Speech Telepractice and Treatment Intensity in a Cantonese-Speaking Case with 22q11.2 Deletion Syndrome Following Late Diagnosis and Management of Velopharyngeal Dysfunction.

This case report explores clinical treatment efficacy in a Cantonese-speaking child with 22q11.2 Deletion Syndrome where diagnosis and management of velopharyngeal dysfunction can be considered late. All treatment sessions were undertaken via telepractice during the peak of the COVID-19 pandemic in Hong Kong. A hybrid of specialized cleft palate speech treatment techniques and traditional treatment approaches in Speech Sound Disorders were utilized. Treatment intensity components including dose, dose form, session duration, and total intervention duration were documented.

Heritability Analysis in Twins Indicates a Genetic Basis for Velopharyngeal Morphology.

The velopharyngeal mechanism is comprised of several muscular components that act in a coordinated manner to control airflow through the nose and mouth. Proper velopharyngeal function is essential for normal speech, swallowing, and breathing. The genetic basis of normal-range velopharyngeal morphology is poorly understood. The purpose of this study was to estimate the heritability of velopharyngeal dimensions.We measured five velopharyngeal variables (velar length, velar thickness, effective velar length, levator muscle length and pharyngeal depth) from MRIs of 155 monozygotic and 208 dizygotic twin pairs and then calculated heritability for these traits using a structural equation modeling approach.The heritability estimates were statistically significant (95% confidence intervals excluded zero) and ranged from 0.19 to 0.46. There was also evidence of significant genetic correlations between pairs of traits, pointing to the influence of common genetic effects.These results indicate that genetic factors influence variation in clinically relevant velopharyngeal structures.

Velopharyngeal Incompetence in Children With 22q11.2 Deletion Syndrome: Velar and Pharyngeal Dimensions.

ABSTRACT: The surgical management of velopharyngeal incompetence (VPI) in children with 22q11.2 deletion syndrome (22q11.2 DS) is challenging. There are numerous approaches and children often undergo more than one operation. Our aim was to develop a method using images from routine lateral videofluoroscopy to study the dimensions of the velopharynx in this cohort.We analyzed 22 pre-operative lateral videofluoroscopy recordings of children with 22q11.2 DS and VPI. Fourteen had a submucous cleft palate (SMCP) and 8 had no obvious palatal abnormality but who were subsequently labelled as having an occult submucous cleft palate (OSMCP). The control data were 10 historic records of children with cleft lip and an intact palate. The authors identified key points on radiographs of the velum at rest and when elevated to measure the total velar length, functional velar length and pharyngeal depth and compared them ratiometrically.The intra-observer reliability was > 0.9 whereas the inter-observer reliability was > 0.74. The velopharyngeal depth/total velar length was significantly greater in 22q11.2 DS than the control group P < 0.001. There was no difference between SMCP and OSMCP patients, P = 0.556. There was no difference in the functional velar length/total velar length between 22q11.2 DS and controls (P = 0.763).In this study, the authors demonstrate a reliable method to gain useful ratiometric measurements of the velopharynx. This may help with treatment planning. Children with 22q11.2 DS and VPI have a larger velopharyngeal depth/total velar length ratio that may explain some of the difficulty in management.

Submucous Cleft Palate Repair in Patients With 22q11.2 Deletion Syndrome.

OBJECTIVE: To determine whether surgical intervention for submucous cleft palate (SMCP) is more common in children with 22q11.2 deletion syndrome (22q DS) compared to children without 22q DS. DESIGN: Retrospective chart review. SETTING: Tertiary pediatric hospital and 22q11.2 DS specialty clinic. PARTICIPANTS: One hundred forty-two children seen at the tertiary hospital or clinic during a 20-year period (June 1999-June 2019) with documented SMCP with and without 22q DS. MAIN OUTCOME MEASURE: Percentage of children with SMCP with and without 22q DS requiring surgical intervention for velopharyngeal insufficiency. RESULTS: Patients with 22q DS had a significantly higher frequency of SMCP repair than those without 22q DS (89.7% vs 32.0%, P < .001, χ2 = 37.75). The odds of requiring SMCP repair were 18.6 times higher in those with 22q DS compared to those without (odds ratio = 18.6, CI = 6.1-56.6). CONCLUSIONS: This study provides new evidence suggesting patients with 22q DS require SMCP surgical repair for velopharyngeal insufficiency at a significantly higher rate than those without 22q DS. As the majority of patients with 22q DS with SMCP require surgical intervention, future prospective studies looking at early versus late repair of SMCP in patients with 22q DS are needed to guide the surgical repair timeline in this population.

