Search

Pre-emptive planning to optimize safety and outcome is a defining principle of pediatric craniofacial surgery, in which "procedures that come before" should enhance and not compromise procedures that are planned to follow.A technical modification of fronto-orbital advancement/remodeling in 2-stage hypertelorism surgery for craniofrontonasal dysplasia is presented, where orbital hypertelorism is accompanied by coronal craniosynostosis. Fronto-orbital advancement/remodeling undertaken by this approach preserves bone in the supero-lateral bandeau and provides optimal quality bone stock for the subsequent orbital box shift osteotomy. In this way the second procedure is protected and enhanced by optimal planning of the primary procedure, with potential benefits to safety, quality, and outcome of the final result.

Mutations in the progressive ankylosis protein (NP_473368, human ANKH) cause craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and widened metaphyses in long bones. The pathogenesis of CMD remains largely unknown, and treatment for CMD is limited to surgical intervention. We have reported that knock-in mice (Ank KI/KI ) carrying a F377del mutation in ANK (NM_020332, mouse ANK) replicate many features of CMD. Interestingly, ablation of the Ank gene in Ank KO/KO mice also leads to several CMD-like phenotypes. Mutations causing CMD led to decreased steady-state levels of ANK/ANKH protein due to rapid degradation. While wild type (wt) ANK was mostly associated with plasma membranes, endoplasmic reticulum (ER), Golgi apparatus and lysosomes, CMD-linked mutant ANK was aberrantly localized in cytoplasm. Inhibitors of proteasomal degradation significantly restored levels of overexpressed mutant ANK, whereas endogenous CMD-mutant ANK/ANKH levels were more strongly increased by inhibitors of lysosomal degradation. However, these inhibitors do not correct the mislocalization of mutant ANK. Co-expressing wt and CMD-mutant ANK in cells showed that CMD-mutant ANK does not negatively affect wt ANK expression and localization, and vice versa. In conclusion, our finding that CMD mutant ANK/ANKH protein is short-lived and mislocalized in cells may be part of the CMD pathogenesis.

Ocular hypertelorism was introduced by Greig as an increased interpupillary distance. The paranasal sinus mucoceles are acquired lesions for various reasons; however, their behavior is progressive, capable of eroding the bone and extending to the orbital and intracranial regions. The objective is to present a clinical case of orbital hypertelorism secondary to mucocele in the paranasal sinuses. This is a 72-year-old male patient who came presenting an increase in volume in the right nasoorbitoethmoidal region. The isodense lesion occupying the maxillary and right ethmoidal sinuses was confirmed by an intimate relationship with the ipsilateral frontal and sphenoidal sinus, with osteolytic involvement of the orbit and nasal region. After incisional biopsy with mucocele results, a wide resection plus facial reconstruction was performed with autologous grafts and osteosynthesis material. Currently, the patient has 1 year of evolution, without significant functional commitment. It is important to consider giant mucoceles as part of the differential diagnoses in patients with deformities in the middle and upper third of the face.

Cohesin is a chromosome-associated protein complex that plays many important roles in chromosome function. Genetic screens in yeast originally identified cohesin as a key regulator of chromosome segregation. Subsequently, work by various groups has identified cohesin as critical for additional processes such as DNA damage repair, insulator function, gene regulation, and chromosome condensation. Mutations in the genes encoding cohesin and its accessory factors result in a group of developmental and intellectual impairment diseases termed 'cohesinopathies.' How mutations in cohesin genes cause disease is not well understood as precocious chromosome segregation is not a common feature in cells derived from patients with these syndromes. In this review, the latest findings concerning cohesin's function in the organization of chromosome structure and gene regulation are discussed. We propose that the cohesinopathies are caused by changes in gene expression that can negatively impact translation. The similarities and differences between cohesinopathies and ribosomopathies, diseases caused by defects in ribosome biogenesis, are discussed. The contribution of cohesin and its accessory proteins to gene expression programs that support translation suggests that cohesin provides a means of coupling chromosome structure with the translational output of cells., (© 2015 The Authors. WIREs Developmental Biology published by Wiley Periodicals, Inc.)

Neurofibromatosis 1 is a complex inherited neurocutaneous disease that is often difficult to diagnose early because of its age-dependent presentation. The diagnosis is also extremely difficult to communicate to patients and their parents because of the disease's clinical variability, unpredictable evolution, and uncertain prognosis. Since 1988, the year of publication of the last Consensus Conference statement concerning the diagnosis of neurofibromatosis 1, our understanding of the disease has naturally increased and, in addition to the availability of increasingly precise molecular analyses, some new clinical signs have been reported such as anaemic nevi, unidentified bright objects, choroidal hamartomas, and a typical neuropsychological phenotype. We critically review the current diagnostic criteria, and suggest the addition of new signs on the basis of published findings and our own clinical experience. This proposal aims to improve diagnostic power in paediatric age, securing a better and more reliable healthcare transition toward adult age. We finally recommend a new Consensus Conference in order to revise the diagnostic criteria, possibly differentiated by age of presentation., (Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

This paper highlights features of dental rehabilitation of patients with Hamamy syndrome. A 10-year-old boy patient with Hamamy syndrome reported pain in the maxillary left central incisor, and all mandibular incisors. Intraoral clinical and radiographical examination showed enamel hypoplasia, severe dilacerated maxillary left central incisor and mandibular incisors, malocclusion, delayed eruption of teeth, taurodontism, and loss of lamina dura. Root canal treatment, strip crown and composite restorations were performed.

Dubowitz syndrome is a rare genetic condition characterized by microcephaly, dysmorphic facial features and delayed general growth. It is transmitted through autosomal recessive inheritance. The purpose of this report is to describe the oral, craniofacial and systemic characteristics of a 7-year 11-month-old boy with Dubowitz syndrome and the dental management provided. The pediatric dentist should possess the ability to recognize this rare alteration, to provide dental treatment and to refer for the necessary medical and multidisciplinary treatment.

Chromosome cohesion, mediated by the cohesin complex, is essential for the process of chromosome segregation. Mutations in cohesin and its regulators are associated with a group of human diseases known as the cohesinopathies. These diseases are characterized by defects in head, face, limb, and heart development, mental retardation, and poor growth. The developmental features of the diseases are not well explained by defects in chromosome segregation, but instead are consistent with changes in gene expression during embryogenesis. Thus a central question to understanding the cohesinopathies is how mutations in cohesin lead to changes in gene expression. One of the prevailing models is that cohesin binding to promoters and enhancers directly regulates transcription. I propose that in addition cohesin may influence gene expression via translational mechanisms. If true, cohesinopathies may be related in etiology to another group of human diseases known as ribosomopathies, diseases caused by defects in ribosome biogenesis. By considering this possibility we can more fully evaluate causes and treatments for the cohesinopathies.

Waardenburg Syndrome (WS) is a rare hereditary disorder that is characterized by the clinical manifestations of oculocutaneous anomalies of pigmentation, congenital deafness, dystopia canthorum, and broad nasal root. It demonstrates both genetically and clinically heterogenous characteristics. In this article, we report an 11-month-old boy with WS1, one of four clinicat types of WS. He exhibited white forelock, hypopigmented macules and patches, heterochromia irides, and dystopia canthorum.

Mutations in the MID1 gene are causally linked to X-linked Opitz BBB/G syndrome (OS), a congenital disorder that primarily affects the formation of diverse ventral midline structures. The MID1 protein has been shown to function as an E3 ligase targeting the catalytic subunit of protein phosphatase 2A (PP2A-C) for ubiquitin-mediated degradation. However, the molecular pathways downstream of the MID1/PP2A axis that are dysregulated in OS and that translate dysfunctional MID1 and elevated levels of PP2A-C into the OS phenotype are poorly understood. Here, we show that perturbations in MID1/PP2A affect mTORC1 signaling. Increased PP2A levels, resulting from proteasome inhibition or depletion of MID1, lead to disruption of the mTOR/Raptor complex and down-regulated mTORC1 signaling. Congruously, cells derived from OS patients that carry MID1 mutations exhibit decreased mTORC1 formation, S6K1 phosphorylation, cell size, and cap-dependent translation, all of which is rescued by expression of wild-type MID1 or an activated mTOR allele. Our findings define mTORC1 signaling as a downstream pathway regulated by the MID1/PP2A axis, suggesting that mTORC1 plays a key role in OS pathogenesis.

Paget disease of bone (PDB) and hyperparathyroidism (HPT) are metabolic osseous disorders which affect ≥2% of the population. As these diseases may share clinical, radiographic, biochemical, and histopathologic features, knowledge of their phenotypic overlap may provide diagnostic utility and improve clinical outcome. Scant information is available in the dental literature regarding patients concurrently affected with both pathologies. We present an unusual case report of a 63-year-old woman coaffected with primary HPT, attributed to a functional oxyphilic parathyroid adenoma, and PDB. Bone scintigraphy revealed pagetoid lesions of the skull, humeral head, spine, sacrum, and hemipelvis. Salient craniofacial features noted were bony involvement of the calvarium and midface, resulting in extensive maxillary overgrowth, hearing loss, telecanthus and consequent visual impairment, nasal deformity, and leontiasis ossea. The patient underwent a partial parathyroidectomy and bisphosphonate administration was to be initiated upon extraction of the remaining dentition., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Introduction: This research was conducted in view of the importance of anthropometric indices of the head and face in forensic medicine, surgery, paediatrics and medical imaging. This study was put forward to determine some of the effects of chronic diseases on head and face of children with homozygous sickle cell disease., Method: A comparative study on canthal and cephalic indexes were carried out on 100 patients, 54 males and 46 females who are homozygous for sickle cell anaemia, who attended the sickle cell clinic at the University of Port-HarcourtTeaching Hospital between the age ranges of 3-18 years. The same was also done for 500 normal growing children 291 males and 209 females between ages 3-18 years who are pupils of the University Kindergarten, Demonstration Primary and Secondary Schools as well as First International Academy Secondary School, Rumuokoro, Port Harcourt. The head length, head breadth, inner and outer canthal distances measured. The results showed a mean cephalic index value of 79.89 +/- 0.87 for the normal growing children while that of the sickle cell children was 79.54 +/- 2.14, which is not statistically significant (P>0.05). The mean canthal index for healthy children was 35.16 +/- 1.01 as against 37.28 +/- 1.65 for the sickle cell children, which is statistically significant., Conclusion: This research determined the possible effects of chronic diseases such as sickle cell anaemia on the diversity of head and face shapes in children.

In treating trigonocephaly, the value of direct surgical correction of orbital hypotelorism is controversial. In many cases of hypotelorism, the distance between the orbits increases over time after traditional fronto-orbital advancement. Still, more severe hypotelorism is not fully corrected and may benefit from a more definitive surgical intervention. We describe an in situ fronto-orbital advancement that improves severe hypotelorism and simplifies the surgical treatment of trigonocephaly. The key modification to traditional fronto-orbital advancement is an in situ medial orbital osteotomy that extends along the medial orbit, posterior to the medial canthus, and then across the inferior orbital rim into the piriform aperture. The procedure is indicated only in patients with more severe hypotelorism on physical examination. Rather than creating a freely removable bandeau during the operation, the bone segment composed of the supraorbital bar and superior orbits remains attached at the medial canthi. A midline osteotomy allows the respective orbital segments to be independently mobilized with the medial canthi left attached, and the space between them widened with gentle lateral traction and placement of an interpositional bone graft. Concomitantly, the lateral orbits and lateral supraorbital bar are contoured, advanced, and fixed with resorbable plates and screws. Representative results are shown. In situ fronto-orbital advancement with medial orbital osteotomies is a safe, efficient, and relatively simple technique that results in immediate improvement of hypotelorism and may be a worthwhile maneuver to consider in selected cases.

There are significant differences in the ocular manifestations of Apert and Crouzon syndromes. Here, we present qualitative and quantitative data about the oculo-orbital region to demonstrate these differences. Although ocular protosis and hypertelorism characterize both disorders, the nature of the orbital dystopia differs. In Crouzon syndrome, ocular proptosis is primarily caused by retrusion of the lateral and inferior orbital margins with a very short orbital floor. In Apert syndrome, the eyeglobe actually protrudes in relation to the cranial base and to the orbit, probably resulting from marked protrusion of the lateral orbital wall. The implications account for some of the differences encountered. Asymmetry is associated with Apert syndrome frequently. Exotropia is found in Crouzon syndrome, whereas the V pattern is more characteristic in Apert syndrome with divergent upgaze and esotropic downgaze. Subluxation of the eyeglobe is found in some cases of Crouzon syndrome but is not found in Apert syndrome. Optic atrophy found in approximately 20% of Crouzon syndrome patients is not characteristic of Apert syndrome. Structural alterations of the extraocular muscles have been associated with some cases of Apert syndrome, suggesting that ocular motility disturbances in Apert syndrome may not be caused solely by mechanical factors. Absence of the superior rectus and other extraocular muscles has been recorded. Furthermore, albinoid alterations of the fundus have also been associated with Apert syndrome.

Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele. We report a case of a 4-month-old male baby, who was referred to our institute with the complaints of decreased vision. This is the first report from Northeastern part of India as per our knowledge.

Craniometaphyseal dysplasia (CMD) is a rare genetically transmitted bone dysplasia characterized by alterations in the development of the craniofacial bones with abnormal remodeling of the metaphyses. Sclerosis of the skull bones can lead to cranial nerve compression that finally may result in hearing loss and facial palsy. CMD occurs in an autosomal dominant (AD) (MIM 123000) and an autosomal recessive (AR) form (MIM 218400). Sclerosis of cranial bones is usually much more severe in the AR form. We present a 36-year-old male with a previous diagnosis of Paget disease. The examination reveals prognathism, ocular hypertelorism, mixed bilateral hypoacusia, nasal bossing, a class III malocclusion and a narrow palatal vault. The patient necessitated several dental extractions, surgical procedures were conducted, and a biopsy of the alveolus was performed and the sample underwent histological examination. The histological report led to an exclusion of the previous diagnosis of Paget disease. The final diagnosis of autosomal dominant CMD was confirmed by the molecular testing of the CMD gene (ANKH).

Objective: To summarize and analyze the diagnosis, treatment protocol, and therapeutic effect of orbital hypertelorism in the past 30 years in our center., Methods: This retrospective study reviews the records of 128 patients from 1978 to 2008. Both radiologic measurements, such as the interorbital distance and the outer orbital distance, and anthropometric measurements, such as the width of the inner canthi (W-IC), the width of the palpebral fissure, the width of the face, and the nasofrontal angle, were conducted before and after the operation to evaluate both osseous and soft tissue alteration. An analysis of the etiology, surgical method, and complication has been undertaken., Results: The main cause of orbital hypertelorism in our center was craniofacial cleft. Significant improvement in cranio-orbital appearance was noted, and 91.4% of the patients were satisfied with the surgical correction. Follow-up examinations showed a statistically significant difference between preoperative and postoperative measurements: interorbital distance; outer orbital distance; facial ratios W-IC/width of the palpebral fissure and W-IC/width of the face (P < 0.01); and nasofrontal angle (P < 0.05). Temporary complications and side effects remained low, with cerebrospinal fluid leakage occurred as the major complication (6.3%)., Conclusion: There are several important protocols regarding the management of orbital hypertelorism that will provide patients with great benefit in achieving more aesthetic facial appearance.

Apert's syndrome is a rare form of craniosynostosis that exhibits with many ocular manifestations. We present two cases of Apert's syndrome. Our first case is a 10-year-old girl admitted with exotropia, V pattern and proptosis on examination. Investigations revealed coronal craniosynostosis, cleft palate, vaginal atresia and syndactyly of the hands and feet. The second case is a 5-year-old boy presented with hypertelorism, exotropia, dissociated vertical deviation and proptosis. Investigations revealed coronal craniosynostosis, bifid uvula and syndactyly of the hands and feet.

The objective of the study was to compare the craniofacial characteristics of children with operated unilateral complete cleft lip and palate (UCLP) with those of noncleft children. Lateral and posteroanterior cephalometric radiographs of subjects with UCLP and controls who were matched for sex, age, and ethnic origin were analyzed and compared. There were a total of 21 subjects with UCLP (10 boys and 11 girls) from the Orthodontic Department of Selcuk University and 15 controls (7 boys and 8 girls) from the Orthodontic Department of Ankara University. The nasal bone length in the group with cleft did not differ significantly from that in the control group. Subjects with UCLP included in the study appeared to have shorter faces, smaller mandibulae, greater lateral orbital width, and smaller sella turcicae compared with controls. Unilateral cleft lip and palate affects the intracranial morphology as well as dentofacial structures.

The Greig cephalopolysyndactyly syndrome (GCPS) is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1-9/1,000,000). The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome. Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above) and a GLI3 mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform. Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. Treatment of the disorder is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations. The prognosis for typically affected patients is excellent. There may be a slight increase in the incidence of developmental delay or cognitive impairment. Patients with large deletions that include GLI3 may have a worse prognosis. The Article is a work of the United States Government. Title 17 U.S.C 5 105 provides that copyright protection is not available for any work of the United States Government in the United States. The United States hereby grants to anyone a paid-up, nonexclusive, irrevocable worldwide license to reproduce, prepare derivative works, distribute copies to the public and perform publicly and display publicly the work, and also retains the nonexclusive right to do all of the above for or on behalf of the United States.

Enophthalmos is defined as a backward, and usually downward, displacement of the globe into the bony orbit. In posttraumatic enophthalmos, the mechanisms that determine globe position are: 1) the enlargement of the orbital cavity; 2) the herniation of orbital fat into the maxillary sinus; and 3) fat atrophy, loss of ligament support, and scar contracture. The aim of this article is to analyze the strategies to prevent enophthalmos and to correct late posttraumatic enophthalmos. In this study, 80 patients (52 cases of orbitozygomatic fractures and 28 late posttraumatic enophthalmos) were treated between January 1998 and January 2005. Fracture reduction in primary enophthalmos was performed. In enophthalmos as sequelae, the treatment consisted of orbital reconstruction in combination with bone grafts harvested from calvaria, iliac crest, and/or orbital osteotomies. In some cases, biomaterials were also used. All these techniques may also be combined depending on the severity of enophthalmos. The results were satisfactory in all cases. It is evident that a perfect correction of the deformity is difficult to achieve. Often soft tissue changes limit the aesthetic and morphologic results, despite adequate bony reconstruction.

Background: Orbital hypertelorism is defined as a lateralization of the total orbit. This condition is associated almost always with congenital abnormalities. An acquired total displacement of the orbit is almost impossible once the bony pillars of the craniofacial complex are established. The aim of this article was to discuss a case of a young man with paranasal sinus mucocele, who developed OHT., Case Description: A 20-year-old man was admitted to us with orbital hypertelorism in 1993. The patient's examination revealed marked orbital hypertelorism, and no other abnormal finding was noted, and he had no congenital defect at birth. Hypertelorism was corrected by surgery, and we find that this condition was acquired secondary to paranasal sinus mucocele., Conclusion: This is the second case of an acquired OHT secondary to paranasal sinus mucocele and the first in which the condition was corrected by surgery in late years of life. We found excellent correction of orbital hypertelorism 13 years after surgery. The authors discuss the possible link between mucocele and possible mechanism for the development of orbital hypertelorism and emphasize the need for early surgery and long-term follow-up.

It is unclear whether Filipinos with sincipital encephaloceles have true orbital hypertelorism or just telecanthus. Knowing this determines whether orbital osteotomies or medial canthoplasty are more appropriate corrective procedures. To evaluate this, 56 sequential Filipino sincipital encephalocele patients (28 female and 28 male, average age 66.6 months, age range 4 days to 21.8 years) were evaluated for orbital width. Soft tissue measurements of inner and outer canthal position and CT measurements of medial and lateral orbital wall position were obtained. Normative data curves by age and sex for orbital bony and soft tissue distances in normal Filipino children were developed. Data was plotted on these curves and analyzed to determine if encephaloceles were associated with medial widening alone or true hypertelorism. Inner canthal measurements for male were approximately +2.8 standard deviation (SD) and female +2.3 SD wider than average. Medial orbital wall dimensions were wider for male +1.5 SD and female +1.4 SD. Lateral orbital measurements for both male and female clustered around the normative mean (males -0.5 SD and females -0.8 SD). Female outer canthal measurements also clustered around the normative mean (+0.6 SD wider) while male outer canthal measurements averaged approximately +1.1 SD wider than mean. As expected, measurements were wider medially when compared to normative data. However, lateral bony and soft tissue widening was minimal or approached normative averages. This suggests the problem is medial widening only and less invasive procedures such as medial canthoplasty or nasal bony contouring may be the most appropriate surgical management.

Objective: To establish a rabbit model of orbital hypertelorism for plastic and reconstructive surgery and evaluate the surgical effects., Methods: Orbital osteotomies and medial translocation was performed in 16 New Zealand rabbits (4 to 6 months old) by combined intracranial-extracranial approach. The interorbital distance (IOD) and bone healing between the orbits were evaluated with gross measurement. X-ray and histological examinations were performed immediately and 12 weeks after the operation., Results: The average IOD of the rabbits was 0.74 cm after completion of the operation, but increased to 0.96 cm 12 weeks after the operation, showing significant relapse of orbital hypertelorism (P<0.01)., Conclusion: The IOD can be decreased successfully in this rabbit model.

We report on two cases (daughter and father) with Greig cephalopolysyndactyly syndrome (GCPS). The clinical manifestations in craniofacial structure, hands and feet are described. We found marked phenotypic variability in these family members with GCPS over the hands and feet. Our patients were seen to have higher rate of feet postaxial polydactyly both clinically and radiologically; they had lower rate of clinical postaxial polydactyly over hands, with feet preaxial polydactyly both clinically and radiologically compared to previous review articles covering 52 cases. Multiple linkage analysis showed one proposita's parental mutant allele was transmitted to the proposita when using linkage mapping set spanning 7p. Some review of the literature is also given, with emphasis on the clinical signs and symptoms of the Greig cephalopolysyndactyly syndrome.

Craniometaphyseal dysplasia is a rare bone disorder of unknown etiology characterized by overgrowth of the skull base or craniofacial bones and abnormal remodeling of the metaphyses of the long bones. We present a sporadic case of craniometaphyseal dysplasia associated with facial paralysis observed in a 4-year-old female, which emphasizes the importance of the early detection of accompanying lesions.

Ameloblastic fibroma is a rare true mixed tumor of odontogenic origin with both mesenchymal and ectodermal components. It usually arises from the mandibular dentition and presents in the second decade of life. It is a benign slow growing tumor that is less infiltrative than an ameloblastoma but tends to expand bone. It infrequently involves the maxilla and hence the management of these tumors in that region is controversial. The goal of therapy is to avoid cosmetic deformity without compromising on tumor eradication. We present the tenth reported case of this type of tumor in the maxilla, and the second one in an infant.

Background: Arytenoid hypertelorism (arytenoid cartilages spaced too widely apart) appears to be the most common initial recognizable physical finding of cricoid chondrosarcoma. Nine cases from the Center for Voice Disorders are presented. With arytenoid hypertelorism caused by cricoid chondrosarcoma, usually the posterior larynx is open. In fact, patients with arytenoid hypertelorism caused by cricoid chondrosarcoma may be aphonic even though the anterior membranous vocal folds make contact during attempted phonation., Methods: Between 1991 and 2002, nine patients were diagnosed with cricoid chondrosarcoma. Patients' charts and video examinations were retrospectively evaluated for symptoms and the presence of arytenoid hypertelorism on endoscopic evaluation. Two were women, and seven were men, with a mean age of 70 (range 53-72) years at diagnosis., Results: Eight (88%) patients had aphonia or dysphonia caused by arytenoid hypertelorism as their presenting symptom. Six were diagnosed after failed medialization laryngoplasty or other laryngeal rehabilitation surgery. All nine patients had a low-grade tumor. The initial treatment in eight patients was hemicricoidectomy, and one patient had a total laryngectomy. In four cases, a second procedure was needed 1 to 6 years later because of recurrence. Seven patients are alive without clinically significant disease; one is alive with moderate disease, and one has died from an unrelated cause., Conclusions: Severely dysphonic, elderly patients presenting with arytenoid hypertelorism of unknown cause should be evaluated by fiberoptic laryngoscopy and by computed tomography scan to rule out cricoid chondrosarcoma. Because these tumors behave so benignly, the authors recommend conservative surgery (unilateral hemicricoidectomy) as the diagnostic/treatment modality of choice.

Frontoethmoidal encephaloceles are herniations of the intracranial contents through a defect in the skull at the junction of the frontal and ethmoidal bones. They are generally classified as nasofrontal, nasoethmoidal, and naso-orbital, although there may be some overlap or multiplicity. The records of 35 patients treated for frontoethmoidal encephaloceles were examined. Of these, 12 cases with complete and accurate medical records were evaluated in detail. The successful correction of frontoethmoidal encephaloceles was shown to depend on the following: a detailed understanding of the pathological anatomy (such as interorbital hypertelorism rather than true orbital hypertelorism and the presence of secondary trigonocephaly), careful planning of the bone movements to correct these deformities, and attention to detail regarding the placement of scars, positioning of the medial canthi, and the nasal reconstruction. Avoiding the "long-nose" deformity often seen after repair should be a priority. In general, the authors recommend a one-stage repair with both a transcranial and external approach.

Background: On basis of clinical observation paediatricians in Kinshasa had the impression that children with homozygous sickle cell disease have a special face characterised by hypertelorism., Objective: The purpose of the study is to determine outer orbital, inner canthal and interpupillary distances as well as proptosis in children with sickle cell disease., Methods: These measurements were performed on 66 Congolese children with homozygous sickle cell disease, aged from 2 to 18 years. The measurements were performed with the Hertel exophthalmometer for the proptosis and the outer orbital distance, with the pupillometer model PD-2 meter for the interpupillary distance and with a ruler for the inner canthal distance. The results were compared with those of 95 healthy children of similar age., Results: All measurements were age related. In every age group the values for inner canthal distance were identical to those of healthy children, but the interpupillary, the outer orbital distances and the proptosis were significantly smaller., Conclusions: A slow growth of orbital tissue in children with homozygous sickle cell was suggested to explain the difference with healthy children. Other biometric studies comparing the orbital measurements with the rest of the body are needed to confirm or refute this hypothesis.

We report on a boy with congenital pure red blood cell aplasia [Diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.

Craniofrontonasal dysplasia (CFND) is a rare X-linked disorder that maps to a 13-cM region on Xp22. Phenotypic features include craniosynostosis, hypertelorism and a broad nasal root with or without a bifid nasal tip. Multiple examples have been reported of males having a less severe phenotype than females. We report haplotype analyses in two CFND families over the critical region to which the gene has been mapped. In pedigree 1, a clinically unaffected male inherited the affected marker haplotype spanning the critical region. We suggest that this individual does have the CFND mutation, but has an extremely mild phenotype that is not detectable with clinical examination. Under the assumption that he is an unknown phenotype, a combined two-point LOD score of 1.68 at zero recombination was obtained, increasing the previously reported total to 5.61 (DXS8022). The data do not narrow down the critical region. This result stresses the importance of subjecting fathers of apparently sporadic cases to a highly critical medical examination and may also explain the unequal ratio of reported female-to-male cases.

The surgical treatment of a very large anterior encephalocele in an infant is presented. Because of the large size of the encephalocele, a combined transfacial-transcranial approach was used for correction of the associated intracranial, cranioorbitonasal bone, and facial skin deformities.

Frontoethmoidal encephaloceles are congenital malformations that cause complex deformities in the frontal, orbital, and nasal regions. As the term implies, with frontoethmoidal encephaloceles, intracranial material has herniated through the dural and skull defect. In this report, 21 patients with frontoethmoidal encephalocele operated by a craniofacial team are presented, and accompanying anomalies, results, and complications are discussed.

Normal pre- and post-natal changes in the interorbital distance are described. Causes of illusory hypertelorism include flat nasal bridge, epicanthic folds, exotropia, widely-spaced eyebrows, narrow palpebral fissures, and dystopia canthorum. Measurements of hypertelorism may involve soft tissues or bone, and a number of indices have also been proposed. Various types of measurements are evaluated and recommendations suggested. Possible pathogenetic mechanisms for hypertelorism include: early ossification of the lesser wings of the sphenoid; failure in nasal capsule development allowing the primitive brain vesicle to protrude into the space normally occupied by the capsule resulting in morphokinetic arrest in the position of the eyes; and disturbances of the cranial base in Apert syndrome. Associations with increased interorbital distance are also discussed: orofacial clefting, nonprotruding lipomas of the corpus callosum, calcification of the falx cerebri, duplication of the crista galli, wrinkling of the nose, and tissue tags of the nose. Finally, experimental models of hypertelorism in animals are discussed.

We describe two malformed infants whose mothers had cervical dilation and uterine curettage. One mother had the procedure at 8 weeks and the other at 6 weeks of gestation. One infant had a facial cleft, hypertelorism, scalp defects, brain malformations, and absent fingernails and a constricting band on the fourth and fifth fingers. The other infant had an area of diminished scalp hair, vertebral anomalies, and a heart defect.

A retrospective statistical analysis of orbital hypertelorism correction was performed by comparing the preoperative and postoperative intercanthal distances of these patients with published age-matched normal values. Forty-five patients who had undergone surgery over a 15-year period with an average follow-up of 5 years (6 months to 14 years) were evaluated. Comparison of age-normalized preoperative and postoperative intercanthal distances revealed a significant difference for orbital hypertelorism patients as a group (p < 0.0001), patients with clefts (p < 0.0001), patients with nasoencephalocele (p < 0.01), and patients with frontonasal dysplasia (p < 0.05), but not for those patients with craniofacial dysostosis (p < 0.20). Multiple analyses of variance revealed a significant interaction existing between the extent of preoperative deformity and the cause of hypertelorism for both the postoperative deformity and the total amount of correction achieved, but not for the type of surgery or for the age at which the surgery was performed.

In 34 patients with hypertelorism aged on the average 12.6 years, 24 underwent intracranial surgery (combined intra- and extracranial approach), 2 (moderate) U-osteotomy (subcranial approach), and 8 (mild) canthoplasties. Improved results were obtained in the patients with various types of hypertelorism. The complications were reviewed. Of the 24 patients undergone intracranial surgery, one died, 4 had cerebrospinal fluid leakage, and 4 had keratitis. No seizure, cerebral edema, meningitis, blindness, and ptosis were observed in these patients. Average blood loss was 72% of blood volume. Average duration of surgery was 7.5 hours. The causes of hypertelorism such as craniofacial cleft, craniosynostosis, frontoethmoidal meningoencephalocele, frontonasal fibrous dysplasia, and trauma were also discussed. Satisfactory appearance was seen in most of the patients.

Noonan syndrome is a genetic condition inherited in an autosomally dominant manner, characterised by congenital heart disease, short stature, abnormal facies and the somatic features of Turner's syndrome, but a normal Karyotype. The ophthalmological and orthoptic findings on 58 patients with Noonan syndrome are reported. External features were hypertelorism (74%), downward sloping palpebral apertures (38%), epicanthic folds (39%) and ptosis (48%). The orthoptic examination revealed strabismus in 48%, refractive errors in 61%, amblyopia in 33%, and nystagmus in 9% of cases. Sixty-three per cent of cases had anterior segment changes consisting of: Prominent corneal nerves (46%), anterior stromal dystrophy (4%), cataracts (8%) and panuveitis (2%). Fundal changes occurred in 20% of the study group, including optic nerve head drusen, optic disc hypoplasia, colobomas and myelinated nerves. Forty-seven per cent required non surgical treatment and a further 16% had undergone surgery for strabismus or ptosis. Only three patients had no visual defects. With such a high incidence of ophthalmic abnormalities it is clearly important that children with Noonan syndrome are screened by an ophthalmologist at an early age.

In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness.

This investigation was designed to test hypothesized pathogenetic mechanisms for orbital hypertelorism (OrH). Serial measurements of bony interorbital distance (BIOD), level of cribriform plate relative to orbital height (LOCP), and cranial width (CW) were made from postero-anterior cephalometric radiographs on two pathologic groups craniofacial clefts (FC) and premature craniofacial synostosis syndromes (PCS) compared with normal controls matched for age and sex. Both groups of malformations showed significantly larger mean values (P less than 0.01) for BIOD alone and when adjusted for CW. The LOCP relative to the orbital height was found to be positioned at a significantly lower level (P less than 0.01) than the norm in both groups. When the growth increments for BIOD were plotted to analyze rates of growth, individuals with FC showed increments similar to those seen for the normal. However, patients with Apert and Crouzon syndromes showed greater than normal increments for BIOD. In these cases, the LOCP remained at a relatively lower level in relation to orbital height. These findings support the hypothesis of a time-specific event during fetal development causing morphokinetic arrest in FC syndromes. In Apert and Crouzon, another mechanism continuing postnatally produces OrH.