Tissue expansion in the reconstruction of Tessier craniofacial clefts: a series of 17 patients

Tessier craniofacial clefts are among the most surgically challenging examples of craniofacial dysmorphology. These clefts are characterized by hypoplasia of soft-tissue and skeletal elements throughout the three-dimensional extent of the cleft. Whereas bone grafting and craniofacial osteotomies have been successful toward correcting the underlying skeletal abnormalities, the ultimate success of these reconstructions has been limited by the deficiency of skin and soft tissue. This deficiency demands reconstruction ideally with tissue of like texture, consistency, and, especially in the face, color. Craniofacial tissue expansion was used toward reconstructing these facial clefts with like-quality tissue, allowing for tension-free reconstruction after osteotomy and bone grafting. Seventeen patients with Tessier craniofacial clefts underwent preoperative craniofacial soft-tissue expansion in the surgical management of their clefts. Tissue expansion was used in the primary correction of facial clefts in eight patients, with nine patients undergoing expansion before secondary surgery. In this series, tissue expansion has evolved as an important element in overcoming the skin and soft-tissue deficiency associated with these clefts, allowing for tension-free closure and improved aesthetic results in these surgically challenging patients.     

Emotional and behavioral reactions to facially deformed patients before and after craniofacial surgery

The present experiment investigated whether observers' emotional and behavioral reactions to facially deformed patients could be substantially improved by surgical procedures conducted by well-trained specialists in an experienced multidisciplinary team. Also investigated was the hypothesis that emotional states mediate the effects of physical attractiveness and facial deformity on social interaction. Twenty patients between the ages of 3 months and 17 years were randomly selected from over 2000 patients' files of Kenneth E. Salyer of Dallas, Texas. Patient diagnoses included facial clefts, hypertelorism, Treacher Collins syndrome, and craniofacial dysostoses (Crouzon's and Apert's syndromes). Rigorously standardized photographs of patients taken before and after surgery were shown to 22 "naive" raters ranging in age from 18 to 54 years. Raters were asked to predict their emotional and behavioral responses to the patients. These ratings indicated that observers' behavioral reactions to facially deformed children and adolescents would be more positive following craniofacial surgery. Similarly, the ratings indicated that observers' emotional reactions to these patients would be more positive following surgery. The results are discussed in terms of current sociopsychologic theoretical models for the effects of attractiveness on social interaction. A new model is presented that implicates induced emotional states as a mediating process in explaining the effects of attractiveness and facial deformity on the quality of social interactions. Limitations of the current investigation and directions for future research are also discussed.     

Cleft lip and/or palate in two cases of 46,X,i(Xq) Turner syndrome

Cleft lip (CL) and/or palate (CP) are uncommon anomalies in Turner syndrome (TS) series. We report two unrelated sporadic 46,X,i(Xq) patients exhibiting orofacial clefts and a peculiar facial appearance masking the clinical diagnosis. CL, and CP in case 1 and CP in case 2, though non-specific of TS, may not be fortuitous findings. The increased frequency of CP and bifid uvula in poly X syndromes, the dermatoglyphic similarities between iXq TS and X polysomies, and the occurrence of Klinefelter phenotype when extra Xq material is present in a male, are all indirect evidences suggesting that Xq material cannot be considered phenotipically inert and facial clefts found in our patients may be syndromal manifestation of trisomic Xq dosage.     

Pathogenesis of median facial clefts in mice treated with methotrexate

Methotrexate (MTX), administered as a single 20 mg/kg intraperitoneal dose to C57Bl/6J mice on their 9th day of pregnancy results in high incidences of median facial clefts in the surviving gestational-day-18 fetuses. We have shown the presence of dilated and congested blood vessels in the frontonasal prominences (FNP) of embryos from treated mothers as early as 3 hours following drug administration. Within 24 hours, large vascular blebs are located in the FNP and the neural tubes appear somewhat distended. By 32 hours after treatment, distention of the neural tube is marked while blebs have become less evident. Subsequent to these changes, FNP mesenchymal deficiency as well as neural tube distention lead to the formation of median facial clefts. It is hypothesized that, as with a number of other teratogenic agents (especially hypoxia), initial fluid imbalance is the primary teratogenic insult.     

