Phosphodiesterase 3A and Arterial Hypertension.

BACKGROUND: High blood pressure is the primary risk factor for cardiovascular death worldwide. Autosomal dominant hypertension with brachydactyly clinically resembles salt-resistant essential hypertension and causes death by stroke before 50 years of age. We recently implicated the gene encoding phosphodiesterase 3A (PDE3A); however, in vivo modeling of the genetic defect and thus showing an involvement of mutant PDE3A is lacking. METHODS: We used genetic mapping, sequencing, transgenic technology, CRISPR-Cas9 gene editing, immunoblotting, and fluorescence resonance energy transfer. We identified new patients, performed extensive animal phenotyping, and explored new signaling pathways. RESULTS: We describe a novel mutation within a 15 base pair (bp) region of the PDE3A gene and define this segment as a mutational hotspot in hypertension with brachydactyly. The mutations cause an increase in enzyme activity. A CRISPR/Cas9-generated rat model, with a 9-bp deletion within the hotspot analogous to a human deletion, recapitulates hypertension with brachydactyly. In mice, mutant transgenic PDE3A overexpression in smooth muscle cells confirmed that mutant PDE3A causes hypertension. The mutant PDE3A enzymes display consistent changes in their phosphorylation and an increased interaction with the 14-3-3θ adaptor protein. This aberrant signaling is associated with an increase in vascular smooth muscle cell proliferation and changes in vessel morphology and function. CONCLUSIONS: The mutated PDE3A gene drives mechanisms that increase peripheral vascular resistance causing hypertension. We present 2 new animal models that will serve to elucidate the underlying mechanisms further. Our findings could facilitate the search for new antihypertensive treatments.

A clinical prediction rule to identify difficult intubation in children with Robin sequence requiring mandibular distraction osteogenesis based on craniofacial CT measures.

BACKGROUND: Airway management is challenging in children with Robin sequence (RS) requiring mandibular distraction osteogenesis (MDO). We derived and validated a prediction rule to identify difficult intubation before MDO for children with RS based on craniofacial computed tomography (CT) images. METHOD: This was a retrospective study of 69 children with RS requiring MDO from November 2016 to June 2018. Multiple CT imaging parameters and baseline characteristic (sex, age, gestational age, body mass index [BMI]) were compared between children with normal and difficult intubation according to Cormack-Lehane classification. A clinical prediction rule was established to identify difficult intubation using group differences in CT parameters (eleven distances, six angles, one section cross-sectional area, and three segment volumes) and clinicodemographic characteristics. Predictive accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The overall incidence of difficult intubation was 56.52%, and there was no significant difference in sex ratio, age, weight, height, BMI, or gestational age between groups. The distance between the root of the tongue and posterior pharyngeal wall was significantly shorter, the bilateral mandibular angle shallower, and the cross-sectional area at the epiglottis tip smaller in the difficult intubation group. A clinical prediction rule based on airway cross-sectional area at the tip of the epiglottis was established. Area > 36.97 mm2 predicted difficult intubation while area < 36.97 mm2 predicted normal intubation with 100% sensitivity, 62.5% specificity, 78.6% positive predictive value, and 100% negative predictive value (area under the ROC curve = 0.8125). CONCLUSION: Computed tomography measures can objectively evaluate upper airway morphology in patients with RS for prediction of difficult intubation. If validated in a larger series, the measures identified could be incorporated into airway assessment tools to guide treatment decisions. This was a retrospective study and was granted permission to access and use these medical records by the ethics committee of Guangzhou Women and Children's Medical Center. TRIALS REGISTRATION: Registration No. ChiCTR1800018252, NaZhang, Sept 7 2018.

De Novo 1.77-Mb Microdeletion of 10q22.2q22.3 in a Girl With Developmental Delay, Speech Delay, Congenital Cleft Palate, and Bilateral Hearing Impairment.

Interstitial deletions of chromosome band 10q22.1q22.3 are rare. We here report a 2.5-year-old female patient with developmental delay, speech delay, congenital cleft palate, and bilateral hearing impairment. The girl's karyotype was normal. Chromosome microarray analysis (CMA) revealed a 1.77-Mb de novo interstitial deletion in 10q22.2q22.3. The deletion harbors 9 genes, including KAT6B, DUPD1, DUSP13, SAMD8, VDAC2, COMTD1, ZNF503, NCRNA00245, and C10orf11. This is the first patient with a deletion of the smallest size in 10q22.2q22.3 as detected using single nucleotide polymorphism (SNP) arrays. Comparisons with patients with overlapping deletions and in neighboring regions demonstrate the clinical impact of each deletion and in the context of other deletions within the 10q22q23 region. Additionally, KAT6B and C10orf11 could represent disease-associated genes that contribute to developmental delay, speech and language delay, and congenital cleft palate.