A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction.

Congenital cranial dysinnervation disorders (CCDDs) comprise a heterogeneous spectrum of diseases characterized by congenital, non-progressive impairment of eye, eyelid and/or facial movements including Möbius syndrome, Duane retraction syndrome, congenital ptosis, and congenital fibrosis of the extraocular muscles. Over the last 20 years, several CCDDs have been identified as neurodevelopmental disorders that are caused by mutations of genes involved in brain and cranial nerve development, e.g. KIF21A and TUBB3 that each plays a pivotal role for microtubule function. In a five-generation pedigree, we identified a heterozygous mutation of TUBB6, a gene encoding a class V tubulin which has not been linked to a human hereditary disease so far. The missense mutation (p.Phe394Ser) affects an amino acid residue highly conserved in evolution, and co-segregates with a phenotype characterized by congenital non-progressive bilateral facial palsy and congenital velopharyngeal dysfunction presenting with varying degrees of hypomimia, rhinophonia, impaired gag reflex and bilateral ptosis. Expression of the mutated protein in yeast led to an impaired viability compared to wildtype cells when exposed to the microtubule-poison benomyl. Our findings enlarge the spectrum of tubulinopathies and emphasize that mutations of TUBB6 should be considered in patients with congenital non-progressive facial palsy. Further studies are needed to verify whether this phenotype is indeed part of the CCDD spectrum.

Palatal evaluation and treatment in 22q11.2 deletion syndrome.

Palatal involvement occurs commonly in patients with 22q11.2 Deletion Syndrome (22qDS), and includes palatal clefting and velopharyngeal dysfunction in the absence of overt or submucous clefts. The reported incidence and distribution of palatal abnormalities vary in the literature. The aim of this article is to revisit the incidence and presenting features of palatal abnormalities in a large cohort of patients with 22qDS, summarize the surgical treatments performed in this cohort, and provide an overview of surgical treatment protocols and management guidelines for palatal abnormalities in this syndrome. Charts of 1,121 patients seen through the 22q and You Center at the Children's Hospital of Philadelphia were reviewed for palatal status, demographic factors, deletion size, and corrective surgical procedures. Statistical analysis was performed using Pearson's chi-squared test to identify differences between gender, deletion size, and palatal abnormality. Of the patients with complete evaluations, 67% were found to have a palatal abnormality. The most common finding was velopharyngeal dysfunction in 55.2% of patients, and in 33.3% of patients, this occurred in the absence of palatal clefting. There was no significant difference in the incidence of palatal abnormalities by gender; however, a difference was noted among race (p < 0.01) and deletion sizes (p < 0.01). For example, Caucasian and Asian patients presented with a much higher prevalence of palatal abnormalities, and conversely those with nested deletions presented with a much lower rate of palatal defects. Overall, 26.9% of patients underwent palatal surgery, and the most common indication was velopharyngeal dysfunction. Palatal abnormalities are a hallmark feature of 22q11.2 Deletion Syndrome; understanding the incidence, presenting features, and treatment protocols are essential for practitioners counseling and treating families affected with this disorder.

22q11.2 Deletion: Surgical and Speech Outcomes of Patients With Velopharyngeal Insufficiency Treated With a Superiorly Based Pharyngeal Flap as the Primary Surgery.

