Ersoy Konaş

Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis

We have characterized a novel autosomal recessive Crouzon‐like craniosynostosis syndrome in a 12‐affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next‐generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice‐site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon‐like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11‐mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon‐like craniosynostosis.

Effect of slow-release 5-Fluorouracil on capsule formation around silicone breast implants: an experimental study with mice.

BackgroundCapsule formation around breast implants, development of tendon adhesions after tendon repair, intestinal brits after laparatomies, hypertrophic scars in skin incisions all are the results of excessive collagen synthesis to the extracellular matrix by fibroblasts. Any intervention that leads to cessation of collagen synthesis in these clinical situations may help to prevent these untoward results of wound healing. Although 5-fluorouracil (5-FU) is used mainly as a cytotoxic drug in chemotherapy protocols, it decreases cellular metabolism and blocks protein synthesis only at lower concentrations. Findings have shown that 5-FU downregulates fibroblast proliferation and differentiation in vitro. It has been used to treat fibroproliferative disorders of the eye and skin and is thought to inhibit thymidylate synthetase, blocking DNA replication.MethodsThis study used five treatment groups: (1) gelatin only, (2) silicone only, (3) silicone + gelatin, (4) silicone + gelatin containing 1 mg of 5-FU, and (5) silicone + gelatin containing 5 mg of 5-FU. The release kinetics of 5-FU from gelatin have been investigated by means of ultraviolet spectrophotometric analysis. Specimens were obtained on postoperative day 30. Gross evaluation and histopathologic examination were conducted for capsule formation and the development of inflammation.ResultsThe silicone group had the most prominent capsule formation among all the groups. The gelatin group was second, and the silicone + gelatin group was third. As compared with the other groups, the 5-FU–containing groups had the least capsule formation. The 5-mg 5-FU–containing group had the most inflammation. The silicone + gelatin group was second in inflammation. Although the silicone, gelatin, and 1-mg 5-FU–containing groups had the same means, the results of the silicone group showed the most divergent data within the group.ConclusionsBecause 5-FU loaded to a gelatin carrier for its slow release seems to prevent capsule formation around silicone blocks, it may be used to prevent capsule formation around silicone breast implants.

Three-layer oronasal fistula repair with sandwiched mastoid fascia graft.

Abstract Oronasal fistula can cause speech problems, hearing loss, velopharyngeal insufficiency, and social problems related with fetor oris and oronasal fluid leakage. The purpose of this study was to achieve 3-layer closure with autogenous mastoid fascia graft in a group of patients with recalcitrant oronasal fistulas. Sixteen patients, aged between 2 and 56 years (mean, 13.9 y), with recalcitrant palatal fistula were operated on and included into the study in a tertiary clinic. Nine patients had previous fistula repairs. The patients’ mean follow-up period was 6.8 months. Fistula closure was obtained in 14 of 16 patients. All 2 failures had type IV + V fistulas according to Pittsburgh Classification. A 3-layer technique for the closure of fistulas with autogenous mastoid fascia graft allows three-dimensional repair of the defect without tension. Using mastoid fascia via postauricular sulcus incision is a good alternative regarding hiding incision scars and not requiring intraoperative repositioning.

Goldenhar complex with atypical associated anomalies: is the spectrum still widening?

Goldenhar syndrome is a well-known developmental anomaly of maxillofacial skeleton and hemi-facial soft tissue, was later included to a broader classification called oculo-ariculo-vertebral spectrum. Here we report a patient presenting goldenhar syndrome with accessory auricula, defined as polyotia, coloboma and bifid tongue.

Acceleration of distraction osteogenesis with drug-releasing distractor.

Objective: The aim of this study was to develop an internal distractor to release a drug to the distraction site during the distraction process and to investigate whether intermittent bone morphogenetic protein 2 (BMP-2)-containing chitosan hydrogel infusion will improve radiologic and histologic parameters of distraction osteogenesis (DO) when compared with control groups. Materials and Methods: Experimental groups were control group (n = 6), 2-&mgr;g single-dose BMP-2-chitosan hydrogel-infused group (n = 6), and 2-&mgr;g intermittent BMP-2-containing chitosan hydrogel-infused group (n = 6). In intermittent BMP-infused group, certain amount of BMP-2 loaded chitosan hydrogel injected into the distraction gap for controlled BMP release from the chitosan with every turning of the geared rod of the distractor. Radiologic and histologic evaluation methods have been conducted. Conclusion: The results of the analysis demonstrated that the newly developed distractor effectively stabilized the DO site while allowing intermittent BMP-chitosan infusion. Application of a BMP-2-chitosan hydrogel infusion to the distraction zone facilitates ossification. Intermittent infusion of BMP-2-containing chitosan hydrogel by use of a developed internal distractor increases ossification even more at the site of DO.

