Caroline Alby1,2, Lucile Boutaud1,2, Maryse Bonnière2, Sophie Collardeau-Frachon3,4, Laurent Guibaud4,5, Estelle Lopez6,7, Ange-Line Bruel6,7, Bernard Aral6,7, Pascale Sonigo8, Philippe Roth9, Claude Vibert-Guigue10, Vanina Castaigne11, Bruno Carbonne12, Nicole Joyé13, Laurence Faivre6,7, Marie-Pierre Cordier14, Antoinette Bernabe Gelot15, Maurizio Clementi16, Isabella Mammi17, Michel Vekemans1,2, Féréchté Razavi1,2, Marie Gonzales2,13, Christel Thauvin-Robinet6,7, Tania Attié-Bitach1,2. 1. INSERM U1163, Institut Imagine, Université Paris Descartes, Paris, France. 2. Unité d'Embryofoetopathologie, Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France. 3. Département d'anatomopathologie, Hôpital-Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, France. 4. Université Claude Bernard Lyon I, CHU de Lyon, Lyon, France. 5. Service de radiologie, Hôpital-Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, France. 6. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Grand-Est, Hôpital d'Enfants, FHU TRANSLAD CHU Dijon Bourgogne, Dijon, France. 7. UMR 1231, GAD Inserm Université de Bourgogne, Dijon, France. 8. Service de Radiologie Pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France. 9. Service de Gynécologie Obstétrique, Necker-Enfants Malades, APHP, Paris, France. 10. Service de Gynécologie-Obstétrique, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France. 11. Unité de Diagnostic Anténatal, Service de Gynécologie Obstétrique, Hôpital Intercommunal de Créteil, Créteil Cedex, France. 12. Service Département de Gynécologie-Obstétrique, Hôpital Princesse Grace, Monaco. 13. Département de Génétique Médicale, Hôpital Armand Trousseau, APHP, UPMC-Sorbonne Universités, Paris, France. 14. Service de génétique, groupement hospitalier Est, HCL, Bron, France. 15. Service d'anatomie pathologique, Hôpital Armand-Trousseau, APHP, Paris, France. 16. Sezione di Genetica Clinica Epidemiologica, Dipartimento di Pediatria, Azienda Ospedaliera Universitaria di Padova, Padova, Italia. 17. Ambulatorio di Genetica Medica, Ospedale Dolo, Dolo, Italia.
Abstract
BACKGROUND: OFD1 syndrome is a rare ciliopathy inherited on a dominant X-linked mode, typically lethal in males in the first or second trimester of pregnancy. It is characterized by oral cavity and digital anomalies possibly associated with cerebral and renal signs. Its prevalence is between 1/250,000 and 1/50,000 births. It is due to heterozygous mutations of OFD1 and mutations are often de novo (75%). Familial forms show highly variable phenotypic expression. OFD1 encodes a protein involved in centriole growth, distal appendix formation, and ciliogenesis. CASES: We report the investigation of three female fetuses in which corpus callosum agenesis was detected by ultrasound during the second trimester of pregnancy. In all three fetuses, fetopathological examination allowed the diagnosis of OFD1 syndrome, which was confirmed by molecular analysis. CONCLUSIONS: To our knowledge, these are the first case reports of antenatal diagnosis of OFD1 syndrome in the absence of familial history, revealed following detection of agenesis of the corpus callosum. They highlight the impact of fetal examination following termination of pregnancy for brain malformations. They also highlight the contribution of ciliary genes to corpus callosum development.
BACKGROUND:OFD1 syndrome is a rare ciliopathy inherited on a dominant X-linked mode, typically lethal in males in the first or second trimester of pregnancy. It is characterized by oral cavity and digital anomalies possibly associated with cerebral and renal signs. Its prevalence is between 1/250,000 and 1/50,000 births. It is due to heterozygous mutations of OFD1 and mutations are often de novo (75%). Familial forms show highly variable phenotypic expression. OFD1 encodes a protein involved in centriole growth, distal appendix formation, and ciliogenesis. CASES: We report the investigation of three female fetuses in which corpus callosum agenesis was detected by ultrasound during the second trimester of pregnancy. In all three fetuses, fetopathological examination allowed the diagnosis of OFD1 syndrome, which was confirmed by molecular analysis. CONCLUSIONS: To our knowledge, these are the first case reports of antenatal diagnosis of OFD1 syndrome in the absence of familial history, revealed following detection of agenesis of the corpus callosum. They highlight the impact of fetal examination following termination of pregnancy for brain malformations. They also highlight the contribution of ciliary genes to corpus callosum development.
Authors: Jennifer F Gardner; Thomas D Cushion; Georgios Niotakis; Heather E Olson; P Ellen Grant; Richard H Scott; Neil Stoodley; Julie S Cohen; Sakkubai Naidu; Tania Attie-Bitach; Maryse Bonnières; Lucile Boutaud; Férechté Encha-Razavi; Sheila M Palmer-Smith; Hood Mugalaasi; Jonathan G L Mullins; Daniela T Pilz; Andrew E Fry Journal: Brain Sci Date: 2018-08-07
Authors: Nunziana Pezzella; Guglielmo Bove; Roberta Tammaro; Brunella Franco Journal: Am J Med Genet C Semin Med Genet Date: 2022-02-02 Impact factor: 3.359