The most frequent palate diagnoses in patients with chromosome 22q11.2 deletion syndrome are a classic submucous cleft, occult, and velopharyngeal insufficiency without cleft, which generates alterations in speech that require surgery. Surgical protocols are controversial owing to syndrome characteristics that make their handling more complex. Pharyngeal flap pharyngoplasty is effective for this type of patient. The objective of this study is to examine the surgical management of velopharyngeal insufficiency in patients with chromosome 22 deletion, using a pharyngeal flap as the primary surgery. The clinical records of patients with chromosome 22 deletion and velopharyngeal insufficiency between 2015 and 2017 were analyzed retrospectively. Eight patients underwent pharyngeal flap pharyngoplasty as a primary surgery, including 1 with velopharyngeal insufficiency without a cleft, 1 with a classic submucous cleft, and 6 with occult submucous cleft. The pre- and postoperative protocol performed by speech therapists and surgeons included clinical evaluation of the oral cavity; perceptual, video recording, and nasometry speech evaluation; and videonasopharyngoscopy. All perceptual parameters and nasometry results significantly changed. Of the cases, 88% achieved a flap with the expected width and height and complete closure of the velopharyngeal sphincter. One patient required flap revision. Four of the 8 patients achieved normal resonance, and 2 of 8 showed mild hypernasality. Using the pharyngeal flap pharyngoplasty as a primary technique to correct velopharyngeal insufficiency in patients with chromosome 22 deletion provides satisfactory outcomes and decreases the number of surgeries. Preoperative planning must be conducted carefully and needs to be individualized to be successful.

Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an in-frame duplication in OTX2.

Agnathia-otocephaly complex is a malformation characterized by absent/hypoplastic mandible and abnormally positioned ears. Mutations in two genes, PRRX1 and OTX2, have been described in a small number of families with this disorder. We performed clinical and genetic testing in an additional family. The proband is a healthy female with a complicated pregnancy history that includes two offspring diagnosed with agnathia-otocephaly during prenatal ultrasound scans. Exome sequencing was performed in fetal DNA from one of these two offspring revealing a heterozygous duplication in OTX2: c.271_273dupCAG, p.(Gln91dup). This change leads to the insertion of a glutamine within the OTX2 homeodomain region, and is predicted to alter this signaling molecule's ability to interact with DNA. The same variant was also identified in the proband's clinically unaffected 38-year-old husband and their 9-year-old daughter, who presented with a small mandible, normal ears and velopharyngeal insufficiency due to a short hemi-palate. This unusual presentation of OTX2-related disease suggests that OTX2 might have a role in palatal hypoplasia cases. A previously unreported OTX2 variant associated with extreme intrafamilial variability is described and the utility of exome sequencing as a tool to confirm the diagnosis of agnathia-otocephaly and to inform the reproductive decisions of affected families is highlighted.

Superiorly based pharyngeal flap for treatment of velopharyngeal insufficiency in patients with 22q11.2 deletion syndrome.

BACKGROUND: There are no previous blinded studies for comparison of preoperative versus postoperative perceptual speech assessments when using a pharyngeal flap for treating velopharyngeal insufficiency (VPI) in patients diagnosed with 22q11.2 deletion syndrome. The aim of the study was to evaluate the effect of superiorly based pharyngeal flap surgery on speech in these patients using blinded judgments of experienced speech therapists. METHODS: A retrospective study of 12 consecutive patients who had undergone pharyngeal flap surgery for treatment of VPI between 2002 and 2009 was conducted. Seven girls and 5 boys between 4 and 15 (median, 6) years old at the time of surgery were included in the study. Six patients were born with a submucous cleft palate (including 2 occult), and 1 patient, with an overt cleft palate. The remaining 5 patients had no signs of a palatal pathology. All palatal clefts had been repaired before pharyngeal flap surgery except in 2 patients with occult submucous cleft palate. Preoperative and postoperative audio recordings were blinded for scoring independently by 3 senior speech therapists. RESULTS: There was a significant improvement in hypernasality (P = 0.002), audible nasal emission (P = 0.033), weak pressure consonants (P = 0.008), and speech intelligibility (P = 0.021) after pharyngeal flap surgery. Hyponasality did not develop significantly with surgery. One patient was diagnosed with obstructive sleep apnea. CONCLUSIONS: Superiorly based pharyngeal flap resulted in a significant speech improvement in 12 consecutive patients with 22q11.2 deletion syndrome having VPI.