Cerebral midline developmental anomalies: spectrum and associated features

Cerebral midline anomalies are defects of anatomical relationships between the two hemispheres. They include holoprosencephalies, septal and commissural agenesis. Agenesis of the olfactory tract (arhinencephalies) are often included in the spectrum of holoprosencephalies and the facial phenotype is thought to be affected and characteristic in the midline development abnormalities. This work concerns a review of the literature and personal experience in two units of Fetopathology in Paris. This study confirms the relationships between various cerebral malformations and their frequent association. However, arhinencephaly and moreover agenesis of corpus callosum should be considered as heterogeneous entities, often totally distinct and independent from the malformative process of the holoprosencephaly. In addition, if major facial anomalies such as cyclopia are almost pathognomonic for holoprosencephaly, minor malformations such as lateral facial clefts of cleft palates result from a great variety of malformative processes.     

Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting

Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Specc1l is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face. In zebrafish, knockdown of a SPECC1L homolog produces a faceless phenotype with loss of jaw and facial structures, and knockdown in Drosophila phenocopies mutants in the integrin signaling pathway that exhibit cell-migration and -adhesion defects. Furthermore, in mammalian cells, SPECC1L colocalizes with both tubulin and actin, and its deficiency results in defective actin-cytoskeleton reorganization, as well as abnormal cell adhesion and migration. Collectively, these data demonstrate that SPECC1L functions in actin-cytoskeleton reorganization and is required for proper facial morphogenesis.     

The case for early bone grafting in cleft lip and palate: a second report

In 1982, the first long-term study of our early bone-grafting and infant maxillary orthopedic approach to newborn complete clefts of the lip, alveolus, and palate was published. The protocol and sequence of procedures were shown on the first 16 consecutively treated orthodontic patients, with a mean age of 14 years. Cephalometric analysis evaluated anteroposterior and vertical facial growth. This report follows the next 37 consecutively treated individuals in a similar manner and includes not only 20 complete unilateral clefts, but also 17 complete bilateral clefts. Results, when evaluated alone and in comparison with the original series, show once again that there are no adverse growth restraints and that early primary bone grafting in our protocol leads to teeth in better overall occlusion than if it had not been undertaken.     

Orofacial clefting: recent insights into a complex trait

Orofacial clefts are common birth defects of multifactorial etiology. Several novel approaches have recently been applied to investigate the causes of clefts. These include examining Mendelian forms of clefting to identify genes that might also be implicated in isolated clefting, analyzing chromosomal rearrangements in which clefting is part of the resultant phenotype, studying animal models in which clefts arise either spontaneously or as a result of mutagenesis experiments, exploring how expression patterns correlate with gene function and examining the effects of gene-environment interactions. Together, these complementary strategies are providing researchers with new clues as to what mechanisms underlie orofacial clefting.     

The pharyngeal pouches and clefts: Development,evolution, structure and derivatives

The pharyngeal arches form the face and neck of the developing embryo. The pharyngeal tissue is divided into distinct arches by the formation of clefts and pouches in between the arches. These clefts and pouches form at the juxtaposition between the ectoderm and endoderm and develop into a variety of essential structures, such as the ear drum, and glands such as the thymus and parathyroids. How these pouches and clefts between the arches form and what structures they develop into is the subject of this review. Differences in pouch derivatives are described in different animals and the evolution of these structures are investigated. The implications of defects in pouch and cleft development on human health are also discussed.     

Rare facial clefts: treatment during charity missions in developing countries

During 10 charity missions in developing countries, 14 patients of a total of 374 children with cleft lip and palate deformities were treated for rare facial clefts. There were three midline clefts (Tessier no. 0 cleft, n = 1; Tessier no. 14 cleft, n = 2), four oblique facial clefts (Tessier no. 3 cleft, n = 2; Tessier no. 5 cleft, n = 2), and seven lateral facial clefts (Tessier no. 7 cleft). Surgical treatment focused on cleft repair by soft-tissue reconstruction apart from two Tessier no. 14 clefts, in which the bony gap was also closed using bone grafts from the iliac crest. The postoperative course was uneventful except for one local wound infection that was treated successfully using oral antibiotics. This article summarizes the authors' experience with the surgical management of these malformations and considers the limitations under conditions of charity missions in developing countries. Furthermore, some rare forms of cleft formation are added to the existing literature.     

