Felicity V. Mehendale

Palate re-repair revisited.

OBJECTIVE To analyze the results of a consecutive series of palate re-repairs performed using the operating microscope and identify predictive factors for outcome. DESIGN Prospective data collection, with blind assessment of randomized recordings of speech and velar function on lateral videofluoroscopy and nasendoscopy. PATIENTS One hundred twenty-nine consecutive patients with previously repaired cleft palates and symptomatic velopharyngeal incompetence (VPI) and evidence of anterior insertion of the levator veli palatini underwent palate re-repairs by a single surgeon from 1992 to 1998. Syndromic patients, those who had significant additional surgical procedures at the time of re-repair (23 patients), and all patients with inadequate pre- or postoperative speech recordings were excluded, leaving a total of 85 patients in the study. INTERVENTIONS Palate re-repairs, with radical dissection and retropositioning of the velar muscles, were performed using the operating microscope with intraoperative grading of anatomical and surgical findings. MAIN OUTCOME MEASURES Pre- and postoperative perceptual speech assessments using the Cleft Audit Protocol for Speech (CAPS) score, measurement of velar function on lateral videofluoroscopy, and assessment of nasendoscopy recordings. RESULTS There were significant improvements in hypernasality, nasal emission, and nasal turbulence and measures of velar function on lateral videofluoroscopy, with improvement in the closure ratio, velopharyngeal gap at closure, velar excursion, velar movement angle, and velar velocity. CONCLUSIONS Palate re-repair has been shown to be effective in treating VPI following cleft palate repair, both in patients who have not had an intravelar veloplasty and those who have had a previous attempt at muscle dissection and retropositioning. Palate re-repair has a lower morbidity and is more physiological than a pharyngoplasty or pharyngeal flap.

Surgical management of velopharyngeal incompetence in velocardiofacial syndrome

Objective To analyze the results of surgery for velopharyngeal incompetence (VPI) in velocardiofacial syndrome. Design Prospective data collection, with randomized, blind assessment of speech and velopharyngeal function on lateral videofluoroscopy and nasendoscopy. Setting Two-site, tertiary referral cleft unit. Patients Forty-two consecutive patients with the 22q11 deletion underwent surgery for symptomatic VPI by a single surgeon. Interventions Intraoral examinations, lateral videofluoroscopy (± nasendoscopy) and intraoperative evaluation of the position of the velar muscles through the operating microscope. Based on these findings, either a radical dissection and retropositioning of the velar muscles (submucous cleft palate [SMCP repair]) or a Hynes pharyngoplasty (posterior pharyngeal wall augmentation pharyngoplasty) was performed. As anticipated, a proportion of patients undergoing SMCP repair subsequently required a Hynes. The aim of this staged approach was to maximize velar function, thereby enabling a less obstructive pharyngoplasty to be performed. Thus, there were three surgical groups for analysis: SMCP alone, Hynes alone, and SMCP+Hynes. Main Outcome Measures Blind perceptual rating of resonance and nasal airflow; blind assessment of velopharyngeal function on lateral videofluoroscopy and nasendoscopy; and identification of predictive factors. Results Significant improvement in hypernasality in all three groups. The SMCP+Hynes group also showed significant improvement in nasal emission. There were significant improvements in the extended and resting velar lengths following SMCP repair and a trend toward increased velocity of closure. Conclusions Depending on velopharyngeal anatomy and function, there is a role for SMCP repair, Hynes pharyngoplasty, and a staged combination of SMCP+Hynes, all of which are procedures with a low morbidity.

Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic form of Pierre Robin Sequence

Heterozygous loss-of-function (LOF) mutations in the gene encoding the DNA-binding protein, SATB2, result in micrognathia and cleft palate in both humans and mice. In three unrelated individuals, we show that translocation breakpoints (BPs) up to 896 kb 3′ of SATB2 polyadenylation site cause a phenotype which is indistinguishable from that caused by SATB2 LOF mutations. This syndrome comprises long nose, small mouth, micrognathia, cleft palate, arachnodactyly and intellectual disability. These BPs map to a gene desert between PLCL1 and SATB2. We identified three putative cis-regulatory elements (CRE1–3) using a comparative genomic approach each of which would be placed in trans relative to SATB2 by all three BPs. CRE1–3 each bind p300 and mono-methylated H3K4 consistent with enhancer function. In silico analysis suggested that CRE1–3 contain one or more conserved SOX9-binding sites, and this binding was confirmed using chromatin immunoprecipitation on cells derived from mouse embryonic pharyngeal arch. Interphase bacterial artificial chromosome fluorescence in situ hybridization measurements in embryonic craniofacial tissues showed that the orthologous region in mice exhibits Satb2 expression-dependent chromatin decondensation consistent with Satb2 being a target gene of CRE1–3. To assess their in vivo function, we made multiple stable reporter transgenic lines for each enhancer in zebrafish. CRE2 was shown to drive SATB2-like expression in the embryonic craniofacial region. This expression could be eliminated by mutating the SOX9-binding site of CRE2. These observations suggest that SATB2 and SOX9 may be acting together via complex cis-regulation to coordinate the growth of the developing jaw.

Surgical Significance of Abnormal Internal Carotid Arteries in Velocardiofacial Syndrome in 43 Consecutive Hynes Pharyngoplasties

Objectives To determine: (1) the incidence of surgically significant, abnormal internal carotid arteries (ICAs) in velocardiofacial syndrome (VCFS); (2) the implications for a Hynes pharyngoplasty; (3) the reliability of preoperative investigations in detecting surgically significant abnormal ICAs. Design Prospective data collection with blind reassessment of nasendoscopy recordings. Setting Two-site, tertiary referral cleft unit. Patients Forty-three consecutive patients with VCFS who underwent a Hynes pharyngoplasty (six had a subsequent revision). Interventions Intraoral examinations, lateral videofluoroscopy, nasendoscopy when possible, and intraoperative palpation of the posterolateral pharyngeal walls. Only one patient had a magnetic resonance angiography (MRA). Main Outcome Measures Incidence of surgically significant pulsations; modifications to surgical procedure; and correlation of surgical findings with preoperative nasendoscopy and MRA. Results Five patients (11.6%) had abnormal pulsations noted at the time of the Hynes. In no patient was the decision to perform a Hynes altered as a result of abnormal pulsations. Two patients had minor adjustments to the Hynes flaps to avoid exposing/damaging the ICA. In one patient an abnormal ICA was exposed during elevation of the left Hynes flap. This was covered uneventfully by routine closure of the secondary defect. Pulsations were noted in only 3 of 24 assessable preoperative nasendoscopies. Conclusions A Hynes pharyngoplasty is not contraindicated in VCFS, even if abnormal pulsations are present. Examination and palpation of the pharyngeal walls after the patient is positioned for surgery appear to be reliable in detecting abnormal pulsations and allow accurate surgical planning. Routine vascular imaging, even in patients with pulsations on preoperative nasendoscopy is not essential and may not always be reliable, as shown by the variation in endoscopic, MRA, and intraoperative findings. This further re-emphasizes the importance of palpating the pharyngeal walls once the patient is positioned for surgery.

Best Practices for the Diagnosis and Evaluation of Infants With Robin Sequence: A Clinical Consensus Report.

IMPORTANCE Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis, and upper airway obstruction. Currently, no consensus exists regarding the diagnosis and evaluation of children with RS. An international, multidisciplinary consensus group was formed to begin to overcome this limitation. OBJECTIVE To report a consensus-derived set of best practices for the diagnosis and evaluation of infants with RS as a starting point for defining standards and management. EVIDENCE REVIEW Based on a literature review and expert opinion, a clinical consensus report was generated. FINDINGS Because RS can occur as an isolated condition or as part of a syndrome or multiple-anomaly disorder, the diagnostic process for each newborn may differ. Micrognathia is hypothesized as the initiating event, but the diagnosis of micrognathia is subjective. Glossoptosis and upper airway compromise complete the primary characteristics of RS. It can be difficult to judge the severity of tongue base airway obstruction, and the possibility of multilevel obstruction exists. The initial assessment of the clinical features and severity of respiratory distress is important and has practical implications. Signs of upper airway obstruction can be intermittent and are more likely to be present when the infant is asleep. Therefore, sleep studies are recommended. Feeding problems are common and may be exacerbated by the presence of a cleft palate. The clinical features and their severity can vary widely and ultimately dictate the required investigations and treatments. CONCLUSIONS AND RELEVANCE Agreed-on recommendations for the initial evaluation of RS and clinical descriptors are provided in this consensus report. Researchers and clinicians will ideally use uniform definitions and comparable assessments. Prospective studies and the standard application of validated assessments are needed to build an evidence base guiding standards of care for infants and children with RS.

Unilateral Moore Pharyngoplasty in the Treatment of Unilateral or Asymmetric Velopharyngeal Incompetence

OBJECTIVE To describe the use of a unilateral modification of the Moore pharyngoplasty in the treatment of unilateral or asymmetric velopharyngeal incompetence (VPI) and analyze the results in a consecutive series of patients operated on by a single surgeon. DESIGN Blind assessment of randomized speech and nasendoscopy recordings. SETTING A two-site tertiary referral cleft unit. PATIENTS Eighteen consecutive patients with asymmetrical or unilateral VPI of varying etiology. INTERVENTIONS A unilateral Moore pharyngoplasty was performed in all patients. Three patients underwent radical dissection and retropositioning of the velar muscles at the same time as the unilateral Moore pharyngoplasty. MAIN OUTCOME MEASURES Pre- and postoperative nasality and nasal airflow using the CAPS score, assessment of nasendoscopy recordings, and the rate of further surgery. RESULTS There was a significant improvement in hypernasality (p =.014). There was a highly significant decrease in the size of the velopharyngeal gap on the side on which the Moore pharyngoplasty was performed (p =.004) as well as a highly significant decrease in the total gap size (p =.003). The Moore flap was effective in obliterating the lateral pharyngeal recess in 11 of 12 patients (p =.004). Three patients required further velopharyngeal surgery. CONCLUSIONS In appropriately selected patients, a unilateral Moore pharyngoplasty is a safe and effective treatment for unilateral or asymmetric VPI. If indicated, a radical dissection and retropositioning of the velar muscles may be combined with a Moore pharyngoplasty.

Submucous cleft palates presenting with a perforation

OBJECTIVE The development of a perforation in a submucous cleft palate (SMCP) is a rare occurrence, with only a few cases reported in the literature. We describe and illustrate four cases of SMCPs with a perforation in the palate. RESULTS AND CONCLUSIONS Recognition of the symptoms and signs of an SMCP should enable early diagnosis and treatment of this condition in symptomatic patients. However, in patients in whom the diagnosis has been missed or in those who have been asymptomatic, the development of a perforation may be the presenting feature of an SMCP. A history of possible trauma to the palate was found in two cases. Relatively minor trauma may cause perforation of the thin translucent central mucosa in an SMCP. In neonates, perforations surrounded by very thin mucosa may increase in size. The perforation can be closed at the same time as the SMCP repair and does not significantly alter the surgical treatment of an SMCP.

A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX.

Pierre Robin sequence (PRS) is an aetiologically distinct subgroup of cleft palate. We aimed to define the critical genomic interval from five different 5q22-5q31 deletions associated with PRS or PRS-associated features and assess each gene within the region as a candidate for the PRS component of the phenotype. Clinical array-based comparative genome hybridisation (aCGH) data were used to define a 2.08 Mb minimum region of overlap among four de novo deletions and one mother-son inherited deletion associated with at least one component of PRS. Commonly associated anomalies were talipes equinovarus (TEV), finger contractures and crumpled ear helices. Expression analysis of the orthologous genes within the PRS critical region in embryonic mice showed that the strongest candidate genes were FBN2 and PHAX. Targeted aCGH of the critical region and sequencing of these genes in a cohort of 25 PRS patients revealed no plausible disease-causing mutations. In conclusion, deletion of ∼2 Mb on 5q23 region causes a clinically recognisable subtype of PRS. Haploinsufficiency for FBN2 accounts for the digital and auricular features. A possible critical region for TEV is distinct and telomeric to the PRS region. The molecular basis of PRS in these cases remains undetermined but haploinsufficiency for PHAX is a plausible mechanism.

Gross unilateral abnormalities of the velum and pharynx.

OBJECTIVE Velopharyngeal incompetence because of gross unilateral velopharyngeal hypoplasia is rare, particularly in patients with no significant hemifacial microsomia or facial asymmetry. We describe the abnormal anatomy and treatment of three patients with gross congenital velopharyngeal asymmetry. RESULTS AND CONCLUSIONS Following surgery, all three patients showed a good improvement in velopharyngeal function and speech. Nasendoscopy and lateral videofluoroscopy were important in confirming the abnormal anatomy and pathology and in evaluating the degree of movement of the affected side of the velum and pharyngeal walls as well as the size and location of the defect. Muscles from the normal side were radically dissected and mobilized across the midline to reconstruct the hypoplastic hemivelum. Mucosal lengthening was achieved by suturing the normal mucosa to the mucosa of the hypoplastic hemivelum and the lateral pharyngeal wall or by insetting a posterolateral pharyngeal flap (modified Moore pharyngoplasty) into the nasal surface of the hypoplastic side.

Effect of Palate Re-Repairs and Hynes Pharyngoplasties on Pediatric Airways: An Analysis of Preoperative and Postoperative Cardiorespiratory Sleep Studies

Objectives To determine whether Sommerlad palate re-repairs and Hynes pharyngoplasties cause obstructive sleep apnea/hypopnea or increased upper airway resistance. Design Prospective before-and-after study. Setting Tertiary cleft unit. Patients A total of 44 patients undergoing a Sommerlad palate re-repair or a Hynes pharyngoplasty. Interventions Preoperative and postoperative multichannel cardiorespiratory sleep studies. Main Outcome Measures The main outcome measures were mean arterial oxygen saturation, desaturation index, percentage of time spent with arterial oxygen saturation <90%, mean pulse rate, number of pulse rate rises (arousals) per hour, inspiratory effort derived from pulse transit time, pulse transit time arousals, and snoring. Results No patient in either group required intervention for airway obstruction or obstructive sleep apnea/hypopnea. Re-repairs caused no significant change in any parameter. Hynes caused an increase in inspiratory effort (P = .04) and obstructive sleep apnea/hypopnea grading (P = .002). All other parameters showed no significant deterioration. No patient developed more than mild/ moderate obstructive sleep apnea/hypopnea. Snoring and arterial oxygen saturation levels were not reliable indicators of increased inspiratory effort. Conclusions A palate re-repair had no significant adverse effect on the airway. A Hynes, in patients with optimized velar function, caused a significant increase in inspiratory effort and obstructive sleep apnea/hypopnea grade. However, compared with studies on midline flaps and on sphincter pharyngoplasties, a Hynes appears to be less obstructive. Failure to study changes in inspiratory effort in patients undergoing velopharyngeal incompetence surgery may underestimate the obstructive effect of pharyngoplasties.