Sphincter Pharyngoplasty for Velopharyngeal Dysfunction: Impact of 22q11.2 Deletion Syndrome.

OBJECTIVE: Patients with 22q11.2 deletion syndrome (22q11DelS) often present with velopharyngeal dysfunction (VPD). VPD in patients with 22q11DelS is multifactorial beyond velopharyngeal insufficiency (VPI) alone, and differences in surgical outcomes are poorly understood. Our objective was to determine whether patients with 22q11DelS have an increased risk for persistent VPI after sphincter pharyngoplasty compared to patients without 22q11DelS. METHODS: We completed a retrospective cohort study of patients with 22q11DelS undergoing sphincter pharyngoplasty between 1995 and 2019 using a VPD clinic database. Patients with 22q11DelS were compared to a cohort of 2:1 frequency-matched (age, degree of velopharyngeal closure) patients without 22q11DelS. Variables included patient characteristics, surgical history, perceptual speech evaluation, and degree of closure on nasopharyngoscopic evaluations. Primary outcomes included postoperative VPI severity and hypernasality. Speech and nasopharyngoscopic characteristics were compared using Fisher's exact test. Postoperative VPI severity and hypernasality were compared between groups via relative risks (RR) from mixed effects Poisson regression models, with random effects of age and velopharyngeal closure. RESULTS: 134 patients (51 22q11DelS, 83 matched) were included, with mean age of 7.3 years (standard deviation 3.0) and 50% male. Cohorts had similar preoperative speech characteristics and nasopharyngoscopic findings. Patients with 22q11DelS had similar postoperative VP function as patients without 22q11DelS (RR 0.85, CI 0.46-1.57 for VPI severity, RR 0.83, CI 0.45-1.53 for hypernasality). Even after adjusting by preoperative variables, no differences were seen between both groups. CONCLUSION: Matched for age and pre-operative velopharyngeal closure, patients with and without 22q11DelS and VPI had similar benefits after sphincter pharyngoplasty. LEVEL OF EVIDENCE: Non-randomized controlled cohort study, 3 Laryngoscope, 133:2813-2820, 2023.

Speech and hearing in adults with 22q11.2 deletion syndrome.

The purpose of the study was to investigate the prevalence of velopharyngeal impairment, compensatory articulation, reduced intelligibility, and to rate the general impression of speech in adults with 22q11.2 deletion syndrome. The second purpose was to study the prevalence and type of hearing impairment in these adults. A referred, consecutive series of 24 adults with confirmed 22q11.2 deletion, 16 female and 8 males, with a mean age of 25 years (19-38 years) was included in the study. A blind assessment of speech by three experienced speech-language pathologists was performed. Sixteen (66%) patients had a mild to severe velopharyngeal impairment. The most prevalent symptoms of velopharygeal impairment were hypernasality and audible nasal airflow. The mean nasalance score was 33% (6-66%). Only two patients had disordered articulation; one of these had glottal articulation. A mean of 96% (88-100%) of single words were rated to be intelligible. To achieve these results half of the patients previously had velopharyngeal flap surgery. Forty-one percent (9/22) had mild-moderate hearing impairment; three had sensorineural type, four conductive and two had a mixed type. In conclusion the majority of the patients had no articulation errors and good intelligibility; while one-third still had moderate to severe problems with velopharyngeal impairment. Around 40% still had some hearing impairment, in most cases with a mild to moderate conductive component. Thus, a high prevalence of speech and hearing problems seems to be a part of the phenotype in adults with 22q11.2DS.

Velopharyngeal dysfunction and 22q11.2 deletion syndrome: a longitudinal study of functional outcome and preoperative prognostic factors.

