Goldenhar Syndrome (Oculo-Auriculo-Vertebral Spectrum):

6 day-old male with limbal dermoids

Jordan M. Graff, MD, Rahul Bhola, MD, and Richard J. Olson, MD

March 31, 2006

Chief Complaint: 6 day-old male patient is referred for evaluation of "fleshy masses" on the lateral aspect of both corneas.

History of Present Illness: The patient was born at 36 weeks gestation and was delivered by normal spontaneous vaginal delivery (NSVD). He had mild neonatal jaundice that did not require treatment and was improving. Shortly after delivery, he was noted to have bilateral "fleshy masses" on the corneas and an irregular right upper eyelid. This prompted initial referral to the University of Iowa Hospitals and Clinics Pediatric Ophthalmology division for evaluation.

(This patient was first seen here in June of 2002 and has been followed and cared for since that time. The description of his initial presentation is here provided and his course of care is described in the Course section of this case presentation).

Past Ocular History: This was the patient's first presentation for eye care.

Medical History: Normal delivery at 36 weeks gestation to a 26-year-old mother in her fourth pregnancy whose first three pregnancies were lost to spontaneous abortion (G4 P1 SAB3). The patient had mild neonatal jaundice not requiring treatment. No other medical issues noted to date and infancy has been otherwise normal with achievement developmental milestones.

Medications: None

Family History: Noncontributory. No family history of facial syndromes or ocular conditions.

Social History: Newborn infant lives at home with his parents.

Newborn Ocular Exam:

Figure 1: External image taken at 10 months of age demonstrates bilateral limbal dermoids at the temporal limbus of both eyes, (OD > OS). The black arrow indicates the site of right upper eyelid coloboma.
External image taken at 10 months of age demonstrates bilateral limbal dermoids at the temporal limbus of both eyes, (OD > OS). The black arrow indicates the site of right upper eyelid coloboma.

Course: The constellation of bilateral limbal dermoids, eyelid coloboma, and preauricular skin tags was consistent with a diagnosis of Goldenhar syndrome. The limbal dermoids did not obstruct the visual axis and the right upper eyelid coloboma did not prevent corneal protection with lid closure. As such, the patient's ocular condition did not require urgent intervention in the first weeks of life. We invited the involvement of the Medical Genetics team to evaluate the patient and aid in additional work-up for more serious malformations that can occur in the oculo-auriculo-vertebral spectrum. The patient was scheduled to return to our clinic within 1-2 months and to be followed closely for any change in visual cues or refraction during the ensuing months.

Evaluation was carried out by the Pediatric and Medical Genetics teams at the University of Iowa. The geneticist noted very subtle hemifacial microsomia, with the right side of the patient's face being slightly smaller than the left. He had no clefting of the lip or palate. Audiology tests on two different occasions were normal. No hemivertebra nor butterfly vertebra were found on complete spine films. MRI of the brain was completely normal. Renal ultrasound at birth was normal. Evaluation by a cardiologist revealed a faint (1/6) vibratory murmur at the cardiac apex which was felt to be benign. Electrocardiogram (EKG) and chest x-ray were within normal limits for age. Peripheral blood analysis revealed a normal 46,XY karyotype.

The patient was followed closely in our clinic during this time. Early cycloplegic refraction revealed significant astigmatism in both eyes:

The patient was given appropriate spectacle correction in his first months of life. The patient continued to be central, steady, and maintained (CSM) in fixation in each eye independently throughout the first several months of life and tolerated his glasses well. By the age of 10 months, the mother began to notice that the eyelid in the right eye would "hang up" on the limbal dermoid. Several times, the mother would find the toddler asleep with the right eye incompletely closed. Given the exposure of the right eye, it was determined to proceed with removal of the right limbal dermoid. The mass was excised primarily with a maximal depth of dissection of 60%. No lamellar keratoplasty was required.

The patient recovered well from this procedure and healed promptly with minimal corneal scar and no recurrence of limbal dermoid in the 2 years that followed. Visual acuity evaulation has consistently shown him to be central, steady, and maintained (CSM) in both eyes with good fixation and following (F&F) in each eye independently. The corneal shape has stabilized on the right side since the surgery and there is still significant astigmatism. The astigmatism in the left eye, without any intervention, has settled down significantly compared to early measurements. Refraction at follow-up in October of 2005 (age 3 yr 4/12 mo) was :

The limbal dermoid on the left side has not changed in size, does not threaten the visual axis and does not inhibit closure of the lids (see Figure 2B and 3). The induced astigmatism from this dermoid is small and readily corrected with spectacles. The left eye continues to be the patient's favored eye, but there is no evidence of amblyopia. Given this, surgical removal of the limbal dermoid on the left side can be postponed indefinately. The lid coloboma (see Figure 3) does not result in corneal exposure and will not require surgery. Small skin tags on the right cheek and preauricular area (see Figure 2C) can be removed, if desired, for cosmesis as the child grows.

