Charles Filip

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.

Autologous fat transplantation to the velopharynx for treating persistent velopharyngeal insufficiency of mild degree secondary to overt or submucous cleft palate

BACKGROUND Autologous fat transplantation to the velopharynx has been described in a few smaller studies including heterogeneous groups of patients for the treatment of velopharyngeal insufficiency (VPI). The aim of this study was to evaluate speech and to measure velopharyngeal closure with magnetic resonance imaging (MRI) in patients who underwent autologous fat transplantation for the treatment of persistent VPI of mild degree secondary to overt or submucous cleft palate. METHODS A prospective study of 16 patients with persistent VPI of mild degree secondary to overt or submucous cleft palate who underwent autologous fat transplantation to the velopharynx. The patients were injected with a median of 5.6 (3.8-7.6) ml autologous fat to the velopharynx. Pre- and 1-year postoperative audio recordings were blinded for scoring independently by three senior speech therapists. Hypernasality, hyponasality, nasal turbulence and audible nasal emission were scored on a five-point scale. Pre- and 1-year postoperative MRIs were obtained during vocal rest and during phonation in 12 patients. Data measured were the velopharyngeal distance in the sagittal plane and the velopharyngeal gap area in the axial plane. RESULTS Hypernasality improved significantly (p=0.030), but not audible nasal emission (p=0.072) or nasal turbulence (p=0.12). The velopharyngeal distance during phonation decreased significantly (p=0.013), but not the velopharyngeal gap area (p=0.16). There was no significant correlation between speech and MRI results. CONCLUSION Autologous fat transplantation to the velopharynx improved hypernasality significantly, but not audible nasal emission or nasal turbulence in patients with persistent VPI of mild degree secondary to overt or submucous cleft palate. Given the low number of patients and the lack of a control group, the value of fat transplantation for the treatment of mild VPI is not proven for sure.

Speech and Magnetic Resonance Imaging Results Following Autologous Fat Transplantation to the Velopharynx in Patients With Velopharyngeal Insufficiency

Objective To measure velopharyngeal closure with magnetic resonance imaging (MRI) and to evaluate speech when treating velopharyngeal insufficiency (VPI) with autologous fat transplantation to the velopharynx. Patients Nine patients were recruited. Six patients had undergone cleft palate repair and subsequently developed VPI. Three were noncleft patients of which one had developed VPI after nasopharyngeal cancer treatment; another patient had developed VPI after combined adenotonsillectomy, and a third patient had VPI of unknown etiology. Main outcome measure Preoperative and 1-year postoperative MRIs were obtained during vocal rest and during phonation. Data measured were the velopharyngeal distance in the sagittal plane and the velopharyngeal gap area in the axial plane. Preoperative and 1-year postoperative audio recordings were blinded for scoring independently by three senior speech therapists. Results When comparing preoperative and 1-year postoperative MRI during phonation we found a significant reduction of the median velopharyngeal distance from 4 to 0 mm (p = .011), and a significant reduction of the median velopharyngeal gap area from 42 to 34 mm2 (p = .038). Nasal turbulence improved significantly (p = .011). Hypernasality/hyponasality and audible nasal emission did not change significantly. Conclusions Autologous fat transplantation to the velopharynx resulted in a significant reduction of the velopharyngeal distance and the velopharyngeal gap area during phonation, as measured by MRI. This was in accordance with a significant improvement in nasal turbulence. However, hypernasality and audible nasal emission did not change significantly and could not be correlated to the MRI findings.

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

BackgroundThere 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. MethodsA 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. ResultsThere 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. ConclusionsSuperiorly based pharyngeal flap resulted in a significant speech improvement in 12 consecutive patients with 22q11.2 deletion syndrome having VPI.

Bilateral Hypodontia in Adolescents With Pierre Robin Sequence

Objective To describe the frequency of hypodontia and left-right symmetry of hypodontia in the permanent dentition of children with Pierre Robin sequence (PRS). Patients and Method The sample consisted of 78 children born with PRS between 1980 and 2006 and referred to the Oslo Cleft Lip and Palate Team (OCLPT). Data were collected retrospectively from the archives of the OCLPT. Panoramic radiographs were evaluated to document hypodontia; third molars were excluded. Results Of the 78 children with PRS, hypodontia was found in 33 (42%). Of the 33 children with hypodontia, 27 (82%) showed hypodontia in the micrognathic lower arch, 24 (73%) were missing two or more permanent teeth, and 2 (6%) had oligodontia. The teeth most often missing were the mandibular second premolar (72%), followed by the maxillar second premolar (29%). Most cases of hypodontia 21 (64%) occurred bilaterally. Bilateral hypodontia of the mandibular second premolar occurred in 27 (73%) of the patients. Conclusion Hypodontia was found in 33 (42%) of the children with PRS, which is seven times higher than the prevalence among children without PRS (6%). Unlike in the general population, bilateral hypodontia was more common than unilateral hypodontia in the micrognathic mandible of children with PRS.

Multidisciplinary Aspects of 104 Patients With Pierre Robin Sequence

Objective To describe Pierre Robin sequence patients with a cleft palate from a multidisciplinary perspective. Patients A total of 104 individuals with Pierre Robin sequence and cleft palate, born between 1980 and 2010. Method Data were collected retrospectively and compared with large control groups. Results Of 104 patients, 19 (18.3%) were treated with a nasopharyngeal or oropharyngeal tube, continuous positive airway pressure, and/or a tracheotomy. The mean weight percentile for newborns with Pierre Robin sequence was 30.9. It decreased to 29.9 at the time of cleft palate repair (mean age, 13.7 months) (P = .78). Of 87 patients, 30 (34.5%) developed normal speech after cleft palate repair. Of 93 nonsyndromic Pierre Robin sequence patients, 31 (33.3%) had or are having surgery for velopharyngeal insufficiency, a rate that is significantly higher when compared with a control group of cleft palate–only patients (19.4%; P = .004). Of 31 patients, 25 (80.6%) developed normal resonance after surgery for velopharyngeal insufficiency. There was no significant difference in the rate of syndromes between the Pierre Robin sequence patients and a control group of cleft palate patients without Pierre Robin sequence (P = .25). Seven of 39 boys (17.9%) with Pierre Robin sequence had a diagnosis of autism spectrum disorder. Conclusion Even though the mean weight percentile for newborns with Pierre Robin sequence was low, the patients did not show a growth spurt during the first year of life. The high rate of velopharyngeal insufficiency after cleft palate repair in patients with Pierre Robin sequence needs further investigation. Also, the high rate of autism spectrum disorder among boys with Pierre Robin sequence prompts further investigation.

Health Status Among Adults Born With an Oral Cleft in Norway

Importance Parents regularly express concern about long-term health outcomes for children who are born with an oral cleft. Objective To assess whether oral clefts affect the health and ability to work of young adults. Design, Setting, and Participants A population-based cohort study was conducted on all individuals born in Norway between calendar years 1967 and 1992 (n = 1 490 401). All patients treated for clefts in Norway during the study period were invited to participate (n = 2860). This study used population-based, long-term follow-up data from national registries to focus on the future health outcomes of individuals with cleft and no additional chronic medical conditions or congenital anomalies. A total of 523 individuals were excluded from the study cohort because they declined participation, could not be reached by mail, or had birth defects other than clefts. The final cohort, consisting of 2337 cases with isolated clefts and 1 413 819 unaffected individuals, was followed up until December 31, 2010, using compulsory national registries and clinical data. Data analysis was conducted from February 13, 2014, to April 18, 2016. Exposures Oral clefts. Main Outcomes and Measures Death, intellectual disability, schizophrenia, mood affective disorders, anxiety disorders, autism spectrum disorders, attention deficit/hyperactivity disorder, severe learning disability, cerebral palsy, epilepsy, muscle or skeletal disorders, trauma, and episodes of reduced health. Results Of 2860 individuals born with an oral cleft, 2337 were included in the analysis; of these, 1401 were male (59.9%). Mean (SD) age in 2010 was 30.6 (7.7) years. Compared with unaffected individuals, no increased risks were found regarding morbidity or mortality among persons with isolated cleft lip only. Among individuals with isolated cleft lip and cleft palate, increased risks of intellectual disability (relative risk [RR], 2.2; 95% CI, 1.2-4.1) and cerebral palsy (RR, 2.6; 95% CI, 1.1-6.2) were found. Individuals with isolated cleft palate (ie, without cleft lip) had increased mortality (hazard ratio, 3.4; 95% CI, 2.1-5.7) in addition to an increased risk of intellectual disability (RR, 11.5; 95% CI, 8.5-15.6), anxiety disorders (RR, 2.9; 95% CI, 1.3-6.5), autism spectrum disorders (RR, 6.6; 95% CI, 2.8-15.7), severe learning disabilities (RR, 10.6; 95% CI, 5.5-20.2), cerebral palsy (RR, 4.8; 95% CI, 2.3-10.0), epilepsy (RR, 4.9; 95% CI, 2.2-10.8), and muscle or skeletal disorders (RR, 2.7; 95% CI, 1.4-5.4). Conclusions and Relevance Young adults who were born with isolated cleft lip only did not differ significantly from unaffected individuals in their risk of health problems. However, individuals with isolated cleft palate had increased health risks and mortality. This information should be provided to genetic counselors, parents of children with clefts, and health care workers involved in the treatment or follow-up of these children.

