Ophthalmology– Goldenhar Syndrome

Basics

Description

Goldenhar syndrome is a congenital craniofacial disorder within the oculo-auriculo-vertebral spectrum (OAVS). It is characterized by a variable combination of epibulbar choristomas, preauricular skin tags or appendages, vertebral abnormalities, and hemifacial microsomia.

The abnormalities usually involve structures derived from the first and second branchial arches. Ocular involvement is common and may affect the conjunctiva, cornea, eyelids, lacrimal system, ocular motility, and visual development.

Epidemiology

Goldenhar syndrome occurs in approximately 1 in 3,500 to 5,600 births. Males are affected somewhat more frequently than females.

The severity and combination of abnormalities vary widely among affected individuals.

Risk Factors

No definitive environmental or maternal risk factor has been established.

Most cases occur sporadically.

Genetics

Most individuals with Goldenhar syndrome have no affected family members.

Both autosomal dominant and autosomal recessive inheritance have occasionally been reported. Familial cases with bilateral auricular involvement may be more suggestive of inherited disease.

Several chromosomal abnormalities have been associated with the phenotype, including abnormalities involving 5p and 22q11.2.

A number of genetic loci have been proposed, and mutations involving SALL1 have been identified in some patients with overlapping phenotypes.

Because the genetic basis is heterogeneous, genetic evaluation is useful when there are atypical findings, multiple affected relatives, or associated systemic abnormalities.

Pathophysiology

Goldenhar syndrome is believed to result from abnormal embryologic development affecting the first and second pharyngeal arches.

One proposed mechanism is impaired migration or development of neural crest cells, which contribute to formation of the craniofacial skeleton, connective tissues, and other structures.

Disruption of these developmental pathways produces variable abnormalities of the maxilla, mandible, ears, vertebrae, eyelids, and ocular surface.

Etiology

The exact etiology is heterogeneous and incompletely understood.

Abnormal development of neural crest-derived structures and the first and second branchial arches is believed to be central to the disorder.

The ocular abnormalities are related particularly to abnormal development of tissues derived from the first branchial arch and adjacent craniofacial structures.

Commonly Associated Conditions

The characteristic craniofacial finding is hemifacial microsomia, in which one side of the face is underdeveloped.

Auricular abnormalities are common and may include microtia, malformed external ears, preauricular appendages, and hearing loss or deafness.

Vertebral abnormalities may cause scoliosis or torticollis.

Other patients have associated cardiovascular, neurologic, musculoskeletal, renal, or genitourinary abnormalities.

Nasal and airway abnormalities may also occur.

Diagnosis

History

A detailed family history should be obtained, with attention to craniofacial abnormalities, hearing loss, ear deformities, vertebral abnormalities, and similar ocular findings.

Developmental history and symptoms related to hearing, breathing, feeding, renal function, or neurologic problems should also be reviewed.

Ophthalmic Examination

A complete ophthalmic examination is essential because several abnormalities can interfere with visual development.

Epibulbar Dermoid

The most common ocular finding is an epibulbar or limbal dermoid.

It is classically located in the inferotemporal limbal region and is usually ipsilateral to the more severely affected side of the face.

The lesion is a congenital choristoma composed of normal tissue located in an abnormal position. It can contain hair follicles and occasionally protruding cilia.

A large limbal dermoid can distort the corneal curvature and cause significant astigmatism, which may lead to amblyopia.

Lipodermoid

A lipodermoid, or dermolipoma, is another common choristoma.

It is usually located temporally, often in the superotemporal or lateral conjunctival fornix. It may extend posteriorly toward orbital tissues and extraocular muscles.

Strabismus and Ocular Motility

Ocular alignment and motility should be carefully assessed.

Duane syndrome and other ocular motility disturbances have been associated with Goldenhar syndrome.

Strabismus itself may contribute to amblyopia.

Eyelid Abnormalities

An upper eyelid coloboma may occur and can sometimes be associated with adhesion between the eyelid and globe.

Other less common abnormalities include ptosis and shortening or distortion of the palpebral fissure.

If an eyelid coloboma prevents adequate ocular surface coverage, exposure-related corneal damage may occur.

Lacrimal Abnormalities

Congenital anomalies of the lacrimal drainage system may occur and can produce chronic tearing or recurrent infection.

Corneal Sensation and Tear Production

Some patients have decreased corneal sensation or reduced tear production.

When severe, these abnormalities can lead to neurotrophic or exposure-related corneal ulceration.

Microphthalmia and Posterior Segment Findings

Less commonly, patients may have microphthalmia, optic nerve hypoplasia, or macular hypoplasia.

The caruncle can also be absent, displaced, or otherwise abnormal.

Visual Assessment

Visual acuity should be assessed using age-appropriate techniques.

Particular attention should be paid to refractive error and amblyopia, because limbal dermoids can induce significant astigmatism even when the lesion itself does not obstruct the visual axis.

Cycloplegic refraction is therefore important in children.

Systemic Examination

A complete systemic evaluation should assess for facial asymmetry, mandibular and maxillary hypoplasia, preauricular appendages, microtia, vertebral abnormalities, hearing impairment, cardiac defects, and renal abnormalities.

