ABSTRACT
Cat eye syndrome (CES) is a rare chromosomal disorder that may be evident at birth. A small supernumerary chromosome is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11) in those affected. It's known that the 22q11 region is associated with disorders involving higher and lower gene dosages. Conditions such as CES, 22q11 microduplication syndrome (Dup22q11) and oculoauriculovertebral spectrum phenotype (OAVS) may share genes belonging to this same region, which is known to have a predisposition to chromosomal rearrangements. The conditions, besides being related to chromosome 22, also share similar phenotypes. Here we have added a molecular evaluation update and results found of the first patient described with CES and OAVS phenotype, trying to explain the potential mechanism involved in the occurrence of this association.
Subject(s)
Chromosome Disorders/genetics , Chromosome Duplication , Eye Abnormalities/genetics , Goldenhar Syndrome/genetics , Aneuploidy , Child , Chromosome Disorders/pathology , Chromosomes, Human, Pair 22/genetics , Comparative Genomic Hybridization , Eye Abnormalities/pathology , Female , Gene Dosage , Goldenhar Syndrome/pathology , HumansABSTRACT
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.
Subject(s)
DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Goldenhar Syndrome/genetics , Transcription Factors/genetics , Branchial Region/pathology , Brazil/epidemiology , DNA Copy Number Variations/genetics , Female , Goldenhar Syndrome/epidemiology , Goldenhar Syndrome/pathology , Humans , Male , Phenotype , Polymorphism, Single Nucleotide/geneticsABSTRACT
OBJECTIVE: To describe the most prominent clinical features of a cohort of patients with oculo-auriculo-vertebral (OAV) dysplasia in Brazil. METHOD: A review of medical records of patients with diagnosis of OAV from 1990 to 2010 was performed in a medical genetics center. RESULTS: 41 patients were included in the study. Their average age at diagnosis was 2y 10mo (34,4±48,8 months) and the female proportion was 53.7%. Mean maternal age at patient's birth was 28.5y (min: 17, max: 46y) for mothers and 31.4y (min: 21, max: 51y) for fathers. Most patients (97.5%) had auricular involvement, with facial manifestation in 90.2%, spinal in 65.9%, ocular in 53.7%, 36.6% with cardiovascular involvement, 29.3% urogenital, and 17% of the cases with central nervous system (CNS) involvement. The classic OAV triad was present in only 34%. All patients except one had concomitant problems in other organs or systems. CONCLUSION: Since the diagnosis of OAV dysplasia relies only on a comprehensive medical evaluation, it is imperative that clinicians be aware of the most common presentation of the syndrome. Once suspected, every patient should undergo a complete medical evaluation of multiple systems including complementary exams. Treatment of these patients is based on surgical correction of malformations and rehabilitation.
Subject(s)
Goldenhar Syndrome/epidemiology , Goldenhar Syndrome/pathology , Brazil/epidemiology , Child, Preschool , Ear/abnormalities , Eye Abnormalities , Face/abnormalities , Female , Goldenhar Syndrome/physiopathology , Humans , Male , Medical Records , Retrospective Studies , Sex Distribution , Spine/abnormalitiesABSTRACT
SUMMARY Objective: To describe the most prominent clinical features of a cohort of patients with oculo-auriculo-vertebral (OAV) dysplasia in Brazil. Method: A review of medical records of patients with diagnosis of OAV from 1990 to 2010 was performed in a medical genetics center. Results: 41 patients were included in the study. Their average age at diagnosis was 2y 10mo (34,4±48,8 months) and the female proportion was 53.7%. Mean maternal age at patient’s birth was 28.5y (min: 17, max: 46y) for mothers and 31.4y (min: 21, max: 51y) for fathers. Most patients (97.5%) had auricular involvement, with facial manifestation in 90.2%, spinal in 65.9%, ocular in 53.7%, 36.6% with cardiovascular involvement, 29.3% urogenital, and 17% of the cases with central nervous system (CNS) involvement. The classic OAV triad was present in only 34%. All patients except one had concomitant problems in other organs or systems. Conclusion: Since the diagnosis of OAV dysplasia relies only on a comprehensive medical evaluation, it is imperative that clinicians be aware of the most common presentation of the syndrome. Once suspected, every patient should undergo a complete medical evaluation of multiple systems including complementary exams. Treatment of these patients is based on surgical correction of malformations and rehabilitation.
RESUMO Objetivo: descrever os principais achados clínicos de uma coorte de pacientes com a displasia óculo-aurículo-vertebral (OAV). Método: revisão de prontuários médicos dos pacientes com diagnóstico de OAV no período de 1990 a 2010, acompanhados em um centro de genética médica. Resultados: foram incluídos no estudo 41 pacientes. A média de idade ao diagnóstico foi de 2 anos e 10 meses (34,4±48,8 meses) e a proporção de pacientes do sexo feminino foi de 53,7%. A média de idade dos pais ao nascimento do paciente foi de 28,5±6,9 anos para as mães e 31,4±7,4 anos para os pais. A maioria dos indivíduos (97,5%) possuía acometimento auricular, 90,2% tinham manifestações faciais, 65,9%, vertebrais, 53,7%, oculares, 36,6%, cardiovasculares, 29,3%, urogenitais e 17%, no sistema nervoso central. Além disso, 34% dos pacientes apresentavam a tríade clássica óculo-aurículo-vertebral, e todos os pacientes exceto um apresentavam concomitantemente problemas em outros órgãos ou sistemas. Conclusão: já que o diagnóstico desta entidade é eminentemente clínico, é imprescindível que os médicos das mais diversas especialidades conheçam os achados mais frequentes na OAV. Diante de um paciente com suspeita diagnóstica, deve ser realizada avaliação detalhada de outros órgãos, tanto clínica como por meio de exames complementares. O tratamento é baseado na correção cirúrgica das malformações e na reabilitação.
Subject(s)
Humans , Male , Female , Goldenhar Syndrome/pathology , Goldenhar Syndrome/epidemiology , Spine/abnormalities , Brazil/epidemiology , Eye Abnormalities , Medical Records , Retrospective Studies , Sex Distribution , Ear/abnormalities , Face/abnormalities , Goldenhar Syndrome/physiopathologyABSTRACT
Oculoauriculovertebral spectrum (OAVS, OMIM 164210) is a complex condition characterized by defects in aural, oral, and mandibular development. Other craniofacial and extracranial anomalies can be present. With the exception of the Tessier number 7 cleft, atypical clefting has rarely been reported in association with OAVS. Here, we report on two unrelated cases with a typical phenotype of OAVS and a Tessier 30 associated cleft. One of them also had other atypical facial clefts. We discuss the association between atypical facial clefts and OAVS.
Subject(s)
Goldenhar Syndrome/diagnosis , Cleft Lip/diagnosis , Cleft Lip/pathology , Facial Bones , Goldenhar Syndrome/pathology , Humans , Infant , Male , Tomography Scanners, X-Ray ComputedABSTRACT
The oculo-auriculo-vertebral spectrum (OAVS) is defined as a group of malformations involving the ears, mouth, mandible, eyes, and cervical spine. Establishing an accurate clinical diagnosis of OAVS is a challenge for clinical geneticists, not only because these patients display heterogeneous phenotypes, but also because its etiology encompasses environmental factors, unknown genetic factors and different chromosome aberrations. To date, several chromosomal abnormalities have been associated with the syndrome, most frequently involving chromosome 22. In the literature, six 22q11.2 microdeletions have been described within the same region, suggesting possible OAVS candidate genes in this segment. Here, we report on a patient with an â¼581-kb 22q11.21 deletion, detected by genomic array and MLPA. This is the 7th case described with OAVS and 22q deletion, suggesting that the 22q11.2 region may be related to the regulation of body symmetry and facial development.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Deletion , Chromosomes, Human, Pair 22/genetics , Goldenhar Syndrome/genetics , Abnormalities, Multiple/pathology , Child, Preschool , Chromosome Banding , Goldenhar Syndrome/pathology , Humans , Infant , Karyotype , Male , Multiplex Polymerase Chain Reaction/methods , Oligonucleotide Array Sequence Analysis/methods , Phenotype , Polymorphism, Single NucleotideABSTRACT
OBJECTIVE: First and second branchial arch involvement during early embryonic development results in a wide spectrum of anomalies that encompass diverse, superimposed, and heterogeneous phenotypes within the so-called oculoauriculovertebral spectrum. Nine members of a Brazilian family presenting typical branchial arch involvement in association with external opthalmoplegia are reported. CONCLUSION: Macrostomia or abnormal mouth contour, preauricular tags, and uni- or bilateral ptosis were present in association in several patients. To our knowledge, this is the first report on this type of autosomal dominant condition. Clinical and genetic aspects are discussed.
Subject(s)
Branchial Region/abnormalities , Goldenhar Syndrome/complications , Macrostomia/etiology , Ophthalmoplegia/etiology , Blepharoptosis/etiology , Brazil , Ear, External/abnormalities , Female , Genes, Dominant , Goldenhar Syndrome/pathology , Humans , Infant, Newborn , Pedigree , SyndromeABSTRACT
OBJECTIVE: To report on a pair of monozygotic female twins discordant for Goldenhar syndrome. DESCRIPTION: The affected twin was a girl, who was delivered by caesarean section at 35 weeks' gestation. Her birth weight was 2,170 g, length 42.5 cm, head circumference 30 cm and her Apgar scores were 3/7. After birth the child developed severe respiratory distress and had to be moved to the neonatal intensive care unit (ICU). The other twin was a girl, born weighing 3,200 g with a length of 49 cm, head circumference of 34 cm and Apgar scores of 8/10. She was transferred to the mother-baby unit soon after birth and was discharged two days later. There was no consanguinity between the twins' parents, who were young and healthy at the time of their conception. The affected child's dysmorphic features included left hemifacial microsomia, severe micrognathia, abnormal ears, bilateral preauricular tags and epibulbar dermoid in the right eye. She developed obstructive apnea due to micrognathia and required tracheostomy. Abdominal and cranial ultrasound findings were normal, as was an ophthalmological assessment. Spine x-ray showed hemivertebra at T9 and T10. An echocardiogram showed Tetralogy of Fallot. GTG-banded karyotyping was performed on peripheral blood cells and revealed 46,XX. Zygosity testing established the pair of twins to be monozygotic with a probability greater than 99:1. COMMENT: Goldenhar syndrome was diagnosed in one of the twins described here. There are several reports of twins discordant for this disorder and therefore non-genetic factors may also play an important role, for instance vascular disruption during morphogenesis.
Subject(s)
Diseases in Twins/pathology , Goldenhar Syndrome/pathology , Twins, Monozygotic , Apgar Score , Female , Humans , Infant, Newborn , Infant, PrematureABSTRACT
OBJECTIVE: To report on a pair of monozygotic female twins discordant for Goldenhar syndrome. DESCRIPTION: The affected twin was a girl, who was delivered by caesarean section at 35 weeks' gestation. Her birth weight was 2,170 g, length 42.5 cm, head circumference 30 cm and her Apgar scores were 3/7. After birth the child developed severe respiratory distress and had to be moved to the neonatal intensive care unit (ICU). The other twin was a girl, born weighing 3,200 g with a length of 49 cm, head circumference of 34 cm and Apgar scores of 8/10. She was transferred to the mother-baby unit soon after birth and was discharged two days later. There was no consanguinity between the twins' parents, who were young and healthy at the time of their conception. The affected child's dysmorphic features included left hemifacial microsomia, severe micrognathia, abnormal ears, bilateral preauricular tags and epibulbar dermoid in the right eye. She developed obstructive apnea due to micrognathia and required tracheostomy. Abdominal and cranial ultrasound findings were normal, as was an ophthalmological assessment. Spine x-ray showed hemivertebra at T9 and T10. An echocardiogram showed Tetralogy of Fallot. GTG-banded karyotyping was performed on peripheral blood cells and revealed 46,XX. Zygosity testing established the pair of twins to be monozygotic with a probability greater than 99:1. COMMENT: Goldenhar syndrome was diagnosed in one of the twins described here. There are several reports of twins discordant for this disorder and therefore non-genetic factors may also play an important role, for instance vascular disruption during morphogenesis.
Subject(s)
Humans , Female , Infant, Newborn , Diseases in Twins/pathology , Goldenhar Syndrome/pathology , Twins, Monozygotic , Apgar Score , Infant, PrematureABSTRACT
OBJECTIVES: The purpose of this paper is to present a variety of imaging findings of oculo-auriculo-vertebral spectrum (Goldenhar syndrome) using three-dimensional reconstructed images from computed tomography (3D-CT), associating clinical and embryological patterns of the syndrome. METHODS: The study population consisted of 10 patients with oculo-auriculo-vertebral spectrum with clinically identified hemifacial microsomia. The patients were examined using spiral CT, and abnormal imaging features were grouped under facial, ear and temporal bone, vertebral, and skull base anomalies. The original CT data were transferred to a networked computer workstation with a computer graphics system to generate 3D-CT volume rendered images of the skull and vertebra. Two observers analysed the bone and muscular setting protocols to assess the relationship between bone and muscular structures. RESULTS: Asymmetric underdevelopment was a characteristic pattern of this syndrome resulting from hypoplasia of the mandibular ramus and condyle, the zygomatic, sphenoid and auricular conduct bones, and the temporal and masseter muscles. The syndrome was associated with local atrophy seen on 3D-CT images using specific bone and muscles protocols in all cases. CONCLUSIONS: Understanding the aetiology, embryology and wide imaging spectrum of this syndrome is essential to make a correct diagnosis, for treatment planning, and for evaluation when associated with a 3D-CT computer graphics system.