Ancient DNA evidence reveals that the Y chromosome haplogroup Q1a1 admixed into the Han Chinese 3,000 years ago.

OBJECTIVES: Y chromosome haplogroup Q1a1 is found almost only in Han Chinese populations. However, it has not been found in ancient Han Chinese samples until now. Thus, the origin of haplogroup Q1a1 in Han Chinese is still obscure. This study attempts to provide answer to this question, and to uncover the origin and paternal genetic structure of the ancestors of the Han Chinese. METHODS: Eighty-nine ancient human remains that were excavated from the presumed geographic source of the Han Chinese and dated to approximately 3,000 years ago were treated by the amelogenin gene polymerase chain reaction test, to determine their sex. Then, Y chromosome single nucleotide polymorphisms were subsequently analyzed from the samples detected as male. RESULTS: Samples from 27 individuals were successfully amplified. Their haplotypes could be attributed to haplogroups N, O*, O2a, O3a, and Q1a1. Analyses showed that the assigned haplogroup of each sample is correlated to the suspected social status and observed burial custom associated with the sample. CONCLUSIONS: The origins of the observed haplotypes and their distribution in present day Han Chinese and in the samples suggest that haplogroup Q1a1 was probably introduced into the Han Chinese population approximately 3,000 years ago.

[Analysis of 22 patients with congenital cleft lip and palate using high-resolution chromosome microarray].

OBJECTIVE: To assess the value of chromosome microarray analysis (CMA) for identifying the etiology of patients with congenital cleft lip and palate. METHODS: Twenty-two patients with no identifiable chromosomal aberrations by conventional cytogenetic technique were selected. DNA was extracted and hybridized with Affymetrix CytoScan(TM) HD arrays following the manufacturer's protocol. The data were analyzed with a CHAS v2.0 software. RESULTS: CMA analysis has identified submicroscopic copy number variants (CNVs) in all of the cases, which have ranged from 100 kb to 1.8 Mb. Potential pathogenic CNVs were identified in 5 patients (22.7%), which involved microdeletions and microduplications on 8p23.1, 10q22.2-q22.3, 6q26, 20p12.1 and 18q12.3. MYST4, MACROD2 and SOX7 genes are likely the causative genes. CONCLUSION: CMA is an effective method for identification of etiology in patients with cleft lip and palate. CMA should be provided for patients with cleft lip and palate but a normal karyotype. Especially for those with additional structural abnormalities, there is a high risk for submicroscopic chromosomal aberrations.

Arterial myogenic response and aging.

The arterial myogenic response is an inherent property of resistance arteries. Myogenic tone is crucial for maintaining a relatively constant blood flow in response to changes in intraluminal pressure and protects delicate organs from excessive blood flow. Although this fundamental physiological phenomenon has been extensively studied, the underlying molecular mechanisms are largely unknown. Recent studies identified a crucial role of mechano-activated angiotensin II type 1 receptors (AT1R) in this process. The development of myogenic response is affected by aging. In this review, we summarize recent progress made to understand the role of AT1R and other mechanosensors in the control of arterial myogenic response. We discuss age-related alterations in myogenic response and possible underlying mechanisms and implications for healthy aging.

The Effect of Timing of Mandibular Distraction Osteogenesis on Weight Velocity in Infants Affected by Severe Robin Sequence.

