Goldenhar syndrome: a report of 3 cases.

We report here 3 cases with the classic signs of Goldenhar syndrome in the form of multiple accessory tragi, bilateral ocular dermoids, mandibular hypoplasia (micrognathia), and facial microsomia. One of the patients also had vitiligo, which is yet to be reported as an association.

What was known?

1. Goldenhar syndrome (oculoauriculovertebral dysplasia with hemifacial microsomia) is a rare congenital developmental anomaly involving the first and second branchial arches.

2. The classic features of this syndrome include ocular changes such as microphthalmia, epibulbar dermoids, lipodermoids and coloboma; aural features such as preauricular tragi, hearing loss and microtia; and vertebral anomalies such as scoliosis, hemivertebrae and cervical fusion.

3. In addition to facial, vertebral, ophthalmic malformations cardiovascular, CNS, genitourinary malformations have been associated with goldenhar syndrome.

Introduction

Goldenhar syndrome (oculoauriculovertebral dysplasia with hemifacial microsomia) is a rare congenital anomaly involving the first and second branchial arches.

It is a disorder where the patient's facial features are incompletely developed on one side, resulting in eye, ear, and jaw abnormalities. When these facial abnormalities are associated with vertebral malformations in the spine and more severe involvement of the eyes, this collection of symptoms is called Goldenhar syndrome. In 85% of patients with Goldenhar syndrome, only one side of the face is affected. Cervical spine vertebral deformities are part of the collection of symptoms. The syndrome was first described in 1952 by the French ophthalmologist Maurice Goldenhar.[1] The incidence of Goldenhar syndrome has been reported to be between 1:3500 and 1:5600, with a male:female ratio of 3:2.[2] The exact etiology is not known. However, it is possible that abnormal embryonic vascular supply, disrupted mesodermal migration or some other factor leads to defective formation of the branchial and vertebral systems.[23] Most of the cases have been sporadic. Autosomal dominant, autosomal recessive, and multifactorial modes of inheritance have also been suggested.[2]

Ingestion of drugs such as thalidomide, retinoic acid, tamoxifen, and cocaine by the pregnant mother may be related to the development of this syndrome. Maternal diabetes, rubella, and influenza have also been suggested as etiologic factors.[4]

The classic features of this syndrome include ocular changes such as microphthalmia, epibulbar dermoids, lipodermoids, and coloboma; aural features such as pre-auricular tragi, hearing loss, and microtia; and vertebral anomalies such as scoliosis, hemivertebrae, and cervical fusion.[14] The abnormalities are found to be unilateral in 85% of cases and bilateral in 10-33% cases.[4] In Goldenhar syndrome, ocular anomalies especially bilateral dermoids are seen in 60% of the cases, vertebral anomalies in 40% of the cases, and ear anomalies also in 40% of the cases.[2]

Other systemic features are found in about 50% of the patients.[5] Tetralogy of Fallot and ventricular septal defects are the most common cardiovascular anomalies associated with OAVS.[4] Cleft lip and palate, macrostomia, micrognathia, webbing of the neck, short neck, tracheoesophageal fistula, abnormalities of sternocleidomastoid muscle, umbilical hernia, inguinal hernia, urologic anomalies, hypoplastic vagina, and anal anomalies may be associated.[4]

Other syndromes associated with multiple pre-auricular tragi include Treacher-Collins syndrome, Wolf-Hirschhorn syndrome, Nager's acrofacial dysostosis, Wildervanck syndrome (cervicooculoacoustic syndrome), Townes-Brocks syndrome, and Delleman syndrome.[6] Treacher Collins syndrome is associated with maxillary and mandibular hypoplasia but is not associated with ocular and aural anomalies.[2]

Case Reports

Case 1

A 1-month-old girl, born of non-consanguineous parents, was referred to our department for assessment of dysmorphic facial features. The patient was full-term normal vaginal delivery with no perinatal complications. Patient had vitiligo on right side of the face below the nose [Figure 1]. Left-sided epibulbar lipodermoid, [Figure 2] B/L pre-auricular tags [Figure 3], malformed pinna of the ear, malformed and hypoplastic right side of face, pulled up angle of mouth, mandibular hypoplasia on right side, vitiligo on right side. No vertebral anomalies were noted. Patient was referred to pediatric surgery for facial features. For vitiligo lesions, patient was not given any treatment and was asked for regular follow-up.

Figure 1

Case 1 showing hemifacial microsomia with vitiligo below nose

Figure 2

Case 1 showing pre-auricular tag, pulled up angle of mouth, malformed pinna

Figure 3

Case 1 showing ocular lipodermoid

Case 2

An 8-year-old girl, presented to skin OPD for treatment of periporitis, was found to have B/L accessory tragus, left-sided epibulbar dermoid, pre-auricular appendices [Figures 4-6]. Patient had no h/o perinatal complications, maternal drug intake, or feeding problems. On further investigation, patient was found to have mild conductive type of deafness.

Figure 4

Case 2 showing ocular lipodermoid and pre-auricular appendices

Figure 6

Case 3 showing pulled up angle of mouth and pre-auricular appendages

Case 3

An 18-year-old girl with conductive type of deafness was referred from ENT department for evaluation of associated skin lesion. On examination, she was found to have B/L epibulbar dermoid [Figure 5], B/L multiple pre-auricular appendages. Vertebral anomalies in the form of scoliosis of thoracic spine were noted. Patient was also having mal-aligned teeth [Figures 7–9], pulled up angle of mouth on left side of face [Figure 6]. The girl was born of non-consanguineous marriage, and mother had no perinatal or antenatal complications. The patient was referred to surgery department for excision of accessory tragus and was referred to ophthalmology department for management of epibulbar dermoid.

Figure 5

Case 3 showing ocular lipodermoid

Figure 7

Case 3 showing misaligned teeth

Figure 9

Case 3 showing scoliosis of spine

Comparison of clinical features of 3 patients is given in Table 1. None of the patient reported had cranial, cardiac, or laryngeal defects. All the patients were of Indian ethnicity.

Table 1

Comparison of features in three cases

Discussion

The treatment of the disease varies with age and systemic associations and is mainly cosmetic in uncomplicated cases. Reconstruction surgeries of the external ear may be performed at the age of 6 to 8 years. In patients with milder involvement, jaw reconstruction surgeries can be done in the early teens; epibulbar dermoids should be surgically excised.[2] Structural anomalies of the eyes and ears can be corrected by plastic surgery.[2] Prognosis of the disease is good in otherwise uncomplicated cases without any systemic associations. Successful treatment requires a multidisciplinary approach involving otolaryngologists, ophthalmologist, pediatrician, dermatologist, orthopedician. We have observed vitiligo as an association in one of the case; however, its significance is not yet known. Mention has been made so as to keep this association, if any, in all cases observed subsequently.

Importance of diagnosis and consequences of avoiding treatment

Severe cases of Goldenhar syndrome or hemifacial microsomia can affect many aspects of the patient's life and sometimes requires immediate intervention from birth. For example, the patient may suffer from severe obstructive sleep apnea due to airway abnormalities Jaw problems may result in a restrictive diet and malnutrition, and issues with the eyelids may lead to subsequent vision problems. Without hearing assistance or surgical reconstruction, individuals with full bilateral microtia and atresia will lead to permanent deaf mutism.

What is new?

1. Though earlier reports showed male preponderance lately majority female cases have been reported.

2. Some of the patients can also have high arched palate, gingival hypertrophy, malaligned teeth, bulbous nose, vitiligo as an atypical association.

3. The treatment of the disease is now possible and varies with age and systemic associations and is mainly cosmetic in uncomplicated cases.

In patients with mandibular hypoplasia, reconstruction can be done with rib grafts and an underdeveloped maxilla can be lengthened by a bone distraction device. In patients with milder involvement, jaw reconstruction surgeries can be done in the early teens; epibulbar dermoids should be surgically excised.