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.

A novel technique for superior-based pharyngeal flaps: 10-year results with formal speech outcomes assessment.

PURPOSE: Describe a novel technique for superior-based pharyngeal flaps allowing restoration of bulk to the soft palate and intraoperative fine-tuning of lateral port size, while avoiding midline palate-splitting. Validated speech assessment tools are employed for quantitative analysis. METHODS: Retrospective review of all patients who underwent superior-based pharyngeal flap in a 10-year period by a single surgeon. Pittsburgh Weighted Values for Speech Symptoms Associated with VPI and the Goldman-Fristoe Test of Articulation were used for formal speech assessment. RESULTS: 78 patients met inclusion criteria with clinical data up to 10years postoperatively. 31 patients had congenital velopharyngeal insufficiency (VPI), and the remainder acquired VPI after cleft palate repair or adenoidectomy. 37 patients had a recognized syndrome. All patients noted subjective improvement in nasality, and evaluation with the validated speech assessment tools demonstrated statistically significant improvement in speech. Only one flap takedown was required in a patient with severe midface hypoplasia who developed sleep apnea several years postoperatively. CONCLUSIONS: This technique is successful in congenital and acquired VPI, and in patients with complex craniofacial syndromes. Customization of lateral ports based on preoperative nasopharyngoscopy, and avoidance of a midline palate splitting incision, make this an attractive option for superior-based flap surgery.

Perioperative risk factors in patients with 22q11.2 deletion syndrome requiring surgery for velopharyngeal dysfunction.

Objective : To determine the prevalence of cardiac, cervical spine, and carotid artery abnormalities in patients with 22q11.2 deletion syndrome (22q11.2DS) undergoing surgery for velopharyngeal dysfunction (VPD), associations between the presence of these abnormalities, and whether these abnormalities caused changes in surgical management or perioperative complications. Design : Retrospective review. Setting : Tertiary pediatric hospital. Patients : Seventy patients with 22q11.2DS with complete preoperative cervical vascular and spine imaging and cardiac evaluation between 1998 and 2011. Main Outcome Measures : Incidence of cardiac, cervical spine, and vascular abnormalities; related perioperative complications; and resulting changes in surgical, anesthetic, or perioperative management plan. Results : Cardiac abnormalities occurred in 45 patients (64.3%), and 8 patients required cardiac anesthesia. Thirty-eight patients (54.3%) had at least one vascular abnormality of the neck, and 14% had medial deviation of the internal carotid artery. Surgery was not performed in one patient, and the surgical plan was altered in three patients because of carotid anomalies. Cervical spine abnormalities were found in 24 patients (34.3%); 8 patients demonstrated radiographic evidence of cervical instability and were treated with spinal precautions during surgery. The presence of one anomaly was not predictive of any other finding, and there were no complications related to the heart, cervical spine, or carotid arteries. Conclusions : Anomalies of the heart, cervical spine, and cervical vasculature occur frequently in 22q11.2DS, vary drastically in severity, and are impossible to predict based on other features of the syndrome. Preoperative diagnosis of these comorbidities with routine imaging can minimize the risk of avoidable surgical complications.

Severe congenital hypoglossia: a case report.

Hypoglossia is referred to a small volume and/or size of the tongue. It is a rare congenital condition caused by failed embryogenesis of the lateral lingual swellings and tuberculum impar during the fourth to eighth weeks of gestation. The anomaly has often occurred in association with limb abnormalities and various syndromes, and it affects facial and mandibular growth. The present report describes a case of severe congenital hypoglossia in a female infant, her systemic and dentofacial features, and the initial management.

Incidence and type of otopathology associated with congenital palatopharyngeal incompetence.