Background: Impaired weight gain is prevalent in Robin Sequence (RS) newborns. Although mandibular distraction osteogenesis (MDO) has been proven to improve oral feeding, its impact on postoperative weight gain remains unclear. The purpose of this study is to explore whether MDO can help RS babies reach a normal weight, as well as the effect of MDO timing on weight velocity. Methods: One hundred infants with severe RS and one hundred with normal controls met the inclusion criteria for the study. Included patients underwent MDO. Weights at different timing points were recorded and analyzed and compared to normal controls. Results: After the distractor removal weights of patients undergoing MDO at <1 month and 1−2 months were close to the normal control (6.81 ± 0.93 kg versus 7.18 ± 0.61 kg, p = 0.012, and 6.82 ± 0.98 kg versus 7.37 ± 0.75 kg, p = 0.033, respectively), the weights of patients undergoing MDO at 2−3 months and 3−4 months still lagged behind (7.56 ± 1.29 kg versus 8.20 ± 0.61 kg, p = 0.000206 and 7.36 ± 1.05 kg versus 8.25 ± 0.77 kg, p = 0.004, respectively). The weights of all RS infants undergoing MDO showed no significant difference compared to the controls when they aged to 1 year (9.34 ± 0.99 kg versus 9.55 ± 0.45 kg, p = 0.254 for MDO at <1 month; 9.12 ± 0.91 kg versus 9.33 ± 0.46 kg, p = 0.100 for MDO at 1 to 2 months; 9.38 ± 0.29 kg versus 9.83 ± 0.53 kg, p = 0.098 for MDO at 2 to 3 months; and 9.38 ± 0.29 kg versus 9.83 ± 0.53 kg, p = 0.098 for MDO at 3 to 4 months). Conclusion: The MDO procedure helped patients with severe RS to reach a normal weight; and MDO intervention was recommended at an early stage for early weight gain.

Myogenic Vasoconstriction Requires Canonical Gq/11 Signaling of the Angiotensin II Type 1 Receptor.

Background Blood pressure and tissue perfusion are controlled in part by the level of intrinsic (myogenic) arterial tone. However, many of the molecular determinants of this response are unknown. We previously found that mice with targeted disruption of the gene encoding the angiotensin II type 1a receptor (AT1AR) (Agtr1a), the major murine angiotensin II type 1 receptor (AT1R) isoform, showed reduced myogenic tone; however, uncontrolled genetic events (in this case, gene ablation) can lead to phenotypes that are difficult or impossible to interpret. Methods and Results We tested the mechanosensitive function of AT1R using tamoxifen-inducible smooth muscle-specific AT1aR knockout (smooth muscle-Agtr1a-/-) mice and studied downstream signaling cascades mediated by Gq/11 and/or ß-arrestins. FR900359, Sar1Ile4Ile8-angiotensin II (SII), TRV120027 and TRV120055 were used as selective Gq/11 inhibitor and biased agonists to activate noncanonical ß-arrestin and canonical Gq/11 signaling of the AT1R, respectively. Myogenic and Ang II-induced constrictions were diminished in the perfused renal vasculature, mesenteric and cerebral arteries of smooth muscle-Agtr1a-/- mice. Similar effects were observed in arteries of global mutant Agtr1a-/- but not Agtr1b-/- mice. FR900359 decreased myogenic tone and angiotensin II-induced constrictions whereas selective biased targeting of AT1R-ß-arrestin signaling pathways had no effects. Conclusions This study demonstrates that myogenic arterial constriction requires Gq/11-dependent signaling pathways of mechanoactivated AT1R but not G protein-independent, noncanonical pathways in smooth muscle cells.

Risk Factors of Prolonged Mechanical Ventilation in Infants With Pierre Robin Sequence After Mandibular Distraction Osteogenesis: A Retrospective Cohort Study.

Background: After mandibular distraction osteogenesis (MDO), most infants with Pierre Robin sequence (PRS) require mechanical ventilation to assist their breathing. However, the optimal duration of intubation during early mandibular distraction osteogenesis activation is poorly understood. This retrospective study was carried out to identify perioperative risk factors of prolonged mechanical ventilation in infants undergoing MDO. Methods: A total of 95 infants with PRS underwent MDO at Guangzhou Women and Children's Medical Center between 2016 and 2018, and the clinical records of 74 infants who met the selection criteria were analyzed. Of the 74 infants, 26 (35.1%) underwent prolonged mechanical ventilation, 48 (64.9%) did not. t-test, Wilcoxon Sum Rank test or chi-squared test were performed to compare variables that might associate with prolonged mechanical ventilation between the two groups, and then, significant variables identified were included in the multivariate logistic regression model to identify independent variables. Results: Univariate logistic regression analysis revealed that age, preoperative gonial angle, and postoperative pulmonary infection were associated with prolonged mechanical ventilation (all P < 0.05). Multivariate logistic regression analysis confirmed that the preoperative gonial angle and postoperative pulmonary infection were independent risk factors of prolonged mechanical ventilation (both P < 0.05). Conclusions: Infants with PRS and smaller preoperative gonial angle or postoperative pulmonary infection may be more likely to undergo prolonged mechanical ventilation after MDO. For others, extubation may be attempted within 6 days after MDO.

