6533b7dbfe1ef96bd127017f
RESEARCH PRODUCT
CNS involvement in OFD1 syndrome: a clinical, molecular, and neuroimaging study
E Del GiudiceM MaccaF ImperatiA D'amicoP ParentL PasquierV LayetS LyonnetV Stamboul DarmencyC Thauvin RobinetB FrancoOral Facial Digital Type I. Ofd1 Collaborative Group Including Bankier AS WhiteF CollinsM GardnerSl KeelingT TanJ McgaughranF MckenzieK LhottaF AbdullaA DestreeK DevriendtG MatthijsR FerrierDr McleodJm FriedmanH HeranGe GrahamR KlattA TeebiP JensenB GilbertS MarlinA TrousseauA ToutainA DavidS OdentD HéronL BurglenM RioPs JoukG PlessisJ LespinasseF GiulianoC Turc CarelRc BetzS HeimM Klehr MartinelliD KotzotM MinneropC Schell ApacikA GalU OrthG Gillessen KaesbachB ZollJ MuckeA TzschachE GoddeR CarmiN BrunettiA ScarcellaP CastelluccioC CastellanO GerolaS BigoniL ZelanteS FoggiaA SabatoG BianchiniAs NuovaR VirdisGiovanni Battista FerreroA SelicorniF GurrieriS CuoreA MegarbaneMa ChiongEm CutiongcoE ObersztynA Kutkowska KazmierczakCr MotaD De MagalhaesG Stevanovic Del Pozo JsMg BarcinaE IwarssonV GraberR OkhowatA ShinzelHg BrunnerI KrapelsV HoversFa BeemerP TerhalP RumpN ElciogluO ToprakJ BurnA HendersonE JonesJ DeanB CastleF MacdonaldP FarndonD WilliamsT HomfrayM LeesS LoughlinFl RaymondD TrumpJ WhittakerS SmithsonJ RankinC TurnerL BirdJ ChibukD Masser FryeS SellS AmyI SchaferLe BartosheskyK JennyP BenkeC CurryA SwenertonT TreismanJw DunlapV ShashiE ReichT ReimschiselR PfauB PoberJ RobertsonJ RoggenbuckH. Thiesesubject
Central nervous systemNeuroimagingNeuropsychological TestsPharmacologyBioinformaticsSettore MED/03 - GENETICA MEDICACiliopathiesCohort Studies03 medical and health sciences0302 clinical medicineNeuroimagingCentral Nervous System DiseasesmedicineHumansGenetics(clinical)Pharmacology (medical)Orofaciodigital type 1Ciliopathies; Neurodevelopmental phenotype; Neuroimaging; OFD1; Central Nervous System Diseases; Cohort Studies; Female; Humans; Magnetic Resonance Imaging; Mutation; Neuropsychological Tests; Orofaciodigital Syndromes; Medicine (all); Genetics (clinical); Pharmacology (medical)Agenesis of the corpus callosumGenetics (clinical)030304 developmental biologyMedicine(all)0303 health sciencesbusiness.industryMedicine (all)ResearchCiliumNeuropsychologyCognitionGeneral MedicineOrofaciodigital Syndromesmedicine.diseasecentral nervous systemMagnetic Resonance ImagingPorencephalyCiliopathies3. Good healthmedicine.anatomical_structureMutationFemaleNeurodevelopmental phenotypeOFD1business030217 neurology & neurosurgerydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 | Orphanet Journal of Rare Diseases |