Goldenhar Research Articles

TOO NEAR, YET TOO FAR: 22Q DELETION AND VELOCARDIOFACIAL SYNDROME MIMIC

<h3>Introduction</h3> Chromosome 22q11.2 contains a cluster of low-copy repeats referred to as LCR22A-H. The deletion of LCR22A-D (proximal-nested) is the most common recurrent microdeletion, which leads to DiGeorge/Velocardiofacial Syndrome. In contrast, deletions in distal regions are less common but have been reported. We report a 36-year-old female with recurrent infections, ear abnormalities, facial asymmetry, and intellectual disability who was found to have deletion of LCR22D-E region. <h3>Case Description</h3> A 36-year-old female presented to our Immunodeficiency Clinic for a second opinion in the setting of recurrent infections and previous diagnosis of Velocardiofacial Syndrome. She was diagnosed with hemifacial microsomia (Goldenhar Syndrome) and ear abnormalities at birth. She was diagnosed with intellectual disability in childhood. At age 30, she developed recurrent infections. She was diagnosed with Velocardiofacial Syndrome at age 24 based on genetic testing. On review of her chromosomal microarray testing, the specific finding noted was a 1.2 mb deletion within the 22q11.21q11.22 at the distal interval, in the LCR22D-E region. <h3>Discussion</h3> Our patient had an outside diagnosis of Goldenhar Syndrome and Velocardiofacial Syndrome. Following re-review of her chromosomal microarray testing, neither of these two diagnoses were accurate. Rather, she had a deletion in the distal LCR22D-E region. Distal deletions are rarer than proximal deletions in the LCR22A-D region that lead to DiGeorge/Velocardiofacial Syndrome. Many patients with distal chromosome 22q11.2 deletions are suspicious for DiGeorge Syndrome due to phenotypic overlap. Reported features for individuals with distal deletions include abnormal ears, facial asymmetry, recurrent infections/immune deficiency, and intellectual disability, all of which our patient had.

Avoidant-restrictive food intake disorder in a male patient with Goldenhar syndrome

BackgroundGoldenhar syndrome (GS) is a rare congenital condition characterized by the underdevelopment of structures deriving from the first and second branchial arches. Clinical phenotype might encompass extra-craniofacial abnormalities, and patients may experience neuropsychiatric disorders with a higher prevalence than healthy controls. To the best of our knowledge, an association between GS and Feeding and Eating Disorders (FED) has never been reported in the literature.Case reportA 15-year-old boy with GS was referred to our outpatient clinic due to severe underweight (BMI of 12.7 kg/m2) and food intake disorder with avoidant restrictive features. After a diagnosis of avoidant-restrictive food intake disorder (ARFID) was made, an inpatient multidisciplinary intervention and outpatient follow-up program were provided, which resulted in the improvement of the boy’s weight and FED psychopathology.ConclusionsThe current report describes the first case of a young male with GS and ARFID. We suggest that ARFID may present itself as part of the spectrum of neuropsychiatric disorders associated with the syndrome; since traumatic experiences and gastrointestinal discomfort play a pivotal role in the development of ARFID among children, attention should be paid to those affected by GS that involves crucial structures in the swallowing process. Further literature evidence will help portray the complex relationship between ARFID and GS more precisely.Level of evidenceLevel V, case report.

The Enigmatic Etiology of Oculo-Auriculo-Vertebral Spectrum (OAVS): An Exploratory Gene Variant Interaction Approach in Candidate Genes.