Age attenuates the T-type CaV 3.2-RyR axis in vascular smooth muscle.

Caveolae position CaV 3.2 (T-type Ca2+ channel encoded by the α-3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca2+ influx to trigger Ca2+ sparks and large-conductance Ca2+ -activated K+ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca2+ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Cav 3.2 channel inhibition by Ni2+ (50 µM) and caveolae disruption by methyl-ß-cyclodextrin or genetic abolition of Eps15 homology domain-containing protein (EHD2) inhibited Ca2+ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Cav 3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Cav 1.2-/- mice, caffeine (RyR activator) and thapsigargin (Ca2+ transport ATPase inhibitor), we found that sufficient SR Ca2+ load is a prerequisite for the CaV 3.2-RyR axis to generate Ca2+ sparks. We identified a fraction of Ca2+ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd3+ (100 µM), but insensitive to CaV 1.2 and CaV 3.2 channel blockade. Our data demonstrate that the VSMC CaV 3.2-RyR axis is down-regulated by aging. This defective CaV 3.2-RyR coupling is counterbalanced by a Gd3+ sensitive Ca2+ pathway providing compensatory Ca2+ influx for triggering Ca2+ sparks in aged VSMCs.

Three-dimensional printing of surgical guides for mandibular distraction osteogenesis in infancy.

Pierre Robin sequence (PRS) is a congenital malformation characterized by micrognathia, glossocoma, and mechanical obstruction of the upper respiratory tract. These deformities impair respiration, sleep, feeding, and swallowing, and can lead to malnutrition, stunted development, and death. Bilateral mandibular distraction osteogenesis, whereby the mandible and tongue root are extended outward, is the standard treatment to relieve upper airway obstruction in severe PRS. Accurate placement of the distraction device is essential but challenging, especially in infants, and requires the pre-operative fabrication of surgical guides based on CT images. Three-dimensional (3D) printing allows for the accurate recreation of objects from digitized models. We compared surgical efficacy and safety of bilateral mandibular distraction osteogenesis using 3D printed or traditionally fabricated surgery guides for treatment of infants with severe PRS.During the period from 2014 to 2016, 22 patients with severe PRS were treated using either traditional or 3D printed surgery guides. We compared outcome measures of operations, including intraoperative bleeding, operation time, and postoperative complications.The 3D printed surgery guide group demonstrated significantly shorter operation time (P <.05) as well as moderately shorter hospital stay and artificial ventilation time (∼1 day less). Furthermore, despite markedly younger average age of the 3D printed group (1.3 vs 3.5 months), there was no increase in postoperative complications using the 3D printed guides.Three-dimensional printed surgery guides were used successfully for bilateral mandibular traction osteogenesis, and according to several outcome, parameters demonstrated superior efficacy and safety compared to traditional guides. Further research is warranted to extend the applications of 3D printed surgical guides for craniofacial surgery.

Elementary calcium signaling in arterial smooth muscle.

Vascular smooth muscle cells (VSMCs) of small peripheral arteries contribute to blood pressure control by adapting their contractile state. These adaptations depend on the VSMC cytosolic Ca2+ concentration, regulated by complex local elementary Ca2+ signaling pathways. Ca2+ sparks represent local, transient, rapid calcium release events from a cluster of ryanodine receptors (RyRs) in the sarcoplasmic reticulum. In arterial SMCs, Ca2+ sparks activate nearby calcium-dependent potassium channels, cause membrane hyperpolarization and thus decrease the global intracellular [Ca2+] to oppose vasoconstriction. Arterial SMC Cav1.2 L-type channels regulate intracellular calcium stores content, which in turn modulates calcium efflux through RyRs. Cav3.2 T-type channels contribute to a minor extend to Ca2+ spark generation in certain types of arteries. Their localization within cell membrane caveolae is essential. We summarize present data on local elementary calcium signaling (Ca2+ sparks) in arterial SMCs with focus on RyR isoforms, large-conductance calcium-dependent potassium (BKCa) channels, and cell membrane-bound calcium channels (Cav1.2 and Cav3.2), particularly in caveolar microdomains.

Optimal duration of mechanical ventilation and influencing factors following mandibular distraction osteogenesis in infants with Pierre Robin sequence.

