3D facial phenotyping by biometric sibling matching used in contemporary genomic methodologies.

The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17-0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation.

Achieving the next level in cleft speech intervention: A protocol of a randomized sham-controlled trial to provide guidelines for a personalized approach in children with cleft palate.

BACKGROUND: Compensatory cleft speech disorders can severely impact speech understandability and speech acceptability. Speech intervention is necessary to eliminate these disorders. There is, however, currently no consensus on the most effective speech therapy approach to eliminate the different subtypes of compensatory cleft speech disorders. AIMS: To compare the immediate, short- and long-term effects of three well-defined speech intervention approaches (i.e., a motor-phonetic approach, a linguistic-phonological approach and a combined phonetic-phonological approach) on the speech and health-related quality of life (HRQoL) in Belgian Dutch-speaking children with cleft palate with or without cleft lip (CP±L) and different subtypes of compensatory speech disorders (i.e., anterior oral cleft speech characteristics (CSCs), posterior oral CSCs or non-oral CSCs). Besides, the perceived acceptability of these three speech intervention approaches will be investigated from the perspectives of caregivers and children with a CP±L. METHODS & PROCEDURES: A two-centre longitudinal randomized sham-controlled trial was used. Children were randomly assigned to one of the three intervention programmes and received 10 h of speech intervention divided over 2 weeks. Block randomization was used, stratified by age and gender. Primary outcome measures included perceptual speech outcomes. Secondary outcome measures included patient-reported outcomes. OUTCOMES & RESULTS: The results of this trial will provide speech-language pathologists evidence-based guidelines to better tailor intervention approaches to the specific needs of a child with a defined compensatory speech disorder. WHAT THIS PAPER ADDS: What is already known on this subject Speech therapy approaches to address cleft palate speech disorders are broadly divided into two categories: motor-phonetic interventions and linguistic-phonological interventions. Some limited evidence demonstrated the positive effects of these approaches in eliminating compensatory cleft speech disorders. Different studies have reported inter-individual variation, suggesting that one child may benefit more from a particular intervention approach than the other child. Perhaps this variation can be attributed to the specific subtype of compensatory speech disorder (i.e., anterior oral CSC, posterior oral CSC or non-oral CSC). What this paper adds to existing knowledge This paper describes a randomized sham-controlled trial that compared the immediate, short- and long-term effects of three well-defined speech intervention approaches (i.e., a motor-phonetic approach, a linguistic-phonological approach and a combined phonetic-phonological approach) on the speech and HRQoL in Belgian Dutch-speaking children with CP±L and different subtypes of compensatory cleft speech disorders (i.e., anterior oral CSCs, posterior oral CSCs or non-oral CSCs) measured by perceptual and psychosocial outcome measures. Besides, the experienced acceptability of these three speech intervention approaches were investigated from the perspectives of caregivers and children. What are the potential or actual clinical implications of this work? This project provides evidence-based knowledge on patient-tailored cleft speech intervention considering both scientific evidence and the perspectives of caregivers and children. The results aid SLPs in better tailoring intervention approaches to the needs of a child with a specific type of compensatory cleft speech disorder.

How acceptable is the use of linguistic-phonological intervention in children with cleft palate? A qualitative study in speech therapists.

