Paediatric Genetics

The department of Translational Genetics is a department in which knowledge and experience from clinical and molecular genetics is used to offer optimal care to children with genetically determined disorders, with or without congenital anomalies and with or without developmental problems. This is offered both to outpatient and inpatient care, but emphasis is on outpatient care. The work of the department is especially visible within a series of expertise clinics.

The department functions within the department of general paediatrics. However, there are good collaborations with the colleagues providing care to adults, and indeed also care to adults can be provided. It has very strong ties to patient support groups and directions in which both care and research developments go, are also determined by these support groups.

The work within the department is performed mainly by paediatricians specialised in care for individuals with heritable and congenital anomalies (a separate specialism in the Netherlands), but clinical geneticists and physicians providing care for individuals with intellectual disabilities (also a separate specialism in the Netherlands) are part of the department as well. Furthermore, if needed paediatricians of other subspecialties can be consulted, and also other specialties within the AMC such as ophthalmology, ENT, dermatology, plastic surgery and all other surgical specialties are available on request.  

Research Topics

The department of Translational Genetics has as philosophy that care can only be ameliorated if research is performed, and therefore (almost) every patient to whom care is offered, can also be part of research if the child and parents or other caregivers give permission to this. The research is both basic science but also clinically  oriented. In the last 5 years the output of the department has been >150 publications in peer-reviewed medical journals of which in >50% a member of the staff of the department was first and/or senior author

Several lines of studies can be recognized:

1. Tumour predisposition syndromes in children

a. The department has been studying disorders that go along with increased chances for children to get cancer. Several new predisposition syndromes have been detected. Further studies to detect tumour predisposition syndromes, and the genes causing these, are in progress. The studies are performed in collaboration with the department of paediatric oncology and the Princess Maxima Centre in Utrecht.

b. In earlier studies the department has development a screening tool to detect children with cancer who are at risk of having a genetically determined disorder. A nation-wide study is performed in which all children with cancer during a period of 2 years are studied with this. The study is performed in collaboration with all departments of paediatric oncology of the academic hospital in the Netherlands

c. One of the known  tumour predisposition syndromes is Beckwith-Wiedemann syndrome. Several studies are performed to characterize this entity better, both clinically and molecularly. The department is one of the leaders of the European consortium on Beckwith-Wiedemann syndrome, and collaborates with all major centres in Europe.

2. Mendelian and Non-Mendelian influences on congenital anomalies

a. Intrauterine growth disturbances. A cohort of children with extreme growth disturbances are studied for chromosome imbalances, variants in Mendelian genes,  and genome wide methylation studies, in order to increase knowledge and understanding of marked growth disturbances. The studies are performed in collaboration with the Institute of Child Health in London

b. Mendelian and Non-Mendelian causes of congenital hypothyroidism. The department has been instrumental in finding two new genes causing congenital hypothyroidism and further studies are in progress. There are also strong clues that hypothyroidism is not only determined by variants in Mendelian genes but also non-Mendelian influences such as methylation may play a role. This is studied both in hypothyroidism in general as in children with Down syndrome in whom it is known they have an increased chance to develop hypothyroidism. The studies are performed in close collaboration with the department of paediatric endocrinology and department of internal medicine of the AMC, and further collaborations exist with local, national and international groups.

c. Mendelian and Non-Mendelian causes of ultra-rare congenital disorders. The department of Translational Genetics has a long-standing interest in studying ultra-rare disorders, and indeed has been instrumental in detecting the genes of >40 disorders. The department is following a large group of children and adults with ultra-rare disorders for which at present no causes are known despite earlier studies. Through own studies and through international collaborations (especially Berlin; Dunedin; London; Rome; Seattle; but also others) studies are performed in a large and diverse group of these disorders


3. Phenotyping of heritable disorders

a. Cornelia de Lange Expertise Centre. The department has been recognized by the Dutch authorities as being a centre for expertise for individuals with a series of rare known congenital disorders going along with intellectual disabilities, and for individuals with these disorders without known cause. Individuals with such disorders are followed in a group of clinics, each time dedicated to the specific group of disorders, such are Rubinstein-Taybi syndrome, Cornelia de Lange syndrome, and Pitt-Hopkins syndrome. Using a IT system that allows an easy collection of data on children and adults visiting the expertise clinics and by very detailed gathering of data, both first class care and data for natural history are gathered. The clinics also aim to perform trials for particular complications going along with some of these disorders, such as keloid formation or particular behavioural problems, and then the natural history data will act as historical controls. The expertise centre is part of a European Reference Network on this group of entities, and collaborates with all major international centres dealing with the same groups of individuals.

b. Phenotyping specific disorders. Next to the general phenotyping also more specific phenotyping is performed. Examples are disorders going along with keloid, disorders going along with lymphatic dysplasia, disorders going along with abnormal fat distribution, and disorders going along with vascular malformations. For each for these groups of disorders the department collaborates with the major European centres working on these topics, and the department is part of the European Reference Network for each group of disorders as well.

c. Phenotyping using modern media. The department has a long tradition gathering data using modern media. This has culminated in a system that allows gathering data from large groups of individuals with rare disorders, living in Europe (the system is available in 8 languages), and which is further extended. Several studies using data on rare disorders have been performed and more studies are being performed, and the department contributes this way significantly to knowledge of each of these disorders.


