European center for Kleefstra in the Netherlands

Officially recognized specialization in Kleefstra syndrome

The Kleefstra report from Radboudumc is not just general. The Dutch Ministry of Health, Welfare and Sport (VWS) has officially recognized the center as a center of expertise, among other things, specifically for the Kleefstra syndrome. The relevant list from Radboudumc also includes syndromes such as DYRK1A, KBG, Koolen-de Vries, and Witteveen-Kolk.

The center gained national recognition in 2015 and since 2017 has been participating in ERN ITHACA, the European Reference Network focusing on rare congenital malformations and neurodevelopmental disorders with intellectual disability.

Participation in the ERN is of particular importance for a rare syndrome such as Kleefstra. The European Reference Networks have been established so that specialized knowledge on rare and complex conditions does not remain isolated in a single hospital or country, but can be interconnected at the European level. The ERN ITHACA Nijmegen Center based in the Department of Genetics at Radboudumc and covers a wide range of genetic syndromes with developmental abnormalities and/or intellectual disability.

Specialized monitoring for children and adults

For individuals for whom the genetic cause of the developmental disorder is already known, Radboudumc operates the specialized clinic Rare, meaning «Rarely». In this, both are monitored children and adults, and Kleefstra syndrome is explicitly listed among the diagnoses covered.

The care model is different from a routine visit to an individual specialist. At the specialized multidisciplinary clinic, the individual with Kleefstra can be evaluated by clinical geneticist, a pediatrician and/or a physician specialized in the care of people with intellectual disabilities. Depending on the needs of the specific patient, appointments with other specialists can also be scheduled on the same day. Radboudumc states that these multidisciplinary visits take place specifically on Thursdays and the family is informed in advance about the specialists who will participate.

The broader team of the center may include, among others, pediatric neurologist, pediatric cardiologist, speech-language pathologist, clinical neuropsychologist, physical therapist, dietitian, rehabilitation physician, child psychiatrist or adolescent psychiatrist, and endocrinologist, depending on the clinical need.

The center also cooperates with Vincent van Gogh Top Clinical Center for Neuropsychiatry and with the center for child and adolescent psychiatry Character, a fact that is particularly important to Kleefstra, since for some individuals, behavior, sleep, and mental health constitute a significant part of the overall clinical picture. These collaborations make it possible, when necessary, to conduct specialized neuropsychological or psychiatric evaluations within the center.

It does not replace the doctor monitoring the child

An important feature of the Radboudumc model is that the specialized center functions primarily as a center for consultation and the provision of specialized knowledge, not necessarily as the sole entity that will undertake all long-term care.

Following the multidisciplinary evaluation, the experts discuss the findings and recommendations among themselves and send a relevant update to both the family and the treating physician. Radboudumc clarifies that the patient continues to be monitored by their own doctor, while the specialized center provides the specific recommendations that may be needed for their treatment and support.

This is particularly practical for families who live far from Nijmegen: the specialized knowledge can be put to use by the team that is already caring for the child or adult in their place of residence.

A center with a special historical connection to Kleefstra

Nijmegen's connection to Kleefstra syndrome goes back much further than the center's current operations. A significant portion of the research that led to the identification of the syndrome and its genetic cause was conducted at Radboudumc. The hospital reports that the clinical geneticist Tjitske Kleefstra and its colleagues in Nijmegen recognized the relationship of the gene in 2006 EHMT1 with the specific form of neurodevelopmental disorder, which was subsequently named after her.

The very creation of the Center of Expertise for Rare Congenital Developmental Disorders was linked to an effort to bridge the gap between genetic diagnosis and long-termlong-term clinical care. In an official announcement by Radboudumc, Kleefstra syndrome is described as a prime example of how interdisciplinary collaboration between genetics, neurocognitive research, behavioral science, and psychiatry can lead to more personalized care.

Why Radboudumc is of particular importance to Kleefstra

The importance of Radboudumc is not only due to the fact that it has expertise in an extremely rare diagnosis. In Nijmegen, three elements are combined that are difficult to coexist in a single center: long history of research into the syndrome itself, officially recognized clinical specialization, and participation in a European network of rare neurodevelopmental disorders.

For families, this means access to a team that does not merely look at an isolated symptom, but understands the complex picture that can accompany Kleefstra at different ages. For researchers, the pooling of clinical expertise, genetic data, and long-term follow-up creates the conditions for a deeper understanding of the disease and for the evaluation of therapeutic approaches that are beginning to be developed today.

Therefore, Radboudumc does not have a separate «Kleefstra Clinic» in the sense of Boston Children's Hospital. However, it does have something equally essential: an officially recognized multidisciplinary Center of Expertise where Kleefstra syndrome is a specific area of expertise, for children and adults.