Parent and Patient Reported Outcomes for Head Shape in Children Undergoing Surgery for Single Suture Synostosis.

ABSTRACT: Assessing outcomes following surgery for single suture craniosynostosis is important to ensure minimum standards are being met, but also to compare results using different surgical techniques and treatment protocols. What constitutes an "outcome" and how this is measured remains a challenge, particularly when assessment should include consideration of aesthetic, functional, and psychological domains.The Oxford Craniofacial Unit has initiated routine collection of parents' and patients' ratings of 2 factors that are closely associated with psychological adjustment; how noticeable the child's headshape is and how much this bothers the parent and/or child. A brief Surgical Outcome Questionnaire is completed by parents and children (over 7 years) at their outpatient appointment; parents are also asked to rate the extent to which they feel surgery made a difference to their child's headshape.Data are presented for 519 parents and 248 children with single suture craniosynostosis who attended the Oxford Craniofacial Unit in 2018 and 2019; this represents over 80% of patients seen in the clinic indicating the questionnaire is acceptable for families and the potential for rapid, relevant data on a continuous basis. Analysis of the data is presented to demonstrate the utility of the Surgical Outcome Questionnaire in exploring the views of both parents and patients of the noticeability and level of concern about the child's headshape for different age groups and diagnoses.The Surgical Outcome Questionnaire provides a novel method of collecting routine data for patients across their craniofacial care pathway, using variables which are relevant and meaningful for patients and parents.

Implications for the Multi-Disciplinary Management of Children With Craniofrontonasal Syndrome.

The purpose of this retrospective study was to assess the genetic and phenotypic features of patients with craniofrontonasal syndrome (CFNS), and the implications of the condition for multidisciplinary management.The subjects were 25 female patients with a mutation of EFNB1, who presented to the Oxford Craniofacial Unit during a 38-year period. Medical records were reviewed for genetic and phenotypic information. Mean duration of follow-up was 12.6 years (range 0-30.7 years).This study examines neurodevelopment in constituent parts, with specific reference to speech, language, and cognition in relation to genotype. Three children had deletions extending beyond the EFNB1 gene; the 2 with available data presented with speech, language, or cognitive delay. The remaining 25 patients had intragenic mutations of EFNB1. Of these 25, those assessed in detail showed variable difficulties with speech and language development; 57% had receptive language difficulties (n = 4/7) and 88% had expressive language difficulties (n = 8/9). 55% presented with speech difficulties (n = 6/11). 2/3 patients with abnormal hearing had speech difficulties; 4/5 with normal hearing had normal speech development. Cognitive assessments indicated that IQ is variable; with full scale IQ ranging from 69 to 100.The complex, multifactorial presentation of patients with CFNS contributed to 41% (n = 7/17) of patients requiring additional educational support.Our results demonstrated significant multidisciplinary input is required, including Speech and Language Therapy, Plastic and Reconstructive Surgery, Genetics, Ear, Nose and Throat, Maxillofacial, Orthodontic, Orthopaedic, Clinical Psychology and Orthoptic teams. The results of this study reinforce the importance of multi-disciplinary long-term follow-up of children with CFNS.

Review of the Use of Stainless Wires in Craniosynostosis Surgery.

BACKGROUND: Controversy exists as to the ideal form of bone fixation in craniosynostosis surgery with the use of resorbable plates predominating in most craniofacial units. However, the use of stainless steel wires has been the preferred fixation method at the Oxford Craniofacial Unit (OCU) since its establishment. Wires have the advantage of being malleable, inexpensive, and quick and easy to use. METHODS: A retrospective review of all patients who underwent craniosynostosis surgery at the OCU between February 1995 and February 2017 was undertaken. Average follow-up period was 141 months (11.7 years), with a minimum of 6 months. RESULTS: A total number of 1226 craniosynostosis procedures were performed. A minimum of 16,160 wires were inserted. No complications were identified resulting from transdural migration of wires. One hundred fifty-six wires were removed in 92 patients during 109 general anesthetic day-care procedures. This was due to discomfort on palpation in the majority of cases. The average time from primary surgery to removal of wires was 37 months (3.1 years). The most common site for wire removal was in the supraorbital and lateral forehead regions, and occurred most frequently in children who had undergone fronto-orbital advancement and remodeling. CONCLUSION: The use of wires in craniofacial surgery is safe. One percent of all wires that were inserted had to be removed. Children undergoing primary craniosynostosis surgery have a 9% chance of needing a subsequent day-care procedure to have a wire removed. Taking into account the cost of this additional surgical procedure, the primary use of wires in craniosynostosis surgery is still significantly cheaper than the use of resorbable plates.

Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption, and supernumerary teeth.

Craniosynostosis and supernumerary teeth most often occur as isolated developmental anomalies, but they are also separately manifested in several malformation syndromes. Here, we describe a human syndrome featuring craniosynostosis, maxillary hypoplasia, delayed tooth eruption, and supernumerary teeth. We performed homozygosity mapping in three unrelated consanguineous Pakistani families and localized the syndrome to a region in chromosome 9. Mutational analysis of candidate genes in the region revealed that all affected children harbored homozygous missense mutations (c.662C>G [p.Pro221Arg], c.734C>G [p.Ser245Cys], or c.886C>T [p.Arg296Trp]) in IL11RA (encoding interleukin 11 receptor, alpha) on chromosome 9p13.3. In addition, a homozygous nonsense mutation, c.475C>T (p.Gln159X), and a homozygous duplication, c.916_924dup (p.Thr306_Ser308dup), were observed in two north European families. In cell-transfection experiments, the p.Arg296Trp mutation rendered the receptor unable to mediate the IL11 signal, indicating that the mutation causes loss of IL11RA function. We also observed disturbed cranial growth and suture activity in the Il11ra null mutant mice, in which reduced size and remodeling of limb bones has been previously described. We conclude that IL11 signaling is essential for the normal development of craniofacial bones and teeth and that its function is to restrict suture fusion and tooth number. The results open up the possibility of modulation of IL11 signaling for the treatment of craniosynostosis.

A novel use of the rigid external distraction frame: acute on-table distraction with autologous bone grafting.

Distraction osteogenesis with an external distraction device such as the rigid external distraction (RED) frame has become an established method for treating midface hypoplasia. It allows for greater advancement of the midface than achievable with traditional Le Fort III osteotomies; however, there are a number of problems associated with frame application such as pin site migration and need for frame removal. We present 2 cases of the novel use of the RED frame, in both a pediatric patient and an adult patient. The RED frame was used to achieve table soft tissue distraction, greater than previously achievable with traditional Le Fort III osteotomy. This was then combined with acute bone grafting, allowing the RED frame to be removed intraoperatively and thereby removing the complications associated with long-term frame application. We believe this to be the first reported use of the RED frame for acute on-table distraction of the midface. This has allowed far greater advancement of the midface than would be achievable with traditional Le Fort III advancement but, when combined with autologous bone grafting, has allowed intraoperative removal of the frame, thus negating some of the complications of long-term distraction osteogenesis using the RED frame.

A variant in IL6ST with a selective IL-11 signaling defect in human and mouse.

The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6ST (p.R281Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6st p.R279Q. We show that human GP130 p.R281Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6st p.R279Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.

Combined internal and external Le Fort III distraction osteogenesis--the "elusive vector".

This article describes a modified surgical technique using both internal and external distractors for distraction osteogenesis at the Le Fort III level. This technique optimizes vector control, superior to single-device techniques, resulting in excellent control and, ultimately, a functional occlusion.

A paramedian cleft of the lower lip.

We report the unusual case of a baby with a paramedian cleft of the lower lip. In 1976, Tessier described a classification of craniofacial clefts based on personal observations, and he predicted the possibility of further clefts being discovered by labeling midline mandibular clefts "30." This case of a paramedian cleft of the lower lip would fit into what could be a new Tessier 28/29 cleft. In the future, clefts in new locations around the mouth may be seen, thus filling the gaps in Tessier's classification.