Most common cause of syndromic hearing loss,get rid of buzzing in ear 05,titus 6 wiki fr,noise and hearing loss in the workplace 5.5 - PDF Review

We will be provided with an authorization token (please note: passwords are not shared with us) and will sync your accounts for you. Orofacial clefts comprise a range of congenital deformities and are the most common head and neck congenital malformation.
Orofacial clefts include a range of congenital deformities most commonly presenting as cleft lip with or without cleft palate (CLP) or isolated cleft palate (CP). Normal development occurs sequentially, thus cleft lip may or may not be associated with cleft palate.
CLP is traditionally classified by phenotype, which can have variable expression ranging from microform to complete clefting, and may involve the alveolar ridge and palate (Figure 1).
CLP refers to a clinical spectrum of cleft lip with or without associated cleft palate (Table 1). Unilateral cleft lip (Figure 1) is associated with typical deformities caused by asymmetric forces on the premaxilla during facial growth. In bilateral cleft lip, the premaxilla grows independently of the maxillae on either side and may protrude considerably, particularly in complete clefts (Figure 2) (18). In contrast to CLP, cleft palate (CP) is primarily characterized by disorientation of palatal muscles which lead to feeding difficulties, velopharyngeal insufficiency, and speech problems. CLP occurs in 1 in 500–2,500 live births depending on ancestry, geographic location, maternal age, prenatal exposures, and socioeconomic status (2, 7). Major population differences have been reported, with the highest rates in Asians and Native Americans (1 in 500 births) and the lowest rate in Africans (1 in 2,500 births) (25).
Cleft lip is consistently more common in males at a 2:1 ratio, in contrast to cleft palate which has a similar ratio in favor of females.
Epidemiologic and etiologic features of CLP differ in the syndromic and non-syndromic forms. Potential teratogens that have been reported include retinoic acid, phenytoin, and valproic acid (54). Thirty percent of newborns with CLP have additional congenital anomalies occurring as part of a syndrome (31, 32). Cleft lip repair is complicated by the distortion of multiple anatomical structures, which can occur with varying severity.
What determines the optimal timing of surgical repair can vary based on surgeon preference, anesthetic risks, comorbid congenital anomalies, and perceived psychological impact on the family. Recently, there had been published results that have shown some successful repairs in neonates 1–8 day old using the modified Tennison technique (60).
Preliminary maneuvers can be used to aid in obtaining a satisfactory result during definitive surgical repair may be considered.
Lip adhesion is a preliminary procedure prior to definitive surgical repair to convert a complete cleft lip into an incomplete cleft so that the final lip repair may be completed with reduced tension.
The use of pre-surgical orthopedics may also be considered and is used as an adjunct for guiding surgical repair.
Passive appliances, called NAM, deliver no force and gradually mold the alveolar segments and position the direction of growth via alveolar molding plates of acrylic. Numerous techniques, as well as modifications to popular techniques, have been extensively described in the literature.
Millard’s rotation-advancement flap is currently the most prevalently used technique in cleft lip repair (Figure 4). Repair of the bilateral cleft lip is often significantly more difficult than the unilateral cleft lip repair due to the presence of the premaxilla and prolabium. The nasal deformity associated with unilateral cleft lip is well defined since the 1950s (88).
Within the past three decades, it is now commonplace for primary surgical correction of the nasal deformity at the time of definitive lip repair. Historically, patients undergoing cleft lip repair have had post op inpatient hospitalization for monitoring (108).
Pinpointing the exact genetic cause of inherited deafness has always involved sequencing one gene at a time, a process that can take up to a year and cost roughly $1,000 per gene. Now, University of Iowa researchers working with colleagues at Baylor College of Medicine have developed a test that can screen all of the genes known to cause deafness in a single run, in one to three months and for about $2,000. The new test, called OtoSCOPE, will be available through the UI's Molecular Otolaryngology and Renal Research Laboratory (MORL) by spring 2011 to clinicians and patients within the U.S. The new method uses the latest DNA sequencing technology to simultaneously screen all 54 genes known to cause non-syndromic deafness -- hearing loss that is not associated with other medical problems -- along with a dozen additional genes that cause syndromic deafness -- hearing loss that occurs with other complications, such as blindness. The test covers two of the most common types of syndromic deafness -- Usher syndrome and Pendred syndrome. The screening test was able to identify the genetic cause of hearing loss in five of the six unknowns.
The results proved that the new technology can provide similar sensitivity and resolution as the current gold standard sequencing test, but because OtoSCOPE can screen all the genes in one run, it is faster and less expensive to identify the mutation causing the hearing loss. The researchers note that this screening test can be applied to other genetic diseases to decrease cost and give more comprehensive results, and it will also be useful for gene discovery. Familiarity with orbital and ocular anatomy is crucial to the understanding of disease processes of the orbit. This is in contrast to patients with optic pathway gliomas in whom vision usually remains stable or spontaneously improves.
2 clicks for more privacy: On the first click the button will be activated and you can then share the poster with a second click. Rapid bedside assessment of the renal function of patients undergoing contrast-enhanced CT.
Researchers from the Miller School of Medicine have identified a gene associated with Alzheimer’s disease in Caucasians.
Miller School researchers collaborated with an international team to identify a new gene associated with the most common form of inherited childhood deafness. First-year medical students at the Miller School now have the opportunity to earn a Master of Science in Genomic Medicine along with their medical degree, a program unique to the University of Miami. Researchers from the Miller School of Medicine collaborated with an international team to identify a gene that could be suppressed to protect a person’s nerve cells after injury. This means that you will not need to remember your user name and password in the future and you will be able to login with the account you choose to sync, with the click of a button. This page doesn't support Internet Explorer 6, 7 and 8.Please upgrade your browser or activate Google Chrome Frame to improve your experience. Clefting has significant psychological and socio- economic effects on patient quality of life and require a multidisciplinary team approach for management. The WHO-supported international collaborative research on craniofacial anomalies project establishes a global network to compile a comprehensive database and coordinate research strategies (6). The medial projections of the maxillary processes form palatal shelves which rise above the tongue, fusing medially at the midline, anteriorly with the primary palate, and superiorly with the septum. Phenotypes have been correlated with specific genetic linkage patterns, suggesting a possible correlation. Palate involvement generally denotes a related but more severe form of this anomaly, although they may have epidemiologic differences (12). The presence of Simonart’s band may reduce the extent of facial deformity with growth by exerting a restorative force (14).
The prolabium, consisting of soft tissues of the premaxilla without muscle fibers, also lacks Cupid’s bow and philtral columns bilaterally. The spectrum ranges from a submucosal cleft to complete clefting of the primary and secondary palate. The latest CDC estimates report the incidence of CLP to be 1 in 940 live births, with 4,437 cases every year (1).
Some have postulated that common maternal hormones may be involved in both sex determination and orofacial clefting (26). While the mechanism is unclear, the observation that the facial artery develops slower on the left may be a factor (28). Monozygotic twin studies suggest that genetics account for 40–60% of orofacial clefting (34). Maternal smoking increases the risk of CLP by up to 30% (40) and a dose-response effect has been consistently reported (41, 42). Other proposed risk factors include various occupational and chemical exposures, hyperthermia, stress, maternal obesity, oral hormone supplementation, ionizing radiation, and maternal infection (10, 53). Over 500 Mendelian syndromes are listed in the Online Mendelian Inheritance in Man (OMIM) database. The challenges of reconstruction can be as distinct as the patient presentations of clefts: unilateral versus bilateral, narrow clefts versus wide clefts, syndromic patients versus non-syndromic patients as previously described.
Proponents of early intervention argue that while there is clear evidence of greater anesthetic complications for children under 12 months of age, there is limited evidence showing greater anesthetic risk for neonates as compared to surgery at 3 months of age. These steps may especially be beneficial for patients with wide clefts with significant misalignment of the alveolar arches that may prevent proper alignment at the time of definitive surgery (62–64).
Typically performed within the first month of life, laterally based flaps obtained from the lip itself (65) or inferiorly based flaps of the vermillion (66) may be used. Active maxillary appliances move alveolar maxillary segments into approximation with controlled force. Newborn cartilage is believed to be soft and lacking in elasticity, and thus would make passive molding an easier endeavor (73).
Straight-line closure, or the Rose-Thompson closure, is an early technique introduced in the early twentieth century that may be procedure of choice for microform clefts (78), and is rarely used as primary technique for cleft repair. Recent surveys have noted that 84% of response from practicing surgeons perform rotation advancement for complete unilateral cleft lip repair compared to 9% utilizing a triangular flap (83).
The prolabium is oftentimes deficient in muscle and vermillion, is small, and attached to the nasal tip with little or no columella present.
Due to fear of interfering with normal growth of the nose, surgeons rarely performed surgery to correct the nasal deformity until the 1970s (89). It is now understood that the nasal growth on the cleft side of the nose is unaffected by early primary nasal surgery (89). As it stands, esthetic results from definitive surgical repair only come to reveal itself after some time has passed.


However, due to economic forces, changes in health care delivery, and the desire to return patients to a familiar home environment (109, 110), the trend has been toward same day discharge, necessitating reevaluation of postoperative complications. UI researchers have developed a comprehensive genetic test for inherited deafness that can screen all known hearing loss genes simultaneously. It means quicker answers for families anxious to determine treatment options or learn the likelihood that future children will have hearing loss.
Smith also is a pediatric otolaryngologist with UI Children's Hospital and director of MORL, which is a not-for-profit lab. It affects 1 in 500 newborns, and an estimated 278 million people worldwide have moderate to severe hearing loss. It also helps the patient and their family prepare for the vision loss," Hildebrand said.
In fact, in addition to finding two known hearing loss mutations, the test also uncovered three new mutations within known genes.
In addition, as more gene mutations are found to cause deafness, they can easily be included in the screening test. 1: Pre contrast soft tissue and bone windows and coronal post contrast CT images of a pediatric patient with retinoblastoma. 2: Axial T1 pre, T1 FS post, and T2 weighted images as well as coronal T1 FS post and T2 weighted images of a patient with bilateral retinoblastomas demonstrate a large enhancing T1 hyper, T2 hypointense right ocular mass with direct extension into the vitreous (thin arrows). 3: Pre and post coronal T1 weighted, coronal T2, axial T1 post, and diffusion weighted images of a patient with primary orbital rhabdomyosarcoma. 4: T1 pre, T1 post, and T2 weighted images of a patient with a large right capillary hemangioma involving the skin, subcutaneous tissues and extraconal space.
6: Pre contrast T1 fat sat image of the liver of a patient with metastatic choroidal melanoma. 7: Axial T1 post, coronal T2 and T1 post, and axial T1 post weighted and T2 Flair images show fusiform enlargement of the left optic nerve (thin arrows). 9: Axial T1 pre and T1 post and coronal post contrast images with fat saturation in a patient with an optic nerve meningioma. 10: Axial T1 pre, T1 post, and T2 fat sat images of a 54 year old female with bilateral orbital lymphoma. Published online October 27 in Neurobiology of Aging, their study demonstrated that a change in the C9ORF72 gene, called a repeat expansion, could be a new cause for late-onset Alzheimer’s disease, mostly in Caucasians.
Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine again supports the importance of structural variation in autism spectrum disorders. The complex interplay between genetic and environmental factors play a significant role in the incidence and cause of clefting.
Optimal management of a child with cleft lip demands an organized multidisciplinary effort involving the fields of otolaryngology, plastic surgery, maxillofacial surgery, orthodontistry, speech therapy, pediatrics, nursing, genetics counseling, audiology, psychology, and social work (7). By the end of week 4, the frontonasal prominence forms from migrating neural crest cells of the first pharyngeal arch. Deformities of the lip, palate, and nose are a result of the disruption of normal development.
CLP and CP are embryologically distinct processes from disruption at different stages of development and possess unique epidemiologic and genetic features (7, 10, 12). Lip clefting may be complete (involving the full vertical height of the lip) or incomplete. There is rotation and distortion of the vermillion with loss of Cupid’s bow and philtral landmarks on the cleft side. The columella is severely shortened or absent while the lateral crura are displaced laterally, producing a broad, flat nasal tip. Perhaps the best studied are orbicularis oris muscle defects in the absence of a visible cleft. An association between cleft laterality and handedness has been proposed (29) but this has not been consistently shown (27, 30). The causes are multifactorial and involve genetics, environmental factors, and teratogens (Table 2) (10, 33). However, the identification of candidate genes is complicated by heterogeneity, non-Mendelian inheritance patterns, and limited sample sizes (10). The complex interplay between genetic and environmental factors undoubtedly play a role in the pathogenesis of CLP.
The most common and well-known syndrome associated with cleft lip is van der Woude syndrome.
The development of pre-surgical orthopedics saw great changes over the past 50 years, and signifies the importance of a collaborative multidisciplinary team approach to the treatment of clefts.
The Latham appliance (72) was designed to anchor on the non-cleft maxillary segment intraorally and actively reposition the lateral alveolar cleft segments and reduce the protruded maxilla (72). Initial devices were designed to correct alveolar cleft only (74, 75), and did not sufficiently address the nasal deformity that is associated with cleft lip.
Straight-line closure typically resulted in notching of the lip and vertical scar contracture (79). The technique utilizes downward rotation of the superiorly displaced medial lip segment with advancement of the lateral lip flap to correct the defect below the nose (18, 59, 84).
The premaxilla also presents a challenge, as it remains highly variable in position and size; it can protrude forward and deviate to one side. As previously described, in unilateral cleft lip, the lower lateral nasal cartilage is typically found to be positioned laterally and inferiorly, leading to a depressed dome, increased alar rim, oblique columella, and overhanging nasal apex (76). This fact is supported by an 18-year follow up study comparing primary nasal repair with normal and unrepaired cleft lip children (92). In unoperated adult cleft patients, there remains normal potential for maxillary growth (94, 95). Therefore it may be necessary for the patient to return to the operating room for revisions to improve function and appearance of the repair (85). Thus, complications related to comorbid congenital abnormalities or anesthetic complications are more easily avoided.
One study noted that emergent complications, if they occurred at all, would arise within 48 h and be due to respiratory difficulties (106). About two-thirds of hearing loss is inherited and can be caused by mutations in many different genes. Note the high attenuation mass in the posterior vitreous of the right eye with prominent calcifications (arrows). 5: This diffusely enhancing right ocular mass was pathologically proven to be a uveal tract melanoma. 8: Axial and coronal T 1 weighted images of a second patient with an optic pathway glioma arising within the right optic nerve (arrows). Note the diffusely infiltrative nature of the lesion which obscures normal orbital anatomy yet conforms to the normal osseous structure of the orbit.
Macdonald Foundation Department of Human Genetics and Director of the Biorepository at the John P. Macdonald Foundation Department of Human Genetics at the Miller School, has been named President-elect of the American Board of Genetic Counseling (ABGC).
Department of Health and Human Services, opened the Miller School’s first conference aimed at ensuring that all populations benefit from the revolutionary promise of genomic medicine by embracing the summit’s theme of urgency. In this review, the embryology, classification, epidemiology, and etiology of cleft lip are discussed. Nasal placodes, representing ectodermal thickening, develop at the caudal end of this structure and divide the paired medial and lateral nasal processes.
Formation of the primary and secondary palates completes the separation of nasal and oral cavities, permitting simultaneous respiration, and mastication (10). Orbicularis oris muscle fibers are asymmetrically oriented along the cleft margins and may be continuous across Simonart’s band in milder forms (15). These are assessed by high-resolution ultrasound (20, 21) and seem to preferentially occur in immediate relatives of those with cleft lip (19, 22). The interferon regulatory factor 6 (IRF6) gene is consistently associated with non-syndromic CLP in multiple studies (10, 35) and is also the causative agent of van der Woude syndrome, the most common syndromic cause of cleft lip.
Maternal alcohol consumption is controversial, although binge drinking may increase risk (44). Investigation of these interactions may open new avenues of research for prevention and management of CLP.
It is caused by a defect in the IRF6 gene on chromosome 1 and is inherited in an autosomal dominant fashion.
Yet, the goal of surgery remains the same: addressing the functional and cosmetic deformity of cleft lip. Granted that the child is otherwise healthy, several series have shown that esthetic and anesthetic results are comparable between repair in the neonatal period and repair at a much older age (60, 61). The lip adhesion procedure is less favored in that it requires the patient to undergo an additional surgery, may have increased scar formation, or may not correctly align the maxillary segments, and may have the potential to dehisce at the surgical site (62).
Surgeons in the nineteenth century initially excised the premaxillary segment, which unfortunately lead to development of mandibular pseudoprognathism, malocclusion, maxillary growth restriction, and midface deficiency (62).
Placement of the device also requires a surgical procedure as it consists of a two-piece maxillary splint anchored by pins to the palate, an expansion screw to adjust the palatal segments, and a chain to retract the premaxillary segment. In unilateral cleft lip, the lower lateral nasal cartilage is typically found to be positioned laterally and inferiorly, leading to a depressed dome, increased alar rim, oblique columella, and overhanging nasal apex (76). Modern repair techniques have utilized the lateral lip flap to fill in the medial defect from the clefting of the lip.
The many advantages of the technique belies its popularity, as it produces minimal tissue loss, creates a suture line consistent with the philtrum on the side of the cleft, preserves the Cupid’s bow, repositions the base of the nasal ala and provides tension to reduce nasal flare, guides the construction of a nasal sill, and is extremely versatile for the type of cleft the surgeon may come upon.
The goals of primary rhinoplasty include closure of the nasal floor, repositioning the lower lateral cartilages, and repositioning the alar base. The nasal deformity is of greater magnitude in bilateral cleft lips which includes bilateral alar deformity, widened alar base, and flattened nasal tip. Deformities following the initial surgeries can range from scars of the mucocutaneous, vermillion, or muscular regions (100).
Notably, the four of the seven patients had known history of respiratory issues and were thus more susceptible to complications (106).


Macdonald Foundation Department of Human Genetics, has been elected a Fellow of the American Association for the Advancement of Science for his scientifically and socially distinguished efforts to advance science by identifying the genetic causes of Mendelian diseases, inherited neuropathies and Parkinson’s disease using innovative and integrated molecular and analytical approaches.
Hussman Institute for Human Genomics, has been awarded $641,140 from the National Multiple Sclerosis Society to expand studies of multiple sclerosis in the Hispanic population. Macdonald Foundation Center for Medical Genetics at the Miller School of Medicine, passed away peacefully in Atlanta early Sunday morning, surrounded by his family.
Macdonald Foundation Department of Human Genetics have been awarded more than $2 million in grants to advance genetic research on Staphylococcus aureus infections, Charcot-Marie-Tooth disease and age-related macular degeneration.
The primary goals of surgical repair are to restore normal function, speech development, and facial esthetics. One of the primary roles of the otolaryngologist is surgical repair to restore normal feeding, speech, and appearance. The primary palate forms from the fusion of the paired medial nasal processes by week 6, giving rise to the premaxilla: central upper lip, maxillary alveolar arch and four incisor teeth, and hard palate anterior to the incisive foramen (8, 9).
A critical period is immediately before the formation of the primary palate and central lip, as the lateral nasal process undergoes a burst of mitotic growth. The soft tissue bridge spanning the cutaneous lip or alveolus in an incomplete cleft lip is termed Simonart’s band and consists primarily of skin with variable amounts of orbicularis oris muscle fibers (13). Histologic studies have shown that the degree of disorientation of muscle fibers near the cleft correlate with cleft severity (16).
Confounding between cigarette and alcohol use occurs frequently and their effects should be analyzed independently.
In order to achieve such goal, the repair should include the creation of an intact and appropriately sized upper lip to compensate for the loss of philtral height on the cleft side, repair of the underlying muscular structure for normal oral competence and function, and primary repair of nasal deformity (57). Lip adhesion cases ought typically be limited to patients in which maxillary segments are expanded without collapse, as the procedure will provide no benefit if the segments are medially collapsed. It subsequently became important to preserve and retract rather than excise the premaxilla so that the cleft lip repair may have the best esthetic result. Due to treatment variations, timing differences, and lack of normative data, the controversy regarding the use of pre-surgical orthopedics remains and the paucity of definitive clinical studies prevent the development of proven guidelines (62).
In bilateral cleft lip, the associated nasal deformity is a widened alar base and flattened nasal tip with a nearly absent columella. This concept, initially developed by Mirault, forms the basis for the modern rotation-advancement flaps, and the interdigitation of the triangular (Figure 3) (80, 81) or quadrangular flaps (82) to correct the cleft lip deformity (79). The versatility of the technique also relies heavily on the surgeon expertise and experience, as it allows a great amount of surgical judgment in order to achieve a good esthetic result (62). The surgeon is thus faced with the challenge of reconstructing the entire central portion of the lip with a deficient prolabium and abnormally displaced premaxilla. The surgical repairs may be made through the same incisions that are used for the cleft lip repair, so that the nasal deformity can be addressed simultaneously (90, 91). The single stage repair involves preoperative Latham device followed by cleft lip and nasal repair.
Animal studies have shown statistically significant effect on the cephalometric growth of the maxilla (96, 97). Recent changes in practices have led to some surgeons to advocate the use of modern medical adhesives as an adjunct technique for skin closure (101, 102).
Early studies have noted major complications for primary lip repair only are postoperative hemorrhage, breakdown of lip repair, pneumonia (4.3%), with minor complications as diarrhea, otitis media, partial separation of suture line, mild upper respiratory infection (58).
Different techniques are employed based on surgeon expertise and the unique patient presentations. Beyond the physical effects on the patient, CLP also has significant psychological and socioeconomic effects on both patient and family, including disruption of psychosocial functioning and decreased quality of life (QOL) (2, 3). During this period, development is highly vulnerable to genetic and teratogenic effects (7). The GENEVA Cleft Consortium study identified different distributions of IRF6 and ch8q24 genes in Europe and Asia, suggesting that associations may be population-specific (37). Pregestational diabetes, and to a lesser extent, gestational diabetes have been linked to non-cardiac defects including orofacial clefts (45).
Popliteal pterygium syndrome is a similar syndrome with orofacial clefting, lower lip pits, popliteal webs, and genitourinary anomalies. Many patients, especially in cases of wide clefts, will also require pre-surgical orthopedics for varying amounts of time to prepare the patient for definitive surgery (62). Despite this, the use of pre-surgical orthopedics remains widely used and many centers continue to promote the improved surgical and esthetic results from its use.
NAM devices reduce the alveolar gap and also include tape to bring the lip segments together and lengthen the columella, and nasal stents to help correct the nasal deformity (75).
The triangular flap technique is a repair utilizing the interdigitation of triangular flaps.
The rotation-advancement flap relies on extensive undermining of the soft tissue of the maxilla in order to close wide clefts, especially in cases without prior lip adhesion so that the technique may not be ideal for wide clefts. The surgical correction involves rim incisions with interdomal stitches between lower lateral cartilages and narrowing of the interalar distance. Clinical follow up, however, mostly fails to demonstrate appreciable effects on maxillary growth in children (95, 98). The same studies have shown that adhesives, like Dermabond, have offers equivalent mature wound cosmesis as traditional suture closure in the repair of cleft lip, and have the added benefit of avoiding additional dressing changes or suture removal under sedation (101, 102).
Later studies have noted complications related to bleeding, feeding difficulty, wound dehiscence, wound infection, pneumonia, respiratory compromise, and respiratory arrest (105–107). Pre-surgical orthopedics are frequently employed prior to definitive repair to improve outcomes.
It is associated with increased mortality from many causes, including suicide (4) as well as substantial healthcare costs (5).
The typical nasal deformity is displacement of the ipsilateral lateral crus of the alar cartilage laterally, inferiorly, and posteriorly. The list of candidate genes is long and includes VAX1 (37), FGFR2 (38), and BMP4 (39) among others. A recent meta-analysis showed that maternal age >40 years increased risk of CLP by 56% compared to maternal age between 20 and 29 years (46). Other syndromes linked to CLP include Stickler syndrome, Hardikar syndrome, Treacher-Collins syndrome, siderius X-linked mental retardation, Loeys–Dietz syndrome, and Malpuech facial clefting syndrome (56). In staged repair of severe incomplete or complete unilateral cleft lips, following the use of Latham device, one group found that pre-surgical lip adhesion provided increased thickness of the lateral orbicular oris muscle that aided in reconstructing the philtral ridge (67). Such techniques can include parental finger massage of the prolabium, tape pressure on the labial segments, intraoral device fixation, or nasoalveolar molding (NAM) (70).
Additionally, NAM contributes to improved definitive surgical repair and helps reduce the overall number of surgical procedures to correct the facial deformity (77). The concept underlying the technique can be similarly compared to a Z-plasty reconstruction of the lip.
In addition, the technique may occasionally sacrifice mucosa and lip tissue if the lateral lip segment has shorter vertical height. One noted report demonstrated functional closure of the lip significantly narrowed the transverse anterior cleft areas in early maxillary growth in patients with complete unilateral cleft lip and palate (99). Folate supplementation in early pregnancy has been found to reduce risk by one third (47) to three quarters (48), although not all studies have reported statistical significance (49). Injection of botulinum toxin into the orbicularis oris muscle preoperatively has recently been suggested as a means of reducing tension and thus improve outcomes in cleft lip repair (77).
The advantage of this technique is that it is based on careful measurements based on landmarks and thus has less room for surgical judgment and flexibility at time of surgery. Thus, the rotation-advancement flap does not contribute well to the ideal construction of the lip (62). Attempts to approximate the lateral lip segments and suture to segments to the prolabium skin without re-establishing the muscle would also produce an inferior result. Anthropometric analysis approximately 5 years post operatively found that nasal length, tip protrusion, and columellar width to be near normal values with symmetry of the lip and nose that were well preserved, validating the strength of the Mulliken procedure (93) in bilateral cleft lip and nasal deformity repair. Affected individuals may present with other congenital anomalies and may be part of a genetic syndrome. The protective effect varies between populations and this may reflect a strong genetic component in the folate metabolism pathway (50).
It has been described as having a similar effect to lip adhesion procedure, though its approach is less invasive (69). Crucial to the repair of the cleft lip is the reconstruction of the orbicularis oris muscle across the cleft. Mulliken (86) and Millard (87) advocated the re-establishment of orbicularis oris sphincter and addressing nasal deformity early on.
The columella is significantly shortened and deviates to the non-cleft side along with the caudal septum. Deficiency of zinc, an important element of neuronal migration, causes clefting in animals (51) and may increase risk in humans (52). Proper alignment of the orbicularis muscle will allow for appropriate sphincter function (57). In general, daily intake of multivitamins is recommended for all pregnant women due to potential benefits and minimal risks if taken properly (53). Limitations to the technique include the scar that is formed across the philtrum and the lack of flexibility (62, 79) as previously noted, no two clefts are the same and some measure of variability may often be required in achieving the intended esthetic result.
In order to accomplish this step, the orbicularis oris muscle must be freed from its attachments and aligned. Figures shown demonstrate a commonly used technique popularized by Mulliken, and is described in detail elsewhere (86) (Figure 5).
Complicated bilateral cleft repair would be an excellent example of the benefits of pre-surgical orthopedics or lip adhesion to aid in definitive surgical repair. Surveys of practicing physician have revealed that 45% will use a modified version of the rotation-advancement flap, with the most common being the Noordhoff vermilion flap, the Mohler modification, and the Onizuka triangular advancement flap, which will not be described here (83).



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