4. Behavioural characteristics of syndromes

a. Self-injurious disorders. One of the entities studied in the expertise clinics is Cornelia de Lange syndrome. This entity goes along with marked self-injurious behaviour of affected individuals. This has led to a series of studies, both clinically, behaviourally and molecularly, in order to characterize the behaviour and to detect clues for directed treatments. The studies are performed in close collaboration with the department of Psychology, University of Birmingham and with Lentis (Assen)

b. Autism. The department performs several studies, both clinical and psychological,  on autism, both syndromic and isolated. Also basic studies to detect causes of isolated autism (without intellectual disability: Asperger syndrome) are performed. The studies are performed in collaboration with the Autism Team North Netherlands (Lentis).


5. Clinical application of CRISPR technology

The CRISPR technology allows changing any basepair in any gene into any other basepair. Especially changing of mutations in Mendelian genes in tissues that are easily accessible would be amenable for application in clinical care. Together with the department of paediatric haematology/immunology, lab for metabolic disorders and Sanquin (Amsterdam) the technique is being set up for clinical application in disorders in which the signs and symptoms are mainly caused by cells derived from bone marrow. The first disorder in which the technique will be applied will be sickle cell anaemia, but also several immunological disorders are under investigation.


6. Biobanking

a. Brain biobanking. There are very limited reports of post-mortem brain studies in individuals with intellectual disability, while such studies can potentially yield a wealth of information. Together with the Netherlands Brain Bank and a large number of national collaborators a study has been started to perform detailed studies of brains of individuals with a known, preferably molecularly confirmed entity.

b. Biobanking of foetuses. Typically studies in individuals with known entities are performed in accessible tissues, mainly blood. The consequences of cytogenetic imbalances or molecular changes for various tissues is hardly studies while it is increasingly known these might vary according to the tissue that is studied. The introduction of non-invasive prenatal testing in clinical practice in the Netherlands has led to an increase of the interruption of pregnancies after a (usually cytogenetic) abnormality has been detected. This offers opportunities to study foetuses with such anomalies in detail. In close collaboration with the department of gynaecology / obstetrics and with many other departments in the AMC permission is being obtained to start the biobanking of a large number of foetuses, in whom almost any tissue will be evaluated by a multifold of techniques.

c. Ethics of Biobanking in children. Biobanking is complex with respect to legal and ethical issues, and this is even more markedly the case in children. The department is performing careful studies in order to come to guidelines for biobanking in children, which studies are performed in close collaboration with the department of public health.


7. Ethics

A major change in medicine is taking place through the introduction of next generation sequencing in research and clinical care. These changes become more pronounced through the use of more sophisticated IT, which allows the use of hospital-wide electronic patient files such as EPIC, but also sharing of enormous numbers of data between researchers. Gradually the borders between research and care become less clear while there are obvious legal and ethical differences between the two. Together with the department of health, law and emerging technologies in Oxford  studies are performed to (?re-)define research and care, and evaluate the way we deal with patients in both situations are still valid and acceptable.

Researchers section Translational Genetics:


Prof dr. Raoul CM Hennekam

Staff Members
Dr Diederik K Bosman
Dr Jan Maarten Cobben
Drs Chris C de Kruiff
Drs Wendela G Leeuwenburg-Pronk
Drs Saskia M Maas
Dr. Leonie A Menke 

Dr Cecilie Bredrup
Dr Channa de Winter

PhD Students
Drs Melanie Baas
Drs Sylvia Huisman
Drs Elcke Kranendonk
Drs Colin Mitchell
Drs Paul Mulder
Drs Floor Postema
Drs Susanne Stalman
Drs Nitash Zwaveling-Soonawala

Secretarial assistance:
Hester A Heidinga

Consulting external experts:
Prof William Dobyns (Seattle)
Prof Jane Kaye (Oxford)
Prof Nicolas Levi (Marseille)
Prof Chris Oliver (Birmingham)
Prof Carlos Lopez Otin (Bilbao)
Dr Sigrid Piening  (Assen)
Prof Stephen Robertson (Dunedin)
Prof Marco Tartaglia (Rome)
Prof Rajesh Thakker (Oxford)
Dr Lydia Thiboul (Harwell)
Dr Inge Van Balkom (Assen)


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