title: Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.
abstract: BACKGROUND
  Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathway, as being responsible for this syndrome.
  
  
  METHODS
  We sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based on facial dysmorphism and brain anomalies.
  
  
  RESULTS
  Seven mutations were identified at the KIF7 locus in these five cases, six of which are novel. We describe the first four compound heterozygous cases. In all patients, the diagnosis was suspected based on the craniofacial features, despite the absence of corpus callosum anomaly in one and of polydactyly in another. Hallux duplication was absent in 4/5 cases.
  
  
  CONCLUSIONS
  These results show that ACLS has a variable expressivity and can be diagnosed even in the absence of the two major features, namely polydactyly or agenesis or hypoplasia of the corpus callosum. Facial dysmorphism with hypertelorism and prominent forehead in all the cases, as well as vermis dysgenesis with brainstem anomalies (molar tooth sign), strongly indicated the diagnosis. KIF7 should be tested in less typical patients in whom craniofacial features are suggestive of ACLS.
authors.affiliation: INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Putoux
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
authors.forename: Albert
authors.initials: A
authors.lastname: Schinzel
authors.forename: Deborah
authors.initials: D
authors.lastname: Bartholdi
authors.forename: Caroline
authors.initials: C
authors.lastname: Alby
authors.forename: Sophie
authors.initials: S
authors.lastname: Thomas
authors.forename: Nadia
authors.initials: N
authors.lastname: Elkhartoufi
authors.forename: Amale
authors.initials: A
authors.lastname: Ichkou
authors.forename: Julie
authors.initials: J
authors.lastname: Litzler
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Férechté
authors.initials: F
authors.lastname: Encha-Razavi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kannan
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
mesh_terms: D055673:Acrocallosal Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis / Q000503:physiopathology; D002675:Child, Preschool; D005260:Female; D005333:Fetus; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000503:physiopathology; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D017689:Polydactyly / Q000175:diagnosis / Q000503:physiopathology
chemical_list: C502069:KIF7 protein, human; D016547:Kinesins