title: Severe X-linked chondrodysplasia punctata in nine new female fetuses.
abstract: OBJECTIVE
  Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations.
  
  
  METHODS
  To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism.
  
  
  RESULTS
  The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation.
  
  
  CONCLUSIONS
  Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations.
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, France.|GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.|Service d'Anatomo-Pathologie, Faculté de Médecine de Dijon, Dijon, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lefebvre
authors.affiliation: APHP, Hôpital Saint-Antoine, Biochimie B, Laboratoire de Référence pour le Diagnostic Génétique des Maladies Rares, Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dufernez
authors.affiliation: GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.
authors.forename: Ange-Line
authors.initials: AL
authors.lastname: Bruel
authors.affiliation: Service de Génétique et d'Embryologie Médicales, Université Paris VI, Hôpital Trousseau, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU Dijon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU Dijon, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Saint-Onge
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU Dijon, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Gigot
authors.affiliation: Center for Medical Genetics, Hospital Erasme, ULB, Brussels, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Desir
authors.affiliation: Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire, Hôpital Erasme, Université Libre de Bruxelles, Brussel, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Daelemans
authors.affiliation: CHU Nantes, Laboratoire d'anatomopathologie A, Nantes, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jossic
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schmitt
authors.affiliation: Department of Gynecology, Hôpital Pellegrin, Bordeaux, France.
authors.forename: Raphaele
authors.initials: R
authors.lastname: Mangione
authors.affiliation: Service de pathologie, CHU de Bordeaux, Bordeaux, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Pelluard
authors.affiliation: Service de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU de Lille, Lille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vincent-Delorme
authors.affiliation: Hôpital de la Croix Rousse, CHU Lyon, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Labaune
authors.affiliation: Génétique médicale, CHRU Arnaud de Villeneuve, Montpellier, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bigi
authors.affiliation: Pathological Anatomy and Cytology Centre, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: D'Olne
authors.affiliation: Department of Developmental Biology, Hôpital Robert Debré, Paris, France.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.affiliation: Service de Génétique, Centre Hospitalo-Universitaire Tours, Tours, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.affiliation: Service de Génétique, Centre Hospitalo-Universitaire Tours, Tours, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Blesson
authors.affiliation: Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.affiliation: GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, France.|GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.
authors.forename: Salima
authors.initials: S
authors.lastname: El Chehadeh
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.affiliation: Service de Génétique et d'Embryologie Médicales, Université Paris VI, Hôpital Trousseau, Paris, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Joyé
authors.affiliation: Service de Gynécologie-Obstétrique, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Vibert-Guigue
authors.affiliation: Service de Gynécologie-Obstétrique, Centre Hospitalier Sud Francilien (CHSF), Corbeil-Essonnes, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Rigonnot
authors.affiliation: Service de Gynécologie, Hôpital Le Bocage, Dijon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Rousseau
authors.affiliation: GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.|Service de dermatologie, Hôpital Le Bocage, Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vabres
authors.affiliation: Service de Gynécologie, Centre Hospitalo-Universitaire Tours, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hervé
authors.affiliation: Laboratory of Mass Spectrometry-APLIPID, Faculté de Médecine Pierre et Marie Curie, ER7-UPMC, Paris, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Lamazière
authors.affiliation: GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.|Laboratoire de Génétique Moléculaire, CHU Dijon, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Rivière
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, France.|GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: Service d'Anatomo-Pathologie, Faculté de Médecine de Dijon, Dijon, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, France.|GAD: EA4271 « Génétique des Anomalies du Développement » (GAD), FHU-TRANSLAD, Université de Bourgogne, Dijon, France.
authors.forename: Christel
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authors.lastname: Thauvin-Robinet
mesh_terms: D002806:Chondrodysplasia Punctata / Q000000981:diagnostic imaging* / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011859:Radiography; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013251:Steroid Isomerases / Q000235:genetics; D016216:Ultrasonography, Prenatal; D049951:X Chromosome Inactivation
chemical_list: D005819:Genetic Markers; D013251:Steroid Isomerases; C090445:EBP protein, human