Continuing Education Activity

Oculo-auriculo-vertebral spectrum (OAVS), also known as Goldenhar syndrome, is a congenital disorder of craniofacial morphogenesis that represents a phenotypic continuum involving malformations of structures derived from the first and second pharyngeal arches. This course outlines the characteristic features of OAVS, including microtia, hemifacial microsomia, epibulbar dermoids, and vertebral anomalies, with frequent multisystem involvement affecting the central nervous, cardiac, renal, and skeletal systems. The underlying multifactorial etiologies are also discussed, involving genetic variants and environmental risk factors, with highly variable clinical expression ranging from isolated facial asymmetry to severe multisystem disease.

This activity reviews OAVS pathophysiological mechanisms, diverse clinical presentation, management strategies, and ocular complications, with particular emphasis on ocular findings and interprofessional care. Participants will also gain an understanding of systemic evaluation, current genetic testing approaches, and coordination with craniofacial, cardiac, orthopedic, ophthalmologic, and rehabilitative teams. This activity for healthcare professionals is designed to enhance the learner's competence in identifying OAVS, performing the recommended evaluation, and implementing an appropriate interprofessional approach to managing this condition, ultimately optimizing patient outcomes and long-term surveillance.

Objectives:

• Identify the diagnostic criteria for oculo-auriculo-vertebral spectrum.
• Evaluate patients with suspected oculo-auriculo-vertebral spectrum using evidence-based diagnostic approaches.
• Implement appropriate surgical and medical management strategies for ocular manifestations of oculo-auriculo-vertebral spectrum.
• Coordinate interprofessional care for patients with oculo-auriculo-vertebral spectrum, effectively communicating across specialties to optimize treatment timing and comprehensive outcomes.

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Introduction

Oculo-auriculo-vertebral spectrum (OAVS) is a congenital disorder of craniofacial morphogenesis, first described by ophthalmologist Maurice Goldenhar in 1952, characterized by an association of ophthalmic, auricular, and facial features. Gorlin et al. subsequently added vertebral anomalies to the classification in 1963.[1] The condition is also known as Goldenhar syndrome, facio-auriculo-vertebral syndrome, or Goldenhar-Gorlin syndrome. The term OAVS, originating from "oculoauriculovertebral dysplasia" as described by Cohen et al in 1989, reflects the phenotypic continuum and significant overlap among malformations of structures derived from the first and second branchial arches.[2]

OAVS affects the eyes, mouth (lips, tongue, and palate), ears, maxilla, and mandible. Multisystem involvement frequently includes the central nervous system, heart, kidneys, and skeletal system, distinguishing it from isolated hemifacial microsomia.[3] Recent advances in genetics have identified multiple causative genes, transforming our understanding of this clinically heterogeneous condition.[4][5] Typical phenotypes include microtia, facial asymmetry, and epibulbar dermoid or lipodermoid. The minimum diagnostic criteria proposed by Tasse et al include either isolated microtia or preauricular tags associated with hemifacial microsomia.[6]

The management of patients with OAVS requires an interprofessional approach due to the wide variety of abnormalities and varying severity of presentations. This review highlights current understanding of etiology, pathogenesis, clinical presentations, and evidence-based management options, with particular emphasis on ocular features.

Etiology

The etiology of OAVS is multifactorial, involving both genetic and environmental factors. While most cases are sporadic, familial cases occur in 2% to 31% of cases, demonstrating a significant genetic contribution.[4][7]

Genetic Factors

Recent genomic studies have revolutionized the understanding of OAVS genetics. Haploinsufficient variants in SF3B2, a component of the U2 small nuclear ribonucleoprotein complex, are the most common genetic cause identified to date, accounting for 3% of sporadic and 25% of familial cases.[5] SF3B2 variants predominantly affect pharyngeal arch I development, with features including mandibular hypoplasia and external ear malformations. Other identified genes include MYT1 (myelin transcription factor 1), involved in the retinoic acid pathway, PAX1, causing a dominantly inherited form, EYA3 with recurrent missense variants, and ZIC3 associated with X-linked inheritance.[8][9][10]

