Holt Oram syndrome: a registry-based study in Europe

Orphanet Journal of Rare Diseases

Helen Dolk^2,21  Christine Verellen-Dumoulin^1,16  David Tucker⁴  Catherine Rounding^1,12  Anke Rissmann^1,15  Judith Rankin⁵  Annette Queisser-Wahrendorf^1,14  Anna Pierini⁷  Vera Nelen^1,11  Bob McDonnell^1,18  Kari Klungsoyr^1,17  Babak Khoshnood⁶  Martin Haeusler⁸  Miriam Gatt^1,19  Judith LS Budd²  Paula Braz¹  Jorieke EH Bergman^2,20  Larraitz Arriola⁹  Marie-Claude Addor^2,22  Elisa Calzolari^1,13  Diana Wellesley^2,23  Ester Garne^1,10  Ruth Greenlees^2,21  Ljubica Boban³  Ingeborg Barisic³ 

[1] Departamento de Epidemiologia, Instituto Nacional de Saude Doutor Ricardo Jorge, Av. Padre Cruz, Lisbon 1649-016, Portugal;Department of Health Sciences, University of Leicester, 22 28 Princess Road West, Leicester LE1 6TP, UK;Zagreb Children¿s Hospital, Medical School, University of Zagreb, Klaiceva 16, Zagreb 10 000, Croatia;Congenital Anomaly Register & Info Service Public Health Level 3 West Wing, Singleton Hospital, Sketty Lane, Swansea SA2 8QA, Wales, UK;Institute of Health & Society, Newcastle University, Newcastle upon Tyne NE2 4AA, UK;Paris Registry of Congenital Malformations, INSERM U953, Maternite de Port?Royal, 53 av de l¿Observatoire, Paris 75014, France;CNR Institute of Clinical Physiology, Via Moruzzi 1, Pisa I 56124, Italy;Styrian Malformation Registry, Medical University of Graz, Auenbruggerplatz 14, Graz AT 8036, Austria;Registro Anomalias Congenitas CAPV. Dirección de Salud Pública. Departamento de Sanidad. Instituto BIO-Donostia, Basque Government CIBER Epidemiología y Salud Pública - CIBERESP, Donostia-San Sebastian 1, Vitoria Gasteiz 01010, Spain;Pediatric Department, Hospital Lillebaelt, Skovvangen 2-6, Kolding DK 6000, Denmark;Provinciaal Instituut voor Hygiene, Kronenbrgstraat 45, Antwerp B-2000, Belgium;National Perinatal Epidemiology Unit, University of Oxford, Old Road, Headington OX3 7LF, Oxford, UK;Registro IMER, Azienda Ospedaliero-Universitaria di Ferrara, Corso Giovecca, Ferrara 202 44121, Italy;Universitätskinderklinik Mainz, Langenbeckstrasse 1, Postfach 3960, Mainz D 55101, Germany;Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke University, Leipzigerstrasse, Haus 39, Magdeburg D 39120, Germany;Institut de Pathologie et de Génétique, Avenue Georges Lemaître 25, Charleroi (Gosselies) 6041, Belgium;Medical Birth Registry of Norway, University of Bergen, Kalfareien 31, Bergen N-5018, Norway;Health Information Unit, Health Service Executive, Dr Stevens Hospital, Dublin 8, Dublin, Ireland;Malta Congenital Anomalies Registry, Directorate of Health Information and Research, G¿mangia Hill PTA 1313, G¿mangia, Malta;Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen 9700 RB, The Netherlands;EUROCAT Central Registry, University of Ulster, Jordanstown Campus, Room 12 L09 Shore Road, Newtownabbey, Co. Antrim, Northern Ireland BT37 0QB, UK;Division of Medical Genetics, CHUV, Lausanne, Switzerland;Wessex Clinical Genetics Service, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK

关键词: Europe;    Epidemiology;    Prenatal diagnosis;    Congenital anomalies;    Holt Oram syndrome;   

Others  :  1149474
DOI  :  10.1186/s13023-014-0156-y

 received in 2014-06-11, accepted in 2014-09-30,  发布年份 2014

【 摘 要 】

Background

Holt-Oram syndrome (HOS) is an autosomal dominant disorder characterised by upper limb anomalies and congenital heart defects. We present epidemiological and clinical aspects of HOS patients using data from EUROCAT (European Surveillance of Congenital Anomalies) registries.

Methods

The study was based on data collected during 1990¿2011 by 34 registries. The registries are population-based and use multiple sources of information to collect data on all types of birth using standardized definitions, methodology and coding. Diagnostic criteria for inclusion in the study were the presence of radial ray abnormalities and congenital heart disease (CHD), or the presence of either radial ray anomaly or CHD, with family history of HOS.

Results

A total of 73 cases of HOS were identified, including 11 (15.1%) TOPFA and 62 (84.9%) LB. Out of 73 HOS cases, 30.8% (20/65) were suspected prenatally, 55.4% (36/65) at birth, 10.7% (7/65) in the first week of life, and 3.1% (2/65) in the first year of life. The prenatal detection rate was 39.2% (20/51), with no significant change over the study period. In 55% (11/20) of prenatally detected cases, parents decided to terminate pregnancy. Thumb anomalies were reported in all cases. Agenesis/hypoplasia of radius was present in 49.2% (30/61), ulnar aplasia/hypoplasia in 24.6% (15/61) and humerus hypoplasia/phocomelia in 42.6% (26/61) of patients. Congenital heart defects (CHD) were recorded in 78.7% (48/61) of patients. Isolated septal defects were present in 54.2 (26/48), while 25% (12/48) of patients had complex/severe CHD. The mean prevalence of HOS diagnosed prenatally or in the early years of life in European registries was 0.7 per 100,000 births or 1:135,615 births.

Conclusions

HOS is a rare genetic condition showing regional variation in its prevalence. It is often missed prenatally, in spite of the existence of major structural anomalies. When discovered, parents in 45% (9/20) of cases opt for the continuation of pregnancy. Although a quarter of patients have severe CHD, the overall first week survival is very good, which is important information for counselling purposes.

【 授权许可】

   
2014 Barisic et al.; licensee BioMed Central Ltd.

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