Risk factors and characteristics of the birth of patients with craniofacial microsomia, a case-control study.

BACKGROUND: Craniofacial microsomia (CM) is characterized by changes in the first and second branchial arches. It is a clinical condition whose etiology is still uncertain, but studies have shown that genetic, nutritional, and environmental factors can result in disorders of blastogenesis of the branchial arches. This study evaluates gestational aspects, focusing on possible risk factors associated with CM. METHODS: This is a case-control study conducted with patients monitored at a medical genetics service and compared to a control group of patients without evidence of malformations, born in a mother and child hospital, both located in Porto Alegre, Southern Brazil. Mothers' data were obtained using questionnaires and by reviewing medical records. The sample consisted of 43 patients with CM (cases) and 129 patients without evidence of malformations (controls), paired by sex, totaling three controls for each case. Data analysis was performed using the two-tailed Fisher's exact test, Pearson's chi-square test, and the t-test. RESULTS: We identified several factors associated with the development of CM, including the use of abortion methods by the mothers of these babies (p = .001), maternal diabetes (p = .009), advanced maternal age (p = .035), and a history of vaginal bleeding (p < .001). Furthermore, these patients exhibited a tendency to be born prematurely (p = .027), with low birth weight (p = .007), and lower Apgar scores (p = .003) when compared to healthy infants. Using a multivariate model, the use of abortion methods (p = .003) and vaginal bleeding (p = .032) remained independently associated with craniofacial microsomia. CONCLUSIONS: We have identified several risk factors for the development of CM, including a propensity for premature birth, low birth weight, and respiratory difficulties. Additionally, women of advanced maternal age and/or those who used abortion methods and/or have diabetes have a higher risk of giving birth to a baby with CM. This information can be valuable in clinical practice, especially for the prevention of future cases.

Craniofacial microsomia - more than a structural malformation.

OBJECTIVES: To analyse the prevalence and distribution of craniofacial microsomia (CFM) cases in Finland and their most frequent comorbidities. The second aim was to analyse the patients' need for specialized healthcare services. MATERIALS AND METHODS: Data were gathered from two complementary registers: The Register of Congenital Malformations and the Care Register for Social Welfare and Health Care (Hilmo) of the Finnish Institute for Health and Welfare (THL). RESULTS: The prevalence of CFM patients in Finland was 1:10 057. They were evenly distributed across the five university hospital districts. Their most frequently used ICD-10 diagnosis codes were F40-48 (Neurotic, stress-related and somatoform disorders), 60% of patients in adolescent and adult psychiatry; Q67.0 (Facial asymmetry), 43% in plastic surgery; Z00.4 (General psychiatric examination, not elsewhere classified), 31% in child psychiatry; Z31.5 (Genetic counselling), 28% in clinical genetics and Q67.40 (Other congenital deformities of the skull, face and jaw, Hemifacial atrophy), 18% in dental, oral and maxillofacial diseases. Of the patients, 70% had had visits in clinical genetics, 60% in plastic surgery, 41% in dental, oral and maxillofacial diseases, 28% in adolescent/adult psychiatry and 21% in child psychiatry. The majority of the patients' plastic surgery visits were concentrated in one university hospital. Other services were mainly provided by patients' own hospital districts. CONCLUSIONS: Even though the majority of CFM patients' visits in specialized healthcare services are related to correction of facial asymmetry and ear malformations, the obvious need for psychiatric care was apparent in all age groups.

Hearing impairment and ear anomalies in craniofacial microsomia: a systematic review.

The aim of this systematic review was to review the literature on hearing impairment and ear anomalies in patients with craniofacial microsomia and to determine their prevalence. Sixty-two records including 5122 patients were included. Ear anomalies were present in 52-100% of patients. The most reported external ear malformations were microtia, pre-auricular tags, and atresia of the external auditory canal. Ossicular anomalies were the most reported middle ear malformations, whereas the most reported inner ear malformations included oval window anomalies, cochlear anomalies, and anomalies of the semicircular canals. Hearing loss in general was reported in 29-100% of patients, which comprised conductive hearing loss, mixed hearing loss, and sensorineural hearing loss. Between 21% and 51% of patients used hearing aids, and 58% underwent a surgical intervention to improve hearing. The relationship between different phenotypes of craniofacial microsomia and the type and severity of hearing loss is mostly unclear. In conclusion, the high prevalence of ear and hearing anomalies in patients with craniofacial microsomia underlines the importance of audiological screening in order to facilitate individual treatment.

Determination of Extra Craniofacial Abnormalities in Patients With Craniofacial Microsomia.

INTRODUCTION: Craniofacial microsomia (CFM) is caused by abnormalities in the development of the first and second pharyngeal arches. One-third to half of the patients with CFM also present with extra craniofacial (ECF) malformations. The knowledge of the visceral alteration related to CFM is vital for optimized care and a better prognosis. AIM: To describe the incidence of ECF malformations in patients with CFM and to infer if there was a correlation between CFM and ECF malformations. MATERIALS AND METHODS: The authors analyzed medical records of patients diagnosed with CFM from 1996 to 2006. The data collected included age, gender, category of craniofacial alteration, and the type of ECF malformation when present. The sample was inspected to find possible correlations between craniofacial abnormalities and ECF malformations. RESULTS: The sample included 102 patients, with a mean age of 7 years and a predominance of males (61.8%). Ear malformations (93.1%) followed by mandible (59.8%) and facial nerve (10.8%) abnormalities were the most common CFM. Among patients with CFM, 37.2% had ECF involvement, mainly in vertebrae (20%), heart (11%), and limbs (9.8%). Multivariate analysis revealed that the presence of ear malformations was related to a higher incidence of nonspecific visceral malformations (P = 0.034) and that mandible malformation was related to an increased incidence of vertebral malformations (P = 0.008). CONCLUSION: A significant percentage of patients with CFM presented associated ECF impairment. Ear and mandible involvement may be predictors of nonspecific visceral malformation and vertebral malformations, respectively.

Parental Reports of Intervention Services and Prevalence of Teasing in a Multinational Craniofacial Microsomia Pediatric Study.

ABSTRACT: Children with craniofacial microsomia (CFM) are at increased risk for educational and social concerns. This study describes intervention services and frequency of teasing in a multinational population of children with CFM. Caregivers of children with CFM ages 3 to 18 years in the US and South America were administered a questionnaire. Additional information was gathered from medical charts and photographs. Participants (N = 169) had an average age of 10.1 ±â€Š6.2 years, were primarily male (60%), and from the US (46%) or Colombia (32%). Most participants had microtia and mandibular hypoplasia (70%). They often had unilateral (71%) or bilateral (19%) hearing loss and 53% used a hearing aid. In the US, special education services were provided for 48% of participants enrolled in school; however, similar services were rare (4%) in South America and reflect differences in education systems. Access to any intervention service was higher in the US (80%) than in South America (48%). Caregivers reported children showed diagnosis awareness by an average age of 4.4 ±â€Š1.9 years. Current or past teasing was reported in 41% of the children, starting at a mean age of 6.0 ±â€Š2.4 years, and most often took place at school (86%). As half of the US participants received developmental and academic interventions, providers should screen for needs and facilitate access to services. Given diagnosis awareness at age 4 and teasing at age 6, providers are encouraged to assess for psychosocial concerns and link to resources early in treatment.

Velopharyngeal Insufficiency in Craniofacial Microsomia: Prevalence, Diagnosis, and Treatment.

ABSTRACT: The purpose of this study was to analyze the prevalence, diagnosis, and management of velopharyngeal insufficiency (VPI) in patients with craniofacial microsomia (CFM).Craniofacial microsomia patients 13 years of age and above treated at 2 centers from 1997 to 2019 were reviewed retrospectively for demographics, prevalence of VPI, and management of VPI. Patients with isolated microtia were excluded. Comparisons were made between patients with and without VPI using chi-square and independent samples t tests.Among 68 patients with CFM (63.2% male, mean 20.7 years of age), VPI was diagnosed in 19 patients (27.9%) at an average age of 7.2 years old. Among the total cohort, 61 patients had isolated CFM, of which 12 (19.6%) were diagnosed with VPI. Of the patients with isolated CFM and VPI, 8 patients (66.7%) were recommended for nasoendoscopy, of which only 2 patients completed. Seven isolated CFM patients (58.3%) underwent speech therapy, whereas none received VPI surgery. In contrast, 7 patients were diagnosed with both CFM and cleft lip and/or palate (CL/P), all of whom had VPI and were recommended for nasoendoscopy, with 5 (71.4%) completing nasoendoscopy, 6 (85.7%) undergoing speech therapy, and 6 (85.7%) undergoing corrective VPI surgery. Overall, we demonstrated that VPI was present in 27.9% of all CFM patients. On subset analysis, VPI was diagnosed in 20% of patients with isolated CFM and 100% of patients with CFM and CL/P. In addition, despite clinical diagnosis of VPI, a sizeable proportion of isolated CFM patients did not undergo therapy or surgical interventions.

Ocular Manifestations of Goldenhars syndrome- A case series.

Goldenhars syndrome also known as facio auriculo vertebral dysplasia or first and second arch branchial syndrome has a prevalence of 1:3500 births to 1: 7500 births with male predisposition. We hereby present a case series of children presenting with Goldenhars syndrome.

Congenital abnormalities associated with microtia: A 10-YEARS retrospective study.

OBJECTIVE: Microtia is a congenital auricular malformation, often part of a syndromic form (35%-55% of cases). The accurate prevalence of associated malformations remains to be determined with regard to the heterogeneous results of the previous studies. This study aims to describe in a large population cohort the abnormalities associated with microtia and to determine the most suitable assessment for these children. METHODS: This is a retrospective and observational cohort study collecting data from the medical records of children affected by microtia, diagnosed or followed-up between 2007 and 2017. Data were collected via a computer database. Clinical data, as well as imaging or genetic results, were noted. RESULTS: Six hundred ninety four children were included, 587 (84.6%) with unilateral and 107 (15.4%) with bilateral microtia. Inner ear malformations were observed in 14.1% of the ears. The main associated anomalies were hemifacial microsomia (29%), velopharyngeal insufficiency (9%), ophthalmologic (6.2%), vertebral (5.9%), cardiac (5.5%) and kidney (3%) abnormalities. Main identified entities were Goldenhar, Treacher-Collins and Guion-Almeida syndromes. CONCLUSION: A comprehensive clinical assessment must be completed when microtia is diagnosed. Besides screening well-known oculo-auriculo-vertebral spectrum malformations, velopharyngeal insufficiency should be systematically sought. Specialized care must be provided to the very frequently associated hemifacial macrosomia. Mild forms of this last malformation may correspond to Guion-Almeida syndrome, especially in cases of learning disability.

Novel MYT1 variants expose the complexity of oculo-auriculo-vertebral spectrum genetic mechanisms.

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by anomalies mainly involving the structures derived from the first and second pharyngeal arches. The spectrum presents with heterogeneous clinical features and complex etiology with genetic factors not yet completely understood. To date, MYT1 is the most important gene unambiguously associated with the spectrum and with functional data confirmation. In this work, we aimed to identify new single nucleotide variants (SNVs) affecting MYT1 in a cohort of 73 Brazilian patients diagnosed with OAVS. In addition, we investigated copy number variations (CNVs) encompassing this gene or its cis-regulatory elements and compared the frequency of these events in patients versus a cohort of 455 Brazilian control individuals. A new SNV, predicted as likely deleterious, was identified in five unrelated patients with OAVS. All five patients presented hearing impairment and orbital asymmetry suggesting an association with the variant. CNVs near MYT1, located in its neighboring topologically associating domain (TAD), were found to be enriched in patients when compared to controls, indicating a possible involvement of this region with OAVS pathogenicity. Our findings highlight the genetic complexity of the spectrum that seems to involve more than one variant type and inheritance patterns.

Ocular and adnexal anomalies in craniofacial microsomia: Type and prevalence in a multicentre cohort study.

The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial microsomia (CFM) and to determine their prevalence. In addition, the relationship between the OMENS-Plus and Pruzansky-Kaban classification for each patient and the presence of ocular anomalies was investigated. A total of 881 patients with CFM from four different craniofacial centres were included. Data on ocular anomalies were gathered from the patient charts. Ocular anomalies were present in 33.9% of patients. Four subgroups of ocular and adnexal anomalies were identified. Type I ocular anomalies were present in 22.2%, type II in 19.0%, type III in 18.4%, and type IV in 14.5%. Several potentially preventable and treatable ocular anomalies were identified. Higher OMENS-Plus classification orbit and soft tissue scores and Pruzansky-Kaban classification mandible scores were associated with an increased risk of ocular anomalies. Based on these results and the clinical implications ocular anomalies may have, we underline the importance of targeted ophthalmological screening in CFM. Healthcare professionals should be aware of the possibility of ocular anomalies in these patients, especially during the critical period for visual development.

[Dental complications of the mandibular distraction osteogenesis]. / Dental'nye oslozhneniya kompressionno-distraktsionnogo osteogeneza nizhnei chelyusti.

THE AIM OF THE STUDY: Was to reveal the prevalence of dental abnormalities in children after mandibular distraction osteogenesis (MDO). MATERIALS AND METHODS: The study comprised 75 children aged 5-16 years (42 boys and 33 girls, mean age 9.8±4.2 years) who underwent MDO because of mandible underdevelopment associated with hemifacial microsomia (n=42), Robin syndrome (n=6), Treacher Collins syndrome (n=6), Hallermann-Streiff syndrome (n=1) or acquired conditions (n=16). The mean age at MDO was 6.3±4.4 years. Controls involved 25 children with mandibular underdevelopment (19 with hemifacial microsomis, 4 - with Robin syndrome and 2 with Treacher Collins syndrome, mean age 6.7±3.6 years) receiving orthodontic treatment and with no history of MDO. RESULTS: In the study group abnormalities of lower molars were revealed in 42 children from 75. The prevalence of the affected first and second molars was 24.7% and 20.5%, respectively. Every tenth child (9.6%) had disorders of both molars. The risks for the first molar developmental defects after MDO was 12 times higher than in controls (OR=12.4; CI=95%). In 21 children delayed eruption or impaction of the first molars was observed. Second molars abnormalities more often included germs displacement and follicular cyst formation (OR=10.4). The age at MDO was significantly higher in children with no dental abnormalities (p<0.01). CONCLUSION: MDO is associated with significant risk of molars disorders. The younger a child is at MDO the more probable and prominent are the dental complications.

Goldenhar syndrome: surgical management protocol in a reference center.

OBJECTIVE: To present our experience treating 42 patients with Goldenhar syndrome. METHOD: A descriptive, observational, retrospective study was carried out using the medical and photographic record of all patients diagnosed with Goldenhar syndrome treated by the craniofacial surgery unit of the plastic and reconstructive surgery department of the Dr. Manuel Gea González hospital between 2010 and 2018. RESULTS: A total of 42 patients were obtained,54% male of which all underwent at least one procedure. The majority of patients were of the first decade of age (57%). Surgical procedures could be divided mainly into 14 auricular (20%), 17 mandibular (24%), 2 Lefort (4%), 10 volume (14%), 9 macrostoma (13%) and 16 other (21%). A total of 71 procedures were performed. CONCLUSION: Goldenhar syndrome is a rare entity that affects various structures, which is why an early diagnosis and multidisciplinary management headed by a team of plastic surgeons is necessary.

OBJETIVO: Presentar nuestra experiencia en el diagnóstico y el tratamiento de 42 pacientes con síndrome de Goldenhar. MÉTODO: Se realizó un estudio descriptivo, observacional y retrospectivo usando el registro médico y fotográfico de todos los pacientes diagnosticados con síndrome de Goldenhar tratados por la unidad de cirugía craneofacial del departamento de cirugía plástica y reconstructiva del hospital Dr. Manuel Gea González entre 2010 y 2018. RESULTADOS: Se obtuvieron 42 pacientes, el 54% varones, con predominio de menores de 10 años (57%), de los cuales todos se sometieron al menos a un procedimiento. Los procedimientos quirúrgicos se dividieron en: 14 auriculares (20%), 17 mandibulares (24%), 2 Lefort (4%), 10 volumen (14%), 9 macrostoma (13%) y 16 otros (21%). En total se realizaron 71 procedimientos. CONCLUSIÓN: El síndrome de Goldenhar es una enfermedad poco frecuente que afecta diversas estructuras y se presenta predominantemente en varones. Es necesario un diagnóstico precoz y un manejo individualizado llevado a cabo por un equipo multidisciplinario encabezado por cirujanos plásticos.

Preferential Associated Malformation in Patients With Anotia and Microtia.

OBJECTIVE: Few epidemiological studies have investigated the external ear malformations anotia and microtia. The authors' study aimed to investigate the relationships between age, sex, type of microtia, and birth place and associated malformation as seen in 1 private Japanese clinic. METHODS: Cases of anotia/microtia that presented in Nagata Microtia and Reconstructive Plastic Surgery Clinic (Saitama, Japan) between 2005 and 2018 were included in the study. The authors identified 1896 patients with anotia/microtia with or without associated malformation. Most were primary cases, with some secondary reconstruction cases wherein the primary surgery was performed at another hospital. Cases were classified with Nagata classification; lobule type, small concha type, concha type, and anotia. Cryptotia was also observed in this study. RESULTS: Among the patients, 61.1% were male, 85.4% had unilateral defects (69.0% LB), and 59.1% had a right-sided defect. Most patients were less than 1 year old (15.0%) or 8 to 10 years old (5.5%-6.3%) on first examination, while 58% were from the Kanto region, including Tokyo. Regarding concomitant disorders, 32.7% had an accompanying malformation, while 13.3% had associated syndromes (eg, craniofacial microsomia, Treacher Collins syndrome). To conclude, in the authors' clinic, most cases of anotia/microtia were LB, unilateral, and seen in male patients. Information regarding several characteristic clinical features was obtained, especially that clefts and musculoskeletal deformities of the skull/face and jaw were the main accompanying malformations.

Microtia and Related Facial Anomalies.

Infants may be born with external ear deformities or malformations that can present a diagnostic clue to an affiliated syndrome while also presenting the possibility of surgical intervention. Microtia is a malformation of the ear that is associated with other craniofacial or systemic anomalies in 50% of cases. Surgical correction of microtia and associated facial anomalies is complex and must be integrated thoughtfully into the overall care plan for children with complex medical needs. Familiarity with types of ear and facial anomalies and their association with more global concerns can allow perinatal practitioners to better serve their patients.

Facial Paralysis in Patients With Hemifacial Microsomia: Frequency, Distribution, and Association With Other OMENS Abnormalities.

Although facial paralysis is a fundamental feature of hemifacial microsomia, the frequency and distribution of nerve abnormalities in patients with hemifacial microsomia remain unclear. In this study, the authors classified 1125 cases with microtia (including 339 patients with hemifacial microsomia and 786 with isolated microtia) according to Orbital Distortion Mandibular Hypoplasia Ear Anomaly Nerve Involvement Soft Tissue Dependency (OMENS) scheme. Then, the authors performed an independent analysis to describe the distribution feature of nerve abnormalities and reveal the possible relationships between facial paralysis and the other 4 fundamental features in the OMENS system. Results revealed that facial paralysis is present 23.9% of patients with hemifacial microsomia. The frontal-temporal branch is the most vulnerable branch in the total 1125 cases with microtia. The occurrence of facial paralysis is positively correlated with mandibular hypoplasia and soft tissue deficiency both in the total 1125 cases and the hemifacial microsomia patients. Orbital asymmetry is related to facial paralysis only in the total microtia cases, and ear deformity is related to facial paralysis only in hemifacial microsomia patients. No significant association was found between the severity of facial paralysis and any of the other 4 OMENS anomalies. These data suggest that the occurrence of facial paralysis may be associated with other OMENS abnormalities. The presence of serious mandibular hypoplasia or soft tissue deficiency should alert the clinician to a high possibility but not a high severity of facial paralysis.

Clinical and cytogenomic findings in OAV spectrum.

The oculoauriculovertebral spectrum (OAVS) is characterized by anomalies involving the development of the first and second pharyngeal arches during the embryonic period. The phenotype is highly heterogeneous, involving ears, eyes, face, neck, and other systems and organs. There is no agreement in the literature for the minimum phenotypic inclusion criteria, but the primary phenotype involves hemifacial microsomia with facial asymmetry and microtia. Most cases are sporadic and the etiology of this syndrome is not well known. Environmental factors, family cases that demonstrate Mendelian inheritance, such as preauricular appendages, microtia, mandibular hypoplasia, and facial asymmetry; chromosomal abnormalities and some candidate genes suggest a multifactorial inheritance model. We evaluated clinical, cytogenomic and molecularly 72 patients with OAVS, and compared our findings with patients from the literature. We found 15 CNVs (copy number variations) considered pathogenic or possibly pathogenic in 13 out of 72 patients. Our results did not indicated a single candidate genomic region, but recurrent chromosomal imbalances were observed in chromosome 4 and 22, in regions containing genes relevant to the OAVS phenotype or related to known OMIM diseases suggesting different pathogenic mechanisms involved in this genetically and phenotypic heterogeneous spectrum.