Chromosomal abnormalities include 5p15.33-pter deletion (most common), deletions involving the WNT5B gene at 12p13.33, microduplications on 14q23.1, and anomalies in the 22q11 region.[11] Copy number variations on chromosomes 4 and 22 have been identified as recurrent findings and contain genes relevant to craniofacial development. The genetic heterogeneity reflects complex pathogenesis involving neural crest cell migration, spliceosome function, and transcription factor regulation.[12][13]

Maternal or Parental Risk Factors

Maternal or parental risk factors include maternal diabetes mellitus, multiple pregnancies, maternal hypothyroidism, assisted reproductive techniques, hormonal therapy, tamoxifen exposure, smoking, vasoactive drug use, and advanced parental age.[14] The most widely accepted hypothesis involves disruption of embryonic blood flow during critical developmental periods. Prenatal exposure to retinoic acid has been associated with OAVS-like phenotypes. Epigenetic mechanisms have been proposed to explain gene-environment interactions.[11][15][16][17]

Epidemiology

OAVS has a prevalence of 1 per 3,500 to 45,000 live births, with estimates varying across populations. Facial abnormalities are typically unilateral with right-sided predominance, though asymmetrical bilateral involvement occurs in 10% to 33% of cases.[18][7] Males are more commonly affected than females (ratio 3:2).[19] Most cases are sporadic, though familial occurrence demonstrates both autosomal dominant and recessive inheritance patterns. Affected individuals typically have normal intelligence and life expectancy, though developmental delay has been reported in some cases.[20]

Pathophysiology

OAVS develops due to abnormal development of the first and second pharyngeal arch derivatives, which form at 4 weeks of gestation.[21] These structures arise from neural, muscular, and skeletal elements through ventrolateral migration of cranial neural crest cells. Defects in neural crest cell formation, migration, proliferation, or survival represent important pathogenic mechanisms.[22][23]

Vascular disruption theory proposes that hematoma formation or interruption of vascular supply in the ear and jaw region (usually involving the stapedial artery) during embryogenesis contributes to the phenotype, though this does not fully explain multisystem involvement.[23] Alternative theories suggest OAVS may represent an ectodermal disorder of nondisjunction involving the otic placode, leading to mesodermal disarray similar to occult spinal dysraphism. Recent evidence supports spliceosome dysfunction and impaired neural crest development as key mechanisms in SF3B2-related cases.[24][25]

History and Physical

Clinical History

OAVS presents with a highly variable phenotypic spectrum ranging from isolated unilateral facial asymmetry to severe multisystem involvement. Most cases present in the neonatal period or early infancy with readily apparent craniofacial features, though milder variants may not be recognized until later childhood. The classic triad involves ocular anomalies (eg, epibulbar dermoids), auricular defects (eg, ear tags or microtia), and vertebral abnormalities (eg, hemivertebrae), often accompanied by mandibular hypoplasia (underdeveloped jaw), which can cause facial asymmetry.[26] Other features include facial asymmetry with hemifacial microsomia. Some infants present with feeding difficulties, respiratory compromise, or failure to thrive secondary to mandibular hypoplasia and airway obstruction. Occasionally, the diagnosis is suspected prenatally through ultrasound detection of severe craniofacial or ear anomalies.

A comprehensive history should include:

• Prenatal history: maternal diabetes, medication exposures (particularly vasoactive drugs, retinoic acid), assisted reproductive techniques, multiple gestation
• Birth history: gestational age, birth weight, and immediate neonatal complications
• Developmental milestones: gross motor, fine motor, speech/language, social-emotional domains
• Feeding history: difficulty with sucking, swallowing, or breathing during feeds
• Family history: consanguinity, similar features in siblings or extended family members.

Physical Examination

Physical examination requires a systematic evaluation of all potentially affected organ systems. Right-sided involvement is more common in unilateral cases, though 10% to 33% demonstrate bilateral asymmetric involvement.[18][7] The examination should proceed systematically, evaluating craniofacial structures, neurological function, sensory organs, cardiovascular system, musculoskeletal system, and other potentially affected systems. Early comprehensive evaluation enables timely intervention for life-threatening complications, particularly airway obstruction and cardiac defects, while facilitating appropriate referrals for subspecialty management.

