title: Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation.
abstract: BACKGROUND
  Corpus callosum malformation (CCM) is the most frequent brain malformation observed at birth. Because CCM is a highly heterogeneous condition, the prognosis of fetuses diagnosed prenatally remains uncertain, making prenatal counseling difficult.
  
  
  RESULTS
  We evaluated retrospectively a total of 138 fetuses, 117 with CCM observed on prenatal imaging examination, and 21 after postmortem autopsy. On ultrasound and/or magnetic resonance imaging, CCM was either isolated (N = 40) or associated with other neurological (N = 57) or extra cerebral findings (N = 21/20, respectively).
  
  
  RESULTS
  Most fetuses (N = 132) remained without a diagnosis at the time of pregnancy termination. This emphasizes the need to establish a neuropathological classification and to perform a genomic screening using comparative genomic hybridization. A neuropathological examination performed on 138 cases revealed a spectrum of CCMs, classified as follows: agenesis of corpus callosum (55), CC hypoplasia (30), CC dysmorphism (24), and CCM associated with a malformation of cortical development (29). Of interest, after fetopathological examination, only 16/40 malformations were classified as isolated, highlighting the importance of the autopsy following termination of pregnancy. Among the 138 cases, the underlying etiology was found in 46 cases: diabetes (one case), cytomegalovirus infection (one case), 23 chromosome abnormalities, and 21 mendelian conditions.
  
  
  CONCLUSIONS
  In our series of 138 cases of CCM, prenatal and postmortem examinations identified a variety of genetic causes. However, no diagnosis could be established in 67% of cases. The classification based on the underlying neurodevelopmental defects paves the way for further genetic studies and genotype-phenotype correlations.
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Service de Gynécologie-Obstétrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Alby
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Lucile
authors.initials: L
authors.lastname: Boutaud
authors.affiliation: Service de Gynécologie-Obstétrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Marangoni
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bessières
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Bonniere
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Amale
authors.initials: A
authors.lastname: Ichkou
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Elkhartoufi
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Université Paris Descartes, Paris Sorbonne Cité|Service de Neuropédiatrie, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.affiliation: Service de Radiologie Pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Sonigo
authors.affiliation: Service de Radiologie Pédiatrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors.forename: Anne-Elodie
authors.initials: AE
authors.lastname: Millischer
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Sophie
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Service de Gynécologie-Obstétrique, Hôpital Necker-Enfants Malades, APHP, Paris, France.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Yves
authors.initials: Y
authors.lastname: Ville
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Férechté
authors.initials: F
authors.lastname: Encha-Razavi
authors.affiliation: INSERM U1163, Institut Imagine, Hôpital Necker-Enfants Malades.|Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France.|Université Paris Descartes, Paris Sorbonne Cité
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
mesh_terms: D000025:Abortion, Eugenic; D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D001344:Autopsy; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005333:Fetus; D015870:Gene Expression; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal
chemical_list: D009419:Nerve Tissue Proteins
keywords: comparative genomics hybridization (CGH); corpus callosum malformation; fetus; neuropathology