ERN-ITHACA – University Medical Centre Groningen


The Groningen Centre of the ITHACA European Reference Network (ERN) has expertise in the field of developmental delay (DD) and multiple congenital anomaly (MCA) syndromes. This includes all DD and MCA syndromes caused by (rare) monogenic or chromosomal abnormalities. The Centre aims to combine patient care, research and education in a multidisciplinary setting with an emphasis on personalized care.

Services to patients

The regional population covered by the Groningen Centre counts more than 1.7 million inhabitants and includes the three northern provinces of the Netherlands. Additionally, a significant part of the patients seen in the Centre are referred from other Dutch regions or from abroad. The Centre offers top-reference and top-clinical care which covers efficient diagnostics (clinical, chemical and genetic), multidisciplinary approach (genetics, paediatrics, neurology, psychiatry, ear-nose-throat (ENT) specialty, ophthalmology), personalized care and follow-up in collaboration with regional disciplines. Moreover, the Centre conducts research aiming to improve patient care. Studies are patient-oriented and the results have led to guidelines and recommendations for rare syndromes (e.g. CHARGE syndrome, Phelan-McDermid syndrome) and registries/databases (,,

Organization of the ITHACA ERN – Groningen Centre

The University Medical Centre Groningen (UMCG) is the top-reference hospital for complex, highly specialized care for the northern provinces of the Netherlands. Collaboration with regional hospitals is essential to keep the routine patient care close at home and concentrate complex care in the centre. Moreover, the UMCG is allied with the University of Groningen and its Graduate School of Medical Sciences (GSMS) for the education of medical and PhD students. The UMCG has 41 expert centres which are qualified by the Dutch government and the Netherlands Federation of University Medical Centres (NFU). Two centres are part of the ERN-ITHACA Groningen Centre: the multidisciplinary CHARGE clinic and the Clinic for Rare Chromosome disorders. In addition, the UMCG has a multidisciplinary clinic for patients with DD, the Groningen Expert centre Developmental delay (Ontwikkelingsachterstand, GEO).

  • CHARGE clinic: CHARGE syndrome is a variable, multiple congenital anomaly syndrome. The incidence is approximately 6 per 100,000 newborns. The clinic is the only expert clinic for CHARGE syndrome in the Netherlands and coordinates the care for children and young adults with CHARGE syndrome. All patients are seen every one to two years by a team of specialists, including at least a clinical geneticist, paediatric endocrinologist, and ENT surgeon, together with a team specialized in communication and language development in children (CSK team). Upon request and based on the patient’s problems, other specialists are also involved in the evaluation and/or in giving advice. A tailor-made programme is offered to the patient at each visit. The clinic has follow-up records on almost 120 patients. Due to the enormous amount of information various research projects have been conducted (n=12) or are still on-going (n=7). More information:
  • The outpatient clinic for Rare Chromosome disorders: This outpatient clinic provides structured follow-up for all patients with rare chromosome disorders in the Netherlands and is also regularly visited by patients from other countries. The main aim of the clinic is to improve surveillance of patients with rare chromosome disorders by collecting as much information as possible, giving advise based on experience and write guidelines. The clinic provides data of all patients (if consent is given) to the European Cytogeneticists Association Register of Rare Chromosome Aberrations (ECARUCA). Guidelines on several chromosomal syndromes are or have been produced. Together with Unique, the international parent support group, information leaflets are translated and new leaflets produced. Translational and clinical research is initiated by the clinic or performed within a research network. The main focus of clinical research at the moment is Phelan-McDermid syndrome (including a clinical trial with intranasal insulin) and Chromosome 6 disorders.
  • Chromosome 6 research: Chromosomal changes, deletions and duplications of chromosome 6, are a significant cause of congenital birth defects and developmental delays in children. Knowledge about the effects of these chromosomal changes is important to ensure the best possible guidance and treatment for these children. While chromosome 6 aberrations as a total are not rare, there are many different deletions and duplications possible, each with different symptoms. We are currently running a unique chromosome 6 project based on social media that resulted in a parent-oriented database with an interactive questionnaire available in seven European languages. In this study we compare the exact changes in chromosome 6 (the genotype) with the effect these genetic changes produce in the appearance and other clinical symptoms of the child (the phenotype). In this way we hope to link specific disease characteristics with specific regions of chromosome 6. Our goal is to produce a detailed genotype-phenotype map of chromosome 6 that can be used to give tailored guidance to patients and their families about the prognosis for their child, ranging from their likely developmental trajectory to additional health problems they could encounter, all with the goal of offering child-specific guidance and treatment. More information:
  • Phelan-McDermid syndrome: Phelan-McDermid syndrome (also known as 22q13.3 deletion syndrome) is one of the most common microdeletion syndromes with more than 600 cases worldwide. As far as we know, the number of patients with Phelan-McDermid syndrome in the Netherlands is approximately 60 children and 40 adults, but it’s probably higher. It is thought that the neurological features (development and behaviour) are mainly caused by a deficiency of SHANK3. In Groningen we studied the effects of administering intranasal insulin to children with Phelan-McDermid syndrome on their development and behaviour. In addition we study:
  • the development and behaviour of Dutch children with Phelan-McDermid syndrome,
  • how adults with Phelan-McDermid syndrome develop,
  • the relationship between SHANK3 and the features seen in Phelan-McDermid syndrome

More information:

  • GEO: the aim is to perform efficient diagnostics to quickly find a diagnosis for DD in a patient-friendly way. A multidisciplinary team is involved in complex cases. Genetic diagnostics are performed earlier in the diagnostic trajectory (array, 800-genes panel testing, whole-exome-sequencing). On indication additional neurologic, psychiatric, ophthalmic, biochemical, neurophysiological and imaging investigations are performed. A total of 137 patients have visited the clinic in 2015 and in 35% a diagnosis could be found, mostly with genetic tests.

Further information

Lead:  Prof Conny van Ravenswaaij-Arts

Department of Genetics

Universitary Medical Centre Groningen
Post Box 30.001

9700 RB Groningen


Tel:        +31-50 3617229