Central nervous system

Neuroimaging studies in OAVS reveal a spectrum of intracranial abnormalities occurring in approximately 47% to 56% of patients.[27] Brain magnetic resonance imaging (MRI) abnormalities reveal occipital encephalocele, absent septum pellucidum, Arnold-Chiari malformation type II, cortical dysplasia, enlarged ventricles, and hypoplasia of craniofacial bones. Functional neurological deficits encompass autism spectrum disorder, global developmental delay, speech abnormalities, dysphagia, and sensory impairments, including hearing loss and visual impairment. Neurodevelopmental concerns warrant early assessment, as approximately 62% of children with global developmental delay may meet criteria for autism spectrum disorder.[28]

Craniofacial anomalies

Craniofacial features are typically unilateral (85% of cases) but may present with asymmetrical bilateral involvement. Hemifacial microsomia manifests as mandibular hypoplasia with malar flattening, often associated with temporomandibular joint abnormalities. Orofacial clefting includes macrostomia, cleft lip, cleft palate, epiglottic fold malformation, and bifid uvula. Dental abnormalities encompass delayed tooth development, premolar and molar agenesis, and enamel-dentin malformations. Cranial nerve involvement may present as facial palsy, trigeminal anesthesia, and asymmetrical palatal elevation.[29] 

Auricular abnormalities

External and middle ear abnormalities predominate in OAVS, with varying degrees of inner ear involvement. External ear abnormalities include microtia (small ears), anotia (absent ears), preauricular tags/fistulas, and atresia of the external auditory canal. Microtia classification ranges from type I (a small but structurally complete external ear) to type IV (anotia with complete absence of external structures). Middle ear abnormalities include reduced cavity size, ossicular chain dysplasia, and oval window atresia, the latter occurring in 74% of examined ears and invariably accompanied by ossicular malformations.[18]

Vertebral malformations

Vertebral anomalies occur in approximately 70% of OAVS patients, predominantly affecting the cervical spine, with extension into the thoracic and, less commonly, the lumbar regions.[7] Cervical findings include hemivertebrae, spina bifida occulta, block vertebrae, cervical ribs, and atlas occipitalization. Thoracic involvement presents with hemivertebrae and block vertebrae. Scoliosis is a significant concern that requires orthopedic surveillance throughout growth and development.[30]

Cardiac abnormalities

Congenital heart defects are reported in approximately 32% to 39% of patients with OAVS, though literature estimates vary widely from 5% to 58% depending on diagnostic criteria.[31][32] Cardiac malformations classified by developmental mechanism include conotruncal defects (39%), septal defects (32%), targeted growth defects (14%), and situs/looping abnormalities (7%).[31] Specific lesions include tetralogy of Fallot (the most common conotruncal defect), ventricular septal defect, atrial septal defect, persistent truncus arteriosus, transposition of great vessels, and aortic arch anomalies.

Early cardiac evaluation with echocardiography is essential, as cardiac malformations significantly impact management and prognosis. Children with OAVS and cardiac defects demonstrate a younger age at first evaluation and higher mortality rates compared to those without cardiac involvement.[31]

Urogenital anomalies

Urogenital anomalies occur in 23% to 39% of patients, ranging from renal agenesis and hypoplasia to hydronephrosis and polycystic kidney disease.[33]

Pulmonary and gastrointestinal manifestations

Gastrointestinal involvement includes tracheoesophageal fistula, esophageal atresia, and various respiratory system abnormalities affecting laryngeal, pharyngeal, and pulmonary structures.[34]

Ocular features

Ocular involvement occurs in 6.7% to 100% of cases, with severe visual impairment in 7.7% to 30%, necessitating comprehensive ophthalmic evaluation. The most common finding is epibulbar or limbal dermoid, followed by lipodermoid and eyelid coloboma. Other manifestations include microphthalmia, anophthalmia, ptosis, strabismus (including Duane retraction syndrome), and lacrimal duct stenosis.