Figure 2
A: Right eye 2 years after removal of large limbal dermoid (see Figure 1). Residual corneal haze (arrows) indicates the former border of the excised dermoid. B: Left eye slit lamp view shows the elevated, fatty appearance of this limbal dermoid. Hair may be seen in these fatty tumors as well. C: Preauricular skin tag, right ear. The ear itself has no deformity or microtia.
Right eye 2 years after removal of large limbal dermoid (see Figure 1). Residual corneal haze (arrows) indicates the former border of the excised dermoid. Left eye slit lamp view shows the elevated, fatty appearance of this limbal dermoid. Hair may be seen in these fatty tumors as well. Preauricular skin tag, right ear. The ear itself has no deformity or microtia.

Figure 3: External image at 3 years of age shows a clear visual asis in both eyes, the right upper eyelid coloboma, and the limbal dermoids at the temporal limbus of the left eye, unchanged since infancy. The light reflex from this photograph gives the appearance of a small exo-deviation, but cover-uncover and alternate-cover testing showed the patient to be orthophoric.
External image at 3 years of age shows a clear visual asis in both eyes, the right upper eyelid coloboma, and the limbal dermoids at the temporal limbus of the left eye, unchanged since infancy. The light reflex from this photograph gives the appearance of a small exo-deviation, but cover-uncover and alternate-cover testing showed the patient to be orthophoric.

Discussion:

Goldenhar syndrome (also known as oculo-auriculo-vertebral spectrum or hemifacial microsmia) is a developmental malformation of the first and second branchial arches. The constellation of abnormalities was first described by Dr. Maurice Goldenhar (Goldenhar, 1952) in a pair of monozygotic twins with epibulbar dermoids, auricular appendages, malformations of the auricle, and hemifacial microsomia. This entity was further described as the oculo-auriculo-vertebral spectrum ten years later (Gorlin, 1963). Given the heterogeneous and variable presentation of this condition, it is probably best to describe it as a spectrum of dysmorphogenesis, the main characteristics of which are 1) epibulbar dermoids, 2) auricular appendages or malformations and 3) skeletal anomalies (including hemifacial microsomia and/or hemivertebra or butterfly vertebra. Other associated facial defects can include microphthalmos, strabismus, eyelid coloboma, preauricular fistulas, macrostomia, maxillary and mandibular hypoplasia, cleft palate, cleft lip, and middle and/or inner ear deformities contributing to hearing loss. In the majority of cases, only one side of the body is affected (interestingly, the right side is usually the more severely affected). Some affected individuals may have congenital heart defects, renal defects (hypoplasia or agenesis), or central nervous sytem (CNS) malformations (intracranial lipomas, hydrocephalus, cranial nerve dysgenesis and mental retardation). No formal minimal diagnostic criteria have been widely accepted, though some have been suggested (Tasse et al, 2005).

The case we present here is certainly a more mild variation of the Goldenhar condition. As was the case with this child, Goldenhar syndrome is generally believed to be a spontaneous malformation in utero, without a predictable inheritance pattern. No isolated genetic defect has been confirmed as responsible for the syndrome, though there are small studies that support both autosomal dominant (Beck et al 2005, Stoll et al 1998, Singer et al 1994) and autosomal recessive (Cohen, 2000) inheritance pattern in some families and underlying gene defects have been theorized. There has been no proven association of Goldenhar syndrome with any maternal infection, medication or other insult. Incidence is between 1 in 3,000 and 1 in 5,600 live births. Males are more affected than females in a 2:1 ratio.

Treatment for the disease varies according to the severity of manifestation. With regards to the role of the ophthalmologist, treatment is directed first at strong amblyogenic risks (including obstruction of the visual axis, severe astigmatism, or strabismus), second at ocular exposure (due to large lid coloboma or limbal dermoid preventing lid closure), and third at working with craniofacial surgeons in cases severe microsomia that requires reconstruction of the upper face. Systemic treatment may be indicated for cardiac, renal, or CNS malformations.