BACKGROUND & AIMS: Even though evidence for the use of linguistic-phonological intervention approaches in children with a cleft (lip and) palate (CP±L) is still limited, these approaches are being used by speech-language pathologists (SLPs) to treat active or compensatory cleft speech disorders in clinical practice. It is, however, unknown to what extent linguistic-phonological intervention is acceptable to SLPs. The aim of this study is to investigate the retrospective acceptability of linguistic-phonological intervention in children with a CP±L from the perspective of SLPs using the theoretical framework of acceptability (TFA). METHODS & PROCEDURES: A total of 18 female community SLPs, aged between 23 and 63 years, were included in the study. An independent interviewer conducted semi-structured interviews. Data were analysed using a deductive coding approach. Statements of the SLPs were related to the seven constructs of the TFA: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. OUTCOMES & RESULTS: The affective attitude and perceived effectiveness of linguistic-phonological intervention differed among the SLPs: some therapists had positive attitudes towards these approaches, while others did not. Positive attitudes were related to the successful use of linguistic-phonological intervention in the past. The construct 'ethicality' revealed that negative attitudes towards these approaches were attributed to the limited available scientific evidence or negative experiences while using these approaches. In contrast, SLPs who had positive attitudes considered these interventions as 'important' and 'valuable'. Some SLPs had negative reflections on linguistic-phonological intervention as these approaches were considered demanding in terms of time needed to gain knowledge on using them in children with a CP±L (constructs 'burden' and 'opportunity costs'). Additionally, some SLPs doubted their self-efficacy to use these approaches in clinical practice. CONCLUSIONS & IMPLICATIONS: The acceptability of linguistic-phonological intervention differed between the SLPs in this sample and was most likely related to their previous experiences with these linguistic-phonological approaches. It is important to increase not only the amount of scientific evidence for linguistic-phonological approaches but also the supply of evidence-based workshops and training courses on this topic. These initiatives should distribute scientific information that is translated into guidelines that are immediately applicable in clinical practice. This may potentially reduce the time-related burden that some SLPs currently experience to gain expertise in this matter. In future research, it is necessary to investigate if there exist differences in acceptability between the different types of linguistic-phonological therapy. WHAT THIS PAPER ADDS: What is already known on this subject Linguistic-phonological speech intervention approaches are often used by SLPs to treat active or compensatory cleft speech disorders in clinical practice. What this paper adds to existing knowledge This study investigated whether linguistic-phonological intervention cleft speech intervention is acceptable to SLPs. Some therapists had positive attitudes towards these approaches, while others did not. Positive attitudes were related to the successful use of these approaches in the past. If SLPs indicated having negative attitudes, these negative feelings were attributed to the limited available scientific evidence or negative experiences while using these approaches. What are the potential or actual clinical implications of this work Even though linguistic-phonological speech intervention approaches are being used in clinical practice, these approaches are not always considered acceptable by SLPs. Acceptability could be enhanced by increasing the amount of scientific evidence for linguistic-phonological approaches, but also by increasing the supply of workshops and training courses on this topic. These initiatives should distribute hands-on information that is immediately applicable in clinical practice. This may potentially reduce the time-related burden that some SLPs currently experience to gain expertise in this matter.

A protocol for a randomized-controlled trial to investigate the effect of infant sign training on the speech-language development in young children born with cleft palate.

BACKGROUND: Children born with a cleft palate with or without cleft lip (CP ± L) are known to be at risk for speech-language disorders that impact educational and social-emotional growth. It is hypothesized that speech-language intervention delivered before the age of 3 years could decrease the impact of CP ± L on speech-language development. Infant sign training in combination with verbal input expands the natural communication of young children including multimodal speech-language input (i.e., verbal and manual input) via caregivers who act as co-therapists. AIMS: To determine the effectiveness of infant sign training in 1-year-old children with CP ± L by comparing different interventions. METHODS & PROCEDURES: This is a two-centre, randomized, parallel-group, longitudinal, controlled trial. Children are randomized to either an infant sign training group (IST group), a verbal training group (VT group) or no intervention control group (C group). Caregivers of children who are assigned to the IST group or VT group will participate in three caregiver training meetings to practise knowledge and skills to stimulate speech-language development. Outcome measures include a combination of questionnaires, language tests and observational analyses of communicative acts. OUTCOMES & RESULTS: It is hypothesized that speech-language development of children with CP ± L will benefit more from IST compared with VT and no intervention. Additionally, the number and quality of communicative acts of both children and caregivers are expected to be higher after IST. CONCLUSIONS & IMPLICATIONS: This project will contribute to the development of evidence-based clinical practice guidelines regarding early speech-language intervention in children with CP ± L under the age of 3 years. WHAT THIS PAPER ADDS: What is already known on the subject Children with CP ± L are known to be at risk for speech-language delays that impact educational and social emotional growth. Given the limited scientific prove of the impact of early speech-language intervention, no standardized clinical practice guidelines are available yet for children with CP ± L under the age of 3 years. Early intervention in this population mostly focuses on improving verbal input via caregivers or professionals without including a multimodal language input. A growing scientific interest has been seen in the use of infant signs to support speech-language development and caregiver-child interaction in typically developing children and children with developmental delays. What this study adds to existing knowledge No evidence is yet available for the effectiveness and feasibility of early intervention based on infant sign training in combination with verbal input to improve speech-language skills in young children with CP ± L. The current project will investigate the effect of infant sign training on the speech-language development in this population. Outcome measures are compared with those of two control groups: verbal training only and no intervention. It is hypothesized that infant signs may support the intelligibility of verbal utterances produced by children with CP ± L. Improving children's intelligibility may increase the opportunities for these children to engage in early, frequent and high-quality interactions with their caregivers resulting in a richer social and linguistic environment. As a result, infant sign training may result in better speech-language skills compared with the control interventions. What are the potential or actual clinical implications of this work? If providing early intervention based on infant sign training is effective, there is the potential for improved speech-language outcomes in early childhood, resulting in increased speech intelligibility, increased well-being of the child and family and less need for speech-language therapy on the long-term. This project will contribute to the development of evidence-based clinical practice guidelines regarding early speech-language intervention in children with CP ± L under the age of 3 years.