Rooijers et al classified ocular anomalies into the following 4 categories:

• Type I: Anatomical anomalies not impairing vision (eg, lid coloboma, lipodermoid, orbital dystopia, lacrimal stenosis)
• Type II: Anatomical anomalies likely impairing vision (eg, epibulbar dermoid, microphthalmos, anophthalmos, exposure keratopathy, cataract, fundal coloboma, optic nerve hypoplasia)
• Type III: Motility disorders (eg, esotropia, exotropia, Duane syndrome, abducent nerve anomaly, ptosis)
• Type IV: Refractive errors (eg, astigmatism, anisometropia, myopia, hyperopia) [35]

Upper eyelid coloboma at the junction of the inner and middle one-third distinguishes OAVS from Treacher Collins syndrome, which features lower eyelid coloboma.

Evaluation

A comprehensive systemic evaluation is warranted in OAVS due to the high frequency of associated multiorgan involvement.

Limbal Dermoid Assessment

Limbal dermoids are benign congenital choristomas presenting as elevated, opaque, yellow-white masses at the limbus with hair follicles and sebaceous glands, most commonly at the inferotemporal location (see Image. Limbal Dermoid). These lesions are usually stable and may cause astigmatism, leading to amblyopia. Anterior segment optical coherence tomography and ultrasound biomicroscopy assess lesion depth and anterior chamber involvement, facilitating surgical planning.[36]

Limbal dermoids are historically and clinically graded using the following 2 primary methods:  

• Classical anatomical grading: This classic 3-tier anatomical grading system is based on lesion size and depth and is the most widely used in clinical practice.[37][38]

  • Grade I: Superficial tumors measuring less than 5 mm and localized strictly to the limbus. These are the most common and typically cause only mild astigmatism.
  • Grade II: Larger tumors that cover a significant portion of the cornea and extend deep into the stroma, reaching down to Descemet’s membrane without involving the anterior chamber.
  • Grade III: The most severe form, involving the entire cornea and extending through the full thickness of the ocular coats, potentially involving the iris and anterior chamber structures.
• New visual scoring system: Proposed in 2017 to better predict visual outcomes after keratoplasty, this system is more functionally focused, assigning points (0–3) to 3 specific clinical criteria (corneal involvement, elevation of the surface, and conjunctival involvement).[39]

Comprehensive Ophthalmic Evaluation

Eye examination should include visual acuity testing, ocular movements, strabismus evaluation, lid and adnexa examination, anterior and posterior segment assessment, and gonioscopy. Eyelid coloboma causing exposure keratopathy requires urgent correction to preserve vision.

Interprofessional Evaluation

Given the multisystem involvement, an interprofessional evaluation is recommended. Otolaryngologic assessment is required for the evaluation of ear malformations. Investigations include CT or MRI, along with conductive and brainstem audiometry for hearing assessment. Cardiac evaluation with echocardiography is essential to identify associated congenital heart defects. An orthopedic assessment should be performed to evaluate vertebral anomalies. Neuropsychiatric evaluation is indicated to assess developmental and cognitive concerns, and a comprehensive pediatric evaluation is necessary to identify and manage systemic involvement.[40]

Genetic Testing and Counseling

While diagnosis is primarily clinical, genetic testing includes chromosomal microarray analysis and next-generation sequencing for identified causative genes. Examination of siblings and family members helps identify inheritance patterns. Recurrence risk for siblings of affected individuals with normal chromosomes and no family history is 2% to 3%.[41] Phenotypic heterogeneity complicates the prediction of disease severity in subsequent children.

Prenatal Diagnosis

Fetal ultrasound detects severe ear anomalies, microtia, preauricular tags, and mandibular hypoplasia. Microphthalmia and orbital hypoplasia can be identified as early as 14 weeks of gestation.[42] Three-dimensional scans identify milder cases. Invasive diagnostics (chorionic villus sampling, amniocentesis) are indicated only when specific genetic mutations are confirmed.[42]

Treatment / Management

Upper Eyelid Coloboma

An upper eyelid coloboma may require repair within days of life to prevent corneal ulceration, perforation, and amblyopia. Initial management includes lubricating drops, gels, and bandage contact lenses. Surgical approach depends on the following defect sizes:

• Small defects (<25% lid length): Direct apposition
• Moderate defects (25%-35%): Tenzel semicircular flap
• Large defects (>35%): Cutler-Beard or Mustarde rotation flap, tarsomarginal grafts, modified Hughes procedure [43]

Limbal Dermoid Management

Management depends on the grade and extent. Indications for surgery include poor vision, noncompliance with spectacles, enlarging lesion encroaching the visual axis, amblyopia, chronic ocular surface inflammation, cosmetic concerns, anisometropia, inadequate lid closure, and all grade II to III dermoids.

