title: CNS involvement in OFD1 syndrome: a clinical, molecular, and neuroimaging study.
abstract: BACKGROUND
  Oral-facial-digital type 1 syndrome (OFD1; OMIM 311200) belongs to the expanding group of disorders ascribed to ciliary dysfunction. With the aim of contributing to the understanding of the role of primary cilia in the central nervous system (CNS), we performed a thorough characterization of CNS involvement observed in this disorder.
  
  
  METHODS
  A cohort of 117 molecularly diagnosed OFD type I patients was screened for the presence of neurological symptoms and/or cognitive/behavioral abnormalities on the basis of the available information supplied by the collaborating clinicians. Seventy-one cases showing CNS involvement were further investigated through neuroimaging studies and neuropsychological testing.
  
  
  RESULTS
  Seventeen patients were molecularly diagnosed in the course of this study and five of these represent new mutations never reported before. Among patients displaying neurological symptoms and/or cognitive/behavioral abnormalities, we identified brain structural anomalies in 88.7%, cognitive impairment in 68%, and associated neurological disorders and signs in 53% of cases. The most frequently observed brain structural anomalies included agenesis of the corpus callosum and neuronal migration/organisation disorders as well as intracerebral cysts, porencephaly and cerebellar malformations.
  
  
  CONCLUSIONS
  Our results support recent published findings indicating that CNS involvement in this condition is found in more than 60% of cases. Our findings correlate well with the kind of brain developmental anomalies described in other ciliopathies. Interestingly, we also described specific neuropsychological aspects such as reduced ability in processing verbal information, slow thought process, difficulties in attention and concentration, and notably, long-term memory deficits which may indicate a specific role of OFD1 and/or primary cilia in higher brain functions.
authors.forename: Ennio
authors.initials: E
authors.lastname: Del Giudice
authors.forename: Marina
authors.initials: M
authors.lastname: Macca
authors.forename: Floriana
authors.initials: F
authors.lastname: Imperati
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Amico
authors.forename: Philippe
authors.initials: P
authors.lastname: Parent
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.forename: Valerie
authors.initials: V
authors.lastname: Layet
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Veronique
authors.initials: V
authors.lastname: Stamboul-Darmency
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy. franco@tigem.it.
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
mesh_terms: D002493:Central Nervous System Diseases / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D009483:Neuropsychological Tests; D009958:Orofaciodigital Syndromes / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology