Hemifacial microsomia: use of the OMENS-Plus classification at the Royal Children's Hospital of Melbourne

Hemifacial microsomia is the most common facial congenital disability after cleft lip and palate, but as yet its pathogenesis remains unknown. Clinical classification systems have evolved over the last 30 years from those classifying only single components of the disorder, to those classifying according to the combination of deformities, to the most recent systems that grade each anatomical component separately, such as the Orbit, Mandible, Ear, Nerve, and Soft tissue (OMENS) system. The aim of the present study was to review the classification of patients with hemifacial microsomia treated by the Melbourne Craniofacial Unit at the Royal Children's Hospital using the OMENS-Plus system of classification and to correlate the findings with data from other centers. Records of patients treated by the craniofacial unit were reviewed and included in the study if adequate clinical records, photographs, and radiographs (anteroposterior, lateral, basal cephalometry, panoramic views) were available. The data were entered into a database file developed for this purpose. Seventy-one patients were identified from the hospital database, of which six were excluded because of incomplete data. Of the 65 patients, there were 31 (48 percent) with right-sided microsomia, 25 (38 percent) with left-sided microsomia, and nine (14 percent) with bilateral microsomia, with an overall male-to-female ratio of 1.2:1. The majority of patients had a normal orbit (77 percent), mildly hypoplastic mandibular ramus-condyle with functioning temporomandibular joint (57 percent with type M1 or M2a), normal facial nerve (76 percent), and mild soft-tissue hypoplasia (73 percent). There was a similar proportion of patients with mild ear anomalies (53 percent with grade 0 or 1) compared with those with more severe anomalies (47 percent with grade 2 or 3). Correlative analysis demonstrated a slight but positive correlation between the severity gradings of the five individual components. The correlation was lowest between the grading of the nerve and ear and that of the mandible and nerve. The data demonstrate the phenotypic variability of hemifacial microsomia and suggest a degree of relationship among the components of hemifacial microsomia. The OMENS-Plus system has provided a major advancement in the classification of hemifacial microsomia. The authors suggest refinements to the grading of the orbit and nerve components.     

Hemifacial microsomia: progress in understanding the genetic basis of a complex malformation syndrome

Hemifacial microsomia (HFM) is a common birth defect involving first and second branchial arch derivatives. The phenotype is extremely variable. In addition to craniofacial anomalies there may be cardiac, vertebral and central nervous system defects. The majority of cases are sporadic, but there is substantial evidence for genetic involvement in this condition, including rare familial cases that exhibit autosomal dominant inheritance. As an approach towards identifying molecular pathways involved in ear and facial development, we have ascertained both familial and sporadic cases of HFM. A genome wide search for linkage in two families with features of HFM was performed to identify the disease loci. In one family data were highly suggestive of linkage to a region of approximately 10.7 cM on chromosome 14q32, with a maximum multipoint lod score of 3.00 between microsatellite markers D14S987 and D14S65. This locus harbours the Goosecoid gene, an excellent candidate for HFM based on mouse expression and phenotype data. Coding region mutations were sought in the familial cases and in 120 sporadic cases, and gross rearrangements of the gene were excluded by Southern blotting. Evidence for genetic heterogeneity is provided by the second family, in which linkage was excluded from this region.     

Hemifacial deficiency induced by a shift in dominance of the mouse mutation far: a possible genetic model for hemifacial microsomia

Hemifacial deficiency appeared in 10% of juvenile mice when BALB/cGaBc mice carrying the recessive lethal mutation far were crossed with ICR/Bc. The hemifacial deficiency increased to 15-20% after one backcross to ICR/Bc and then remained at that level for 11 additional generations of backcrossing of far into ICR/Bc. Neither the ICR/Bc strain nor BALB/cGaBc (+/far) produces hemifacial deficiency. Genetic and anatomical studies of adults and fetuses showed that the hemifacial deficiency was due to +/far in the ICR/Bc strain genome; that is, far becomes an incomplete dominant in the ICR/Bc strain background. The hemifacial deficiency (38% of +/far) is probably caused by premature synostosis of the maxilla and premaxilla, observable on day 16 of gestation. An additional 20% of +/far in ICR/Bc have cleft palate and die at birth. Most +/far in both strains have a hidden anomaly, bilateral splitting of the maxillary branch of the trigeminal nerve. far/far homozygotes of both strain backgrounds have a syndrome of severe bilateral deficiency of the derivatives of the maxillary prominence. In human pedigrees, where the equivalents of the dominance modifiers in BALB/cGaBc and ICR/Bc would segregate within families, it would be difficult to recognize that sporadic hemifacial deficiency and severe bilateral maxillary deficiency were due to the same gene. We suggest that human bilateral and unilateral abnormalities of tissue derived from the first branchial arch should be analyzed with the awareness that, in mice, at least, the two kinds of syndrome are due to the same mutant gene.     

Craniofacial changes in hemifacial microsomia

Cephalometry, X-ray cephalometry, and somatoscopy were used in the studies of 65 adult males with a severe unilateral microtia subdivided into three groups: with marked asymmetry, with slight asymmetry, and without any obvious facial asymmetry. The group with marked asymmetries was designated as hemifacial microsomia. In this group the affected side of the face was depressed on the average from above and from below towards the level of the external auditory canal. The center of the anteroposterior reduction was situated in the region in front of the pterygomaxillar fissure. The anteroposterior and vertical facial dimensions on the affected side were reduced most markedly, while the width dimensions showed the slightest changes. Hypoplasia was most severe within the lower face and increased towards the otocephalic centre. The mandibular joint was displaced in an anteroinferior and medial direction. Hypertelorism did not occur, but the orbit on the affected side was smaller in height and was frequently vertically dislocated. The facial profile was unchanged except for retrusion of the chin and increased frequency of bite disorders. The mobility of the mandible was limited. Hemihypoplasia also exerted an influence on structures that were not of branchiogenic origin, e.g., the cranial base (narrowing, asymmetry, and more pronounced curvature), the neurocranium (depression in mastoid and tympanotemporal regions, posterior rotation of the vault), and the frontonasal component (deviation of the nose and premaxilla). The cranial vault and the bottom of the occipital bone showed on the average no asymmetries. The similar character of deviations in slightly affected groups revealed that in spite of the high variability of changes typical for branchiogenic malformations the development of the face in these defects was subjected to certain rules. Marked facial asymmetry occurred only in every fifth patient with a severe degree of microtia, while definite signs of asymmetry were absent in every third patient.     

Genetic aspects of hemifacial microsomia

Summary The majority of patients with hemifacial microsomia (HM) including Goldenhar syndrome are sporadic cases. The sporadic nature of this disorder is emphasized by the discordant occurrence of HM in one of female monozygotic twins reported here. Previous publications, however, also suggest autosomal dominant and autosomal recessive modes of inheritance. Possible formes frustes will also have to be considered when giving genetic counsel.     

Microsurgical Treatment of Hemifacial Spasm

Five cases of idiopathic hemifacial spasm have been successfully treated by operative manipulation of arterial branches compressing the VIIth nerve in the posterior fossa. Terminology, clinical presentation, pathology and therapeutic approaches to hemifacial spasm are discussed. Hearing loss due to operatively induced vascular impairment of the inner ear, a complication in our first case, should be avoidable.Our experience indicates that hemifacial spasm reflects mild chronic compression of the facial nerve. The proposed mechanism is transaxonal excitation between afferent and efferent fibers.     

Gulf War veterans and hemifacial microsomia

BACKGROUND: Concerns have been raised that more infants with Goldenhar syndrome were born to U.S. Gulf War veterans than expected. Goldenhar syndrome is considered a variant of the malformation hemifacial microsomia (HFM). We used data collected from a case-control study of HFM to estimate risk in relation to parental military service and, in particular, Gulf War service. METHODS: Cases with HFM who were three years old or younger were identified at craniofacial clinics in 24 U.S. cities and matched to controls by age and pediatrician. The mothers of 232 cases and 832 controls were interviewed between April 1996 and November 2002 about pregnancy events and exposures, including military service before the child was born and Gulf War deployment five to 11 years before the child was born. Odds ratios were adjusted for family income, race, and body mass index in early pregnancy. RESULTS: Four (1.7%) case mothers and 10 (1.2%) control mothers served in the military. Among fathers, 30 (12.9%) cases and 100 (12.0%) controls served in the military. The parents of four (1.7%) cases and 23 (2.8%) controls served in the Gulf War (multivariate adjusted odds ratio [MVOR], 0.8; 95% confidence interval [CI], 0.3-2.3). All four case parents with Gulf War service were in the Army compared to 9 of 23 control parents. The MVOR for parental Gulf War service in the Army was 2.8 (95% CI, 0.8-9.6). The corresponding MVOR for any parental service in the Army was 2.4 (95% CI, 1.4-4.2), based on 22 cases and 45 controls. CONCLUSIONS: The risk of HFM in offspring was not associated with parental service in the Gulf War five to 11 years before birth. The odds ratio for service in the Army was independent of Gulf War service and was associated with a modest increase in risk. Our findings for service in the Army may be confounded by unmeasured lifestyle factors.     

Analysis and treatment of hemifacial microsomia

Our experience over the past 25 years leads us to conclude that hemifacial microsomia is a progressive skeletal and soft-tissue deformity with the earliest skeletal manifestations in the mandible. We find that not only does the mandibular asymmetry become worse with time, but as the contralateral side grows, the deformed mandible also increases ipsilateral secondary deformation of the maxilla, nose, and orbit. We also find that there is virtually no "catch up" growth on the affected side of the face and that these patients always become more deformed with age. The psychological problems also increase with time and progression of the facial deformity. Based on our experience with correction of end-stage deformities, we now treat these patients at the earliest possible age, as determined by the patient's skeletal classification. We treat the mandible first in the hope that this repositioning in a more physiologic position will unlock the growth potential of the adjacent structures, minimize secondary deformity, and improve function and appearance to the greater benefit of the skeletal and psychological growth of the patient.     