Mandibular distraction osteogenesis (MDO) is an effective treatment for tongue-based airway obstruction in infants with severe Pierre Robin sequence (PRS). Most infants receiving MDO require postoperative mechanical ventilation (MV) to assist breathing. Optimal MV time for each individual patient and factors influencing the time must be identified to guide clinical decision-making.A retrospective analysis was performed on 75 infants with PRS receiving MDO from November 2016 to August 2018. Twenty-six were females and 47 were males. Data extracted from the hospital information system included sex, age, weight, history of preterm labor, preoperative pulmonary infection, laryngomalacia/tracheomalacia, laryngoscope exposure classification, anesthesia duration, operation duration, postoperative treatment site, situation of distraction, postoperative complications and MV duration. Statistical analyses were conducted to investigate the potential associations of these factors with MV time.Seventy-three PRS syndrome patients received anesthesia for MDO device procedures were considered eligible for study. Patient sex, history of preterm labor, preoperative pulmonary infection, laryngomalacia/tracheomalacia, laryngoscopy exposure difficulty, postoperative treatment site (neonatal or pediatric intensive care unit), ventilator-associated pneumonia, age, weight, anesthesia duration, and operation duration had no significant influence on postsurgical MV time (P > .05). Amount of distraction at the time of extubation had statistically significant influence on postoperative MV time (P < .05). In addition, scatter plots revealed linear relationships between postoperative MV time and amount of distraction at extubation.According to this analysis, amount of distraction was associated with MV time following MDO for severe PRS and roughly 6 days post-surgery is a generally safe extubation time.

Transverse facial cleft (macrostomia) repair: Modification of a traditional technique.

OBJECTIVE: Outcomes from surgical repair of transverse facial cleft (macrostomia) may not be very satisfactory when conventional methods are used to position the oral commissure to be repaired. To improve patient outcomes, we developed a modified oral commissure positioning and reconstruction method for transverse facial cleft repair. METHOD: In the modified positioning method, the oral commissure at the abnormal side was positioned precisely and reconstructed by a combination of two conventional methods, namely, the distance measurement method and the anatomical charateristics method. The function of the orbicularis oris muscle was preserved. Postoperative surgical scar score and oral commissure symmetry score were determined and compared between patients and healthy controls. The scores ranged from one to five, with one representing the best and five indicating the worst results. RESULTS: Nine patients aged 4-31 months (7 girls) underwent the modified transverse facial cleft repair surgery. All the patients had unilateral transverse facial cleft with or without microsomia and/or complete cleft lip. The patients were followed up for one to five years. Although average surgical scar scores of patients (close-mouth: 1.8 ± 0.8, range: 1.0-2.8; open-mouth: 1.8 ± 0.9, range 1.0-3.6) remained significantly higher (P < 0.05) than those of the healthy controls (N = 8, close-mouth 1.1 ± 0.4, range: 1.0-1.4, open-mouth: 1.1 ± 0.3, range: 1.0-1.2) 6 months after the surgery, their average close-mouth oral commissure symmetry score (1.9 ± 0.7, range: 1.6-2.8) was similar (P = 0.381) to those of the healthy controls (1.8 ± 0.8, range: 1.0-2.6). CONCLUSIONS: The modified procedure appears to lead to promising long-term benefit on restoring oral commissure symmetry.

Application of high resolution SNP arrays in patients with congenital oral clefts in south China.

Chromosome microarray analysis (CMA) has proven to be a powerful tool in postnatal patients with intellectual disabilities. However, the diagnostic capability of CMA in patients with congenital oral clefts remain mysterious. Here, we present our clinical experience in implementing whole-genome high-resolution SNP arrays to investigate 33 patients with syndromic and nonsyndromic oral clefts in whom standard karyotyping analyses showed normal karyotypes. We aim to identify the genomic aetiology and candidate genes in patients with congenital oral clefts. CMA revealed copy number variants (CNVs) in every patient, which ranged from 2 to 9 per sample. The size of detected CNVs varied from 100 to 3.2 Mb. In 33 patients, we identified six clinically significant CNVs. The incidence of clinically significant CNVs was 18.2% (6/33). Three of these six CNVs were detected in patients with nonsyndromic clefts, including one who presented with isolated cleft lip with cleft palate (CLP) and two with cleft palate only (CPO). The remaining three CNVs were detected in patients with syndromic clefts. However, no CNV was detected in patients with cleft lip only (CLO). The six clinically significant CNVs were as follows: 8p23.1 microduplication (198 kb); 10q22.2-q22.3 microdeletion (1766 kb); 18q12.3 microduplication (638 kb); 20p12.1 microdeletion (184 kb); 6q26 microdeletion (389 kb); and 22q11.21-q11.23 microdeletion (3163 kb). In addition, two novel candidate genes for oral clefts, KAT6B and MACROD2, were putatively identified. We also found a CNV of unknown clinical significance with a detection rate of 3.0% (1/33). Our results further support the notion that CNVs significantly contributed to the genetic aetiology of oral clefts and emphasize the efficacy of whole-genome high-resolution SNP arrays to detect novel candidate genes in patients with syndromic and nonsyndromic clefts.

