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Antenatal spectrum of CHARGE syndrome in 40 fetuses with CHD7 mutations
  1. Marine Legendre1,2,
  2. Marie Gonzales3,4,
  3. Géraldine Goudefroye5,
  4. Frédéric Bilan2,6,
  5. Pauline Parisot7,
  6. Marie-José Perez8,
  7. Maryse Bonnière5,
  8. Bettina Bessières5,
  9. Jelena Martinovic9,
  10. Anne-Lise Delezoide10,11,
  11. Frédérique Jossic12,
  12. Catherine Fallet-Bianco13,
  13. Martine Bucourt14,
  14. Julia Tantau15,
  15. Philippe Loget16,
  16. Laurence Loeuillet17,
  17. Nicole Laurent18,
  18. Brigitte Leroy17,
  19. Houria Salhi15,
  20. Nicole Bigi8,
  21. Caroline Rouleau19,
  22. Fabien Guimiot10,11,
  23. Chloé Quélin20,
  24. Anne Bazin21,
  25. Caroline Alby22,
  26. Amale Ichkou5,
  27. Roselyne Gesny5,
  28. Alain Kitzis2,6,
  29. Yves Ville22,23,
  30. Stanislas Lyonnet1,5,23,
  31. Ferechte Razavi1,5,23,
  32. Brigitte Gilbert-Dussardier2,
  33. Michel Vekemans1,5,23,
  34. Tania Attié-Bitach1,5,23
  1. 1INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France
  2. 2Service de Génétique, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
  3. 3Service de Génétique et d'Embryologie Médicales, Hôpital Armand Trousseau, Assistance Publique Hôpitaux de Paris (APHP), Paris, France
  4. 4Université Pierre et Marie Curie, Paris, France
  5. 5Département de Génétique, Hôpital Necker-Enfants Malades, APHP, Paris, France
  6. 6UMR CNRS 6187, Université de Poitiers, Poitiers, France
  7. 7Service de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France
  8. 8Service de Génétique Médicale, Hôpital Arnaud de Villeneuve, Montpellier, France
  9. 9Service de Biologie du Développement, Hôpital Robert Debré, APHP, Paris, France
  10. 10Université Paris Diderot, Paris, France
  11. 11Unité de Foetopathologie, Hôpital Antoine Béclère, Clamart, France
  12. 12Département de Fœtopathologie, Hôpital de Nantes, Nantes, France
  13. 13Unité de Foetopathologie, Maternité Port-Royal, Groupe Hospitalier Cochin-Hotel-Dieu, APHP, Paris, France
  14. 14Service d'Anatomie et de Cytologie Pathologiques, Hôpital Jean Verdier, APHP, Paris, France
  15. 15Service d'Anatomopathologie, Hôpital Cochin-Saint-Vincent de Paul, APHP, Paris, France
  16. 16Service d'Anatomie et de Cytologie Pathologiques, CHU Pontchaillou, Rennes, France
  17. 17Service d'Anatomie et de Cytologie Pathologiques, CHI Poissy, Saint Germain en Laye, France
  18. 18Service d'Anatomie Pathologique, CHU Dijon, Dijon, France
  19. 19Département d'Anatomopathologie, Hôpital Lapeyronie, Montpellier, France
  20. 20Service de Génétique Clinique, Hôpital Sud, Rennes, France
  21. 21Département de Génétique, Laboratoire CERBA, Cergy Pontoise, France
  22. 22Service de Gynécologie Obstétrique, Hôpital Necker-Enfants Malades, APHP, Paris, France
  23. 23Université Paris Descartes, Paris, France
  1. Correspondence to Professor Tania Attie-Bitach, Département de Génétique et INSERM U-781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France; tania.attie{at}inserm.fr

Abstract

Background CHARGE syndrome is a rare, usually sporadic disorder of multiple congenital anomalies ascribed to a CHD7 gene mutation in 60% of cases. Although the syndrome is well characterised in children, only one series of 10 fetuses with CHARGE syndrome has been reported to date. Therefore, we performed a detailed clinicopathological survey in our series of fetuses with CHD7 mutations, now extended to 40 cases. CHARGE syndrome is increasingly diagnosed antenatally, but remains challenging in many instances.

Method Here we report a retrospective study of 40 cases of CHARGE syndrome with a CHD7 mutation, including 10 previously reported fetuses, in which fetal or neonatal clinical, radiological and histopathological examinations were performed.

Results Conversely to postnatal studies, the proportion of males is high in our series (male to female ratio 2.6:1) suggesting a greater severity in males. Features almost constant in fetuses were external ear anomalies, arhinencephaly and semicircular canal agenesis, while intrauterine growth retardation was never observed. Finally, except for one, all other mutations identified in our antenatal series were truncating, suggesting a possible phenotype–genotype correlation.

Conclusions Clinical analysis allowed us to refine the clinical description of CHARGE syndrome in fetuses, describe some novel features and set up diagnostic criteria in order to help the diagnosis of CHARGE syndrome after termination of pregnancies following the detection of severe malformations.

  • Clinical genetics
  • Congenital heart disease
  • Genetic screening/counselling
  • Molecular genetics

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