A C T A O P H T H A L M O L O G I C A V O L . 4 8 1 9 7 0

From the University Eye Hospital, Oulu (Head: Prof . H . Forsizrs, M . D . )

THE SYNDROME OF GOLDENHAR AFFECTING TWO SIBLINGS

BY

U. KRAUSE

The triad of epibulbar dermoids, accessory auricular appendages and pretragal fistulas is termed the Goldenhar syndrome (Goldenhar 1952). This triad is of- ten found in combination with other malformations, e. g. hemifacial microso- mia, coloboma of the upper lids (Sinha & Mishra 1950), ptosis (Proto & Scullica 1966), coloboma of the iris and choroid (Ballantyne 1933), imperforated exter- nal auditory meatus (Stallard & Martin 1931), and deafness (Sen, Mohan & Gupta 1969). Numerous vertebral coloumn anomalies are common, such as oc- cipitalization of the atlas, spina bifida, spondylolisthesis, etc. (see Gorlin & Pindborg 1964, Tost 1969). The vertebral bony anomalies tend to be overlooked (e. g. Leiber & Olbrich 1966) but are common, and McKusick (1968) uses the term oculo-auriculo-vertebral dysplasia synonymously with the Goldenhar syn- drome. Scebe (1948) describes lipoma conjunctivae in three generations. Ac- cording to Waardenburg, Franceschetti & Klcin (1961) there is nothing to indi- cate that epibulbar dermoids or lipodermoids might be hereditary in man, either alone or combined with the syndrome of Goldenhar. Saraux, Grignon & Dhermy (1963) describe two affected sisters, Proto & Scullica (1966) three ca- ses of epibulbar dermoids in one and the same family. Since few data are avail- able on heredity in the Goldenhar syndrome, it seems desirable to report two siblings thus affected.

Received December 20th 1969.

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Case reports

Case 1. II/3. R. L., male, born 1960. The proband. Auricular appendages were present bilaterally at birth, the midwife tied threads round them and they later fell off. A dark red elevated tumour was seen, likewise at birth, on the right side of the nape of the neck. The patient therefore entered another hospital in 1963 for the diagnosis Haemangioma nuchae 1 . dx. The tumour was extirpated; the pathologist’s diagnosis was hemangioma. At the age of 7 years impaired vision was found in the left eye and the patient now (April 1969) sees an ophthalmologist because the left eye has “a pecu- liar appearance”.

Right eye. Vision 1.4, refraction + 1.5 D. Eyelids were normal. A small flat lipoma- like tumour was seen on the conjunctiva close to the lateral angle. There were no hairs on its surface. The cornea was clear, the pupil round and responded normally to Iight. Above, between 11 and I o’clock, there was indistinct thickening of the iris, crypts were lacking, but the appearance of the iris was elsewhere normal. The lens was clear, a small remnant of the arteria hyaloidea persistens was seen. The papilla and the eye ground were normal.

Left eye. Vision 0.9, refraction + 1.0 D. Eyelids normal. On the conjunctiva, tem- porally below, a small non-hairy elevation resembling a lipoma appeared near the corneal border. In this region the conjunctiva was seen to extend for a distance over the cornea, which was elsewhere clear; the anterior chamber was of normal depth. The pupil was drawn upward to some extent (Fig. l ) , not completely circular and reacted slowly to light. I t was somewhat smaller than the right pupil. On retroillumination, a defect appeared above, in the layer of pigment epithelium the iris stroma extended further out towards the edge of the pupil and showed a partial transition into a greyish membrane. Below, a normal iris collarette was visible; above, this collarette ap- proached the pupillary margin with which i t seemed to coincide. The iris tissue was thickened above, and normal crypts were not discernible. The vitreous, papilla and eye ground were normal.

There were distinct remnants of preauricular appendages in front of both ears (Fig. 2 ) and on the left a slight indication of a preauricular fistula. No facial asymmetry

Fig. 1. Left eye of case 1. The iris is thickened above, crypts are absent and, temporally above,

transition of the iris stroma into a membrane is seen a t the papillary margin.

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Fig. 2 A and B . A. Right eye of case 1 with remnants of pretragal appendices.

B. In front of the left ear there is an a remnant indication of a preauricular fistula (arrow).

was observed. On the right side of the nape of the neck there was a scar remaining after hemangioma excision. X-ray films showed a normal thoracic spine.

Case 2. II/I. T. L., a sister of case 1, born 1956. The patient entered our Clinic in March 1968 for extirpation of a conjunctival tumour at the external angle of her left eye. This tumour, already present at birth, had caused the patient no discomfort. It was excised in local anesthesia. The pathologist’s diagnosis was Lipoma. In March 1968 the status was as follows:

Right eye. Vision 1.4, eyelids and conjunctiva were normal, and the cornea clear. The iris and the lens, as well as the eye ground, appeared normal.