Long-term follow-up of the inside-out technique for treatment of preauricular sinuses: observational study.

PURPOSE: This long-term follow-up study aims to externally validate the inside-out technique for surgical treatment of preauricular sinuses. METHODS: We analyzed the medical records of all patients who underwent the IO procedure at University Hospitals Leuven from 1 November 2005 to 30 November 2019 (N = 110). We were able to contact 77 of these 110 patients for a telephone interview, where we used a standardized questionnaire to evaluate recurrence, patient satisfaction and aesthetic result. RESULTS: We studied 110 patients (68 males, 77 females), resulting in 145 PAS (35 left, 40 right, 35 bilateral), with a median follow-up of 53 months. Fifteen PAS (10.3%) developed an early (< 4 weeks) postoperative complication (wound dehiscence, infection, abcedation, swelling). Two PAS (2 different patients) needed revision surgery because of recurrence, one after 15 months, the other after 4 years. The 5-year Kaplan-Meier recurrence-free percentage was 97.7%, equating to an estimated recurrence rate of 2.3%. Ninety-four percent was satisfied with the aesthetic result, giving 4 or 5 points on a 5-point Likert scale. CONCLUSIONS: This study was able to externally validate the IO technique for the treatment of PAS. The IO technique should be first choice, since it guarantees low recurrence rates, excellent aesthetic results, and good patient satisfaction.

Morphing as a Selection Tool in the Rhinoplasty Consult: A Cross-Sectional Study.

Despite the recognized value of morphing in the literature, this preoperative tool has never been studied in the context of selection process in rhinoplasty. The main purpose of this article is to identify the use of morphing as a filter for unsuitable patients, the attrition rate from the initial consultation to surgery, and whether patients' appreciation on morphing influence their decision-making process. Three-hundred thirty-four consecutive patients, seeking rhinoplasty, underwent two-dimensional computer imaging and completed a 14-question survey about their opinion on morphing. Based on the presence or absence of patient/physician consensus on the expected outcomes during simulation, patients were divided into accepted or rejected candidates for surgery. Accepted candidates were scheduled for rhinoplasty and subdivided into those who underwent surgery, those who postponed their surgery (static), and those who cancelled their procedure. Their responses to the survey were compared between different patients' categories. Forty-four patients (13.2%) were rejected for rhinoplasty since consensus was not achieved during morphing. From 290 accepted patients, 178 underwent their operation (53.3%), 74 patients (22.1%) postponed their rhinoplasty, and 38 (11.4%) cancelled their surgery. Fifty-seven percent of rejected patients and 42% of the static group were not satisfied with the proposed results of morphing, in contrast with 16% of the operated group. Sixty-four percent of rejected patients, and 47% of the static group were not reassured after morphing, compared with 26% of the operated group. Presence or absence of consensus during morphing can guide the surgeon regarding a given patients' suitability for surgery. Patient satisfaction and reassurance with the morphed images can be a good predictor of patients who will proceed to surgery, calling attention to the value of morphing as a selection tool for surgeons and patients alike.

Pregnancy Termination in the Case of an Orofacial Cleft: An Investigation of the Concept of Reproductive Autonomy.