The role of tissue expansion in the treatment of atypical facial clefting

Tissue expansion can be a valuable tool in the reconstruction of soft-tissue defects in craniofacial clefts. To our knowledge, there have been no reports in the literature of the use of tissue expanders to help solve this problem. We report the case of a child with an atypical Tessier no. 3 craniofacial cleft who had a forehead tissue expander placed, inflated, and thus used to provide sufficient local facial skin for repair of the soft-tissue defect.     

The Ultrastructure of Schmidt-Lanterman Clefts and Related Shearing Defects of the Myelin Sheath

Schmidt-Lanterman clefts in frog sciatic nerves have been studied in thin sections by electron microscopy utilizing permanganate fixation and araldite embedding. It is shown that they are shearing defects in myelin in which the lamellae are separated widely at the major dense lines. Each lamella consisting of two apposed Schwann cell unit membranes ~ 75 A across traverses the cleft intact. The unit membranes composing each lamella sometimes are slightly (~ 50 to 100 A) separated in the clefts. The layers between the lamellae contain membranous structures which may be components of the endoplasmic reticulum. These layers are continuous with the outer layer of Schwann cytoplasm and the thin and inconstant cytoplasmic layer next to the axon (Mauthner's sheath). Each of these layers in perfect clefts constitutes a long helical pathway through the myelin from the axon. One of these is connected with Schwann cytoplasm and the other directly with the outside. A type of cross-sectional shearing defect, not hitherto recognized, is described and shown to be a kind of Schmidt-Lanterman cleft. Incomplete clefts are seen and interpreted as representing stages in a dynamic process whereby the myelin lamellae may be constantly separating and coming together again in life.     

TFAP2A mutations result in branchio-oculo-facial syndrome

Branchio-oculo-facial syndrome (BOFS) is a rare autosomal-dominant cleft palate-craniofacial disorder with variable expressivity. The major features include cutaneous anomalies (cervical, infra- and/or supra-auricular defects, often with dermal thymus), ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies. The molecular basis for this disorder is heretofore unknown. We detected a 3.2 Mb deletion by 500K SNP microarray in an affected mother and son with BOFS at chromosome 6p24.3. Candidate genes in this region were selected for sequencing on the basis of their expression patterns and involvement in developmental pathways associated with the clinical findings of BOFS. Four additional BOFS patients were found to have de novo missense mutations in the highly conserved exons 4 and 5 (basic region of the DNA binding domain) of the TFAP2A gene in the candidate deleted region. We conclude BOFS is caused by mutations involving TFAP2A. More patients need to be studied to determine possible genetic heterogeneity and to establish whether there are genotype-phenotype correlations.     

Dynamic restoration in Möbius and Möbius-like patients

M?bius syndrome is classically characterized by bilateral facial nerve and abducens nerve paralysis in combination with limb defects. In the past 110 years, physicians diagnosed children as having the syndrome on the basis of heterogeneity of symptoms and used the term "M?bius syndrome" or "M?bius-like syndrome" for patients with multiple cranial nerve involvement. The cause and the exact pathogenesis of the syndrome still elude understanding. Genetic work-ups, radiological findings, and data from autopsies differ in their approaches and their findings of the basic causes of M?bius syndrome. In the international literature, about 301 case reports are found scattered through the past century. The appearance of the facial deformity is easy to recognize, because the M?bius patient is impaired in his or her ability to communicate nonverbally. Despite ophthalmologic problems, it is the search for a smile that brings these patients to the reconstructive surgeon. Over the past 100 years, surgical efforts attempted to improve the mask-like appearance by static and dynamic procedures, usually local muscle transpositions. Today, combinations of microsurgical procedures and aesthetic techniques are being used to restore some movement to the expressionless face of these patients by nerve and muscle transplantation. This article discusses the heterogeneity of M?bius syndrome, advocates a new classification system, presents the clinical findings of 42 patients who were seen and examined in consultation, and discusses the surgical management of 20 patients who underwent dynamic restorative microsurgery. Exemplary cases illustrating the preoperative work-up regimen and possible outcomes are reported.     