Based upon the known association of cleft palate and middle ear disease, a study was undertaken to determine the incidence and type of middle ear pathology associated with velar anomalies exclusive of cleft palate which may produce congenital palatal pharyngeal incompetence. The range of velar anomalies encountered was subdivided into congenital palatal incompetence Type 1 (clinically manifested by one or more of a triad of visible palatal anomalies including submucous deficiency of the hard palate, bifid uvula, and a diastasis of velar musculature) and congenital palatal incompetence Type 2 (no visible velar anomalies but radiographic anomalies of the velopharyngeal region such as short or thin velum and/or enlarged nasopharyngeal dimensions consequent to vertebral and skull base anomalies). Middle ear disease was assessed separately in CPI Types 1 and 2 in order to differentiate the effects upon middle ear function between overt and occult velar anomalies. Middle ear disease was more frequent in CPI Type 1 than in CPI Type 2. The predominant otopathologic finding was serous otitis media, paralleling the type associated with cleft palate. Tympanic membrane atrophy, tympanosclerosis and tympanic membrane perforation, often considered sequelae of chronic serous otitis media, were noted infrequently. This investigation supports the concept that middle ear disease frequently occurs with congenital palatal incompetence as it does with cleft palate.

Nasal and paranasal sinus disease in patients with congenital velopharyngeal insufficiency.

OBJECTIVE: To investigate nasal and paranasal disease in patients with congenital velopharyngeal insufficiency (CVPI). DESIGN: Case series. SETTING: Patients with CVPI or cleft palate were investigated at Kyoto (Japan) University Hospital. PATIENTS AND OTHER PARTICIPANTS: Consecutive sample (60 patients with CVPI and 333 with cleft palate). No eligibility criteria or sociodemographic features. Random sample (normal subjects). MAIN OUTCOME MEASURES: The incidence of sinusitis and septal deviation, nasal airway resistance, nasal mucociliary function by saccharin test, and ciliary beating frequency were examined. These findings in patients with cleft palate and normal subjects were compared to clarify the features of nasal disease in CVPI. RESULTS: The incidence of sinusitis in CVPI was 46.7% and approximately equal to that in cleft palate (44.1%). The incidence of septal deviation in CVPI (26.7%) was low and nasal airway resistance was almost normal. In contrast, in patients with bilateral, unilateral, or incomplete cleft palate, the incidence of septal deviation was significantly more frequent (78.9%) than that in CVPI (P < 0.001), and nasal airway resistance was significantly higher than that in CVPI (P < .0001). In patients with submucosal cleft, septal deviation was found in 40.8% and nasal airway resistance was significantly higher than that in CVPI (P < .02). Although saccharin time was significantly prolonged (P < .001) and ciliary beating frequency was significantly lower (P < .005) in patients with cleft palate than in normal subjects, values for these tests in patients with CVPI were normal. CONCLUSIONS: The incidence of sinusitis was high in CVPI. However, the frequency of septal deviation and nasal airway resistance was almost normal. Nasal mucociliary function (saccharin time and ciliary beating frequency) was also normal.

Use of the pharyngeal flap in the treatment of congenital velopharyngeal incompetence.

Seventy-four patients were referred to the senior author because of presumed velopharyngeal incompetence without cleft palate. As a result of an extensive preoperative evaluation that included assessment of articulation patterns, nasal emission, oronasal resonance, and general speech intelligibility, 57 of the 74 patients were selected for a pharyngeal flap procedure. In 54 of the 57 patients (95 percent), the operation corrected inappropriate nasal emission and hypernasality and improved intraoral air pressure to allow normal speech production.

A rationale for modifying the site of insertion of the orticochea pharyngoplasty.

A modification of the insertion level of Orticochea flaps is proposed. The purpose of the modification is to place the pharyngoplasty at a higher site, in the area of attempted velopharyngeal contact. The site of velopharyngeal contact can be identified using lateral radiographic techniques. A success rate of 93 percent was achieved in improved oral-nasal resonance balance when the pharyngoplasty was placed at a site in the nasopharynx.

Congenital velopharyngeal incompetence in Kabuki make-up syndrome.

