Sleep-disordered Breathing in Children With Craniofacial Anomalies.

Sleep-disordered breathing (SDB) is a common disorder in children, characterized by snoring and/or increased breathing force due to narrowing and increased upper airway collapse while sleeping. Over the last decade, it has been recognized that SDB occurs more frequently in children with craniofacial anomalies, but data in Thailand is quite limited. This study retrospective descriptive study aims to find the prevalence of SDB among children with craniofacial anomalies in Thailand and associated risk factors by collecting data among Thai children with congenital craniofacial anomalies younger than 15 years old who visited the Princess Sirindhorn Craniofacial Center at King Chulalongkorn Memorial Hospital between 2016 and 2021. All children were defined into syndromic and nonsyndromic groups. Data collected from the electronic medical record includes baseline characteristics, diagnosis of craniofacial anomalies, associated risk factors, diagnosis of SDB, diagnostic tools, and treatment. Total of 512 children, there were 80 children (15.4%) who had SDB. The most diagnosis was 51 (10%) obstructive sleep apnea followed by 27 (5.3%) primary snoring and 2 (0.4%) obstructive hypoventilation. The prevalence of SDB in the syndromic group was 43 (46.7%) while the nonsyndromic group was 37 (8.6%), ( P <0.001). The risk factors associated with SDB were overweight, allergic rhinitis, tonsillar hypertrophy, high arch palate, micrognathia, and syndromic craniofacial anomalies. The prevalence of SDB is higher in children with syndromic craniofacial anomalies than in the nonsyndromic group. Knowledge of the prevalence and related factors can lead to better care, including early screening and monitoring of SDB in craniofacial patients.

Epidemiological Characteristics of Children With Non-Cleft Lip/Palate Craniofacial Anomalies.

ABSTRACT: Non-cleft craniofacial anomalies are not as common as cleft lip and palate but resultant disability can be very severe. Although there are epidemiological studies of the clefts in the medical literature, the non-cleft group is still not well known. This study was to examine the epidemiological characteristics of the non-cleft craniofacial anomalies. Patients younger than 18 years old were included during a 1-year period. Patient information was retrieved from medical records and a questionnaire filled by primary caregivers.There were 139 patients included in the study with an average age of 6 years and 7 months (4-194 months). Fifty-eight percent were male, 56% were first-born children, whereas 61.9% had siblings. Family history was positive in 6.5%. Almost all patients were in age-appropriate educational levels. Using Whitaker classification, Synostoses was the most common at 48.9%, followed by Unclassified, Clefts, Neoplasia-Hyperplasia, and Atrophy-Hypoplasia. Their anomalies were mostly detected at the regional hospitals. Outpatient visits throughout the course ranged from 1 to 100. Eighty-two percent of patients had at least 1 hospitalization, whereas 78% experienced at least 1 surgical treatment.Generally, non-cleft craniofacial anomalies were nonfamilial. We found a wide variety of anomalies. Patients were from all regions of the country. Their geographical location did not prevent access to receiving proper care and education. Having a child with an anomaly did not discourage the family from having more descendants. Among the available classifications, the Whitaker system is easier for clinical use.

Combined Intralesional Neodymium-Doped Yttrium Aluminium Garnet Laser and Intratumoral Ligation as Curative Treatment for Craniofacial Arteriovenous Malformations.