Melanotic neuroectodermal tumor of infancy: A case report and review of the surgical treatment.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, fast-growing, benign tumor originating from the neural crest. The tumor most often occurs during the first year of life. The predilection site of MNTI is the anterior maxilla, whereas lesions of the mandible are uncommon and account for only 6% of all cases. At present, the most common treatment for MNTI is surgical resection, however, tumor recurrence arises in 10-60% of cases. The optimal extent of surgical resection is a matter of debate; rapid growth and the possibilities of malignant transformation and metastasis indicate aggressive surgical resection. However, extensive resection may interfere with post-operative growth and development. The procedure should therefore preserve as much of the surrounding tissue as possible. The present case study examines a rare case of right-sided mandibular MNTI in a two-month-old female. The association between the tumor and the surrounding sclerotin, affected dental germ and the condition of the inferior alveolar nerve, were observed during the operative and post-operative periods. In addition, previous cases of MNTI were reviewed to evaluate the optimal scope of surgical resection.

Ancient DNA reveals that the genetic structure of the northern Han Chinese was shaped prior to 3,000 years ago.

The Han Chinese are the largest ethnic group in the world, and their origins, development, and expansion are complex. Many genetic studies have shown that Han Chinese can be divided into two distinct groups: northern Han Chinese and southern Han Chinese. The genetic history of the southern Han Chinese has been well studied. However, the genetic history of the northern Han Chinese is still obscure. In order to gain insight into the genetic history of the northern Han Chinese, 89 human remains were sampled from the Hengbei site which is located in the Central Plain and dates back to a key transitional period during the rise of the Han Chinese (approximately 3,000 years ago). We used 64 authentic mtDNA data obtained in this study, 27 Y chromosome SNP data profiles from previously studied Hengbei samples, and genetic datasets of the current Chinese populations and two ancient northern Chinese populations to analyze the relationship between the ancient people of Hengbei and present-day northern Han Chinese. We used a wide range of population genetic analyses, including principal component analyses, shared mtDNA haplotype analyses, and geographic mapping of maternal genetic distances. The results show that the ancient people of Hengbei bore a strong genetic resemblance to present-day northern Han Chinese and were genetically distinct from other present-day Chinese populations and two ancient populations. These findings suggest that the genetic structure of northern Han Chinese was already shaped 3,000 years ago in the Central Plain area.

[Simultaneous repair of complete cleft lip and palatein infancy-preliminary observation (271 cases report)].

OBJECTIVE: To Verify the safety and reliability of one-stage repair of complete cleft Lip and palate in infancy and to obtain the primary result. METHODS: The simultaneous repair of complete cleft Lip and palate in infants 3 to 12 months of age were performed in 271 cases. The deformities include 185 cases of typical complete unilateral clefts and 75 cases of complete bilateral clefts, and other 11 atypical cleft infants. The preoperative orthopedic treatment for wide alveolar cleft was undertaken in 24 infants and the lip appearance and speech outcome were evaluated in 116 children by 1 to 4 years' postoperative follow-up. RESULTS: All infants, except for dyspnea in 2 babies, palatal fistula formation in 6 cases and temporary wound hemorrhage in 5 infants, were recovered without complications. After orthopedic treatment, the width of the alveolar cleft was reduced 6.1 mm in average. The evaluation showed that 93.1% of children had got good or excellent lip appearance. And the acceptable or excellent speech was found in 94.8% children. CONCLUSIONS: Simultaneous repair of complete cleft lip and palate in infancy is safety and reliable. The preoperative orthopedic procedure is able to reduce the wide alveolar cleft and to achieve alignment of alveolar segments. The acceptable and or excellent lip appearance and speech function could be obtained in this one-stage operative procedure in infants.