title: Agenesis and dysgenesis of the corpus callosum: clinical, genetic and neuroimaging findings in a series of 41 patients.
abstract: Agenesis of the corpus callosum (ACC) is among the most frequent human brain malformations with an incidence of 0.5-70 in 10,000. It is a heterogeneous condition, for which several different genetic causes are known, for example, ACC as part of monogenic syndromes or complex chromosomal rearrangements. We systematically evaluated the data of 172 patients with documented corpus callosum abnormalities in the records, and 23 patients with chromosomal rearrangements known to be associated with corpus callosum changes. All available neuroimaging data, including CT and MRI, were re-evaluated following a standardized protocol. Whenever feasible chromosome and subtelomere analyses as well as molecular genetic testing were performed in patients with disorders of the corpus callosum in order to identify a genetic diagnosis. Our results showed that 41 patients with complete absence (agenesis of the corpus callosum-ACC) or partial absence (dysgenesis of the corpus callosum-DCC) were identified. Out of these 28 had ACC, 13 had DCC. In 11 of the 28 patients with ACC, the following diagnoses could be established: Mowat-Wilson syndrome (n = 2), Walker-Warburg syndrome (n = 1), oro-facial-digital syndrome type 1 (n = 1), and chromosomal rearrangements (n = 7), including a patient with an apparently balanced reciprocal translocation, which led to the disruption and a predicted loss of function in the FOXG1B gene. The cause of the ACC in 17 patients remained unclear. In 2 of the 13 patients with DCC, unbalanced chromosomal rearrangements could be detected (n = 2), while the cause of DCC in 11 patients remained unclear. In our series of cases a variety of genetic causes of disorders of the corpus callosum were identified with cytogenetic anomalies representing the most common underlying etiology.
authors.affiliation: Institute of Social Pediatrics and Adolescent Medicine of the University of Munich, München, Germany. schell-apacik@gmx.de
authors.forename: Chayim Can
authors.initials: CC
authors.lastname: Schell-Apacik
authors.forename: Kristina
authors.initials: K
authors.lastname: Wagner
authors.forename: Moritz
authors.initials: M
authors.lastname: Bihler
authors.forename: Birgit
authors.initials: B
authors.lastname: Ertl-Wagner
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinrich
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
authors.forename: Hubertus
authors.initials: H
authors.lastname: von Voss
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D061085:Agenesis of Corpus Callosum; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009421:Nervous System Malformations / Q000175:diagnosis / Q000235:genetics*; D011859:Radiography
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