The clinical diagnosis of oculo-auriculo-vertebral spectrum (OAVS) is established when microtia is present in association with hemifacial hypoplasia (HH) and/or ocular, vertebral, and/or renal malformations. Genetic and non-genetic factors have been associated with microtia/OAVS. Although the etiology remains unknown in most patients, some cases may have an autosomal dominant, autosomal recessive, or multifactorial inheritance. Among the possible genetic factors, gene-gene interactions may play important roles in the etiology of complex diseases, but the literature lacks related reports in OAVS patients. Therefore, we performed a gene-variant interaction analysis within five microtia/OAVS candidate genes (HOXA2, TCOF1, SALL1, EYA1 and TBX1) in 49 unrelated OAVS Mexican patients (25 familial and 24 sporadic cases). A statistically significant intergenic interaction (p-value &lt; 0.001) was identified between variants p.(Pro1099Arg) TCOF1 (rs1136103) and p.(Leu858=) SALL1 (rs1965024). This intergenic interaction may suggest that the products of these genes could participate in pathways related to craniofacial alterations, such as the retinoic acid (RA) pathway. The absence of clearly pathogenic variants in any of the analyzed genes does not support a monogenic etiology for microtia/OAVS involving these genes in our patients. Our findings could suggest that in addition to high-throughput genomic approaches, future gene-gene interaction analyses could contribute to improving our understanding of the etiology of microtia/OAVS.

Aortopulmonary window, aortic arch interruption, and anomalous origin of the right pulmonary artery in a neonate with Goldenhar syndrome.

The combination of aortopulmonary window, interruption of the aortic arch, and anomalous origin of the right pulmonary artery from the ascending aorta is a rare and complex congenital cardiac malformation. Despite good prenatal care in our case, this cardiac anomaly was not detected prior to birth. Untreated infants who do not undergo surgical correction have a mortality rate of 70% in their first year, and 30% will die within the first 3 months of life.

Airway management in Goldenhar syndrome: See it big, Keep it simple!!

Airway management in Goldenhar syndrome: See it big, Keep it simple!!

Oculo-auriculo-vertebral spectrum and maternal drug ingestion: cause or coincidence?

Introduction Oculo-auriculo-vertebral spectrum (OAVS) is aetiologically/pathogenetically a heterogeneous disorder. This study focuses on investigating of maternal drug intake during pregnancy in OAVS cases. Materials and methods Our sample was composed of 114 paediatric cases of OAVS. For each patient, an evaluation form seeking identity, medical history, pregnancy and family data, physical/dysmorphological findings and results from complementary tests was applied. Through the analysis of all the forms applied, the history of drug exposure/maternal diseases were retrospectively studied. Results The age of the population studied ranged between 1 month and 18 years, the majority being male. Regarding otological features, most had pinna involvement: microtia (86.6%); preauricular appendices (41.6%) and preauricular sinus (15.7%). External auditory canal atresia/stenosis was observed in 61.0% of the cases. Most had conductive hearing loss (75.5%) and imaging study revealed middle/inner ear malformations in 21.1% of the cases. Regarding nonotological characteristics, ophthalmological, osteoarticular and cardiac involvement were the 3 most frequently observed. Most cases had no evident cause for the development of anomalies (68.4%). However, in 16.7% a positive family history was identified. A history of drug intake has been elicited in 14.9% of the participants. The drugs intake during pregnancy found in our study were: isotretinoin, fluoxetine, oral contraceptives, levothyroxine, domperidone, enalapril, acyclovir and pseudoephedrine/triprolidine and gestational diabetes in need of treatment. Conclusion Some drugs are unquestionably associated with the development of malformation, such as isotretinoin, however, the other drugs cannot be underestimated, since their synergistic effect with other environmental agents and genetic background may be in the origin of OAVS.

VivaSight Single-Lumen Tube Combined With Hyperangulated Videolaryngoscopy to Rescue Failed Tracheal Intubation in a Patient With Goldenhar Syndrome: A Case Report

This report describes a patient with Goldenhar syndrome undergoing anesthesia for whom Macintosh videolaryngoscopy failed, as the epiglottis was adhered to the posterior pharynx and could not be lifted with a tracheal introducer (Cormack-Lehane grade 3B). Hyperangulated videolaryngoscopy revealed only the arytenoids (Cormack-Lehane grade 2B), even after direct lifting of the epiglottis, and endotracheal tube advancement failed due to unclear tissue resistance. Hyperangulated videolaryngoscopy was combined with a tube-mounted camera (VivaSight single lumen tube). The combination of both camera perspectives was successfully used to allow placement of the endotracheal tube underneath the epiglottis and through the vocal cords.