Because the syndrome is multisystem, evaluation frequently requires several specialties.

Diagnostic Tests and Interpretation

Laboratory Testing

Routine laboratory testing is not required when the syndrome is isolated and the diagnosis is clinically evident.

Laboratory evaluation should be directed by associated systemic findings, particularly when renal or genitourinary abnormalities are suspected.

Imaging

Facial and neurologic imaging may be obtained when significant craniofacial abnormalities are present.

Cervical spine imaging is often useful because vertebral abnormalities are an important component of the syndrome.

CT or MRI may be indicated depending on associated craniofacial, neurologic, or orbital abnormalities.

Audiology

All affected patients should undergo appropriate hearing assessment, because hearing impairment is common and may substantially affect language development.

Renal Evaluation

A renal ultrasound may be appropriate when there are clinical findings suggesting renal involvement or as part of a broader syndromic evaluation.

Genetic Evaluation

Genetics consultation can assist with diagnosis, identification of associated syndromes, selection of molecular or chromosomal testing, and recurrence counseling.

Pathological Findings

Epibulbar dermoids contain collagenous connective tissue covered by conjunctival or corneal epithelium.

They may contain skin appendages such as hair follicles, sebaceous glands, or sweat glands, reflecting their choristomatous nature.

Differential Diagnosis

Conditions with overlapping craniofacial abnormalities include Treacher Collins syndrome, Pierre Robin sequence, Townes-Brocks syndrome, oculoectodermal syndrome, and other craniofacial or branchial arch disorders.

The characteristic combination of epibulbar dermoid, ear abnormalities, hemifacial microsomia, and vertebral defects strongly supports the diagnosis of Goldenhar syndrome.

Treatment

There is no medication that treats the underlying congenital disorder.

Management is directed toward preserving vision, correcting associated abnormalities, and treating systemic complications.

Amblyopia Treatment

Amblyopia should be treated promptly when present.

This may involve full correction of refractive error, patching, or other standard amblyopia therapy.

Because astigmatism induced by a limbal dermoid is a common cause of amblyopia, accurate optical correction is particularly important.

Surgical Treatment

Limbal Dermoid

Surgical excision of a limbal dermoid may be considered when there is significant cosmetic concern, chronic irritation, foreign-body sensation, induced astigmatism contributing to amblyopia, progressive corneal involvement, or other corneal complications.

Surgery does not always eliminate the induced astigmatism, so refractive and amblyopia treatment may still be required afterward.

Depending on the depth and size of the lesion, ocular surface reconstruction or corneal procedures may be necessary.

Lipodermoid

Lipodermoid excision should be approached cautiously.

These lesions may extend deeply and can lie close to extraocular muscles, the lacrimal gland, and orbital structures. Aggressive removal can cause restrictive strabismus, scarring, or other complications.

Therefore, only the symptomatic or cosmetically significant accessible portion may be removed in selected cases.

Eyelid Surgery

Eyelid colobomas, ptosis, and other lid abnormalities may require reconstructive surgery, particularly when the cornea is exposed or the visual axis is obstructed.

Craniofacial Surgery

Craniofacial and plastic surgical procedures may be required for significant hemifacial microsomia, mandibular hypoplasia, auricular abnormalities, or other facial malformations.

Treatment is often staged according to growth and functional needs.

Referral

Management is frequently multidisciplinary.

Patients may require referral to ophthalmology, pediatric ophthalmology, craniofacial or plastic surgery, otolaryngology, audiology, genetics, orthodontics, oral and maxillofacial surgery, and other specialties according to the associated abnormalities.

Ongoing Care and Follow-Up

Children require regular ophthalmologic follow-up to monitor visual acuity, refractive error, amblyopia, strabismus, corneal health, and growth or symptoms related to choristomas.

A limbal dermoid that remains stable and asymptomatic may be observed, but refractive effects should still be monitored carefully.

Hearing, craniofacial development, vertebral abnormalities, and associated systemic conditions should also be followed by the appropriate specialists.

Patient Education

Families should understand that Goldenhar syndrome has a wide spectrum of severity and that not every affected child develops all associated abnormalities.

The importance of early treatment of refractive error and amblyopia should be emphasized because visual loss from amblyopia may be preventable.

Children with hearing impairment should receive early audiologic intervention and appropriate educational support.

Genetic counseling may help families understand the usually sporadic nature of the disorder and the possibility of recurrence in familial cases.

Prognosis

The ocular prognosis is generally good when amblyopia, refractive error, exposure, and strabismus are recognized and treated early.

Visual outcome may be less favorable when significant microphthalmia, optic nerve hypoplasia, macular abnormalities, or severe corneal disease is present.

Overall prognosis depends largely on the severity of associated craniofacial and systemic abnormalities.

Complications

Ocular complications include amblyopia, significant astigmatism, strabismus, corneal dellen, exposure keratopathy, neurotrophic corneal disease, and corneal ulceration.

Large or symptomatic choristomas may cause chronic irritation or progressive corneal distortion.

Associated hearing impairment and craniofacial abnormalities can also substantially affect development and quality of life if they are not identified and managed early.