Recent advances in surgical techniques include:

• Simple excision with adjuvants: The use of 0.02% mitomycin C for 2 minutes may help prevent pseudopterygium formation.[44]
• Amniotic membrane transplantation (AMT): Multilayered AMT with fibrin glue promotes epithelial healing and reduces scarring.
• The Bowman membrane lenticule with limbal stem cell transplantation: A novel technique using autologous simple limbal epithelial transplantation (AutoSLET) and a Bowman membrane lenticule provides rapid epithelialization and significant visual improvement.[45]
• Lamellar keratoplasty: The treatment is used for deeper lesions with stromal involvement
• Corneal tattooing: This procedure improves the cosmetic appearance of residual scars.

Postoperative astigmatism occurs in approximately 67% of cases and requires ongoing management.[46]

Lipodermoid Management

Lipodermoids, predominantly in the superotemporal quadrant, rarely cause functional impairment. Surgical treatment is primarily for cosmetic purposes and involves simple excision with conjunctivoplasty, with or without AMT.

Management of OAVS requires a highly coordinated, interprofessional approach due to its multisystemic nature and the variable timing of required interventions. Because the syndrome affects the first and second branchial arches, the team is typically led by a craniofacial center consisting of the various specialists, including:

• Pediatricians: These teams are responsible for the comprehensive management of children with multiple systemic disorders with OAVS.
• Ophthalmologists: These specialists are responsible for managing the "oculo" portion of the triad, including the staged excision of limbal dermoids and the correction of eyelid colobomas and strabismus.
• Plastic and craniofacial surgeons: Mandibular reconstruction (often via distraction osteogenesis), repair of macrostomia, and soft tissue augmentation for hemifacial microsomia are the focus of these specialty teams.
• Otolaryngologists (ENT) and audiologists: These team members address microtia, external auditory canal atresia, and conductive hearing loss through hearing aids or bone-anchored hearing systems.
• Orthodontists: Orthodontists coordinate with surgeons to manage malocclusion and jaw asymmetry, often requiring long-term monitoring as the child grows.
• Orthopedic surgeons: These specialists monitor and treat vertebral anomalies, eg, scoliosis or hemivertebrae.
• Speech-language pathologists: management of articulation difficulties arising from macrostomia, cleft palate, or hearing impairment requires the expertise of speech-language pathologists.
• Geneticists: These teams perform genetic analysis and prenatal counselling.
• Anesthetists: The presence of congenital malformations makes anesthesia challenging, requiring special precautions and making anesthetists essential.[47]

• Pediatric cardiologists and urologists: These specialist teams perform baseline screenings for congenital heart defects and renal anomalies soon after diagnosis.
• Psychologists and social workers: Psychosocial support for patients and families navigating the challenges of visible facial differences and frequent surgeries involves coordinated interventions with psychologists and social workers.[48]

Differential Diagnosis

Various inheritable disorders and syndromes have overlapping clinical features with OAVS.[11] However, unlike OAVS, these syndromes have distinct, recognizable phenotypic features (see Table 1).

Table

Table 1. Differential Diagnoses of Oculo-Auriculo-Vertebral Spectrum.

Staging

OAVS lacks a universally accepted formal staging system. Instead, severity is described using severity-based classification frameworks.

Pruzansky-Kaban Classification of Mandibular Hypoplasia

The Pruzansky-Kaban classification and the OMENS classification system (see Table 2) are the most commonly used systems to characterize the phenotypic spectrum.[49] The Pruzansky-Kaban classification is divided into the following types:

• Type I

  • Mild mandibular hypoplasia
  • The temporomandibular joint (TMJ) is normal or nearly normal
  • Surgical reconstruction is usually straightforward
• Type IIa

  • Moderate mandibular hypoplasia
  • TMJ is small or abnormally shaped but functional
  • Reconstruction is possible with moderate difficulty
• Type IIb

  • Severe mandibular hypoplasia
  • TMJ is malformed or hypoplastic
  • Reconstruction is complex and may require distraction osteogenesis or grafting.
• Type III

  • Complete absence of the mandibular ramus and TMJ
  • Reconstruction is highly complex and often staged, sometimes requiring costochondral grafts or advanced craniofacial techniques.[50]

Table

Table 2. OMENS Classification:[49].

