Journal Article

Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome

Cormier-Daire, Valérie, Bartholdi, Deborah, Ichkou, Amale, Schinzel, Albert, Alby, Caroline, Putoux, Audrey, Laurent, Nicole, Beales, Philip L, Encha-Razavi, Férechté, Thomas, Sophie, Rauch, Anita, Kannan, Rajesh, Nampoothiri, Sheela, Faivre, Laurence, Litzler, Julie, Elkhartoufi, Nadia, Vekemans, Michel, Munnich, Arnold, Boddaert, Nathalie, Attié-Bitach, Tania

2012

Overview

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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Acrocallosal Syndrome - diagnosis / Acrocallosal Syndrome - genetics / Acrocallosal Syndrome - physiopathology / Agenesis of Corpus Callosum - diagnosis / Agenesis of Corpus Callosum - physiopathology / Biological and medical sciences / Child, Preschool / Clinical genetics / Cryptorchidism / Developmental / Diagnosis / Diseases of the osteoarticular system / Female / Fetus / Fetuses / Fundamental and applied biological sciences. Psychology / Genetics of eukaryotes. Biological and molecular evolution / Hernias / Humans / Intellectual disabilities / Intellectual Disability - diagnosis / Intellectual Disability - physiopathology / Kinesin - genetics / Male / Malformations and congenital and or hereditary diseases involving bones. Joint deformations / Medical genetics / Medical sciences / Middle Aged / Molecular and cellular biology / Molecular genetics / Mutation / Neurology / Patients / Phenotype / Polydactyly - diagnosis / Polydactyly - physiopathology / Signal transduction