Subject(s)
Goldenhar Syndrome/diagnostic imaging , Adolescent , Adult , Branchial Region/embryology , Child , Facial Asymmetry/diagnostic imaging , Facial Asymmetry/etiology , Female , Goldenhar Syndrome/complications , Goldenhar Syndrome/embryology , Goldenhar Syndrome/pathology , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Infant , Infant, Newborn , Male , Tomography, Spiral ComputedABSTRACT
GoldenharÆs syndrome is a rare condition described initially in the early 1950Æs. It is characterized by a combination of anomalies: dermal epibulbar cysts, auricular appendices and malformation of the ears. In 1963, Gorlin suggested the name oculo-auriculo-vertebral (OAV) dysplasia for this condition and also included vertebral anomalies as signs of the syndrome. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. This work reports a case of GoldenharÆs syndrome in an 11-year-old female, who presented all classical signs of this rare condition.
Subject(s)
Child , Female , Humans , Goldenhar Syndrome/pathology , Dermoid Cyst/pathology , Eyelid Neoplasms/pathology , Facial Asymmetry/pathology , Lip Diseases/congenital , Mandible/abnormalities , Mandibular Condyle/abnormalitiesABSTRACT
Goldenhar's syndrome is a rare condition described initially in the early 1950's. It is characterized by a combination of anomalies: dermal epibulbar cysts, auricular appendices and malformation of the ears. In 1963, Gorlin suggested the name oculo-auriculo-vertebral (OAV) dysplasia for this condition and also included vertebral anomalies as signs of the syndrome. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. This work reports a case of Goldenhar's syndrome in an 11-year-old female, who presented all classical signs of this rare condition
Subject(s)
Goldenhar Syndrome/pathology , Child , Dermoid Cyst/pathology , Eyelid Neoplasms/pathology , Facial Asymmetry/pathology , Female , Humans , Lip Diseases/congenital , Mandible/abnormalities , Mandibular Condyle/abnormalitiesABSTRACT
BACKGROUND: Microtia is a malformation of the ear with extreme variability of expression. It is generally seen as an isolated malformation. However, some authors consider it to be a minimal manifestation of the oculo-auriculo-vertebral spectrum (OAVS), where, in addition, there are facial, vertebral, and renal abnormalities, among others. METHODS: A total of 145 pediatric patients with unilateral or bilateral microtia not considered as part of a syndrome were studied. All patients were subjected to an intentional clinical examination, a familial history, and radiographic imaging studies for ruling out associated malformations. Patients were classified into two groups: group 1 (60%), with isolated microtia; and group 2 (40%), considered as OAVS, with microtia associated with hemifacial skeletal microsomia, vertebral and/or renal malformations. RESULTS: No significant differences were found between the groups when the following variables were compared: gender; presence of unilateral or bilateral microtia; atretic external auditory canal; presence of preauricular tags; hearing loss of any type, and affection of the seventh cranial nerve, as well as associated malformations of other organs or systems. There were significant differences in relation to the presence of soft-tissue hemifacial microsomia, more frequently seen in patients with OAVS, because the majority of these patients had bone microsomia. Over 66% of the cases were sporadic and the rest were familiar. In 28.3% of the cases, the history suggested an autosomal-dominant inheritance pattern, and in 5.5%, an autosomal-recessive inheritance pattern, although in some familial cases, multifactorial inheritance could not be ignored. Some members in several families had isolated microtia, and others had mild characteristic manifestations of OAVS. CONCLUSIONS: Our results support the hypothesis that isolated microtia is a minimal expression of OAVS. Therefore, it is recommended that patients with microtia be subjected to intentional studies that search for malformations and physical examinations of first-degree relatives for adequate genetic counseling and management.