Prognosis

Prognosis varies with disease severity and the timing of intervention. Early management of airway obstruction and cardiac complications is critical. Life expectancy is generally normal with appropriate care. Visual prognosis is favorable with early correction of lid coloboma and excision of the dermoid to prevent amblyopia. Social stigma significantly impacts mental health in affected children. School-age children may experience social alienation, poor self-image, depression, and feelings of isolation. Family functioning may be affected by the stress of caring for a child with complex medical needs. Psychiatric consultation and counseling are essential components of comprehensive care.[51] The presence of intellectual disability affects quality of life, emphasizing the importance of early management of speech abnormalities and developmental support.[52]

Complications

Ocular complications include amblyopia, corneal opacity, vision loss, exposure keratopathy, corneal ulceration, chronic ocular surface inflammation, inadequate lid closure, and postoperative astigmatism. Long-term follow-up is essential for detecting and managing these complications.[53]

Postoperative and Rehabilitation Care

Postoperative rehabilitation includes proper refractive correction and aggressive amblyopia management following dermoid excision. Regular monitoring for astigmatism progression and corneal scarring is necessary. Speech therapy, hearing rehabilitation, and developmental support optimize functional outcomes.[54]

Consultations

Management of OAVS requires an interprofessional approach. Early referral for timely evaluation should include a pediatrician, cardiologist, oro-maxillofacial surgeon, ophthalmologist, orthodontist, otolaryngologist, orthopedic surgeon, neurologist, nephrologist, and psychiatrist. Genetic consultation is recommended for counseling and family planning.

Deterrence and Patient Education

Education and counseling should begin in the prenatal period if OAVS is suspected. Families should be informed that this is a congenital malformation with variable severity and that management requires an interprofessional approach. Early evaluation and timely intervention are critical for the correction of structural and functional anomalies. Genetic counseling and assessment of other family members are recommended to guide family planning and evaluate recurrence risk.

Enhancing Healthcare Team Outcomes

OAVS, also known as Goldenhar syndrome, is a congenital disorder of craniofacial development involving derivatives of the first and second pharyngeal arches. It presents with variable combinations of microtia, hemifacial microsomia, epibulbar dermoids, vertebral anomalies, and frequent cardiac, neurologic, renal, and skeletal involvement. Clinical severity ranges from mild unilateral facial asymmetry to complex multisystem disease requiring staged surgical and medical interventions. Early recognition is critical to identify airway compromise, feeding difficulties, congenital heart defects, hearing impairment, and vision-threatening ocular lesions. Because manifestations evolve with growth and development, affected children require longitudinal monitoring and coordinated specialty care.

Effective management demands advanced clinical skills in comprehensive assessment, risk stratification, and timely referral. Pediatricians and general practitioners coordinate initial evaluation and longitudinal oversight, while ophthalmologists, otolaryngologists, maxillofacial surgeons, cardiologists, orthopedists, and geneticists address organ-specific concerns. Family screening and genetic counseling provide valuable information for family planning.[55][56] Nurses and advanced practitioners reinforce surveillance, education, and care continuity, and pharmacists support safe medication use. Speech therapists, psychologists, and social workers address developmental and psychosocial needs. Structured interprofessional communication, shared care plans, family-centered counseling, and regular team conferences enhance patient safety, optimize timing of interventions, and improve functional and psychosocial outcomes.

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Disclosure: Venkata Sushma Chamarthi declares no relevant financial relationships with ineligible companies.

Disclosure: Phani Prabhakara Srinivasa Sastry Chamarthi declares no relevant financial relationships with ineligible companies.

Disclosure: Koushik Tripathy declares no relevant financial relationships with ineligible companies.