Craniofacial arteriovenous malformation (AVM), although very rare, has been a very difficult problem to treat especially when it is large and involves important structures. Surgical resection often results in unacceptable complications but still not curative. At our institution, treatment by combined intralesional neodymium-doped yttrium aluminium garnet laser and intratumoral ligation has been successful in venous malformation. This minimally invasive technique was then applied to more challenging AVM on the head and neck. Disease control was studied using clinical parameters and magnetic resonance imaging.Four patients with moderate-to-severe (Schobinger 2-4) craniofacial AVM were treated by this technique from 2001 to 2011. Patient age ranged from 2 to 51 years (mean: 25 years). After 2 to 4 treatments and follow-up period of 1456 days, 3 (75%) were cured. One of them was infant with huge mass and secondary pulmonary hypertension. Clinical cure was achieved after 3 treatments without residual cardiovascular compromise. The other patient (25%) had cheek mass with intraorbital involvement. The authors did not treat periorbital lesion so as to avoid triggering intraorbital spreading. The rest of the cheek lesion was clinically and radiologically cured.Laser energy setting, ablative technique, and skin cooling are the main factors determining the success. Individualized laser settings and properly set endpoints can increase treatment effectiveness in shorter period. In conclusion, this minimally invasive technique was successful in curing AVM without complication. With more clinical study and development of soft tissue monitoring tools, it is possible that intralesional laser could become the treatment of choice for all cutaneous AVM.

FGFR1 and FGFR2 mutations in Pfeiffer syndrome.

Pfeiffer syndrome (PS) (MIM 101600) is one of the most common syndromic forms of craniosynostosis. It is characterized by craniosysnostosis, midface hypoplasia, broad and medially deviated thumbs, and great toes with partial syndactyly of the digits. Here, we described clinical and genetic features of 12 unrelated Thai individuals with PS. All 12 patients were sporadic, and advanced paternal age was found in 50% of the cases. Polymerase chain reaction sequencing of FGFR1 exon 5 and FGFR2 exons 8, 10, 15, 16, and 17 was performed in all PS patients and revealed 9 recurrent mutations in all patients. Most of the mutations clustered in exons 8 and 10 (9/12) accounting for 75% of PS cases. The most frequently detected mutation, p.S351C, was associated with the severe form of PS in the Thai population. Less frequent mutations in exons 16 (p.K641R) and 17 (p.G663E) were also identified. In addition, the p.P252R mutation in FGFR1 was detected in 1 PS patient with unilateral coronal craniosynostosis expanding the phenotypic spectrum of PS with this particular mutation. Knowing the mutation spectrum of the responsible genes could lead to the most effective strategy in identifying mutations causing Pfeiffer syndrome in the Thai population.

Cadaveric study of the nasal periosteum and implant position after augmentation rhinoplasty.

Augmentation rhinoplasty is one of the most common cosmetic procedures done in Asia. A technique believed to be helpful in reducing complications is subperiosteal placement of silicone implant. A deeply placed implant should benefit from having thicker soft tissue coverage. Tough periosteal tissue is hoped to provide better implant fixation and prevent undesirable mobility. Experienced surgeons often claim that they can preserve the nasal periosteum and achieve complete implant coverage via nasal rim incision(s). However, success of implant placement and preservation of periosteal integrity after nasal augmentation has never been studied before.Nose augmentation with silicone implant was conducted in 12 fresh cadavers with the closed technique used in real practice. Open dissection of the nose was then carried out to verify implant position and the integrity of the periosteum. Factors that could affect the outcomes, including blade sizes of periosteal elevators, use of Aufricht retractor, and surgeon's experience, were analyzed.We found that all silicones could be implanted in the subperiosteal plane independent of instruments, surgeon's technique, and experience. Nonetheless, the covering nasal periosteum was always torn at its periphery and disconnected from the surrounding bone. As a result, lateral sides of the inserted silicones were not immediately covered with the periosteum.In conclusion, the surgeon's experience, the size of the periosteal elevator, and the Aufricht retractor did not affect the success of implant placement in the subperiosteal plane. Periosteal coverage was always incomplete and did not provide immediate implant fixation as previously understood.

PTPRF is disrupted in a patient with syndromic amastia.

BACKGROUND: The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences. METHODS: Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis. RESULTS: We enabled to identify its breakpoint on chromosome 1 interrupting the protein tyrosine receptor type F gene (PTPRF). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, PTPRF's RNA and protein of the patient were significantly less than those of her unaffected family members. CONCLUSIONS: Although ptprf has been shown to involve in murine mammary gland development, no evidence has incorporated PTPRF in human organ development. We, for the first time, demonstrated the possible association of PTPRF with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development.