Long-term efficacy of glycopyrrolate on sialorrhea in Goldenhar syndrome: a case report

BackgroundGoldenhar syndrome (GS) is a rare congenital disease characterized by impaired development of different facial structures and deformations of the teeth structures. Sialorrhea, which can cause difficulties in breathing and language impairment, is very common in GS and often difficult to treat. This case report highlights the short- and long-term importance of the therapeutic choice – glycopyrronium in oral solution - for the treatment of sialorrhea in children with poly-malformative syndrome, complicated by outcomes of post-hemorrhagic hydrocephalus.Case presentationWe report the case of a 6-year-old child with GS, carrying a percutaneous endoscopic gastrostomy after tracheostomy. The child also presented developmental dysfunction of oral motor skills of feeding, complicated by severe sialorrhea, related to the maxillo-facial dysmorphism. Sialorrhea caused several respiratory tract infections and led to an increase in the care burden. Both the inoculations of botulinum toxin and the treatment with scopolamine transdermal patch have shown mild and transient efficacy. The therapeutic choice of glycopyrronium in oral solution was the most suitable for this patient, leading to long-term sialorrhea control.ConclusionsThis clinical experience represents the first long-term efficacy and tolerability evaluation in using glycopyrrolate oral solution in treating drooling in children with GS. The reduction of drooling over time and the lack of clinically relevant adverse events have contributed to the decrease of respiratory tract infections, the development of oral motor skills, and determining a positive psycho-social impact on the patient's quality of life and her family.

Overlap of Delleman-Oorthuys syndrome and Goldenhar syndrome

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

OROFACIAL FEATURES IN GOLDENHAR SYNDROME

Goldenhar syndrome (GS) or hemifacial microsomia (OMIM #164210) is a rare genetic disorder related to gene 14q32, which involves defects in the 1st and 2nd branchial arches reflecting in craniofacial, cardiac, vertebral, and central nervous system alterations. The objective of this work was to demonstrate orofacial characteristics in Goldenhar syndrome. A 7-year-old male patient with GS was referred for dental treatment. Medical history revealed bronchitis and asthma, recurrent pneumonia, and epilepsy, along with motor and sensory impairment and surgeries for ear concha reconstruction and testicle repositioning. On physical evaluation, facial asymmetry, auricular, ocular, and maxillomandibular alterations were observed. Intraoral examination revealed mixed dentition with delayed eruption, caries lesions, poor oral hygiene, and occlusal alteration. Panoramic x-ray was requested. Dental management consisted in caries removal and oral hygiene instructions. Dentists should be aware of oral features of GS for proper dental management.

SURGICAL MANAGEMENT OF GOLDENHAR SYNDROME PATIENT WITH ORTHOGNATHIC SURGERY AND HEMIMANDIBULAR PROSTHESIS: A CASE REPORT

Goldenhar syndrome, also known as hemifacial microsomia (HFM), is a rare congenital disease associated with facial asymmetry and hypoplasia of the jaw. We describe the clinical case of a 13-year-old boy with HFM treated with orthognathic surgery and a customized biphasic calcium phosphate (BCP) bioceramic hemimandibular prosthesis. Clinical and radiographic examination revealed facial asymmetry, right hemifacial microsomia, hypoplasia of the mandible, retrognathism, hypomentonism, canted occlusal plan, and epibulbar dermoid. The primary treatment consisted of bimaxillary orthognathic surgery for occlusal plane correction. Five years later, the patient underwent surgery for hemimandibular reconstruction using BCP customized prosthesis for correction of asymmetry. An improvement of esthetics was noted after surgery.

THE IMPORTANCE OF KNOWLEDGE OF CRANIOFACIAL CHARACTERISTICS OF GOLDENHAR SYNDROME FOR ORAL HEALTH TEAMS: A CASE REPORT

Goldenhar syndrome (GS), also known as oculo-auriculo-vertebral dysplasia, is a rare and multiple congenital disorder with yet an unknown etiology. This study describes the case of a 16-year-old girl with characteristics of GS presenting craniofacial deformities, congenital anomalies/malformations/conditions in the left ear classified as microtia, preauricular appendix in the right ear, as well as the presence of epibulbar dermoid in the left eye, in addition to a vertebral pathology (scoliosis, type S). Through panoramic radiography, we observed the presence of included third molars and the shortening of the left mandibular ramus, which explained the facial asymmetry, and ultimately the patient's facial birth defect called hemifacial microsomy. After clinical and radiographic analysis, the person responsible for the patient was informed about the need for periodic follow-up appointments by a multidisciplinary team. The ability of the dentist to recognize facial abnormalities is essential to perform early diagnosis and adequate treatment.

Orthognathic Surgery in Goldenhar Syndrome With a Rare Course of the IAN.

Although there are multiple variations of accessory foramina described in the literature, to our knowledge there is only 1 report of an isolated mandibular foramen and inferior alveolar neurovascular bundle that courses through the lateral ramus, particularly in those with branchial arch syndromes. Goldenhar syndrome, of the oculo-auriculo-vertebral spectrum, is a rare congenital condition, which most characteristically presents with hemifacial microsomia. Depending on the severity of hemifacial microsomia, there are predictable treatment modalities to correct the consequent facial asymmetry. We report on a patient with Goldenhar syndrome who was found to have a unique course of the inferior alveolar nerve during orthognathic surgery work-up and treatment.

Wormian Bone and Goldenhar Syndrome-Is There Any Association?

Wormian Bone and Goldenhar Syndrome-Is There Any Association?

Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome

Oculo-auriculo-vertebral syndrome (OAVS) is a clinically heterogeneous disorder, with both genetic and environmental contributors. Multiple genes have been associated with OAVS and common molecular pathways, such as retinoic acid and the PAX-SIX-EYA-DACH (PSED) network, are being implicated in the disease pathophysiology. Biallelic homozygous nonsense or hypomorphic missense mutations in PAX1 cause otofaciocervical syndrome type 2 (OTFCS2), a similar but more severe multi-system disorder that can be accompanied by severe combined immunodeficiency due to thymic aplasia. Here we have identified a multi-generational family with mild features of OAVS segregating a heterozygous frameshift in PAX1. The four base duplication is expected to result in nonsense-mediated decay, and therefore cause a null allele. While there was full penetrance of the variant, expressivity of facial and ear features were variable. Our findings indicate there can be monoallelic and biallelic disorders associated with PAX1, and further implicate the PSED network in OAVS.

Tessier cranio-facial clefts presenting to a tertiary eye care center in Northern India: Ophthalmic features and a review of management.

Purpose:Tessier classification is used to classify congenital facial cleft disorders utilizing the anatomical location of the cleft and its extension. The orbital and ocular morbidities associated with the birth disorder are numerous. The authors decided to perform a retrospective analysis of the clinical features of the patients who presented to a tertiary care hospital with orbito-cranial clefts.Methods: The authors retrospectively evaluated the records of patients with craniofacial clefts who had presented to a tertiary eye care hospital in northern India in the last 2 years (January 2019–December 2020). The clinical features were studied, entered in MS Excel, and the data were evaluated.Results: The data of 40 patients with Tessier cleft were found. The majority of the patients were male and presented in the pediatric age group. Unilateral involvement was more common, with maxillary hypoplasia being the most common facial anomaly associated. Eyelid coloboma and euryblepharon was the most common periocular finding; lateral epibulbar dermoid and corneal opacity were the most common ocular surface anomaly. The majority of patients had presented for cosmetic correction. The syndromic association was with Goldenhar syndrome (n = 13), Fraser (n = 2), and one each of Treacher Collins, blepharocheilodontic, organoid nevus, and oculo-dento-digital syndrome. Combined clefts were also seen.Conclusion: Tessier cleft classification is a useful tool to classify cranio-facial left anomalies. Multitudes of ocular and orbital anomalies can be associated with their different forms. Better knowledge and understanding of the classification will aid immensely in predicting the ocular defects and planning their management.