Progression of facial asymmetry in hemifacial microsomia

Hemifacial microsomia is a common craniofacial anomaly, variably affecting structures derived from the first and second pharyngeal arches. Correction of the skeletal deformity in children has been advocated to improve growth potential and reduce secondary deformity. However, contrary reports have suggested that facial asymmetry in hemifacial microsomia does not increase with growth; therefore, skeletal correction can be postponed, even until adolescence. The purpose of this study was to test the hypothesis that facial asymmetry in hemifacial microsomia is progressive. This is a retrospective evaluation of 67 patients with untreated hemifacial microsomia. The patients were categorized as: group I (mandible type I, IIa), n = 38, and group II (mandible type IIb, III), n = 29. Pretreatment posterior-anterior cephalometric radiographs were used to analyze asymmetry by measuring the angle between the true horizontal and the following planes: piriform rim, maxillary occlusal plane, and intergonial angle. Angular measurements were averaged for patients in the deciduous (<6 years), mixed (> or =6<13 years), and permanent dentition (> or =13 years). In group I, angle piriform rim, maxillary occlusal plane, and intergonial angle increased from 7.0, 4.3, and 4.4 to 8.4, 6.6, and 6.1 degrees, respectively [mean age, 4.1 (deciduous) to 8.6 (mixed) to 21.0 (permanent) years]. In group II, angle piriform rim, maxillary occlusal plane, and intergonial angle increased from 9.5, 6.2, and 5.3 to 11.7, 7.6, and 8.0 degrees, respectively [mean age, 3.4 (deciduous) to 8.0 (mixed) years]. These data demonstrate that hemifacial microsomia is progressive and underscores the importance of early surgical correction of mandibular asymmetry in this disorder.     

Branch retinal artery occlusion in a patient with multisystem vascular disease

Branch retinal artery occlusion (BRAO) is an acute, ocular condition causing blockage of a branch of the central retinal artery with subsequent infarction of the retinal tissue supplied by the distal artery. This article includes a case presentation of BRAO and a review of the clinical features and management of this condition. The need for investigation into possible underlying systemic disorders will be stressed.     

Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats

In Parkinson's disease, nigral dopaminergic neurones degenerate, whereas post-synaptic striatal target neurones are spared. In some atypical parkinsonian syndromes, both nigral and striatal neurones degenerate. Reduced activity of complex I of the mitochondrial respiratory chain has been implicated in both conditions, but it remains unclear if this affects the whole organism or only the degenerating brain structures. We therefore investigated the differential vulnerability of various brain structures to generalized complex I inhibition. Male Lewis rats infused with rotenone, a lipophilic complex I inhibitor [2.5 mg/kg/day intraveneously (i.v.) for 28 days], were compared with vehicle-infused controls. They showed reduced locomotor activity and loss of striatal dopaminergic fibres (54%), nigral dopaminergic neurones (28.5%), striatal serotoninergic fibres (34%), striatal DARPP-32-positive projection neurones (26.5%), striatal cholinergic interneurones (22.1%), cholinergic neurones in the pedunculopontine tegmental nucleus (23.7%) and noradrenergic neurones in the locus ceruleus (26.4%). Silver impregnation revealed pronounced degeneration in basal ganglia and brain stem nuclei, whereas the hippocampus, cerebellum and cerebral cortex were less affected. These data suggest that a generalized mitochondrial failure may be implicated in atypical parkinsonian syndromes but do not support the hypothesis that a generalized complex I inhibition results in the rather selective nigral lesion observed in Parkinson's disease.     

Congenital nasal anomalies: a classification scheme

The purpose of this work was to develop a simple yet comprehensive classification scheme dedicated to congenital nasal anomalies. To date, no such classification system has been proposed and widely used. A 22-year retrospective review was performed. Two hundred sixty-one patients with congenital nasal anomalies were identified. From this extensive database, a systematic morphogenic classification system was devised. Congenital nasal deformities were classified into four categories. Type I, hypoplasia and atrophy, represents paucity, atrophy, or underdevelopments of skin, subcutaneous tissue, muscle, cartilage, and/or bone. Type II, hyperplasia and duplications, representing anomalies of excess tissue, ranging from duplications of parts to complete multiples, are categorized here. In the type III category, clefts, the comprehensive and widely utilized Tessier classification of craniofacial clefts is applied. Type IV deformities consist of neoplasms and vascular anomalies. Both benign and malignant neoplasms are found in this category.