Pharyngeal Airway Changes Associated With Maxillary Distraction Osteogenesis in Adult Cleft Lip and Palate Patients

PURPOSE To investigate 1) the changes in pharyngeal airway sizes associated with maxillary distraction osteogenesis and 2) the correlations between maxillary skeletal variables and the pharyngeal airway in adult patients with cleft lip and palate. PATIENTS AND METHODS The study was carried out in 14 adult subjects with cleft lip and palate. Predistraction records were taken at a mean age of 22.7 ± 4.6 years. All patients had placement of a rigid external distraction device (RED I; KLS Martin, Tuttlingen, Germany) after Le Fort I osteotomy. Lateral cephalograms were assessed before surgery and at short-term follow-up (8.0 ± 6.4 months). The cephalometric skeletal and pharyngeal airway variables were statistically evaluated by use of the Wilcoxon signed-rank test. Spearman ρ correlation was performed to check the correlations between maxillary skeletal and pharyngeal variables. RESULTS The maxillary movement was 8.7 mm (P < .01). The maxillary depth angle (+7.9°) and effective maxillary length (9.4 mm) increased significantly (P < .01) after distraction, whereas the palatal plane angle remained unchanged. Anterior nasal spine (8.2 mm) and Posterior nasal spine (6.9 mm) moved anteriorly. The overjet increased (9.5 mm) significantly (P < .01). Posterior, superoposterior, and middle airway spaces increased significantly, with mean differences of 7.5 mm, 5.1 mm, and 3.3 mm, respectively. The soft palate moved anteriorly, with the greatest movement at its superior point. Significant positive correlations were observed for the posterior and superoposterior airway spaces and maxillary movement. PNS changes showed the highest correlation with posterior airway changes. CONCLUSIONS The significant anterior movement of the maxilla resulted in significant increases in posterior, superoposterior, and middle airway spaces. The posterior airway space showed the highest significant positive correlation with the movement of PNS. The posterior and superoposterior airway spaces also showed significant positive correlations with the maxillary skeletal variables.

Volumetric assessment of results of treatment of vascular malformations of the head and neck regions treated with a minimally invasive surgical technique after embolization procedure.

Treatment of large soft tissue vascular lesions, one of the greatest challenges facing plastic surgeons, is patient specific in almost all cases, and preoperative angiographic evaluation and embolization of these lesions are standards of care. The aim of this study was to evaluate the usefulness of 3-dimensional demonstration and volumetric assessment of soft tissue vascular lesions both in the treatment of these lesions with curettage and in the participation of the patients to the decision-making process of the disease. Five patients with vascular malformation of the head and neck regions were included to this prospective trial. All patients were evaluated with preoperative angiography, and selective embolizations of the soft tissue vascular lesions were done in the same session by the same interventional radiologists. The amount of embolic agent injected was determined according to the size and vascularization of the lesions. Surgery was done by curettage of the embolized lesions 7 to 10 days after the embolization procedure. The raw data obtained from preoperative and postoperative high-resolution computed tomographic scans of the patients were processed with a Mimics 9.22 Software (Materialises Interactive Medical Image Control System, Leuven, Belgium). Volume and surface area of the injected embolic agent were assessed. Statistical analysis was performed using the software package SPSS 10.0 for Windows (SPSS Inc, Chicago, IL). Wilcoxon signed rank test was used to compare the measurements of the volume and the surface area of injected sclerosing agent preoperatively and postoperatively. There were no complications related to either the preoperative angiography or embolization procedure. All the patients emphasized (assessed) that the 3-dimensional demonstration of the lesions and their relation with other anatomic structures helped them to understand the extent of their pathology and aim of the proposed treatment. The difference between the volumetric measurements before and after the treatment was found statistically significant. Treatment of large soft tissue vascular lesions with curettage after embolization has acceptable cosmetic results. Although it is not possible to remove all of the sclerosing agent from its injection site with this technique, a significant amount of it can be removed, and the 3-dimensional vascular architecture of the lesion is disturbed. Reactive chronic inflammation against the remaining sclerosing agent and the intralesional scarring caused by curettage lead to further improvement. Using 3-dimensional imaging modalities helps patients and/or their relatives to understand their disease and participate in the decision-making process.

Congenital maxillomandibular syngnathia: a new management technique using distraction techniques.

Complex zygomaticomandibular syngnathia is an extremely rare condition with an unknown etiology. The main goal of the surgery is to release the ankylosis, establish good functioning mandible, and prevent reankylosis, if possible. In our case, we offer a new solution to have an adequate oral opening and to prevent reankylosis. After the release of bony syngnathia, we placed a distractor between mandibular segment and maxillozygomatic complex. To our best knowledge, this is the only syngnathia case in the literature treated using distraction techniques. There is a major improvement in the patients status. Distraction may broaden our horizons in this rare and difficult-to-treat deformity.

Management of serious isolated gingival synechia in a newborn: case report and review of the literature

Congenital synechia of the gums is a rare malformation. The fusion may be partial or complete and may be associated with other facial dysmorphologic malformations. The synechia can be fibrous or bony and may develop between the upper and lower alveolar ridges. The authors report a newborn with partial, but broad and continuous, synechia of the gums and discuss its management during the first days of life.

A Salvage Procedure in Cleft Palate Repair: Suturing Nasal Mucosa Directly to Palatine Process

Objective: Palatal fistulas are among the complications of cleft palate repair requiring additional surgery. Suturing the nasal mucosa and mucoperiosteal flaps together in a tension-free manner to create a double-layered closure in the hard palate is one of the most important points in prevention of dehiscence and fistula formation. In this report, we describe a salvage procedure to repair nasal mucosa that might be lacerated while being freed from the upper surface of the palatal process. Method: To restore the nasal lining, an ipsilateral vomer mucoperiosteal flap or the opposite nasal mucosa flap is advanced to the palatine bone and sutured directly to the palatal process in order to guarantee an intact cleft palate repair. Results: This method is an easy, simple, and time-saving procedure. It should be a useful addition to the armamentarium of every plastic surgeon, especially those working as consultants in training units.