The Kabuki make-up syndrome is characterized by peculiar cranio-facial abnormalities, including cleft lip and palate. A case with velopharyngeal incompetence in a 7-year-old boy is reported. The significance of a possible association of this syndrome with congenital velopharyngeal incompetence is also discussed.

[The Tübingen palatal plate--an innovative therapeutic concept in Pierre-Robin sequence]. / Die Tübinger Gaumenplatte--Ein innovatives Therapiekonzept bei Pierre-Robin-Sequenz.

Infants with Pierre-Robin sequence (PRS) may suffer severe upper airway obstruction resulting in hypoxemia that is difficult to treat. We are currently evaluating a new therapeutic approach involving an oral appliance that widens the pharynx by pulling the base of the tongue forward using a preepiglottic baton. Here we present a patient treated with this device who showed a decrease in his desaturation index from 50 to < 1.

[Otitis media with effusion in patients with cleft palate and congenital velopharyngeal insufficiency].

The incidences of otitis media with effusion (OME), otoscopic findings of the ear drum, hearing acuity and tympanometric findings were evaluated in 56 cases of cleft palate (CP), 33 cases of submucous cleft palate (SMCP) and 25 cases of congenital velopharyngeal insufficiency without cleft (CVPI). In all the cases, the incidences of OME, the pathological findings in otoscopy and the hearing test were far poorer in the group 8 years old and up than in the younger group. In the younger age group, the incidence of OME was 69% among the CP group, 62% in the SMCP group and showed significantly less incidence in the CVPI group (28%). The incidence of pathological findings in the ear drum was significantly less in the CVPI group than in either the CP group or the SMCP group. Hearing impairment was more frequent in the CP group than in both the SMPC and CVPI groups, while fewer incidences of abnormal tympanogram were found in the CVPI group than in the other two groups. Nearly 14% of the younger CP group developed pathological findings after surgery for velopharyngeal improvement. Most cases were found after push back operations, but rare after pharyngeal flap operations.

Management of velopharyngeal insufficiency in the presence of enlarged tonsils: comparing a one-stage versus two-stage treatment result.

Alterations in velopharyngeal function after removal of enlarged tonsils were noted. However, the changes varied from previous reports. The purposes of this study were to examine the effect of tonsillectomy on velopharyngeal function and to look for proper management of velopharyngeal insufficiency in the presence of enlarged tonsils. Thirty patients who received tonsillectomy at one craniofacial centre were reviewed. The influence of tonsillectomy on velopharyngeal function was examined and correlations to nasopharyngoscopic or videofluoroscopic findings were made. The outcomes between simultaneous and staged tonsillectomy and velopharyngeal surgery were compared. Tonsillectomy was found to either improve or impair velopharyngeal function in a small proportion of patients; however, it did not alter the surgical management of velopharyngeal insufficiency. Nasopharyngoscopic or videofluoroscopic findings did not predict the influence of tonsillectomy on velopharyngeal function. Finally, simultaneous tonsillectomy and velopharyngeal surgery had an efficacy and complication rate comparable to that of the staged approach.

The prevalence of congenital heart disease among the population of a metropolitan cleft lip and palate clinic.

The entire infant population of the Tufts-New England Medical Center Cleft Palate Clinic was reviewed, and the prevalence rates of congenital cardiac anomalies were calculated. The overall prevalence rate of congenital heart disease among the facial cleft clinic population was 6.7%, with a prevalence rate of 9.1% among patients with submucous cleft palate, 7.7% with congenital palato-pharyngeal incompetence, 0% with cleft lip only, 5.3% with unilateral cleft lip and palate, 12.5% with bilateral cleft lip and palate, 4.3% with cleft palate only, 13.6% with Pierre-Robin anomaly, 7.1% with cleft lip and palate and a syndrome diagnosis, 16.7% with cleft palate and a syndrome diagnosis.

A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome.

