Utrecht has the ambition to be a leading international healthcare provider, medical school and research institute that is exciting for its people, attractive to talent and embodies a culture of teamwork, innovation, sustainability and high performance. As a patient-centered organization, its 11,000 employees are dedicated to prevent disease, improve healthcare, develop new treatment methods and refine existing ones, with patient safety and quality as cornerstones. Strategic research programs are Brain, Child Health, Circulatory Health, Infection & Immunity, Personalized Cancer Care and Regenerative Medicine & Stem Cells. UMC Utrecht is embedded in a vibrant and entrepreneurial science community where knowledge about health, disease and healthcare is generated, validated, shared and applied. For more information, visit or follow us on Twitter @UMCU_INTL.