Vertebral anomalies in craniofacial microsomia: a retrospective analysis of 991 patients.

Craniofacial microsomia (CFM) is characterized by an underdevelopment of the facial structures arising from the first and second branchial arches, but extracraniofacial anomalies such as vertebral anomalies may be present. This retrospective study was performed to determine the prevalence and types of vertebral anomalies and the association with other extracraniofacial anomalies in patients with CFM. The charts of all patients diagnosed with CFM seen in four craniofacial centres were reviewed for the presence of vertebral anomalies, symptoms, extracraniofacial anomalies, and the OMENS classification including the Pruzansky-Kaban type of mandibular deformity. A total of 991 patients were included and 28% of the patients had vertebral anomalies. The most common vertebral anomalies included scoliosis, block vertebrae, and hemivertebrae. Only 44% of the patients with vertebral anomalies had clinical symptoms; torticollis, back or neck pain, and limited neck movement were the most frequently seen. The prevalence of vertebral anomalies was greater in patients with bilateral CFM and in patients with a more severe mandibular deformity, and/or orbit, facial nerve, and/or soft tissue involvement. Patients with vertebral anomalies had significantly more extracraniofacial anomalies than patients without vertebral anomalies. Therefore, patients with vertebral anomalies should undergo cardiac, renal, and neurological evaluation.

Central nervous system anomalies in craniofacial microsomia: a systematic review.

Extracraniofacial anomalies, including central nervous system (CNS) anomalies, may occur in craniofacial microsomia (CFM). This systematic review was performed to provide an overview of the literature on the prevalence and types of CNS anomalies and developmental disorders in CFM, in order to improve the recognition and possible treatment of these anomalies. A systematic search was conducted and data on the number of patients, patient characteristics, type and prevalence of CNS anomalies or developmental delay, and correlations between CFM and CNS anomalies were extracted. Sixteen papers were included; 11 of these described developmental disorders. The most common reported anomalies were neural tube defects, corpus callosum agenesis or hypoplasia, intracranial lipoma, Arnold-Chiari malformations, hydrocephaly, ventriculomegaly, and cerebral hypoplasia. The prevalence of CNS anomalies in CFM varied from 2% to 69%. The prevalence of developmental disorders, such as intellectual disability, language or speech developmental delay, and neuropsychomotor delay, varied from 8% to 73%. This study suggests that CNS anomalies and developmental disorders are seen in a substantial proportion of patients with CFM. Further research should focus on determining which features of CFM are correlated with CNS anomalies to allow adequate screening and timely care.

Obstructive sleep apnoea in craniofacial microsomia: analysis of 755 patients.

A retrospective cohort study was set up to analyse the prevalence and treatment of obstructive sleep apnoea (OSA) in relation to the severity of the deformity in patients with craniofacial microsomia (CFM). This study included a population of 755 patients with CFM from three craniofacial centres. Medical charts were reviewed for severity of the deformity, types of breathing difficulty, age at which breathing difficulty first presented, treatment for OSA, and treatment outcome. In total, 133 patients (17.6%) were diagnosed with OSA. Patients with Pruzansky IIB/III classification or bilateral craniofacial microsomia were significantly more often diagnosed with OSA than unilaterally affected patients of Pruzansky I/IIA classification. The initial treatment of OSA consisted of adenotonsillectomy, tracheotomy, or non-invasive positive pressure ventilation. Thirty-seven patients received more than one treatment (range 1-3). In this study, the prevalence of OSA in patients with CFM was higher than the prevalence in the healthy population described in the literature. Although several treatment modalities are available for the treatment of OSA in patients with CFM, treatment should be individualized and based on clinical symptoms, the severity of the deformity, and comorbidities.