OBJECTIVE: To describe the effect of time after velopharyngoplasty on outcome and to search for preoperative prognostic factors for residual hypernasality in patients with 22q11.2 deletion syndrome. DESIGN: Retrospective chart review. SETTING: Tertiary hospital. PATIENTS: Patients with 22q11.2 deletion syndrome and velopharyngeal dysfunction who underwent a primary (modified) Honig velopharyngoplasty between 1989 and 2009. MAIN OUTCOME MEASURES: Clinically obtained perceptual and instrumental measurements of resonance, nasalance, and understandability before and after velopharyngoplasty. RESULTS: Data were available for 44 of 54 patients (81% follow-up), with a mean follow-up time of 7.0 years (range, 1.0 to 19.4 years). During follow-up, 24 (55%) patients attained normal resonance and 20 (45%) had residual hypernasality or underwent revision surgery. Mean postoperative nasalance and understandability scores were closer to the norm than mean preoperative scores were (2.0 versus 5.5 standard deviations for the normal passage, 1.3 versus 8.1 standard deviations for the nonnasal passage, and score 2.3 versus 4.1 understandability). Serial measurements revealed that hypernasality only resolved an average of 5 years after surgery, and three patients whose resonance initially normalized later relapsed to hypernasality. Gender, age at surgery, lateral pharyngeal wall adduction, velar elevation, presence of a palatal defect, previous intravelar veloplasty, nasalance, understandability, adenoidectomy, hearing loss, and IQ were not able to predict poor outcome following primary velopharyngoplasty (all p > .05). CONCLUSIONS: In this chart review of patients with 22q11.2 deletion syndrome and velopharyngeal dysfunction, residual hypernasality persisted in many patients after velopharyngoplasty. None of the preoperative factors that were studied had prognostic value for the outcome.

Is there a correlation between skull base flexure and palatal anomalies in patients with 22q11 deletion syndrome and velopharyngeal dysfunction?

The study aimed at assessing the relationship between skull base morphology, represented by skull base and nasopharyngeal angles, and palatal anatomy among patients with 22q11DS and velopharyngeal dysfunction. Retrospective analysis of patients with 22q11DS and velopharyngeal dysfunction. Age, sex, severity of velopharyngeal dysfunction, type of cleft (overt cleft palate, submucous cleft palate, occult submucous cleft palate, or no-CP, and cephalometric skull base angles were reviewed. Correlations between type of palatal anomaly and the angles were assessed. Among 132 patients, 71 were male (53.8%) and 61 were female (46.2%), ages 3.3-40.0 years (mean 8.3 ± 6.10). No difference in the mean cranial-base angle (P = 0.353) or in the distribution of the three types of cranial base angle sizes was found among the palatal anomaly groups (P = 0.137). More men had normal cranial base angles and more women had acute angulation (P = 0.008). A positive correlation was found between the skull base and nasopharyngeal angles (P = 0.001, r = -0.590). No direct correlation was found between cranial base morphology and palatal anomalies in patients with 22q11DS, and velopharyngeal dysfunction. This is probably because skull base and palate morphology contribute independently to velopharyngeal dysfunction.

The importance of neurology and genetic testing in the patient with non-cleft velopharyngeal dysfunction.

OBJECTIVE: A significant proportion of the referrals made to a speech investigation clinic in a cleft unit include patients with non-cleft velopharyngeal dysfunction (VPD). This study aims to quantify the underlying diagnoses of these patients and describe the investigative pathway and diagnostic information subsequent to presentation in our clinic. MATERIALS AND METHODS: The case notes of 136 consecutive patients with non-cleft VPD who attended our Velopharyngeal Investigation (VPI) clinic from July 2014-December 2019 were reviewed. RESULTS: In the paediatric group (n = 118) the most common cause was 22q11 chromosomal anomalies (n = 46), while post palatal tumour resection was the commonest cause of acquired non-cleft VPD in adults (n = 8). Fifty-nine patients were referred to the clinic with a known underlying pathology such as a syndromic diagnosis. Of those presenting without a known aetiology, fifty-eight were referred onto our genetics and/or neurology colleagues. Although a genetic or neurological cause could not be identified in some of those patients, thirty-one patients received a new diagnosis, with subsequent implications for ongoing care. CONCLUSION: There are a wide range of diagnoses resulting in non-cleft VPD, but there are very few large-scale studies focusing on investigating these patients for an underlying aetiology. This study highlights the role of genetics and neurology in the diagnosis and management plan for this cohort of patients.