Severe craniofrontonasal syndrome in a male patient mosaic for a novel nonsense mutation in EFNB1.

Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by mutations in EFNB1. Uncommonly and paradoxically, female patients with CFNS exhibit significantly more severe symptoms than male patients. This is explained by "cellular interference". Nevertheless, there have been a few reports of male patients severely affected with CFNS due to postzygotic mosaicism. Here, we demonstrated a male patient with severe CFNS. Whole exome sequencing showed that he harbored both wild type and nonsense mutation, c.253C > T (p.Gln85Ter), in the EFNB1 gene. Sanger sequencing of his leukocytes, buccal swab, and hair root revealed a variable level of mosaicism. This nonsense mutation is absent in his parents and has never been previously reported. Our findings expand the mutational spectrum of EFNB1 and substantiates that males with severely affected CFNS are mosaic.

Three novel mutations of the IRF6 gene with one associated with an unusual feature in Van der Woude syndrome.

Van der Woude syndrome (VWS) is a dominantly inherited disorder characterized by cleft lip with or without cleft palate and lip pits. It remains the most common syndromic form of oral clefts. Mutations in the interferon regulatory factor 6 (IRF6) gene have been identified in patients with VWS. We reported three unrelated families with lower lip anomalies. Two had lower lip pits, a cardinal sign of VWS, but the other had a heart-shaped mass on lower lip without pits, oral clefts, or hypodontia. This isolated anomaly has not been previously observed in VWS. We performed mutation analysis by PCR-sequencing the entire coding region of the IRF6 gene. Three potentially pathogenic mutations, c.145C>T (p.Q49X), c.171T>G (p.F57L), and 1306C>G (p.L436V) were successfully identified. All the missense mutations were not detected in 100 unaffected ethnic-matched control chromosomes and have never been previously reported. The p.Q49X and p.F57L mutations were located in the highly conserved DNA binding domain while the p.L436V was located at the carboxy-terminal region. This study reported an undescribed clinical feature of VWS and three novel mutations, expanding the phenotypic spectrum of VWS and mutational spectrum of IRF6.

Risk factors associated with the occurrence of frontoethmoidal encephalomeningocele.

OBJECTIVES: To determine factors associated with the occurrence of frontoethmoidal encephalomeningocele (FEEM), a congenital defect with unique geographical distribution. METHODS: The subjects of this study were 160 unrelated cases of FEEM. Subjects were recruited between 1999 and 2006 from 15 medical centers throughout Thailand. Data obtained from FEEM cases were analyzed and compared with data from 349 cases of oral clefts studied in the same centers and during the same time and those from the general population (GP) taken in 2003. RESULTS: About 52% of FEEM cases had brain anomalies which were not different among types of FEEM. We found familial aggregation reflected by an increased risk to siblings. All of the FEEM cases were of Thai nationality and came from low socioeconomic status. Seven FEEM cases had amniotic rupture sequences. Compared with oral clefts, advanced maternal age (OR: 1.08, 95% CI: 1.02-1.15) was found to be associated with FEEM. In addition, the interpregnancy interval between the FEEM cases and their previous siblings was significantly longer than that of the oral cleft patients and unaffected sibs (OR: 1.17, 95% CI: 1.06-1.28). CONCLUSIONS: Low socioeconomic status, advanced maternal age, and a long interpregnancy interval may lead to an unfavorable intrauterine environment which, with a certain genetic background such as Thai ethnicity, could contribute to the occurrence of FEEM.

Frontoethmoidal encephalomeningocele: surgical correction by the Chula technique.

This study reevaluates a surgical technique known as the Chula technique, previously reported in 1991 for correction of frontoethmoidal encephalomeningocele. From 1986 to 1999, 108 patients were operated on with this technique, which could remove the herniation mass, repair dural and bone defects, reconstruct the naso-orbital area, and restore aesthetic facial appearance in a single stage. Formal frontal craniotomy was not necessary. The result has been very satisfying in terms of safety, cure rate, and aesthetic outcome. Spontaneous improvement of lacrimal passage obstruction occurred in 85.2 percent of cases, and dacryocystorhinostomy was required in the rest. There was no mortality. Complications (e.g., wound infection, 6.5 percent; wire extrusion, 3.7 percent; meningitis, 2.8 percent; cerebrospinal fluid leakage, 2.8 percent; and postoperative increased intracranial pressure, 2.8 percent) were much less frequent than in other reports. With a mean follow-up period of 439 days (maximum, 12 years), there has been no recurrence.

