Raoul C M Hennekam

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (492)2503.78 Total impact

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    ABSTRACT: We report on a sister and two brothers born to healthy Iranian parents with mild intellectual disability, progressive muscle weakness, and characteristic facies. including highly arched eyebrows, down-slanting palpebral fissures, prominent nasal bridge, prominent nose, columella extending below alae nasi, narrow mouth, narrow palate, and dental caries, and in one of them an inability to abduct the left eye. Electrophysiological studies showed signs of myopathy, and muscle biopsies demonstrated only nonspecific signs. Brain MRIs in two of the sibs showed leukencephalopathy with delayed myelination, frontal and parietal hyperintensities, and hippocampal atrophy in one. We have been unable to find a description of this association of features in literature. Based on the occurrence in siblings, no significant difference in phenotype between the brothers and sister, absence of manifestations in parents, and a likely consanguinity between parents we performed a homozygosity mapping. A single identical-by-descent bloc encompassing 57 genes located at 3p24.3-p25.3 was found to segregate within the family with this phenotype. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 07/2015; DOI:10.1002/ajmg.a.37248 · 2.16 Impact Factor
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    Dataset: OMIM 601559
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    Dataset: 601559[1]
  • 07/2015; 2(Suppl 1):A12. DOI:10.1186/2194-7791-2-S1-A12
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    ABSTRACT: Maternal Uniparental Disomy of chromosome 14 (matUPD(14)) resembles Prader-Willi syndrome. Since positive effects of growth hormone (GH) are observed in individuals with PWS, treatment with GH may be useful in individuals with matUPD(14) as well. The aim of this study was to investigate the effect of GH treatment on growth and body composition in children with matUPD(14). Prospective observational study of GH treatment in two girls with matUPD(14) during 2 years, and spontaneous growth in another matUPD(14) girl of similar age. Three girls (patient A, B and C, aged 8.9, 11.4 and 12.7 years respectively) with matUPD(14). Patients A and B were treated with GH during two years. Patient C was not treated with GH, as she was diagnosed at an age at which she attained near-final height. Main outcome measures included height, weight, body proportions, IGF-1, bone age, DXA scan for body composition. In both treated girls a considerable increase in height (from -2.3SD and -1.2SD to -1.2SD and -0.6SD, respectively) and IGF-1 levels (from +0.1SD and -1.4SD to +1.3SD and +0.9SD, respectively), and in patient A a decrease in weight (+1.2 SD to -0.7SD), and improved body composition (fat percentage from 51.5% to 45.4%). Both experienced improved muscle strength. GH treatment in matUPD(14) cases can show beneficial effects on growth and body composition if started in time. Larger, international studies to determine detailed effectivity and side-effects are suggested. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 06/2015; DOI:10.1111/cen.12841 · 3.46 Impact Factor
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    ABSTRACT: Robin sequence (RS) can be defined as the combination of micrognathia and upper airway obstruction/glossoptosis causing neonatal respiratory problems, with or without a cleft palate and either isolated or non-isolated. Pathogenesis varies widely. We hypothesize that optimal treatment depends on pathogenesis and therefore patients should be stratified according to diagnosis. Here, we evaluate diagnoses and (presumed) pathogeneses in an RS cohort. Medical records of all RS patients presenting between 1995-2013 in three academic hospitals were evaluated. Four clinical geneticists re-evaluated all information, including initial diagnosis. Diagnoses were either confirmed, considered uncertain, or rejected. If uncertain or rejected, patients were re-evaluated. Subsequent results were re-discussed and a final conclusion was drawn. We included 191 RS patients. After re-evaluation and changing initial diagnoses in 48 of the 191 patients (25.1%), 37.7% of the cohort had isolated RS, 8.9% a chromosome anomaly, 29.3% a Mendelian disorder, and 24.1% no detectable cause. Twenty-two different Mendelian disorders were diagnosed, of which Stickler syndrome was most frequent. Stratification of diagnoses according to (presumed) pathogenic mechanism in 73 non-isolated patients with reliable diagnoses showed 43.9% to have a connective tissue dysplasia, 5.5% a neuromuscular disorder, 47.9% a multisystem disorder, and 2.7% an unknown mechanism. We diagnosed more non-isolated RS patients compared to other studies. Re-evaluation changed initial diagnosis in a quarter of patients. We suggest standardized re-evaluation of all RS patients. Despite the relatively high diagnostic yield pathogenesis could be determined in only 59.7% (71/119), due to limited insight in pathogenesis in diagnosed entities. Further studies into pathogenesis of entities causing RS are indicated. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 05/2015; 167(9). DOI:10.1002/ajmg.a.37154 · 2.16 Impact Factor
  • Elcke J Kranendonk · M Corrette Ploem · Raoul C M Hennekam
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    ABSTRACT: Many current paediatric studies concern relationships between genes and environment and discuss aetiology, treatment and prevention of Mendelian and multifactorial diseases. Many of these studies depend on collection and long-term storage of data and biological material from affected children in biobanks. Stored material is a source of personal information of the donor and his family and could be used in an undesirable context, potentially leading to discrimination and interfering with a child's right to an open future. Here, we address the normative framework regarding biobanking with residual tissue of children, protecting the privacy interests of young biobank donors (0-12 years). We analyse relevant legal documents concerning storage and use of children's material for research purposes. We explore the views of 17 Dutch experts involved in paediatric biobank research and focus on informed consent for donation of leftover tissue as well as disclosure of individual research findings resulting from biobank research. The results of this analysis show that experts have no clear consensus about the appropriate rules for storage of and research with children's material in biobanks. Development of a framework that provides a fair balance between fundamental paediatric research and privacy protection is necessary.European Journal of Human Genetics advance online publication, 15 April 2015; doi:10.1038/ejhg.2015.59.