Use of array comparative genome hybridization in orofacial clefting.

Orofacial clefting is a common condition found in 1 per 700 to 1 per 1000 births. Although most cases are isolated, a subset is caused by a specific genetic mutation. Specific gene tests have been used for recognizable syndromes such as velocardiofacial syndrome or van der Woude syndrome, where the cleft is associated with other anomalies. However, many cleft lip and palate patients have other anomalies but do not fit in to a recognizable syndrome. For these patients, chromosome analysis has been a first-line genetic test; however, in the past few years, a new form of genetic testing has become available for these patients: array comparative genome hybridization (aCGH). We present a 7-month-old male infant with cleft palate, developmental delay, and a family history of velopharyngeal insufficiency in whom aCGH array was used to identify a small deletion on the short (p) arm of chromosome 7. This defect, which was also found in the mother, was undetected by chromosome analysis. In summary, this case demonstrates that aCGH is a new diagnostic tool that is useful in the evaluation of select cases of orofacial clefting. Array comparative genome hybridization should be considered when the suspicion for a genetic etiology of the clefting remains strong despite a normal cytogenetic analysis.

Utilization of three-dimensional computed tomography for craniofacial phenotypic analysis in children with velocardiofacial syndrome.

OBJECTIVES: To analyze variants of the craniofacial phenotypes in children with velocardiofacial syndrome (VCFS) and children with cleft palates with a new protocol of landmarks using a three-dimensional computed tomography (CT)-reconstructed model in a cross-sectional group experimental design. MATERIALS AND METHODS: We present a retrospectively reviewed case series of 21 patients with VCFS, verified by short-tandem repeat techniques, and 20 children with cleft palate with age- and sex-matched controls from the Craniofacial Cleft Department of Oral and Maxillofacial Surgery of the 9th Shanghai People's Hospital. The records during the period between January 2005 and December 2008 were analyzed. The sample population of 41 children in this study was scanned with spiral CT. These images were reconstructed into three-dimensional models by SimPlant 11.2 and were analyzed with a new protocol of landmarks to test the variants of craniofacial phenotypes. RESULTS: All of the children with VCFS demonstrated velopharyngeal incompetence and craniofacial deformities. Measurements in the standard coordinate system demonstrated significant shorter cranial base, cervical vertebrae, longer maxilla height, and palatal angle. For the velopharyngeal variants, greater depth but lesser width of the pharyngeal cavity was shown in the VCFS group. CONCLUSIONS: Three-dimensional CT can provide precise data on craniofacial variants in children with distinctive morphologic features of VCFS.

Occult subtotal cleft of the secondary palate with VPI associated to 8q22.2 deletion.

BACKGROUND: Submucous cleft palate is a cleft of the secondary palate with low phenotypic gene expression. It can occur as an isolated malformation or associated with a syndrome that includes certain facial features and other vocal tract malformations. Velopharyngeal insufficiency (VPI) is rare in cases of non - syndromic occult clefts of the secondary palate (OSCSP). In contrast, syndromic OCSP has a high prevalence of VPI. VPI requires surgical treatment in the vast majority of cases. OBJECTIVE: To present a case of OSCSP with VPI after partial tonsillectomy and adenoidectomy (T & A) associated with facial features and other vocal tract malformations. A chromosomal abnormality (8q22.2 deletion) was demonstrated by cytogenetic testing. CASE PRESENTATION: Eight year old female with VPI following partial T & A. OSCSP was diagnosed. Complete T & A was performed in preparation for a pharyngeal flap. Pharyngeal flap surgery was customized according to findings of videonasopharyngoscopy (VNP) and multiplanar videofluoroscopy (MPVF). VPI was corrected without intraoperative or postoperative complications. CONCLUSION: The presence of multiple vocal tract malformations should be a red flag for suspecting a syndromic OSCSP. Surgical treatment of VPI in cases of OSCSP should be performed after complete T & A, Imaging procedures for assessing neck blood vessels and it should be customized according to imaging (VNP and MPVF) findings.

