Cleidocranial dysplasia and novel RUNX2 variants: dental, craniofacial, and osseous manifestations

Cleidocranial dysplasia (CCD) is a skeletal disorder affecting cranial sutures, teeth, and clavicles, and is associated with the RUNX2 mutations. Although numerous patients have been described, a direct genotype–phenotype correlation for RUNX2 has been difficult to establish. Further cases must be studied to understand the clinical and genetic spectra of CCD. Objectives: To characterize detailed phenotypes and identify variants causing CCD in five unrelated patients and their family members. Methodology: Clinical and radiographic examinations were performed. Genetic variants were identified by exome and Sanger sequencing, data were analyzed by bioinformatics tools. Results: Three cases were sporadic and two were familial. Exome sequencing successfully detected the heterozygous pathogenic RUNX2 variants in all affected individuals. Three were novel, comprising a frameshift c.739delA (p.(Ser247Valfs*)) in exon 6 (Patient-1), a nonsense c.901C>T (p.(Gln301*)) in exon 7 (Patient-2 and affected mother), and a nonsense c.1081C>T (p.(Gln361*)) in exon 8 (Patient-3). Two previously reported variants were missense: the c.673C>T (p.(Arg225Trp)) (Patient-4) and c.674G>A (p.(Arg225Gln)) (Patient-5) in exon 5 within the Runt homology domain. Patient-1, Patient-2, and Patient-4 with permanent dentition had thirty, nineteen, and twenty unerupted teeth, respectively; whereas Patient-3 and Patient-5, with deciduous dentition, had normally developed teeth. All patients exhibited typical CCD features, but the following uncommon/unreported phenotypes were observed: left fourth ray brachymetatarsia (Patient-1), normal clavicles (Patient-2 and affected mother), phalangeal malformations (Patient-3), and normal primary dentition (Patient-3, Patient-5). Conclusions: The study shows that exome sequencing is effective to detect mutation across ethnics. The two p.Arg225 variants confirm that the Runt homology domain is vital for RUNX2 function. Here, we report a new CCD feature, unilateral brachymetatarsia, and three novel truncating variants, expanding the phenotypic and genotypic spectra of RUNX2 , as well as show that the CCD patients can have normal deciduous teeth, but must be monitored for permanent teeth anomalies

MOESM1 of Ankle ligament reconstruction after wide resection of the osteosarcoma of the distal fibula: a case report

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Lisfranc injury: Refined diagnostic methodology using weightbearing and non-weightbearing radiographs

Background: To compare diagnostic parameters for Lisfranc instability on WB and NWB radiographs and to assess the inter-observer reliability of a standardized diagnostic protocol. Patients and methods: Patients who had undergone surgical treatment for subtle, purely ligamentous Lisfranc injury with both WB and NWB post-injury, pre-surgery films (n = 26) were included in this multicentre, retrospective comparative study. Also included was a control group (n = 26) of patients with isolated fifth metatarsal avulsion fractures who similarly had both WB and NWB films. Multiple midfoot distance and alignment measurements were used to evaluate the Lisfranc joint on both WB and NWB views. To evaluate interobserver reliability, measurements were made by two independent observers across a cohort subset. Results: When comparing the NWB views between groups, only C1M2 (medial cuneiform- second metatarsal) distance was found to be significantly larger (∆ = 1.35 mm, p 0. 90 were found when interpreting WB radiographs and ICC's ranging between 0.61 and 0.80 were found when interpreting NWB radiographs. Conclusion: Using WB imaging for diagnosing subtle Lisfranc instability reveals larger diastasis in the tarsometatarsal joint and has a higher interobserver reliability compared to NWB imaging. Clinical concern for subtle or occult Lisfranc instability in any patient should therefore trigger WB radiographic assessment since such injuries may be missed on NWB views

Lisfranc injury: Refined diagnostic methodology using weightbearing and non-weightbearing radiographs

Background: To compare diagnostic parameters for Lisfranc instability on WB and NWB radiographs and to assess the inter-observer reliability of a standardized diagnostic protocol. Patients and methods: Patients who had undergone surgical treatment for subtle, purely ligamentous Lisfranc injury with both WB and NWB post-injury, pre-surgery films (n = 26) were included in this multicentre, retrospective comparative study. Also included was a control group (n = 26) of patients with isolated fifth metatarsal avulsion fractures who similarly had both WB and NWB films. Multiple midfoot distance and alignment measurements were used to evaluate the Lisfranc joint on both WB and NWB views. To evaluate interobserver reliability, measurements were made by two independent observers across a cohort subset. Results: When comparing the NWB views between groups, only C1M2 (medial cuneiform- second metatarsal) distance was found to be significantly larger (∆ = 1.35 mm, p 0. 90 were found when interpreting WB radiographs and ICC's ranging between 0.61 and 0.80 were found when interpreting NWB radiographs. Conclusion: Using WB imaging for diagnosing subtle Lisfranc instability reveals larger diastasis in the tarsometatarsal joint and has a higher interobserver reliability compared to NWB imaging. Clinical concern for subtle or occult Lisfranc instability in any patient should therefore trigger WB radiographic assessment since such injuries may be missed on NWB views