    European journal of human genetics: EJHG 04/2015; DOI:10.1038/ejhg.2015.59 · 4.35 Impact Factor
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    ABSTRACT: Frontometaphyseal dysplasia (FMD) is a distinctive sclerosing skeletal dysplasia associated with a number of non-skeletal manifestations including hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. Some, but not all, patients have mutations in FLNA causing the condition. Consonant with the X chromosomal location of FLNA males are generally more severely affected than females. FLNA mutations can be detected in 82% of affected males. We describe seven patients (one male, six females) all of whom have the major clinical and radiological features of FMD, but without detectable mutations in FLNA. The females in our cohort are affected to a similar degree as is usually found in males. In addition, all patients have marked keloid formation at various body sites, including the eye, from an early age. Other features that may indicate a different etiology in these patients are the increased frequency of cleft palate, Robin sequence, tracheal stenosis, and mild intellectual disability, which all occur in three of more patients in the present group. All patients are isolated. We hypothesize that the presently reported patients represent further evidence that phenotypes strongly resembling FMD exist that are not accounted for by mutations in FLNA. Since the frequency of several of the manifestations, their sporadic presentations, and the presence of keloid formation differ from the X-linked form of this condition we propose de novo autosomal dominant acting mutations in a gene functionally related to FLNA, underpin this disorder. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 04/2015; 167(6). DOI:10.1002/ajmg.a.37044 · 2.16 Impact Factor
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    ABSTRACT: Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotype - phenotype correlations in more detail. We gathered information on 103 cytogenetically or molecularly confirmed affected individuals. TRPS I was present in 85 individuals (22 missense mutations, 62 other mutations), TRPS II in 14, and in 5 it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations in patients with TRPS I and TRPS II do not show a significant difference. In the limbs the main findings are short hands and feet, hypermobility, and a tendency for isolated metacarpals and metatarsals to be shortened. Nails of fingers and toes are typically thin and dystrophic. The radiological hallmark are the cone-shaped epiphyses and in TRPS II multiple exostoses. Osteopenia is common in both, as is reduced linear growth, both prenatally and postnatally. Variability for all findings, also within a single family, can be marked. Morbidity mostly concerns joint problems, manifesting in increased or decreased mobility, pain and in a minority an increased fracture rate. The hips can be markedly affected at a (very) young age. Intellectual disability is uncommon in TRPS I and, if present, usually mild. In TRPS II intellectual disability is present in most but not all, and again typically mild to moderate in severity. Missense mutations are located exclusively in exon 6 and 7 of TRPS1. Other mutations are located anywhere in exons 4-7. Whole gene deletions are common but have variable breakpoints. Most of the phenotype in patients with TRPS II is explained by the deletion of TRPS1 and EXT1, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm conclusions. Copyright © 2015. Published by Elsevier Masson SAS.
