Cognitive, Behavioural, Speech, Language and Developmental Outcomes Associated with Pathogenic Variants in the ERF Gene.

ABSTRACT: Pathogenic variants of the ERF gene were previously associated with craniosynostosis, craniofacial dysmorphism and Chiari malformation. This study investigates cognitive, behavioural, speech, language, and developmental outcomes in the first 5 children identified at the Oxford Craniofacial Unit as having ERF- related craniosynostosis, together with three of their carrier parents.There were no consistent findings related to overall intelligence. However, a pattern of cognitive difficulties is described, which includes poor attention, impulsivity and difficulties with functional fine motor skills, such as handwriting. A high frequency of speech, language and communication difficulties was evident, which was most often related to early language difficulties, speech sound difficulties, hyponasal resonance and concern regarding social communication skills and emotional immaturity.It was common for these children to have needed input from ear, nose and throat services. Problems with tonsils and/or adenoids and/ or fluctuating conductive hearing loss were found which may be contributors to early speech, language and communication difficulties.The authors make recommendations regarding the need for formal assessment of a range of developmental aspects upon diagnosis of a pathogenic variant in the ERF gene. The aim of this report is to give clinical guidance to anyone who may have care of patients with the ERF -related mutation.

The Craniofacial Collaboration UK: Developmental Outcomes in 3-Year-Old Children With Metopic Synostosis.

ABSTRACT: The Craniofacial Collaboration UK (CC-UK) has been established across the 4 highly specialized craniofacial centers in the UK since 2015. This joint collective aims to address the current limitations within developmental craniofacial research, using robust clinical data from a homogenous sample of children. This paper presents the third wave of findings from the CC-UK, with consideration to developmental and behavioral parent-report measures. Whilst previous data for sagittal synostosis have been presented, this article summarizes the analysis of these outcomes for children with metopic synostosis (MS) at 3 years who have undergone primary corrective surgery. Results highlight similar patterns to that of earlier CC-UK work, with the majority of children falling within 1 standard deviation of the population normative means across all measures. However, statistically significant difficulties were found between group means for children with MS on various developmental and behavioral domains. Prosocial skills and peer difficulties were reported as the greatest areas of behavioral concern for parents, with prosocial skills found to be below the level expected for their chronological age. In order to further understand the developmental trajectory of children with MS, longitudinal examination of individual diagnostic and specific age groups with single-suture craniosynostosis is crucial. The continuation of the CC-UK provides an opportunity to attain this goal.

Psychosocial Impact of Coronal Access Scars in Craniosynostosis Procedures on Patients and Their Families.

ABSTRACT: The coronal incision is the mainstay for access in craniosynostosis surgery. Scarring is a common concern of parents whose children are offered an open procedure. To the author's knowledge, there are no previous studies looking at the psychosocial impact of scarring from coronal access incisions for craniosynostosis procedures. The author's study focused on patients undergoing procedures for nonsyndromic single-suture craniosynostosis.This study comprised 3 parts: worldwide survey regarding coronal access incisions for craniosynostosis surgery, questionnaire to determine the psychosocial impact of the scars on patients and their parents, and measurement of postoperative scars in craniosynostosis patients.Survey responses from 46 craniofacial centers worldwide revealed a zig-zag was the most commonly utilized incision. Seventy-two percent of survey responses reported problems with postoperative stretching of the scar; only 20% of centers reported formal data collection of whether families were affected by this.Psychology questionnaires revealed that the majority of patients and their parents were not bothered by the zig-zag coronal scars. Patient felt the scars were less noticeable than the parents. Parent perceptions improved with age and time postsurgery.Coronal access scars following craniosynostosis surgery appear to stretch more in the supra-auricular region compared with the midline.These findings are useful for the craniofacial multidisciplinary team to inform parents contemplating surgery and who may be concerned about the impact of the scar in the future.

Neurodevelopmental, Cognitive, and Psychosocial Outcomes for Individuals With Pathogenic Variants in the TCF12 Gene and Associated Craniosynostosis.