Retropharyngeal lipostructure in the treatment of velopharyngeal insufficiency: A prospective study and update.

INTRODUCTION: Retropharyngeal lipostructure is a recent procedure in velopharyngeal insufficiency (VPI), offering an effective alternative to heavier surgery. OBJECTIVES: To update and assess retropharyngeal lipostructure as a treatment for VPI in the University Hospital Center of Rouen (France). TYPE OF STUDY: Single-center prospective study, from May 2012 to May 2014. PATIENTS AND METHODS: Six patients (4 girls, 2 boys) presenting with VPI were treated by retropharyngeal lipostructure. Age at surgery ranged between 6 and 12 years. Four of the patients bore a 22q11 microdeletion. Treatment was indicated in case of Borel-Maisonny type 2b (n=2) or 2m (n=4) despite well-conducted speech therapy and of≥50% velopharyngeal sphincter closure on nasal endoscopy. Patients were assessed preoperatively and at 3 months, by a multidisciplinary team. Borel-Maisonny type was assessed by a speech therapist. Nasality was measured on assisted vocal evaluation (EVA®). Sphincter closure was assessed on dynamic MRI. RESULTS: Between 6 and 8cm3autologous fat was injected. At 3months, 4 children showed 1-grade improvement in Borel-Maisonny type. Nasality decreased systematically, from a mean 14.5% preoperatively to 10.5% postoperatively. MRI showed improvement in all cases, with complete closure in occlusive vowels in 3 children. CONCLUSION: EVA® and MRI provide precise objective assessment of VPI. Retropharyngeal lipostructure is a simple, relatively non-invasive, reproducible technique, providing good results in VPI.

Musculo-mucous web velum and velopharyngeal dysfunction associated with 8q22.1-22.2 microduplication.

This report presents a rare case of isolated non-cleft velopharyngeal dysfunction (VPD). An eight-year-old child presented 1. a phenotypically unique band-gap pattern of the velar musculature with anteroposterior insertion; 2. a mosaic partial trisomy on chromosome 19 as well as microduplications on chromosomes 8 and 22. Following cytogenetic analysis, microduplication on chromosome 8 was found in another member of her family. A family history of VPI with hypernasality and nasal regurgitation was reported over three different generations on the patient's maternal side. Since only one case of velum malformation is found in this family, we cannot conclude to a link between the palatal anomaly or VPD and the DNA rearrangements.

GWAS reveals loci associated with velopharyngeal dysfunction.

Velopharyngeal dysfunction (VPD) occurs when the muscular soft palate (velum) and lateral pharyngeal walls are physically unable to separate the oral and nasal cavities during speech production leading to hypernasality and abnormal speech reduction. Because VPD is often associated with overt or submucous cleft palate, it could be present as a subclinical phenotype in families with a history of orofacial clefting. A key assumption to this model is that the overt and subclinical manifestations of the orofacial cleft phenotype exist on a continuum and therefore share common etiological factors. We performed a genome-wide association study in 976 unaffected relatives of isolated CP probands, 54 of whom had VPD. Five loci were significantly (p < 5 × 10-8) associated with VPD: 3q29, 9p21.1, 12q21.31, 16p12.3 and 16p13.3. An additional 15 loci showing suggestive evidence of association with VPD were observed. Several genes known to be involved in orofacial clefting and craniofacial development are located in these regions, such as TFRC, PCYT1A, BNC2 and FREM1. Although further research is necessary, this could be an indication for a potential shared genetic architecture between VPD and cleft palate, and supporting the hypothesis that VPD is a subclinical phenotype of orofacial clefting.