    European journal of medical genetics 03/2015; 58(5). DOI:10.1016/j.ejmg.2015.03.002 · 1.47 Impact Factor
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    ABSTRACT: Hydrops fetalis is an excessive fluid accumulation within the fetal extra vascular compartments and body cavities. Non-immune hydrops fetalis (NIHF), due to causes other than Rh alloimmunization, is the cause in >85% of all affected individuals. Herein we present an update of our earlier systematic literature review [Bellini et al., 2009] using all publications between 2007 and 2013. We excluded most of the initial 31,783 papers by using strict selection criteria, thus resulting in 24 relevant NIHF publications describing 1,338 individuals with NIHF. We subdivided the affected individuals into 14 classification groups based on the cause of NIHF (percentage of the total group): Cardiovascular (20.1%), Hematologic (9.3%), Chromosomal (9.0%), Syndromic (5.5%), Lymphatic Dysplasia (15.0%), Inborn Errors of Metabolism (1.3%), Infections (7.0%), Thoracic (2.3%), Urinary Tract Malformations (0.9%), Extra Thoracic Tumors (0.7%), TTTF-Placental (4.1%), Gastrointestinal (1.3%), Miscellaneous (3.6%), Idiopathic (19.8%). We discuss the results of the review. There may be some shifts in the percentages of etiological categories as compared to the previous review, but the small numbers within each category make drawing firm conclusions hazardous. We highlight the need for multi-center series of NIHF cases collected and classified using the same schemes in diagnostic work-ups to allow for comparisons of larger numbers of cases. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 02/2015; 167(5). DOI:10.1002/ajmg.a.36988 · 2.16 Impact Factor
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    ABSTRACT: Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with "DA2A with severe neurological abnormalities" and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with "atypical" forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s). Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 02/2015; 96(3). DOI:10.1016/j.ajhg.2015.01.003 · 10.93 Impact Factor
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    ABSTRACT: Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of sixteen patients with CdLS-like features caused by mutations in SMC3. Modelling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared to typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for ∼1-2% of CdLS-like phenotypes. This article is protected by copyright. All rights reserved.
    Human Mutation 02/2015; DOI:10.1002/humu.22761 · 5.14 Impact Factor
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    ABSTRACT: Background Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene. In remaining M-D patients, no genetic factor has been established, indicating genetic heterogeneity.Methods Patients were included in a prospective clinical database and recruited from referral centers and general neurology clinics in The Netherlands. To investigate new genetic causal factors in M-D syndrome, we performed homozygosity mapping combined with exome sequencing in a three-generation M-D family and genetically screened 24 additional patients with M-D.ResultsWe found co-segregation of the rare missense variant Thr1904Met in the RELN gene. By additional screening of an M-D cohort, we identified co-segregation of RELN variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic RELN mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 SGCE-negative M-D patients carried RELN rare missense variants.Conclusion We propose that RELN mutations contribute to the genetic heterogeneity of M-D. Reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures and modulation of synaptic transmission and plasticity. © 2015 International Parkinson and Movement Disorder Society
    Movement Disorders 02/2015; 30(3):n/a-n/a. DOI:10.1002/mds.26070 · 5.68 Impact Factor
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    ABSTRACT: Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome- and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care.
    European Journal of HumanGenetics 01/2015; 23(9). DOI:10.1038/ejhg.2014.279 · 4.35 Impact Factor
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    ABSTRACT: Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7), spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders.
    American Journal of Medical Genetics Part A 01/2015; 167(3). DOI:10.1002/ajmg.a.36922 · 2.16 Impact Factor
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    ABSTRACT: Singleton-Merten syndrome (SMS) is an infrequently described autosomal-dominant disorder characterized by early and extreme aortic and valvular calcification, dental anomalies (early-onset periodontitis and root resorption), osteopenia, and acro-osteolysis. To determine the molecular etiology of this disease, we performed whole-exome sequencing and targeted Sanger sequencing. We identified a common missense mutation, c.2465G>A (p.Arg822Gln), in interferon induced with helicase C domain 1 (IFIH1, encoding melanoma differentiation-associated protein 5 [MDA5]) in four SMS subjects from two families and a simplex case. IFIH1 has been linked to a number of autoimmune disorders, including Aicardi-Goutières syndrome. Immunohistochemistry demonstrated the localization of MDA5 in all affected target tissues. In vitro functional analysis revealed that the IFIH1 c.2465G>A mutation enhanced MDA5 function in interferon beta induction. Interferon signature genes were upregulated in SMS individuals' blood and dental cells. Our data identify a gain-of-function IFIH1 mutation as causing SMS and leading to early arterial calcification and dental inflammation and resorption. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 01/2015; 96(2). DOI:10.1016/j.ajhg.2014.12.014 · 10.93 Impact Factor
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    ABSTRACT: The European Journal of Human Genetics is the official Journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports, News and Commentary articles and reviews in the rapidly expanding field of human genetics and genomics.
