Emin Mavili

ALX4 dysfunction disrupts craniofacial and epidermal development

Genetic control of craniofacial morphogenesis requires a complex interaction of numerous genes encoding factors essential for patterning and differentiation. We present two Turkish families with a new autosomal recessive frontofacial dysostosis syndrome characterized by total alopecia, a large skull defect, coronal craniosynostosis, hypertelorism, severely depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, callosal body agenesis and mental retardation. Using homozygosity mapping, we mapped the entity to chromosome 11p11.2-q12.3 and subsequently identified a homozygous c.793C-->T nonsense mutation in the human ortholog of the mouse aristaless-like homeobox 4 (ALX4) gene. This mutation is predicted to result in a premature stop codon (p.R265X) of ALX4 truncating 146 amino acids of the protein including a part of the highly conserved homeodomain and the C-terminal paired tail domain. Although the RNA is stable and not degraded by nonsense-mediated RNA decay, the mutant protein is likely to be non-functional. In a skin biopsy of an affected individual, we observed a hypomorphic interfollicular epidermis with reduced suprabasal layers associated with impaired interfollicular epidermal differentiation. Hair follicle-like structures were present but showed altered differentiation. Our data indicate that ALX4 plays a critical role both in craniofacial development as in skin and hair follicle development in human.

Reconstruction of postburn breast deformities

Postburn breast deformity is a sequela of severe scar contraction of the burned chest. During the past 3 years, 24 female patients with such deformities required reconstruction, the surgery was performed in our department. These patients, the types of the deformities and the techniques used for reconstruction have been reviewed. For mild deformities (10 patients) reconstructions with skin grafts and local skin flaps were found to be satisfactory. For deformities which affected the mammary development (14 patients), mammary prostheses directly or under the soft tissue obtained by skin expansion or musculocutaneous flaps were used. In three of our patients, reduction mammaplasty or mastopexy was needed to symmetrize the breasts.

Solvent-dehydrated calvarial allografts in craniofacial surgery.

Craniofacial surgery almost always requires the use of bone grafting. Although autografts are the standard procedure for bone grafting, it is sometimes not possible to harvest bone, and autografts have particular risks. The use of allograft bone provides a reasonable alternative to meet the need for graft material. Solvent dehydration is a multistage procedure in which human cadaveric bone is processed by osmotic exchange baths and gamma sterilization. This processing avoids the risk of infection transmission, decreases antigenicity, and does not weaken the mechanical properties of the bone. Solvent-dehydrated, gamma-irradiated human calvarial bone allografts were used for reconstruction of craniofacial deformities in 24 patients between 1988 and 2002. Resorption of the allografts and results of the surgical intervention were evaluated with plain radiographs and three-dimensional computed tomography 12 months after surgery, in 21 patients. Serologic tests for human immunodeficiency virus-1 antibody, hepatitis B surface antigen, and hepatitis C antigen were also performed. Biopsy specimens were taken from the allografts. Average follow-up in this group was 30 months (range, 8 to 60 months), and results of serologic tests were negative in all patients. Seventy-one percent of the patients (15 of 21) showed no resorption, with partial and complete allograft fusion. One patient had nearly total graft loss and the remaining five patients had 10 to 25 percent graft resorption. Rigid fixation of the allograft, contact with the dura and periosteum, and prevention of dead spaces around the allograft are the most important factors in achieving a satisfactory result. In solvent-dehydrated bone allografts, sterilization and antigenic tissue cleaning are achieved after several steps with a minimal dose of radiation. The result is a nonantigenic, sterile mechanical scaffold that can tolerate external forces. Although autografts are the standard in craniofacial surgery, solvent-dehydrated calvarial bone allografts produced successful results in selected cases.

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.