ABSTRACT: Heterozygous mutations in the TCF12 gene were discovered in 2013 as a cause of craniosynostosis (CS). However, limited information regarding the behavioral phenotypic profile is available. Here the authors provide the first detailed study of the neurodevelopmental, cognitive, and psychosocial outcomes for patients with a pathogenic TCF12 variant and associated CS.A clinical casenote audit was conducted at the 4 UK highly specialized craniofacial centers. A total of 35 patients aged 18 months to 10 years with an identified TCF12 pathogenic variant and CS (bicoronal CS = 45.7%, unicoronal CS = 40.0%, multisuture = 14.3%) were included. Standardized screening and/or assessment of full-scale intelligence quotient, social communication, development, behavior, and self-concept were conducted.In the majority of cases, outcomes were consistent with age-related expectations. About 75% of patients demonstrated no delay across any early developmental domain, while 84.6% demonstrated full-scale intelligence quotient scores within 1 standard deviation of the population mean. Significant behavioral difficulties were demonstrated by parent reporters in 26.3% to 42.1% of cases (dependent upon domain). Clinically elevated social communication profiles were present in (41.7%) of parent-reported cases. Levels of self-concept (at age 10) were consistent with age-related normative data.Most patients with a TCF12 pathogenic variant had a mild behavioral and cognitive phenotype, although they may be at a slightly increased risk of social communication difficulties and psychosocial issues. Although not measured statistically, there were no clear associations between surgical history and cognitive, behavioral, or psychosocial outcomes. This paper highlights the need for robust integrated developmental assessment of all CS patients, particularly those with an identified syndrome.

Craniofacial Collaboration UK: Developmental Outcomes in 5-Year-Old Children With Sagittal Synostosis.

ABSTRACT: The Craniofacial Collaboration UK (CC-UK) is a joint initiative that seeks to address some of the limitations of previous developmental research with this patient group by providing systematically collected, robust data from clinically and chronologically homogenous representative samples of children. The current paper outlines the developmental outcomes at the age of 5 for children who had previously undergone primary surgery for single-suture sagittal synostosis (SS). It shows broad consistencies with the previous CC-UK work, indicating that the majority of children with SS will perform within the average range compared to peers across a number of developmental, behavioral and emotional domains. However, the group mean for children with SS indicates significantly greater difficulties with fine motor skills and hyperactivity, relative to normative data. Unexpectedly, children with SS had significantly better problem solving skills. While it is reassuring that the majority of children are broadly developing in line with their unaffected peers, these small but significant differences may be early indicators of some of the subtle difficulties documented in older children with craniosynostosis. Longitudinal follow up is therefore important to understand the developmental trajectory for children with SS and identification of potentially 'at risk' sub groups within this diagnostic cohort.

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.

Preliminary Analysis From the Craniofacial Collaboration United Kingdom Developmental Outcomes in Children With Sagittal Synostosis.

The Craniofacial Collaboration United Kingdom (CC-UK) was established across the 4 Highly Specialized Craniofacial Centres (HSCCs) in the UK in 2015. This is the first wave of data to be analyzed, looking at 3-year-old children with sagittal synostosis who have had primary corrective surgery. This is a comprehensive, homogenous dataset, looking at parental measures of development and behavior. The results indicate that the majority of children are rated by their parents as falling within one standard deviation of the mean for both developmental and behavioral measures. However, there was a trend across the age groups within the sample which, although not statistically significant, indicates that more developmental difficulties may become apparent as children get older. Behavior was rated as more problematic, and the areas of greatest parental concern were Conduct (challenging or confrontational behavior) and Hyperactivity domains, where 24% of children were rated as within the clinically significant range. Although the majority of children were rated as falling within the average range, the difference in the mean between the sagittal and the normative group was significant in 5 of the 6 behavioral domains. Further research is required to examine whether these findings are stable over time and to look at the mechanism which might be driving these changes. It is anticipated that future CC-UK analysis will elucidate this more clearly.

Introduction to the Craniofacial Collaboration UK: A Developmental Screening Protocol at the United Kingdom's Four Highly Specialized Craniofacial Centers.

The clinical psychologists at the 4 highly specialized craniofacial centers in the United Kingdom have developed a systematic, developmental screening protocol, called the Craniofacial Collaboration UK (CC-UK). Previous systematic reviews of the literature into the developmental sequelae of single-suture craniosynostosis have identified a number of methodological flaws which the CC-UK seeks to avoid. This study presents an introduction to the rationale for its development, as well as the methodology of the CC-UK.

The Value of a Photobook in Informing Families About the Cosmetic Results of Surgery in Craniosynostosis.

This paper outlines the development and evaluation of a photobook resource to support parents' decision making regarding potential craniofacial surgery for their child. The photobook was developed at a UK Craniofacial Unit and consisted of preoperative and postoperative photographs of patients with craniosynostosis. It was intended to act as a visual adjunct to detailed verbal discussion of surgical treatment options. No changes in the uptake rate of surgery were detected following the introduction of the photobook. An evaluation of parents' views of the photobook indicates that families generally welcomed the resource and did not report any adverse responses. Ethical considerations of the use of such a resource cannot be discounted, and careful presentation of such a resource in the context of a specialist team is recommended.