Subject(s)
Ear/abnormalities , Adolescent , Child , Child, Preschool , Congenital Abnormalities/epidemiology , Female , Goldenhar Syndrome/epidemiology , Goldenhar Syndrome/genetics , Goldenhar Syndrome/pathology , Government Agencies , Humans , Infant , Male , Mexico/epidemiology , Pediatrics , PedigreeABSTRACT
Background. Microtia is a malformation of the ear with extreme variability of expression. It is generally seean as an isolated malformation. However, some authors consider it to be a minimal manifestation of the oculo-auriculo-vertebral spectrum (OAVS), wherem, in addition, there are facial, vertebral, and renal abnormalities, among others. Methods. A total of 145 pediatric patients with unilateral or bilateral microtia not considered as part of a syndrome were studied. All patients were subjected to an international clinical examination, a familial history, and radiographic imaging studies for ruling out associated malformations. Patients were classified into two groups: group 1 (60 percent), with isolated microtia; and group 2 (40 percent), considered as OAVS, with microtia associated with hemifacial skeletal microsomia, vertebral and/or renal malformations. Results. No significant differences were found between the groups when the following variables were compared: gender; prescence of unilateral or bilateral microtia; atretic external auditory canal; presence of preauricelar tags; hearing loss of any type, and affection of the seventh cranial nerve, as well as associated malformations of other otgans or systems. There were significant differences in relation to the presence of soft-tissue hemifacial microsomia, more frequently seen in patients with OAVS, because the majority of these patients had bone microsomia. Over 66 percent of the cases were sporadic and the rest were familiar. In 28.3 percent of the cases, the history suggested an autosomal-dominant inheritance pattern, and in 5.5 percent, an autosomal-recessive inheritance pattent, although in some familial cases, multifactorial inheritance could not be ignored . Some members in several familes has isolated microtia, and others had mild characteristic manifestations of OAVS. Conclusions. Our results support the hypothesis that isolated microtia is a minimal expression of OAVS. Therefore, it is recommended that patients with microtia be subjected to intentional studies that search for malformations and physical examinations of firstdegree relatives for adquate genetic counseling and management
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Adolescent , Government Agencies , Ear/abnormalities , Goldenhar Syndrome/epidemiology , Goldenhar Syndrome/genetics , Goldenhar Syndrome/pathology , Congenital Abnormalities/epidemiology , Mexico/epidemiology , PediatricsABSTRACT
A apresentaçäo do caso clínico mostra uma paciente com sídrome de Goldenhar em sua forma incompleta, que é a mais frequente, e chama atençäo para as possíveis malformaçöes oculares e sistêmicas, que podem estar associadas aos sinais clássicos
Subject(s)
Humans , Female , Goldenhar Syndrome/pathology , BrazilABSTRACT
Os autores fazem revisäo bibliográfica e apresentaçäo de umc aso clínico da síndrome de Goldenhar-Gorlin (Displasia-aurículo-vertebral - Microssomia Hemifacial)
Subject(s)
Humans , Child, Preschool , Female , Mandibulofacial Dysostosis/pathology , Goldenhar Syndrome/pathology , Diagnosis, Differential , Fundus Oculi , Mandibulofacial Dysostosis/genetics , Goldenhar Syndrome/diagnosis , Goldenhar Syndrome/genetics , Visual AcuityABSTRACT
Se estudió la aplicación de un caso de síndrome de Goldenhar's'', el cual presentó después de haber confirmado su diagnóstico por historia clínica, biomicroscopia, oftalmoscopia directa e indirecta, ecografía, RX cráneo, órbita y columna vertebral, TAC, exámenes de gabinete, etc. Este caso ha sido estudiado en conjunto por los servicios de pediatría, neurocirugía, oftalmología, cardiología, cirugía plástica y radiología. Llegando a resolver su neuroquirúrgico, quedando por solucionar la ciruga del quiste dermoide y del mamelón preuricular
Subject(s)
Child, Preschool , Humans , Female , Eye/embryology , Eye/pathology , Ear/embryology , Ear/pathology , Goldenhar Syndrome/diagnosis , Goldenhar Syndrome/pathologyABSTRACT
Rangel, C.; Macrí, A.; Méndez, A. Síndrome de Goldenhar. Salus Militiae, 1987; 12:. El síndrome de Goldenhar es una enfermedad genética poco frecuente en la cual se asocian defectos en los ojos y oidos, con anormalidades en las vertebras, corazón y pulmones. En el Servicio de la Cirugía Cardiovascular, FUNDACARDIN, y en la Sección de Genética del Hospital Central de las FF.AA. "Dr. Carlos Arvelo", estudiamos 3 casos de pacientes que por su cuadro clínico y radiológico se diagnosticaron como Síndrome de Goldenhar. Se destacan los aspectos más importantes de la enfermedad y se hacen consideraciones acerca del estudio integral de los pacientes para ofrecer a la familia el asesoramiento genético adecuado
Subject(s)
Child , Humans , Female , Goldenhar Syndrome/pathologyABSTRACT
Os autores apresentam um caso da sindrome de Goldenhar.