    European journal of human genetics: EJHG 12/2014; 23(10). DOI:10.1038/ejhg.2014.270 · 4.35 Impact Factor
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    ABSTRACT: Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimidine metabolism. Deficiency of this enzyme leads to an accumulation of thymine and uracil and a deficiency of metabolites distal to the catabolic enzyme. The disorder presents with a wide clinical spectrum, ranging from asymptomatic to severe neurological manifestations, including intellectual disability, seizures, microcephaly, autistic behavior, and eye abnormalities. Here, we report on an 11-year-old Malaysian girl and her 6-year-old brother with DPD deficiency who presented with intellectual disability, microcephaly, and hypotonia. Brain MRI scans showed generalized cerebral and cerebellar atrophy and callosal body dysgenesis in the boy. Urine analysis showed strongly elevated levels of uracil in the girl and boy (571 and 578 mmol/mol creatinine, respectively) and thymine (425 and 427 mmol/mol creatinine, respectively). Sequence analysis of the DPYD gene showed that both siblings were homozygous for the mutation c.1651G>A (pAla551Thr).
    Molecular syndromology 12/2014; 5(6):299-303. DOI:10.1159/000366074
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    ABSTRACT: The internet pre-eminently marks an era with unprecedented chances for patient care. Especially individuals with rare disorders and their families can benefit. Their handicap of low numbers vanishes and can become a strength, as small, motivated and well-organized international support groups allow easily fruitful collaborations with physicians and researchers. Jointly setting research agendas and building wikipedias has eventually led to building of multi-lingual databases of longitudinal data on physical and behavioural characteristics of individuals with several rare disorders which we call waihonapedias (waihona meaning treasure in Hawaiian). There are hurdles to take, like online security and reliability of diagnoses, but sharing experiences and true collaborations will allow better research and patient care for fewer costs to patients with rare disorders. Copyright © 2014. Published by Elsevier Masson SAS.
    European Journal of Medical Genetics 11/2014; 58(1). DOI:10.1016/j.ejmg.2014.10.006 · 1.47 Impact Factor
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    ABSTRACT: Robin Sequence (RS) is characterized by micrognathia and upper airway obstruction (UAO), with or without cleft palate, causing respiratory and feeding problems. Management options are: positioning; nasopharyngeal airway (NPA); tongue-lip adhesion (TLA); mandibular distraction (MDO); and tracheostomy. Controversy exists in literature regarding RS definition and management. Here we describe definitions, management strategies and criteria in opting for management strategies, used by Dutch and Belgian cleft teams.
    Journal of Cranio-Maxillofacial Surgery 11/2014; 43(1). DOI:10.1016/j.jcms.2014.10.015 · 2.93 Impact Factor

Publication Stats

16k Citations
2,503.78 Total Impact Points


  • 2015
    • VU University Medical Center
      • Department of Clinical Genetics
      Amsterdamo, North Holland, Netherlands
  • 1993–2015
    • University of Amsterdam
      • • Department of Paediatrics
      • • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2014
    • Cedars-Sinai Medical Center
      • Medical Genetics Institute
      Los Angeles, California, United States
  • 1993–2014
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Paediatrics
      • • Academic Medical Center
      • • Department of Clinical Genetics
      Amsterdamo, North Holland, Netherlands
  • 2005–2013
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Institute of Child Health Calcutta
      Kolkata, West Bengal, India
    • University of Utah
      • Department of Pediatrics
      Salt Lake City, Utah, United States
  • 2005–2011
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      • Department of Clinical Genetics
      Londinium, England, United Kingdom
  • 2010
    • Maastricht University
      Maestricht, Limburg, Netherlands
    • Ghent University
      • Department of Molecular Biotechnology
      Gent, VLG, Belgium
  • 2007–2010
    • University College London
      • Institute of Child Health
      Londinium, England, United Kingdom
    • St. James University
      Сент-Джеймс, New York, United States
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • University of California, San Francisco
      • Department of Neurology
      San Francisco, California, United States
  • 2009
    • Institute for Child Health Policy (ICHP)
      Florida, United States
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      Giovanni Rotondo, Apulia, Italy
  • 2005–2009
    • National Human Genome Research Institute
      Maryland, United States
  • 2008
    • Clinical Molecular Genetics Society
      Londinium, England, United Kingdom
    • University of London
      Londinium, England, United Kingdom
  • 2006
    • University of the Ryukyus
      Okinawa, Okinawa, Japan
    • Leiden University Medical Centre
      • Department of Molecular Cell Biology
      Leyden, South Holland, Netherlands
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 1989–2005
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 2004
    • Universitair Ziekenhuis Ghent
      • Centre for Medical Genetics
      Gand, Flanders, Belgium
  • 2000
    • Utrecht University
      Utrecht, Utrecht, Netherlands
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
  • 1996
    • Accare – Kinder- en Jeugdpsychiatrie
      Assen, Drenthe, Netherlands
  • 1995
    • Leiden University
      • Molecular Cell Biology Group
      Leyden, South Holland, Netherlands
  • 1992
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands