Goldenhar Research Articles

Most common congenital syndromes with facial asymmetry: A narrative review.

Symmetry is present in various aspects of everyday life. A symmetrical face is considered attractive, whereas a lack of facial symmetry is regarded as a source of functional and aesthetic problems. Most of the people exhibit slight asymmetries, but some of them reveal severe asymmetries. Among patients presenting with severe facial asymmetries, there may be those with congenital defects. Congenital defects may manifest at the time of birth or be a result of birth trauma.One of the most prevalent asymmetrical birth defects is cleft lip and/or cleft palate. Other congenital defects include craniofacial syndromes, such as Treacher Collins syndrome (TCS) and Goldenhar syndrome. Among the rare syndromes with facial asymmetries, Klippel-Feil syndrome (KFS), PHACE (posterior fossa brain malformation, hemangiomas, arterial anomalies, cardiac anomalies, and eye abnormalities) syndrome, plagiocephaly, and Parry-Romberg syndrome are worth noticing. The majority of craniofacial asymmetries require surgery to improve the patient's facial appearance. The treatment is multidisciplinary and long, and the most common procedures involve reparative and regenerative surgeries. The aim of this review was to present the most common congenital defects with facial asymmetry.

Incidence of Oblique Traction Vector of the Pterigomasseteric Sling in Relapse of Mandibular Distraction Osteogenesis after Proportional Overcorrection in Goldenhar Syndrome: Case Report

Distraction osteogenesis in the facial territory is a very useful tool in patients with dysmorphosis and syndromes. It allows histiogenesis after progressive traction of the intervened bone tissue, which increases in size according to the planned vector and the range of distraction. The existence of post-distraction osteogenic relapse depends on multiple factors. In the maxillary region, it corresponds to approximately 10% of the total number of millimetres (mm) distracted. Anatomical and biomechanical factors play a fundamental role in the variability of these results. The purpose of our work is to present the results obtained after vertical distraction of the mandibular ramus in a pediatric patient with Goldenhar syndrome. Following a proportional overcorrection, an asymmetric relapse was evident in the postoperative 3D measurements, with a greater relapse at the posterior border of the mandibular ramus. Additionally, we provide a literature review regarding the possible role of the pterygomasseteric sling vector of forces in the postoperative outcomes of these patients.

A Curious Case of Multimorbidity in a Patient With Goldenhar Syndrome Presenting With Vomiting

A Curious Case of Multimorbidity in a Patient With Goldenhar Syndrome Presenting With Vomiting

Chromatin assembly factor subunit CHAF1A as a monogenic cause for oculo-auriculo-vertebral spectrum.

Oculo-auriculo-vertebral spectrum (OAVS) is characterized by abnormal development of the 1st and 2nd branchial arches. Despite arguments against a monogenic condition, a few genes have been involved in a minority of cases. We now report heterozygous, presumably loss-of function variants in the CHAF1A gene in 8 individuals, including 3 members of the same family. Four cases fulfill stringent diagnostic criteria for OAVS, including asymmetric ear dysplasia, preauricular tags, mandibular asymmetry +/- vertebral malformations. Two patients also presented with kidney malformations. CHAF1A encodes a subunit of CAF-1 (chromatin assembly factor-1), a heterotrimeric protein complex responsible for the deposition of newly synthesized histones H3-H4 onto the newly synthetized DNA strand during replication. The identification of loss-of-unction variants in CHAF1A is consistent with the hypothesis of early developmental genes dysregulation driving OAVS and other associations recently lumped under the acronym Recurrent Constellations of Embryonic Malformations (RCEM).

Goldenhar Syndrome Complicated by Hemifacial Microsomia and Unilateral Cleft Palate Absence.

Goldenhar syndrome, also known as oculo-auriculo-vertebral spectrum (OAVS) or hemifacial microsomia (HFM), is characterized by developmental anomalies in structures such as the eyes, ears, upper jaw, lower jaw, upper palate, and spine. The facial abnormalities, stemming predominantly from branchial arch malformation, are sometimes categorized as the first and second branchial arch syndromes. Its incidence is estimated to be ∼1 in 3500. Here, the authors present a case of Goldenhar syndrome in a male infant at the age of 10 months, showcasing a particularly unique manifestation of cleft palate, for which we employed myomucosal flap reconstruction of the soft palate.

Goldenhar syndrome associated with increased risk of respiratory failure and reoperations following spinal deformity surgery.

Goldenhar syndrome is a rare congenital disease that presents with a spectrum of clinical sequelae related to the vertebrae and other organs. The spinal manifestations of the syndrome are associated with scoliosis for which fusion may be considered. The current study aimed to evaluate the risks of adverse events and reoperations following posterior spinal fusion for those with Goldenhar syndrome relative to those with adolescent idiopathic scoliosis (AIS). Patients with Goldenhar syndrome and AIS between the ages of 10 and 17 who underwent posterior spinal fusion were abstracted from the 2010 to 2022 PearlDiver Database. The Goldenhar syndrome patients were matched 1:4 to patients with AIS based on age, sex, and Elixhauser Comorbidity Index. All 90day postoperative adverse events, readmissions, and 5year reoperations were identified using administrative coding. Incidence of adverse events between the cohorts were compared using multivariate logistic regression. A total of 11,742 patients with AIS and 72 (0.61%) Goldenhar syndrome undergoing deformity surgery were identified. On matched comparison, patients with Goldenhar syndromes had higher odds ratio (OR) of respiratory failure (OR: 2.99, p = 0.009), severe adverse events (p = 2.29, p = 0.01), and readmissions (p = 2.26, p = 0.02). Over 5years, they had a significantly higher incidence of reoperation compared to those with AIS (18.1% versus 5.5%, p = 0.005). In this national sample of patients with Goldenhar syndrome undergoing posterior spinal fusion, patients with Goldenhar had increased odds of respiratory failure, readmissions, and reoperations. Targeted risk mitigation strategies may be appropriately considered for those with Goldenhar syndrome undergoing such surgeries. Level III; Case-control study or retrospective cohort study.

Hearing rehabilitation in a patient with Goldenhar syndrome – a case report

Hearing rehabilitation in a patient with Goldenhar syndrome – a case report

Goldenhar syndrome in a 5-year-old child.

Goldenhar syndrome in a 5-year-old child.

Orthodontic and surgical management of Goldenhar's syndrome, including joint replacement, orthognathic surgery, and polyetheretherketone implants, using virtual surgical planning

Orthodontic and surgical management of Goldenhar's syndrome, including joint replacement, orthognathic surgery, and polyetheretherketone implants, using virtual surgical planning

COEXISTENCE OF GOLDENHAR SYNDROME WITH JUVENILE IDIOPATHIC ARTHRITIS: A CAUSAL LINK OR MERE COINCIDENCE?

Goldenhar syndrome, a rare congenital anomaly primarily affecting the face, external ear and vertebrae, and juvenile idiopathic arthritis (JIA), a chronic inflammatory disease in children under 16, represent distinct and uncommon clinical entities. We report the case of a five-and-a-half-year-old girl, with a history of treated congenital hip dislocation, admitted for persistent joint pain for over 6 months, affecting both knees, wrists and ankles with inflammatory signs without associated visceral manifestations. Clinical examination revealed a dysmorphic facies characteristic of Goldenhar syndrome, including facial asymmetry with mandibular hypoplasia, auricular anomalies such as a bilateral pre-tracheal appendix, an acrochordon on the right cheek, a pre-auricular sinus, microtia, and a closed right external auditory canal. A lumbar scoliosis was also identified on dorsolumbar spine imaging, with a CT scan of the rock that objectified an imperforation of the right external auditory canal and lack of visualization of the tympanic membrane, consolidating the diagnosis of Goldenhar syndrome.Biologically, the patient presented with inflammatory anemia with a moderate inflammatory syndrome, as well as hypergammaglobulinemia detected by protein electrophoresis. Tests for antinuclear antibodies and rheumatoid factor were negative (15 IU/mL). X-rays of the affected joints were taken, and the diagnosis of Idiopathic Juvenile Arthritis was retained after eliminating all differential diagnoses. This unusual coexistence raises complex diagnostic and therapeutic challenges, requiring a multidisciplinary approach and ongoing surveillance for comprehensive management.

Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations

The term "recurrent constellations of embryonic malformations" (RCEM) is used to describe a number of multiple malformation associations that affect three or more body structures. The causes of these disorders are currently unknown, and no diagnostic marker has been identified. Consequently, providing a definitive diagnosis in suspected individuals is challenging. In this study, genome-wide DNA methylation analysis was conducted on DNA samples obtained from the peripheral blood of 53 individuals with RCEM characterized by clinical features recognized as VACTERL and/or oculoauriculovertebral spectrum association. We identified a common DNA methylation episignature in 40 out of the 53 individuals. Subsequently, a sensitive and specific binary classifier was developed based on the DNA methylation episignature. This classifier can facilitate the use of RCEM episignature as a diagnostic biomarker in a clinical setting. The study also investigated the functional correlation of RCEM DNA methylation relative to other genetic disorders with known episignatures, highlighting the common genomic regulatory pathways involved in the pathophysiology of RCEM.

Using three-dimensional geometric morphometry for facial analysis in patients with the oculo-auriculo-vertebral spectrum.

To utilize three-dimensional (3D) geometric morphometry for visualization of the level of facial asymmetry in patients with the oculo-auriculo-vertebral spectrum (OAVS). Three-dimensional facial scans of 25 Czech patients with OAVS were processed. The patients were divided into subgroups according to Pruzansky classification. For 13 of them, second 3D facial scans were obtained. The 3D facial scans were processed using geometric morphometry. Soft tissue facial asymmetry in the sagittal plane and its changes in two time spots were visualized using colour-coded maps with a thermometre-like scale. Individual facial asymmetry was visualized in all patients as well as the mean facial asymmetry for every Pruzansky subgroup. The mean colour-coded maps of type I and type IIA subgroups showed no differences in facial asymmetry, more pronounced asymmetry in the middle and the lower facial third was found between type IIA and type IIB (maximum 1.5 mm) and between type IIB and type III (maximum 2 mm). The degree of intensity facial asymmetry in affected middle and lower facial thirds did not change distinctly during the two time spots in all subgroups. The 3D geometric morphometry in OAVS patients could be a useful tool for objective facial asymmetry assessment in patients with OAVS. The calculated colour-coded maps are illustrative and useful for clinical evaluation.

Whole genome sequencing of a family with autosomal dominant features within the oculoauriculovertebral spectrum.

Oculoauriculovertebral Spectrum (OAVS) encompasses abnormalities on derivatives from the first and second pharyngeal arches including macrostomia, hemifacial microsomia, micrognathia, preauricular tags, ocular and vertebral anomalies. We present genetic findings on a three-generation family affected with macrostomia, preauricular tags and uni- or bilateral ptosis following an autosomal dominant pattern. We generated whole genome sequencing data for the proband, affected parent and unaffected paternal grandparent followed by Sanger sequencing on 23 family members for the top 10 candidate genes: KCND2, PDGFRA, CASP9, NCOA3, WNT10A, SIX1, MTF1, KDR/VEGFR2, LRRK1, and TRIM2 We performed parent and sibling-based transmission disequilibrium tests and burden analysis via a penalized linear mixed model, for segregation and mutation burden respectively. Next, via bioinformatic tools we predicted protein function, mutation pathogenicity and pathway enrichment to investigate the biological relevance of mutations identified. Rare missense mutations in SIX1, KDR/VEGFR2, and PDGFRA showed the best segregation with the OAV phenotypes in this family. When considering any of the 3 OAVS phenotypes as an outcome, SIX1 had the strongest associations in parent-TDTs and sib-TDTs (p=0.025, p=0.052) (unadjusted p-values). Burden analysis identified SIX1 (RC=0.87) and PDGFRA (RC=0.98) strongly associated with OAVS severity. Using phenotype-specific outcomes, sib-TDTs identified SIX1 with uni- or bilateral ptosis (p=0.049) and ear tags (p=0.01), and PDGFRA and KDR/VEGFR2 with ear tags (both p<0.01). SIX1, PDGFRA, and KDR/VEGFR2 are strongly associated to OAVS phenotypes. SIX1 has been previously associated with OAVS ear malformations and is co-expressed with EYA1 during ear development. Efforts to strengthen the genotype-phenotype co-relation underlying the OAVS are key to discover etiology, family counseling and prevention.

FBLN2 is associated with Goldenhar syndrome and is essential for cranial neural crest cell development.

Goldenhar syndrome, a rare craniofacial malformation, is characterized by developmental anomalies in the first and second pharyngeal arches. Its etiology is considered to be heterogenous, including both genetic and environmental factors that remain largely unknown. To further elucidate the genetic cause in a five-generation Goldenhar syndrome pedigree and exploit the whole-exome sequencing (WES) data of this pedigree, we generated collapsed haplotype pattern markers based on WES and employed rare variant nonparametric linkage analysis. FBLN2 was identified as a candidate gene via analysis of WES data across the significant linkage region. A fbln2 knockout zebrafish line was established by CRISPR/Cas9 to examine the gene's role in craniofacial cartilage development. fbln2 was expressed specifically in the mandible during the zebrafish early development, while fbln2 knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the bone morphogenic protein (BMP) signaling pathway in the zebrafish model. This study demonstrates the role of FBLN2 in CNCC development and BMP pathway regulation, and highlights FBLN2 as a candidate gene for Goldenhar syndrome, which may have implications for the selection of potential screening targets and the development of treatments for conditions like microtia-atresia.

A rare association of optic disc pit with Goldenhar syndrome

A rare association of optic disc pit with Goldenhar syndrome

The Chimeric LFC and DCIA Flap in Combined Mandibular and Condylar Head and Neck Reconstruction-A Case Series.

Background: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct. Reconstruction is mainly based on the use of alloplastic joint prosthesis, costochondral grafting, distraction osteogenesis of the dorsal part of the mandibular ramus, or osseous microvascular flaps of various origin. With the objective of developing a method that overcomes the restrictions of these methods, we recently introduced a sequential chimeric flap consisting of a lateral femoral condyle flap (LFC) and deep circumflex iliac artery flap (DCIA) for reconstruction of up to half of the mandible and the condylar head and neck. Methods: The chimeric flap was used in four patients with the following diagnoses: therapy-refractory osteomyelitis, extended recurrent odontogenic keratozyst, Goldenhar syndrome, and adenocarcinoma of the parotid gland. After a diagnostic workup, LFC and DCIA flaps were harvested in all patients and used in a sequential chimeric design for the reconstruction of the mandibular body and condylar head and neck. Results: Follow-up from at least 24 months up to 70 month after surgery showed a successful reconstruction in all four patients. The LFC provided a cartilaginous joint surface, allowing for a satisfactory masticatory function with a stable occlusion and unrestricted mouth opening and preserved or regained lateral and medial excursions in all patients. The DCIA allowed for a bony reconstruction anatomically resembling a non-atrophied mandibular body. No flap-related complications were observed. Conclusions: The sequential chimeric LFC and DCIA flap is an appropriate method for reconstructing up to half of the mandible and the condylar head and neck. It is suitable in cases where alloplastic joint replacement cannot be used or where other methods have failed. Due to the necessity of harvesting two flaps, the burden of care is increased, and a careful indication is required. The technique is reserved for maxillofacial surgeons who have already gained significant experience in the field of microsurgery.

Management of sleep-disordered breathing in patients with syndromic hemifacial macrosomia.

Patients with syndromic hemifacial microsomia (SHFM) are at risk of obstructive sleep apnea (OSA). The aim of the study was to describe the prevalence of OSA and its management, especially in patients with Goldenhar syndrome (GS). The respiratory polygraphies and clinical management of 15 patients, aged 2 to 23years, evaluated at a national reference center, were analyzed. Four (27%) patients had no OSA, 4 (27%) had mild OSA, and 7 (46%), of whom 5 were ≤ 2years old, had severe OSA. None of the patients had central apneas. Only one patient had alveolar hypoventilation, and another one had nocturnal hypoxemia. Two patients had severe OSA despite prior adenoidectomy or mandibular distraction osteogenesis. Median duration of follow-up was 3.5years (range 0.5-9years). None of the patients without OSA or with mild OSA at baseline respiratory polygraphy developed OSA during the follow up. Among the 7 patients with severe OSA, 3 required continuous positive airway pressure or noninvasive ventilation, and one patient required a tracheostomy. In conclusion, patients with SHFM are at high risk of severe OSA at any age, underlining the importance of systematic sleep studies to diagnose and evaluate the severity of OSA. Individualized treatment should be privileged, based on a careful examination of the entire upper airway, taking in account potential associated risk factors. All patients with SHFM should be managed by a pediatric expert multidisciplinary medical/surgical team until the end of post pubertal growth.

Lacrimal Drainage Anomalies in Goldenhar, Rubinstein-Taybi, and Ectodermal-Ectrodactyly-Clefting Syndromes.

