Enhancing the vermilion in adult secondary cleft lip repair with a continuous V plasty without closure of the donor defect-a case series.

The aim of this paper was to describe a modification to an old method to enhance the vermillion in adult cleft patients. We present ten consecutive patients who requested enhancement of the upper lip vermillion. The technique involves a continuous V plasty within the non-visible mucosa to elevate the vermillion. Each V incision is of a different size to match the defect. Then the V flaps are sutured to one another but the donor defect is left open to epithelialise. Adjunctive procedures are possible at the same time. There were no major complications but one patient was over corrected and needed reduction of mucosa. The technique offers a permanent enhancement of the vermillion and is a safe alternative to other methods of lip augmentation including fillers.

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.

Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency. RESULTS: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies. FUNDING: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US).

Use of the Sphenoid Flap in Repair of the Wide Cleft Palate.

OBJECTIVE: In wide palatal defects, closure of the nasal layer can prove a considerable challenge. Mobilizing nasal flaps posteriorly usually facilitates soft palate closure. However, the defect is often too wide within the hard palate; hence, bilateral vomerine flaps are frequently required. Despite this, there is often a small defect in the nasal layer at the posterior septum (typically equating to the hard-soft palate junction), which has to be left to heal by secondary intention with the resulting increased risk of fistula formation and the potential deleterious long-term effect on speech due to cicatricial migration of the reconstructed levator sling anteriorly. We describe our experience in the use of the sphenoid flap to obtain tension-free primary closure of the nasal layer. METHODS: A retrospective multi-center study assessing all sphenoid flap procedures undertaken at both Birmingham Children's Hospital and Great Ormond Street Hospital. Key demographic and medical data was collected pre-, peri-, and postoperatively across the 2 sites. RESULTS: A total of 66 patients underwent the use of a sphenoid flap to aid closure of the nasal layer. The average age at time of repair was 9.7 months. More than half (55%, n = 36) were isolated cleft palates, and 35% (n = 23) were BCLPs. Forty-two percent of all patients had Robin sequence. The average cleft width was 14.4 mm. The overall fistula rate was 25.8% (n = 17). CONCLUSIONS: We describe the operative technique, indications, and our experience in the use of the sphenoid flap in wide cleft palate repair.

Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations.

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations. In contrast to common unifocal venous malformation, which is most often caused by the somatic L914F TIE2 mutation, multifocal forms are predominantly caused by double (cis) mutations, that is, two somatic mutations on the same allele of the gene. Mutations are identical in all lesions from a given individual. T1105N-T1106P is recurrent in blue rubber bleb nevus, whereas Y897C-R915C is recurrent in sporadically occurring multifocal venous malformation: both cause ligand-independent activation of TIE2, and increase survival, invasion, and colony formation when expressed in human umbilical vein endothelial cells.

A Standard Set of Outcome Measures for the Comprehensive Appraisal of Cleft Care.

Care of the patient with cleft lip and/or palate remains complex. Prior attempts at aggregating data to study the effectiveness of specific interventions or overall treatment protocols have been hindered by a lack of data standards. There exists a critical need to better define the outcomes-particularly those that matter most to patients and their families-and to standardize the methods by which these outcomes will be measured. This report summarizes the recommendations of an international, multidisciplinary working group with regard to which outcomes a typical cleft team could track, how those outcomes could be measured and recorded, and what strategies may be employed to sustainably implement a system for prospective data collection. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of cleft care that intercenter comparisons can become possible. This is important for quality-improvement endeavors, comparative effectiveness research, and value-based health-care reform.

A Reliable Method to Measure Lip Height Using Photogrammetry in Unilateral Cleft Lip Patients.