This report describes a pattern of similarities among 12 patients which are felt to represent a newly recognized congenital malformation syndrome. The symptoms shown most consistently by the 12 patients were overt or submuscous clefts of the secondary palate, ventricular septal defects, typical facies, and learning disabilities. Other symptoms were noted with varying frequency. The occurrence of velopharyngeal insufficiency in all twelve patients reflected poor motion in the lateral pharyngeal walls, thus necessitating specific forms of treatment. Treatment was often dependent on the extent of cardiac lesions.

Middle ear disease in children with congenital velopharyngeal insufficiency.

OBJECTIVE: To examine the incidence and natural history of middle ear disease in children with congenital velopharyngeal insufficiency (VPI) without cleft palate. SETTING AND SUBJECTS: Children with congenital VPI attending the combined cleft clinic at a tertiary cleft center. The diagnosis of congenital VPI in all cases was confirmed be the observation of hypernasality, nasal air escape, or both by a speech and language therapist and the demonstration of incompetence of the velopharyngeal sphincter by means of nasoendoscopy or videofluoroscopy. Children with overt cleft palate or postsurgical VPI were excluded. DESIGN: The children's medical records were reviewed, and a questionnaire regarding history of ear problems was sent to all parents. Children were divided into those with Pruzansky type I VPI (showing bifid uvula, midline diastasis of soft palate, or submucous cleft of the hard palate) and Pruzansky type II VPI (no visible stigmata). MAIN OUTCOME MEASURES: Incidence of reported ear problems, ear infections, hearing loss, and surgical intervention for middle ear disease in the whole group and in each of the subgroups. RESULTS: Seventy-one parents returned completed questionnaires. The overall incidence of middle ear disease was 63%, with 28% reported to have below-normal hearing. There was no significant difference between children with Pruzansky types I and II VPI with respect to incidence of otopathology or hearing loss. CONCLUSIONS: Irrespective of the presence of any visible palatal abnormalities, children with congenital VPI showed a substantial incidence of otopathology and should thus be closely monitored.

[Study of congenital velopharyngeal insufficiency and hypernasality].

OBJECTIVE: To evaluate 27 congenital veloparyngeal insufficiency(CVPI) subjects and 6 normal articulation subjects with airflow pressure techniques. METHODS: A compare analysis was performed in two groups (CVPI subjects and normal articulation subjects) during speech production of /hemper/ and /papa/. RESULTS: There wasn't statistical significance between two groups in oral air pressure and velopharyngeal orifice areas, however, CVPI group differed significant in nasal airflow on the articulation of /hemper/ and /papa/. CONCLUSIONS: When the degree of CVPI subject's VP opening was small, hypernasality appeared to be related to duration of the opening-closing movements.

[A study on the treatment of congenital velopharyngeal insufficiency].

OBJECTIVE: To evaluate the effectiveness of speech therapy after pharyngoplasty in patients with congenital velopharyngeal insufficiency (CVPI). METHODS: Seven patients with CVPI had received pharyngoplasty and speech therapy. The blowing test and the Chinese articulation clear degree test were measured before and after speech therapy. RESULTS: The treatment results of seven patients appeared to be reasonably satisfactory after speech therapy. Both the index of blowing test and the Chinese articulation clear degree test increased significantly after speech therapy. CONCLUSION: Pharyngoplasty combined with speech therapy is effective in the treatment of patients with CVPI.

Evaluation of a modified sphincter pharyngoplasty in the treatment of speech problems due to palatal insufficiency.

Results are presented of the first 10 children treated with a sphincter-type pharyngoplasty for speech defects due to velopharyngeal insufficiency. Seven of these children had cleft palates, 4 of the submucous variety. The operation, modified from one devised by Orticochea, is described in detail and emphasizes the importance of sphincter action closure of the nasopharynx. We believe this closure must be at a very high level. Preoperative and postoperative assessments of the patients by 4 observers are detailed in depth. Eight of the 10 patients showed improvement and none were made worse. We believe this operation, which places a functioning sphincter near the optimum site, is of considerable value in the treatment of selected patients suffering speech defects resulting from velopharyngeal incompetence.