To describe in detail the lacrimal drainage system anomalies and review of literature in patients with Goldenhar syndrome, Rubinstein-Taybi syndrome (RTS), and Ectodermal-Ectrodactyly-Clefting syndrome (EECS), their management and outcomes. A retrospective chart review from January 2011-June 2023 of all cases presenting to the Dacryology clinic with Goldenhar syndrome, RTS, and EECS was obtained. Data collected included demographics, laterality, clinical presentations, proximal and distal lacrimal drainage anomalies, associated systemic features, management, and outcomes. Eight children with Goldenhar syndrome (n = 13), three with RTS (n = 5) and three with EECS (n = 5) presented with lacrimal drainage system involvement. Cases with Goldenhar syndrome showed male predominance (5/8), and the mean age at presentation was 14.75 months. Four cases had simple CNLDO, seven cases with complex CNLDO (4 - buried probe and 3 - atonic sacs) and a single neonate presented with bilateral dacryocele. Patients with RTS presented with mean age of 36.33 months with male predominance. Probing under endoscopic guidance explored the anatomy thoroughly and those with altered nasal anatomy increased the probability of complex CNLDO. Those with EECS (n = 5) presented with a greater involvement of proximal lacrimal drainage system compared with Goldenhar syndrome and RTS, including anomalies like punctal agenesis, incomplete punctal canalization (IPC), ectopic puncta, canalicular stenosis, and complex CNLDO. A step-wise approach to assessing the proximal and lacrimal drainage system in those affected with craniofacial malformations and addressing them can result in satisfactory outcomes for the majority of patients.

Goldenhar Syndrome in a 9-year-old Patient – A Rare Case Report

Abstract The complex and rare condition known as Goldenhar syndrome (GHS) is characterized by mandibular hypoplasia, ear abnormalities, ocular dermoid and vertebral problems, and hemi facial macrosomia. The age of the patient and any systemic clinical manifestations will determine the treatment plan, which frequently calls for a multidisciplinary approach. This case study details a 9-year-old boy who presented to the Department of Pediatric Dentistry, Dr R Ahmed Dental College and Hospital, Kolkata, with ear tags, ocular dermoid, and mandibular hypoplasia. The diagnosis was made using mainly the clinical features. Since GHS is a developmental disorder that can affect a patient’s quality of life in many areas, treatment must begin as soon as the child is born.

Rhabdomyomatous Mesenchymal Hamartoma: Report of 4 Cases With Histochemical and Immunohistochemical Findings and Emphasis on Potential Pitfalls.

Rhabdomyomatous mesenchymal hamartoma (RMH) typically presents as a congenital midline head and neck cutaneous polyp in infants. Perianal and mucocutaneous lesions have been reported, and recently, acquired adult-onset variants have been proposed. This makes the true prevalence, etiopathogenesis, and clinicopathologic distribution and classification of RMHs in children compared with those in adults uncertain. We performed a retrospective review to highlight the salient histopathologic, histochemical, and immunohistochemical features in RMHs and to emphasize their specific clinicopathologic criteria to avoid diagnostic pitfalls. We found 4 (0.3%) infants [2 female infants and 2 male infants, average age: 4 months] with mental, nasal, lingual, and perianal midline RMHs (average size: 1.0 cm) of 1303 patients with cutaneous polypoid lesions. Three were isolated, and 1 was associated with Goldenhar syndrome. The cutaneous polyps demonstrated intermixed skeletal muscle, adipose, and fibrocollagenous core stroma that extended into the dermis and around the dermal appendages. The lingual lesion demonstrated skeletal muscle and fibrocollagenous stroma with prominent nerve bundles and little adipose tissue. All showed interstitial loose mesenchyme. Masson trichome demarcated the triphasic stromal components. Alcian blue demonstrated the loose myxoid mesenchyme. Elastic van Gieson did not show elastic fibers. Desmin demonstrated the skeletal muscle bundles, S100 highlighted the adipose tissue lobules and the nerve bundles, and CD34 displayed the mesenchymal stroma. Ki67 showed a low proliferation index in the loose mesenchyme. Smooth muscle actin did not reveal smooth muscle bundles, but with CD31, they highlighted the thick blood vessels. CD117 revealed prominent mast cells. From our retrospective review series, 4 cases that originally diagnosed as RMHs were excluded. Likewise, we found some examples of the reported cases in the English literature that might have been mistaken for RMHs. This is because they did not fulfill the diagnostic clinicopathologic criteria. RMH constitutes a rare entity with specific clinicopathologic features. Most lesions are isolated. Some are associated with congenital anomalies and syndromes. Strict clinicopathologic diagnostic criteria should be applied to avoid mislabeling look-alike lesions for RMHs.