There is still no reliable tool to determine the outcome of the repaired unilateral cleft lip (UCL). The aim of this study was therefore to develop an accurate, reliable tool to measure vertical lip height from photographs. The authors measured the vertical height of the cutaneous and vermilion parts of the lip in 72 anterior-posterior view photographs of 17 patients with repairs to a UCL. Points on the lip's white roll and vermillion were marked on both the cleft and the noncleft sides on each image. Two new concepts were tested. First, photographs were standardized using the horizontal (medial to lateral) eye fissure width (EFW) for calibration. Second, the authors tested the interpupillary line (IPL) and the alar base line (ABL) for their reliability as horizontal lines of reference. Measurements were taken by 2 independent researchers, at 2 different time points each. Overall 2304 data points were obtained and analyzed. Results showed that the method was very effective in measuring the height of the lip on the cleft side with the noncleft side. When using the IPL, inter- and intra-rater reliability was 0.99 to 1.0, with the ABL it varied from 0.91 to 0.99 with one exception at 0.84. The IPL was easier to define because in some subjects the overhanging nasal tip obscured the alar base and gave more consistent measurements possibly because the reconstructed alar base was sometimes indistinct. However, measurements from the IPL can only give the percentage difference between the left and right sides of the lip, whereas those from the ABL can also give exact measurements. Patient examples were given that show how the measurements correlate with clinical assessment. The authors propose this method of photogrammetry with the innovative use of the IPL as a reliable horizontal plane and use of the EFW for calibration as a useful and reliable tool to assess the outcome of UCL repair.

Does nasogastric feeding reduce distress after cleft palate repair in infants?

AIMS: To determine the effect of nasogastric (NG) feeding compared with oral feeding on morphine requirements after primary cleft palate repair, and secondarily on enteral intake. METHODS: This was a pilot study involving 50 infants, aged five to ten months, who were randomised to receive NG or oral feeding after palate repair. All infants received the same anaesthetic and analgesic management. Post-operatively, paracetamol and ibuprofen were administered regularly and intravenous (IV) morphine was given on demand using a nurse-controlled analgesia device. The primary outcome measure was the total morphine consumption in the first 24 hours. Secondary outcome measures included the numbers of painful episodes and the volumes of IV fluid and enteral feed administered. RESULTS: Of the 50 infants enrolled, 18 and 23 received either NG or oral feeding, respectively, and completed the study. Numbers of painful episodes and morphine consumption in the first 24 hours were similar in each group. Volumes of feed administered in the first 24 hours were significantly different: the NG group received approximately three times more than the oral group. Nine of the oral group required IV fluids in the 24 hours compared with none in the NG group. CONCLUSION: NG feeding was more effective than oral feeding in the first 24 hours after surgery, but numbers of painful episodes recorded were similar. Further research is required.

Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects.

Mutations in the angiopoietin receptor TIE2/TEK have been identified as the cause for autosomal dominantly inherited cutaneomucosal venous malformation (VMCM). Thus far, two specific germline substitutions (R849W and Y897S), located in the kinase domain of TIE2, have been reported in five families. The mutations result in a fourfold increase in ligand-independent phosphorylation of the receptor. Here, we report 12 new families with TEK mutations. Although the phenotype is primarily characterized by small multifocal cutaneous vascular malformations, many affected members also have mucosal lesions. In addition, cardiac malformations are observed in some families. Six of the identified mutations are new, with three located in the tyrosine kinase domain, two in the kinase insert domain, and another in the carboxy terminal tail. The remaining six are R849W substitutions. Overexpression of the new mutants resulted in ligand-independent hyperphosphorylation of the receptor, suggesting this is a general feature of VMCM-causative TIE2 mutations. Moreover, variation in the level of activation demonstrates, to the best of our knowledge for the first time, that widely differing levels of chronic TIE2 hyperphosphorylation are tolerated in the heterozygous state, and are compatible with normal endothelial cell function except in the context of highly localized areas of lesion pathogenesis.

Two siblings with an unusual nasal malformation: further instances of craniorhiny?

We report a brother and sister born to consanguineous parents. The siblings have hypertelorism, bifid nose, upturned nares, histologically proven intranasal dermoid, and soft-tissue swellings of the philtrum. One sibling also has a midline cleft lip and the other has narrowing of the posterior choanae. We suggest that they have craniorhiny, despite the absence of an abnormal skull shape. The differential diagnosis is discussed.

Midline cleft lip and nasal dermoids over five generations: a distinct entity or autosomal dominant Pai syndrome?

A family with midline nasal dermoids in four members over five generations is described. Two of these individuals also had a midline cleft lip. The pattern of inheritance appears to be autosomal dominant with variable expression. To our knowledge, no familial cases of midline clefting with nasal dermoids have previously been reported in the literature. Cranial imaging to look for intracerebral extension of the dermoid is recommended in such cases.