CHARGE Association in newborns: a registry-based study

The CHARGE Association is a nonrandom occurrence of congenital malformations that has been described in clinical series. Reported patients have been selected on the basis of certain prior criteria. In this article, we try to identify a congenital malformation pattern corresponding to the CHARGE Association, using statistical methods and analyzing 5,260 infants with multiple malformations collected from four large registries of congenital malformations. Care was taken to identify a number of confounding characteristics that can influence the ascertainment and registration of specific congenital malformations. We have identified a cluster of malformations that generally agreed with the current clinical definition of the CHARGE Association and have added some further malformations (e.g., facial clefts). We demonstrate that others (e.g. , esophageal atresia) are probably not part of the pattern. Heart defects (H in the acronym) seems to be less helpful in identifying infants with the association. We suggest a method to select infants who probably represent the CHARGE Association for analyses of possible risk factors.     

The physical attractiveness of facially deformed patients before and after craniofacial surgery

The present experiment investigated whether the physical attractiveness of craniofacially deformed children and adolescents could be improved by surgical procedures. Twenty patients between the ages of 5 months and 17 years were randomly selected from patient files. Patient diagnoses included facial clefts, hypertelorism, Treacher Collins syndrome, and craniofacial dysostosis (Crouzon's and Apert's syndromes). Rigorously standardized photographs of patients taken before and after surgery were shown to 40 "naive" raters ranging in age from 17 to 52 years. Raters analyzed the photographs with regard to global physical attractiveness. These ratings indicated that the patients' physical attractiveness was reliably (62 percent) improved following surgery. The results are discussed in light of recent evidence that untreated craniofacial patients may be at risk for psychosocial disorders and in terms of the growing evidence of the importance of physical appearance for the development of cognitive and social-emotional competence. In addition, a standardized assessment system is described that can be used to facilitate the compilation of actuarial data predicting surgical outcomes. Finally, the importance of empirically evaluating the effectiveness of surgical procedures and practitioners on a continuing basis is emphasized.     

Birth Prevalence of Neural Tube Defects and Orofacial Clefts in India: A Systematic Review and Meta-Analysis

Background

In the last two decades, India has witnessed a substantial decrease in infant mortality attributed to infectious disease and malnutrition. However, the mortality attributed to birth defects remains constant. Studies on the prevalence of birth defects such as neural tube defects and orofacial clefts in India have reported inconsistent results. Therefore, we conducted a systematic review of observational studies to document the birth prevalence of neural tube defects and orofacial clefts.

Methods

A comprehensive literature search for observational studies was conducted in MEDLINE and EMBASE databases using key MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND India). Two reviewers independently reviewed the retrieved studies, and studies satisfying the eligibility were included. The quality of included studies was assessed using selected criteria from STROBE statement.

Results

The overall pooled birth prevalence (random effect) of neural tube defects in India is 4.5 per 1000 total births (95% CI 4.2 to 4.9). The overall pooled birth prevalence (random effect) of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to 1.5). Subgroup analyses were performed by region, time period, consanguinity, and gender of newborn.

Conclusion

The overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based. The quality of these studies ranged from low to moderate. Further well-designed, high quality community-based observational studies are needed to accurately estimate the burden of neural tube defects and orofacial clefts in India.     

Application of the two-flap method for nasal alar contracture

Reconstruction of the contracted nasal ala has been a very difficult problem for plastic surgeons. Numerous surgical procedures have been reported. However, most operations require multiple stages and leave conspicuous facial scarring and a thick, asymmetrical nostril rim. We have used the two-flap method introduced by Thomson and Sleightholm for isolated naso-ocular clefts, but we have added some modifications to this method: making a deeper backcut into the dome on the mesial side of the contracture and using thinner flaps than were originally used. As a result, we have achieved reasonable symmetry, good color match, appropriate thickness, and no conspicuous facial scarring in every patient.