INTU‐related oral‐facial‐digital syndrome type VI: A confirmatory report

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.

Identical IFT140 Variants Cause Variable Skeletal Ciliopathy Phenotypes—Challenges for the Accurate Diagnosis

“…Therefore, we can speculate that the detected INTU variant adds to the burden of the IFT140 variants on proper functioning of the IFT-A complex. Recent literature has shown that mutations in INTU are causative for a short-rib polydactyly syndrome phenotype ( Toriyama et al, 2016 ; Bruel et al, 2018 ). The INTU variant c.1354G > A that was detected in patient 2 has previously been described to be causative in a 13-year old female with nephronophthisis, ESRD at 10 years of age and growth retardation.…”

Healthcare recommendations for Joubert syndrome

“… Note : The following genes are not listed due to lack of sufficient evidence that they are associated with JS (only one family, insufficient clinical information, and/or lack of biallelic variants): TTC21B (no biallelic variants in JS, variants reported in families with other ciliopathies; Davis et al, ), ZNF423 (one family with possible JS; Chaki et al, ), CLUAP1 (one family with JS; Johnston et al, ), EXOC8 (one family with JS; Dixon‐Salazar et al, ), CELSR2 (one family in each of two papers, variants not reported for one family; Shaheen et al, ; Vilboux et al, ), POC1B (one family; Beck et al, ), CEP164 (one family with JS, variants reported in families with other ciliopathies; Chaki et al, ; Vilboux and others, ), INTU (insufficient imaging informaton in several patients with ciliopathy phenotypes; Bruel et al, , ; Toriyama et al, ).…”

“…Seizures have been described in a number of individuals with JS (minimum prevalence 10%; Bachmann-Gagescu, and must be specifically sought out during recording of the medical history. No single seizure type appears to dominate and there Bruel et al, 2017Bruel et al, , 2018Toriyama et al, 2016). Abbreviations: ACC, agenesis of the corpus callosum; Chr, chromosome; OFD, oral facial digital features; PCD, primary ciliary dyskinesia; PD, polydactyly; Unk, unknown (not found in the UW cohort).…”

INTU‐related oral‐facial‐digital syndrome XVII: Clinical spectrum of a rare disorder

“…But he did not have any developmental delay. Molecular analysis revealed a single nucleotide variant in INTU gene and a deletion encompassing it [NM_015693.3; p.(Gly523Ser) and deletion in 4q28.1] (Bruel et al, 2018).…”