OBJECTIVE: To describe ethical approaches to the issue of pregnancy termination after prenatal detection of cleft lip ± palate. RESULTS: Gynecologists and cleft surgeons are sometimes confronted with the demand for a pregnancy termination after ultrasound detection of an isolated cleft lip/cleft palate. In this article, we discuss different ethical theories and principles that can be applied to the dilemma at hand. We formulate recommendations that will respect the right to autonomy of the pregnant woman and at the same time acknowledge that a termination of pregnancy for a cleft lip may in most cases not be the best option. CONCLUSION: The recognition of each person's right to reproductive autonomy also entails that clinicians should make sure that prospective parents are provided with up-to-date and relevant clinical information.

Vestibular dysfunction is a manifestation of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is the second most common cause of developmental delay after Down syndrome. Impaired cognitive development is highly prevalent, but also motor abnormalities such as hypotonia and delays in achieving motor milestones are described. Instability is frequently detected in children, adolescents, and adults and is mostly attributed to their limited motor performance. Until now, vestibular function has not been investigated in these patients, despite the growing evidence that they often have inner ear malformations. The aim of this prospective study was to identify the presence and character of vestibular dysfunction in 22q11.2DS. We investigated 23 subjects with proven 22q11.2DS, older than the age of 12. We performed caloric testing and pendular rotation chair tests with videonystagmography, cervical vestibular-evoked myogenic potential (c-VEMP)-testing, and posturography. Additional otoscopy and audiometry were performed on all subjects. We found a unilateral caloric hypofunction in 55% of patients, a certain absent c-VEMP response in 15% of ears, an inconclusive c-VEMP response in 33% of ears, and abnormal posturography in 68% of patients, of whom 42% displayed a typical vestibular pattern. Remarkably, 90% revealed uni- or bilateral weak caloric responses, independent of caloric symmetry. Vestibular dysfunction is frequent in subjects with 22q11.2DS. This knowledge should be taken into account when assessing motor performance in these patients. Additional larger studies are needed to determine whether this dysfunction implicates a therapeutic potential.

Olfactory function in patients with nonsyndromic orofacial clefts and their unaffected relatives.

Nonsyndromic orofacial clefting is one of the most frequently occurring congenital conditions. The aim of the study was to investigate the prevalence and nature of reduced olfactory function in patients with nonsyndromic cleft lip and/or cleft palate (NSCL/P) and their unaffected first-degree relatives. Olfactory function was tested using the Sniffin' Sticks identification test in patients with NSCL/P, in their unaffected relatives, and in control subjects. MR imaging was performed to measure olfactory bulb (OB) volumes and olfactory sulcus (OS) depths. A reduced olfactory function was seen in significantly more patients with NSCL/P (p = .002) than in control subjects, regardless of the cleft type. Strikingly, unaffected relatives of patients with NSCL/P also had a higher rate of hyposmia (p = .001). In hyposmic patients, the OB volumes (left: p = .01 and right: p = .003) and the depth of the left OS (p = .02) were significantly smaller than in controls. In hyposmic relatives, both OS depths (left: p = .02 and right: p = .03) were significantly smaller. Patients with NSCL/P and their unaffected relatives have an increased prevalence of reduced olfactory function, associated with changes in the central olfactory structures.

Testing the face shape hypothesis in twins discordant for nonsyndromic orofacial clefting.

Nonsyndromic orofacial clefts (OFCs) are complex traits characterized by multifactorial inheritance and wide phenotypic variability. Numerous studies have shown subtle differences in the faces of unaffected relatives from cleft families compared to controls, the implication being that such outward differences are an incomplete expression reflecting an underlying genetic predisposition. Twins discordant for OFCs provide a unique opportunity to further test this idea, as the unaffected co-twin shares on average 50% (for dizygotic twins) and 100% (for monozygotic twins) of the genetic risk factors as the affected twin. We used 3D surface imaging and spatially-dense morphometry to compare facial shape in a sample of 44 unaffected co-twins and age- and sex-matched unaffected controls (n = 241). Unaffected co-twins showed statistically significant differences in the midface, lateral upper face, and forehead regions, compared to controls. Furthermore, co-twins were characterized by a distinct pattern of midfacial retrusion, broader upper faces, and greater protrusion of the mandible and brow ridges. This same general facial pattern was shown in both unaffected monozygotic and dizygotic co-twin subsets. These results provide additional support that altered facial shape is a phenotypic marker for OFC susceptibility.