Diagnosis: Goldenhar Syndrome (Also known as Oculo-Auriculo-Vertebral spectrum, craniofacial dysostosis, or first and second branchial arch syndrome)

EPIDEMIOLOGY

  • Sporadic, no documented inheritance pattern
  • No proven environmental insult during pregnancy (medication, infection, or otherwise)
  • Males affected 2:1 compared to females
  • Incidence between 1 in 3,000 and 5,600 live births

SIGNS

  • Limbal dermoids (bilateral in 25% of cases)
  • Eyelid colobomas
  • Preauricular appendages/skin tags
  • Microtia or anotia of external ear, can be associated with hearing loss with or without middle ear malformation
  • Vertebral abnormalities (butterfly vertebrae or hemivertebrae)
  • Congenital heart disease (numerous anomalies have been reported)
  • Central nervous system abnormalities (hydrocephalus, intracranial lipomas, cranial nerve dysgenesis and mental retardation have been described)

SYMPTOMS

The syndrome is almost always diagnosed early in life, before there is any complaint of symptoms by the infant patient. Symptoms could include:

  • Double vision (motility restriction or strabismus)
  • Dry eye (exposure due to coloboma or large dermoid)

TREATMENT

  • Large eyelid colobomas resulting in exposure keratopathy may require surgical repair
  • Spectacle
  • Superficial keratectomy may be required to excise large limbal dermoids causing occlusive or astigmatic amblyopia or exposure
  • Cleft lip and palate will require surgical repair, if present
  • Severe underdevelopment of the mandible may require reconstruction, perhaps with the aide of a bone graft (i.e. from the rib)
  • In cases of microtia or other ear defect, external ear reconstruction is generally done between 6 and 8 years of age and is a multi-stage process
  • Further facial reconstruction may be required
  • Cardiac defects (ventricular or atrial septal defect, other) are treated accordingly
  • If the facial or tongue malformation is severe, speech therapy may be indicated

Differential Diagnoses for Goldenhar Syndrome (especially the facial abnormalities)

Differential Diagnoses for Limbal Dermoid

References

  1. Bayraktar S, Bayraktar ST, Ataoglu E, Ayaz A, Elveli M. Goldenhar's syndrome associated with multiple congenital abnormalites. J Trop Pediatr. 2005;51(6):377-9.
  2. Beck AE, Hudgins L, Hoyme HE. Autosomal dominant microtia and ocular coloboma: new syndrome or an extension of the oculo-auriculo-vertebral spectrum? Am J Med Genet A. 2005;1;134(4):359-62.
  3. Cohen J, Schanen NC. Branchial cleft anomaly, congenital heart disease, and biliary atresia: Goldenhar complex or Lambert syndrome? Genet Couns. 2000;11(2):153-6.
  4. Gorlin RJ, et al. Oculo-auriculovertebral dysplasia. J Pediatr. 1963;63:991-999.
  5. Goldenhar M. Associations malformatives de l'oeil et l'oreille, en particulier le syndrome dermoide épibulbaire-appendices auriculaires-fistula auris congenita et ses relations avec la dysostose mandibulo-faciale. J Genet Hum 1952;1:243-282.
  6. "Oculoauriculovertebral Dysplasia." Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164210.
  7. Schaefer, Bradley G, Olney A, Kolodziej P. Oculoauriculo-vertebral Spectrum. ENT—Ear, Nose & Throat Journal. 1998;77:17-18.
  8. Singer SL, Haan E, Slee J, Goldblatt J. Familial hemifacial microsomia due to autosomal dominant inheritance. Case reports. Aust Dent J. 1994;39(5):287-91.
  9. Stoll C, Viville B, Treisser A, Gasser B. A family with dominant oculoauriculovertebral spectrum. Am J Med Genet. 1998;78(4):345-9.
  10. Tasse C, Hohringer S, Fisher S, Ludecke HJ, Albrecht B, et al. Oculo-auriculo-vertebral spectrum (OAVS): clinical evaluation and severity scoring of 53 patients and proposal for a new classification. Eur J Med Genet. 2005;48(4):397-411.

Suggested Citation Format: Graff JM, Bhola R, Olson RJ: Goldenhar Syndrome (Oculo-Auriculo-Vertebral Spectrum): 6 day-old male with limbal dermoids. Eyerounds.org. March 31, 2006; Available from: http://www.EyeRounds.org/cases/55-GoldenharSyndromeLimbalDermoidColoboma.htm.