INTU-related oral-facial-digital syndrome type VI: A confirmatory report
Authors: Y Capri
N Elenga
L Perrin
Y Vial
H Lucron
A-L Bruel
A Defo
A Favre
L Faivre
J Levy
A Verloes
C Thauvin-Robinet
S Passemard
A-C Tabet
Journal: Clinical Genetics (2018)
Discipline: CLINICAL MEDICINE
Keywords: CPLANE; INTU; NGS; oral-facial-digital syndrome.
Affiliations: UMR 1231 GAD, G√©n√©tique des Anomalies du D√©veloppement; Universit√© de Bourgogne- et Franche-Comt√©; Dijon France, FHU TRANSLAD; Centre Hospitalier Universitaire de Bourgogne et Franche Comt√©; Dijon France, Department of Genetics; APHP-Robert Debr√© University Hospital; Paris France, Department of Pediatrics Andr√©e Ros√©mon Regional Hospital; Cayenne French Guiana France, Antilles-Guyane University; Cayenne French Guiana France, Neonatal intensive care Unit; Andr√©e Ros√©mon Regional Hospital; Cayenne French Guiana France, Antilles-Guyane M3C Pediatric Cardiology Center; Centre Hospitalier Universitaire de Martinique; Fort-de-France France, Denis Diderot Medical School; Sorbonne-Paris-Cit√© University and INSERM U1141; Paris France, Centre de G√©n√©tique, Centre de r√©f√©rence Labellis√© Maladies rares Anomalies du D√©veloppement et syndromes malformatifs de l'est; H√¥pital d'Enfants, CHU Dijon Bourgogne; Dijon France

Abstract:  Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished by the co-occurrence of hamartomas and/or multiple frenula of the oral region and digital anomalies. Several clinical forms of OFD syndromes are distinguished by their associated anomalies and/or inheritance patterns, and at least 20 genetic types of OFD syndromes have been delineated. We describe here a child with preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect, delayed development and cerebellar peduncles displaying the molar tooth sign. Whole-exome sequencing and SNP array identified compound heterozygous variants in the INTU gene, which encodes a protein involved in the positioning of the ciliary basal body. INTU is a subunit of the CPLANE multiprotein complex essential for the assembly of IFT-A particles and intraflagellar transport. This report of a second patient with INTU-related OFD syndrome and the further delineation of its neuroimaging and skeletal phenotype now allow INTU-related OFD syndromes to be classified within the OFD syndrome type VI group. Patients display a phenotype similar to that of mice with a hypomorphic mutation of Intu, but with the addition of a heart defect. 

Retracted: No

PubPeer comments:
 Oral-facial-digital syndrome type VI is ill-defined.  I am surprised to read that the authors describe molar tooth sign on this MRI. The fastigium (yellow arrow) is not rostrally placed (as it should be in case of molar tooth), axial section involves the pons (red arrow) and not the mesencephalon. This is not the correct criteria for molar tooth sign. For me, there is no molar tooth sign. , 
 #1 You are right. Furthermore, the authors describe an abnormal cerebral MRI  Corpus callosum was considered as thin (i.e. hypoplastic) but see the normal appearance of the corpus callosum at this age.  White matter is considered as underdeveloped. But compare with the normal aspect at this age. For me cerebral MRI is normal, this feature rules out the diagnosis of OFD VI. This should be corrected by the senior author Dr Verloes. ,