PT - JOURNAL ARTICLE AU - Audrey Putoux AU - Sheela Nampoothiri AU - Nicole Laurent AU - Valérie Cormier-Daire AU - Philip L Beales AU - Albert Schinzel AU - Deborah Bartholdi AU - Caroline Alby AU - Sophie Thomas AU - Nadia Elkhartoufi AU - Amale Ichkou AU - Julie Litzler AU - Arnold Munnich AU - Férechté Encha-Razavi AU - Rajesh Kannan AU - Laurence Faivre AU - Nathalie Boddaert AU - Anita Rauch AU - Michel Vekemans AU - Tania Attié-Bitach TI - Novel <em>KIF7</em> mutations extend the phenotypic spectrum of acrocallosal syndrome AID - 10.1136/jmedgenet-2012-101016 DP - 2012 Nov 01 TA - Journal of Medical Genetics PG - 713--720 VI - 49 IP - 11 4099 - http://jmg.bmj.com/content/49/11/713.short 4100 - http://jmg.bmj.com/content/49/11/713.full SO - J Med Genet2012 Nov 01; 49 AB - 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.