Quantitative study of new bone formation in distraction osteogenesis of craniofacial bones by bone scintigraphy.

Although distraction osteogenesis is widely accepted as a technique to augment the craniofacial skeleton, timing to start distraction after an osteotomy or to remove distractors is basically based on studies on long bones. Because bone scintigraphy is well known to be the gold standard for quantitative measurement of bone formation, we conducted this pilot study to evaluate its feasibility as a tool for assessing new bone formation by distraction osteogenesis. Five patients with midface hypoplasia and four with mandibular hypoplasia were studied. Each patient had five bone scans: before surgery, 3 and 30 days after stopping distraction, and 3 days before and 3 months after distractor removal. Radiotracer uptake values at distraction sites were measured at 1 and 3 hours. Each uptake value was compared with preoperative study as uptake ratio. A typical pattern of radiotracer uptake ratio was observed in all cases with successful distraction. Uptake rose to the maximum during the consolidation period and remained at or above the preoperative level until the study end point. In one patient who had mandibular distraction and nonunion of the right ramus, there was no uptake peak during early consolidation as seen in the successfully distracted body and in the other cases. Bone scintigraphy was found to be a useful investigation in craniofacial distraction. It showed the dynamic of new bone formation by demonstrating the osteoblastic activity, which is important objective information for determining distraction rate and consolidation duration in each case. It may also be a tool that can predict the outcome of distraction osteogenesis.

Correction of the frontoethmoidal encephalomeningocele with minimal facial incision: modified Chula technique.

BACKGROUND: At present all surgical techniques to correct the frontoethmoidal encephalomeningocele require extensive incisions over the mass and perinasal area, thus adding scars to the already-disfigured faces. This study demonstrates a possibility of doing definitive surgery with minimal facial incision. METHODS: The technique follows the principles of the "Chula technique," which is the one-stage definitive technique without formal frontal craniotomy. However facial incision was kept to minimum, or even avoided, while amputation of the herniation, dural repair, skull defect closure, and repositioning of the medial canthal ligaments were performed mainly via the coronal incision. RESULTS: There were 20 patients operated on using this modified Chula technique. No perinasal incision was needed at all in three patients (15%) with F1 masses (small- and medium-sized masses according to the "FEEM classification"). Three patients with F1 masses had only small stab incisions just medial to the medial canthus for medial canthopexy. The rest (70%) consisting of two F2 (large-sized) masses and twelve F1 masses had limited nasal incisions just to help removing the facial masses and correcting facial deformity. With an average of 287 days of follow-up period (14-997 days), there had been no cerebrospinal fluid leakage or disease recurrence. CONCLUSIONS: Correction of the frontoethmoidal encephalomeningocele can be done safely via the coronal incision alone while facial incision can be omitted or, if necessary, kept to minimum.

Reduction malarplasty without external incision: a simple technique.

BACKGROUND: The concept of Eastern facial beauty is different from that of the Western. Prominent malar bones are perceived as unattractive by Easterners, including the Thai. Many techniques for malar reduction, such as chiseling or burring of the zygomatic body, are ineffective in reducing facial width. At present, the concept of medial movement of the zygomatic body is accepted as the treatment of choice. However, all current approaches leave some external facial scars, usually at the preauricular area. OBJECTIVE: A new, effective, and simple technique for reduction malarplasty that leaves no external scars is described here by the authors. METHOD: The technique consists of a purely intraoral approach to remove a segment of anterior zygomatic body, to create a greenstick fracture at each zygomatic arch, and to medially mobile the zygomatic body, which is then fixed by wiring at the end. RESULTS: All eight patients who underwent this surgical procedure have satisfactory results without complications after one to six years of follow-up. CONCLUSION: This technique represents another step of improvement in cosmetic craniofacial surgery to reduce both anterior and lateral projections of the malar eminences for better facial harmony.