Extraordinary Large Giant Congenital Melanocytic Nevus Treated with Integra Dermal Regeneration Template

Summary: Garment-like giant congenital melanocytic nevi are very rare, and those being treated are most often offered excision and split-thickness skin transplantation. Due to the risk of restricted mobility secondary to shrinkage and hypertrophic scarring of the transplant, we treated to date the largest reported giant congenital melanocytic nevus (16% total body surface area) with Integra dermal regeneration template (Integra Life Sciences, Plainsboro, N.J.), giving a more functional skin reconstruction. In addition, the dermal regeneration template had to be covered with split-thickness skin transplant including multiple smaller nevi due to lack of larger area with normal skin.

Adults with 22q11.2 deletion syndrome have a different velopharyngeal anatomy with predisposition to velopharyngeal insufficiency

AIM To find out if subjects with 22q11.2 deletion syndrome (DS) have a different velopharyngeal anatomy which could cause velopharyngeal insufficiency (VPI). METHODS A prospective study of 16 subjects >16 years of age with 22q11.2 DS, without overt cleft palate and without previous VPI surgery, and 48 healthy controls >18 years of age were included in the study. Speech was recorded and scored blindly by two independent senior speech therapists. All 64 individuals had MRI scans, which were analyzed blindly by a consultant radiologist. RESULTS Subjects with 22q11.2 DS had a mild degree of weak pressure consonants (mean score); borderline to mild degree of hypernasality and audible nasal emission (mean score). All controls had normal speech. When comparing subjects (22q11.2 DS) to controls, we found the subjects to have the following: A shorter distance between left and right points of origin of the levator veli palatini muscle (LVP) (p < 0.0001); a more obtuse angle of origin of the LVP (bilaterally) (p < 0.009); a thinner LVP bilaterally and in the midline (p < 0.0001); a shorter LVP bilaterally (p < 0.0001); a shorter velum (p = 0.007); a larger osseous pharyngeal depth:velar length ratio (p = 0.01); a more obtuse anterior cranial base angle (nasion to sella to basion) (p < 0.0001) and posterior cranial base angle (sella to basion to foramen magnum) (p < 0.0001); a wider velopharyngeal width (p = 0.002) and a larger pharyngeal airway volume (p = 0.0007). CONCLUSION Compared with healthy controls, adults with 22q11.2 DS showed a different velopharyngeal anatomy, which will make these individuals more prone to VPI.

Socio-Economic Status and Reproduction among Adults Born with an Oral Cleft: A Population-Based Cohort Study in Norway.

Background It has been reported that people born with orofacial clefts do worse in life than their peers regarding a range of social markers, such as academic achievement and reproduction. We have compared otherwise healthy individuals with and without clefts, to investigate if these differences are due to the cleft or other background factors. Materials and Methods In a retrospective national cohort study, based on compulsory registers with data collected prospectively, we included everybody born in Norway between 1967 and 1992 (1490279 individuals, 2584 with clefts). This cohort was followed until the year 2010, when the youngest individuals were 18 years old. In order to ensure that the individuals were not affected by unknown syndromes or diseases, we excluded all individuals with any chronic medical condition, or who had other birth defects than clefts, hydroceles and dislocated hips. Individuals with oral clefts who were included in the study are said to have isolated clefts. Results Isolated cleft patients are similar to the general population regarding education, income and social class. Isolated cleft patients have lower fertility than the background population, but considering only married couples this difference in fertility disappeared. Conclusions An oral cleft did not appear to affect future socioeconomic status or chances of becoming a parent for children born in Norway. An exception was males with cleft lip and palate, but differences were small.