Visual and surgical outcomes of limbal dermoid excision at a tertiary care eye hospital.

To evaluate the presenting complaints, surgical management, surgical outcomes, complications, and postoperative visual acuity following limbal dermoid excision. Retrospective cohort study. Medical records of patients with limbal dermoid presenting between January 2012 and December 2020 were retrieved to extract data regarding demographics, presenting profiles including the best-corrected visual acuity (BCVA), symptoms, anterior segment examination, and refraction. The outcomes included cosmesis, complications, graft transparency, and BCVA at the last follow-up. Fifty-one eyes from 50 patients (27 males) were evaluated. The median age at the time of surgery was 11.5 years (interquartile range, IQR: 0.0-45.7). The median follow-up time was 5 years (IQR: 4-6). Goldenhar syndrome was noted in 5 patients (10%). The indications for surgery were cosmetic concerns (n = 20, 39%), anisometropia (n = 3, 6%), decreased vision (n = 4, 8%), and growth or Dellen formation (n = 2, 4%). Forty-eight were operated upon, opting for simple excision (n = 12, 23.5%), amniotic membrane transplantation (n = 16, 31.4%), lamellar keratoplasty (n = 15, 29.4%), and penetrating keratoplasty (n = 5, 9.8%). The most common complications were corneal scarring (n = 19, 37.2%), corneal vascularization (n = 2, 3.9%), and infection (n = 1, 2%). Astigmatism > 1 D was observed in 34 (66.7%) eyes after dermoid management (p < 0.001). There were no complications in 14 eyes (27%), BCVA was > 20/60 in 43 eyes (84.3%), and only two eyes had BCVA < 20/400. Surgical management of limbal dermoids offers promising functional and anatomic outcomes. However, postoperative astigmatism may require further follow-up and management.

Commentary: Corneal neurotization

Commentary: Corneal neurotization

Oculo auriculo vertebral dysplasia; Goldenhar Syndrome

Goldenhar’s syndrome is a rare condition which was described at first in the early 1950’s. which was characterized by a combination of anomalies such as dermal epibulbar cysts, auricular appendices and malformation of the ears. In 1963, the name oculo-auriculovertebral (OAV) dysplasia for this condition was suggested by gorlin and he also incorporated vertebral anomalies as one of the signs of syndrome. Here, we describe a case of 7 month old male patient with preauricular ear tags, limbal dermoid, cleft palate with tongue tie.

NAD+ deficiency in human congenital malformations and miscarriage: A new model of pleiotropy.

Pleiotropy is defined as the phenomenon of a single gene locus influencing two or more distinct phenotypic traits. However, nicotinamide adenine dinucleotide (NAD+) deficiency through diet alone can cause multiple or single malformations in mice. Additionally, humans with decreased NAD+ production due to changes in pathway genes display similar malformations. Here, I hypothesize NAD+ deficiency as a pleiotropic mechanism for multiple malformation conditions, including limb‐body wall complex (LBWC), pentalogy of Cantrell (POC), omphalocele‐exstrophy‐imperforate anus‐spinal defects (OEIS) complex, vertebral‐anal‐cardiac‐tracheoesophageal fistula‐renal‐limb (VACTERL) association (hereafter VACTERL), oculoauriculovertebral spectrum (OAVS), Mullerian duct aplasia‐renal anomalies‐cervicothoracic somite dysplasia (MURCS), sirenomelia, and urorectal septum malformation (URSM) sequence, along with miscarriages and other forms of congenital malformation. The term Congenital NAD Deficiency Disorder (CNDD) could be considered for patients with these malformations; however, it is important to emphasize there have been no confirmatory experimental studies in humans to prove this hypothesis. In addition, these multiple malformation conditions should not be considered individual entities for the following reasons: First, there is no uniform consensus of clinical diagnostic criteria and all of them fail to capture cases with partial expression of the phenotype. Second, reports of individuals consistently show overlapping features with other reported conditions in this group. Finally, what is currently defined as VACTERL is what I would refer to as a default label when more striking features such as body wall defects, caudal dysgenesis, or cloacal exstrophy are not present.