Normal palatal sutures in newborns and fetuses: a critical fact for successful palatal distraction.

Distraction osteogenesis (DO) has recently been applied to the palate. Successful posterior lengthening and medial advancement of the palates was continuously reported. Based on these studies, it is obvious that DO will play a major role in the management of problems related to palatal defects in the near future. Although the results are appealing, they may not be applicable for humans due to anatomic differences. All experimental studies used normal palatal sutures of young dogs for size expansion. Therefore, it is necessary to know normal palatal sutures in infants before one can clinically apply this new technique. With consent, palates of fetuses and neonates who died of various causes were examined. Eight fresh cadavers were available for the dissection, with two being skeletonized using the boiling process. There were three fetal deaths in utero (33-41 weeks of gestational age) and five postnatal deaths (aged between 5 hours and 6 months). All specimens were grossly normal in shape and size except for one with a unilateral complete cleft of lip and palate. A midline palatal suture was found in every noncleft specimen, while premaxillary and transverse palatomaxillary sutures were present in every specimen. Laterally, there was no true suture except for the most posterior portion, which was contiguous with the greater palatine foramen. The palatal sutures of third-trimester fetuses and neonates are not different from adult ones. There is no lateral suture that will allow distraction in the medial direction. It is only the posterior hard palate (palatine bones) that can potentially be moved medially and posteriorly by sutural expansion with DO.

FGFR2 mutations among Thai children with Crouzon and Apert syndromes.

Crouzon and Apert syndromes have been reported to be associated with mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) gene in various ethnic groups, but never in Southeast Asian subjects. Therefore, the authors conducted a study to characterize 11 Thai patients: four with Crouzon syndrome and seven with Apert syndrome. All cases are sporadic. Mean paternal and maternal ages were 38.7 and 28.6 years, respectively. Molecularly, all patients were found to have mutations in the FGFR2 gene. Three mutations (C278F, S347C, S351C) were detected in all Crouzon patients with two having S351C. The seven patients with Apert syndrome have either S252W or P253R mutation. The authors' findings that sporadic cases were associated with advanced paternal age and that they all had mutations in FGFR2 are consistent with previous reports. This is another observation supporting the causative role of FGFR2 mutations in Crouzon and Apert syndromes.

Frontoethmoidal encephalomeningocele: new morphological findings and a new classification.

Given a lack of a comprehensive classification for the frontoethmoidal encephalomeningocele (FEEM), clinical, photographic, and computed tomography (CT) data of 23 nonoperated patients were reviewed. Extracranial pathological findings of interest included herniation masses, facial deformities, and frontonasal bone morphology. Intracranial pathological findings of interest included morphology of the anterior cranial floor and brain malformations. Stereographic software processed data from a new-generation CT scanner into three-dimensional pictures that revealed some interesting morphological findings not often appreciated (eg, herniation mass without underlying external bone defect; mass at location far from external bone defect ["sequestrated cephalocele"]; new type of external bone defect characterized by a combination of nasoethmoidal and naso-orbital defects; correlation between mass, external bone defect, and exit pathway of herniation). Given these observations plus current knowledge available in the medical literature, a new classification system was developed that covers phenotypes and severity of the disease. The "FEEM classification" is an alphanumeric system based on facial deformities, external bone defect, exit pathway of herniation, and malformation of brain. It was tested in 42 patients for usability and validity. When combined with a newly designed "FEEM diagram," relevant pathological findings can be recorded in an objective manner so that diagnosis becomes more precise and uniform and comparison of outcome is possible. It also emphasizes the fact that FEEM has a range of manifestations governed by dynamic interaction between structural defects and herniation. Each clinical entity is a final result of its own disease course (stable, progressive, or regressive FEEM), with a varying degree of communication between the external mass and the central nervous system.