Lef t eye. Vision 1.4. Eyelids were normal. Under the upper lid temporally at the lateral angle, there was a lightcoloured slightly prominent tumour. A few hairs were seen on the overlying conjunctiva. The cornea, iris, lens and eye ground were normal. The ears were normal, no preauricular appendages or auricular fistulae were seen. The face was physiologically asymmetrical without demonstrable atrophy.

The presence of two similar anomalies in two siblings led to the examination of other siblings and the parents (Fig. 3).

1112. J. L., male, born 1957. According to the history, this was a case of precipitate delivery, and the boy, weighing 3500 g at birth, had neonatal asphyxia. When he was 14 months of age, the mother noticed that his right leg was in abnormal position. In 1963 he was operated on for spastic hemiplegia (Allongatio tendinei achillei 1. dx.).

Vision bilaterally 1.4. The conjunctivae and the iris were normal, the lenses clear and the eye grounds showed normal circumstances. The ears were of normal appea- rance and there was no facial asymmetry. The right leg was 1 cm shorter than the left.

The youngest sibling, IU4, J. L., male, born 1964, had an entirely normal ophthal-

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Fig. 3. Pedigree of family including two cases of syndroma Goldenhar. All these family

affected member. -+ propositus. members were examined.

mological picture. The parents ( I / l and I/2), who were not known to be blood relations, did not reveal any findings of special ophthalmological interest.

Discussion

The syndrome of Goldenhar consists of the complete triad of epibulbar der- moids, accessory auricular appendages and pretragal fistulae, but the diagnosis is further substantiated if there are coincidental vertebral anomalies. The mul- titude of additional symptoms reported make diagnosis more difficult. The pre- sence of incomplete forms of the syndrome has been referred to by Sugar (1966), etc.

The propositus showed epibulbar dermoids, preauricular appendages, and, unilaterally, remnants of preauricular fistulae. The diagnosis of the Goldenhar syndrome seems justified in spite of the fact that there was no evidence of ver- tebral anomalies. The iris anomaly in the left eye was of a type not previously described in connection with this syndrome (see Garner 1951). It is difficult to decide whether the anomaly was primarily neurodermal or mesodermal. The configuration of the iris in the right eye was also pathological, and this was evidently a milder form of the same anomaly as affected the left eye.

As seen for instance in the case of the proband, the syndrome displays vary- ing penetrance: for instance the picture differs on the right and the left side. Despite the absence of other anomalies, it is therefore well warranted to regard the sister’s (II/1) dermoid as an atypical form of the Goldenhar syndrome and not as a sporadic case of quite another origin. If we accept these conclusions concerning heredity, the question as to the localization and properties of the pathological gene arouses interest. W e cannot say anything else with certainty than that the gene is not localized in the X-chromosome and that it seems to be of recessive type.

The spastic hemiplegia of one of the brothers had obviously resulted from a

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cerebral lesion. This was very likely connected with the precipitate delivery and the postnatal asphyxia. Another possibility is that it was a neurological le- sion due to vertebral anomaly; such a mechanism would be of interest from the point of view of the pathological changes in the vertebral column seen in the syndrome of Goldenhar. In such a case, however, the paresis would present a different clinical picture.

Addendum. Besides the proband (11/3), another patient attended our Clinic with the Goldenhar syndrome and cutaneous hemangioma. The patient was a girl of 2 years showing epibulbar dermoids, preauricular appendages, facial asymmetry, and a mild left-sided macrostomy. In the temporal region there was a hemangioma, 1 X 2 cm in size (Fig. 4). A correlation possibly exists between the syndrome of Goldenhar and hemangioma.

Summary

Two cases of the Goldenhar syndrome, in a brother and sister, are reported. The brother in addition showed anomalies of the iris of a type not hitherto described in this context and also a hemangioma on the nape of the neck. An- other brother had spastic hemiplegia, probably a result of birth trauma. The correctness of the diagnosis is discussed and the site of the pathological gene dealt with. The possible correlation between syndroma Goldenhar and cutane- ous hemangioma is considered.

Fig. 4. Two-year old girl with syndroma Goldenhar and hemangioma in the left temporal

region.

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References

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Gorlin, R & Pindborg, 1.: Syndromes of the head and neck. McGraw-Hill, New York 1964, 419.

Leiber, B. & Olbrich, Gertrud: Die klinischen Syndrome. Urban & Schwarzenberg, Miinchen 1966, 275.

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