Partially de‐epithelialised and buried V‐Y advancement flap for reconstruction of sacrococcygeal and ischial defects

Defects in the sacrococcygeal and ischial soft tissues can be treated with gluteus maximus and posterior thigh V‐Y advancement flaps. However, late complications include recurrence and dehiscence of the suture line. Increasing the amount of the soft tissues over the bony prominences and multilayered closure may have an advantage for long‐term durability. We modified the V‐Y advancement technique by de‐epithelialising the medial parts of the flap and burying them under the opposing edge of the wound or the flap. Sixteen patients with various defects of the sacrococcygeal and ischial soft tissues were operated on using this technique. All the flaps healed well with no partial or complete loss of the flap. Three patients developed complications. The main advantage of our technique is the use of healthy tissues to obliterate the dead spaces under the edges of the wound or the opposing flap. In this way, not only the defect in the skin but the defect in the subcutaneous tissue, with its iceberg tip at the surface, is treated effectively. To have an additional layer of tissue between the bone and the superficial tissues provides an extra cushion of soft tissue and avoids putting the suture line directly over the bony prominences. We used this modification safely for both unilateral and bilateral flaps. It could also be used successfully in other parts of the body.

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.

Two new intramedullary implant designs for phalanx fixation in digital replantation: an experimental study.

&NA; Bone fixation in digital replantation must provide adequate rigidity, and must be applied in a fast and easy manner. Various fixation methods have been used so far with certain advantages and disadvantages. The authors report two new intramedullary proximal phalangeal implant designs to secure two amputated bone segments tightly. They compare their intramedullary implants with commonly applied K‐wire fixation methods and plate fixation via biomechanical analysis in terms of bending rigidity and distraction strength. Their two‐sided asymmetrical screw provided the highest rigidity and distraction strength, whereas the hook‐trap system was nearly equal to cross‐K‐wire fixation. Intramedullary bone fixation may be a feasible method of bone fixation, and resorbable implant materials and different implant configurations deserve further investigation. Kayikçioğlu A, Karamürsel S, Mavili E, Keçik A. Two new intramedullary implant designs for phalanx fixation in digital replantation: an experimental study. Ann Plast Surg 2000;45:258‐263

Use of bone wax as a template for intraoperative evaluation of facial defects and shaping of polyethylene implants.

With the advent of polymer chemistry, an increasing number of alloplastic materials are now available for use as onlay implants for reconstruction of facial bony and soft-tissue deformities. An optimal clinical result of a facial contour deformity surgery will depend not only on the choice of implant, but also on the method of giving exact shape to the implant to be used. The latter is particularly important to fit the implant into the complex configuration of a specific defect of bone and soft tissue. A template greatly enhances the accuracy of implant design. In this paper we describe a new method of fabricating polyethylene implants by using bone wax as an intraoperative template. We used this technique in four patients aged 8 to 35 years (average, 18 years) with posttraumatic and congenital facial defects without any complications. We present this method as a simple, inexpensive, and accurate alternative to the more sophisticated, but expensive and time-consuming, computer-assisted implant generation.

Intrasphenoidal migration of a premaxillary Kirschner wire.

OBJECTIVE The use of Kirschner wire for the fixation of premaxilla is a well-known method in bilateral cleft lip surgery. We report a case in which the Kirschner wire of the premaxillary fixation had migrated intrasphenoidally. RESULTS AND CONCLUSIONS The foreign body was accidentally discovered during a cephalometric analysis and was taken out surgically through an upper lip sulcus incision. Although the wire remained asymptomatic for 10 years, it constituted a potential danger for intracranial migration.

Hair transplantation using a freely transferred nonhair-bearing skin flap.

Cicatricial alopecia is a common sequela of burns involving the head region. The authors present a case of an extensive form of cicatricial alopecia in an 18-year-old female patient who sustained a burn to the head at 2 years of age. The patient was treated with combined scalp reduction with the aid of tissue expanders and micrografting of the freely transferred, preexpanded deep inferior epigastric artery nonhair-bearing skin flap. The aim of this article is to show that hair transplantation on the freely transferred nonhair-bearing skin flap may be associated with infection and fat necrosis, and the end result is not satisfactory, as in the cases of hair transplantation on a normal bald scalp.