Goldenhar syndrome: rare case reported from secondary health care facility in Himachal Pradesh

Dr. Maurice Goldenhar, a renowned Swiss ophthalmologist classified the clinical features and named the malformation complex as Goldenhar Syndrome and described it as a congenital defect characterized by constellation of malformations classically involving the face, eyes and ears. Principal deformities of the Goldenhar syndrome are often combined with various malformations, like Cleft lip and/or palate, tongue cleft, unilateral tongue hypoplasia, and parotid gland aplasia, Rib anomalies, Congenital heart disease (ventricular septal defects). A 12-year-old female patient diagnosed with Goldenhar syndrome at secondary care Regional Hospital Bilaspur, Himachal Pradesh. She was diagnosed with a case of Goldenhar syndrome on clinic-radiological investigations. The patient reported to ophthalmology OPD of the hospital with the chief complaint of soft tissue structure in left eye with decreased vision. On examination limbal dermoid was observed. Patient was having pre-auricular tissue tag on both sides, hemifacial micrognathia and microstomia. Correlating the history and physical findings a provisional diagnosis of Goldenhar Syndrome was made with differential diagnosis of Franschetti syndrome or Treacher – Collins syndrome, Nager syndrome or acro-facial dysostosis and Townes-Brocks syndrome. Based on the clinical and radiographic findings a diagnosis of Goldenhar syndrome was made. Severe cases of GS can affect the routine and social life of the patient. Early detection can help avoid complications at a later stage of life. Such patients will have an increased risk for psychosocial difficulties. The study of this condition is still controversial because the symptoms and the physical features may vary greatly in range and severity from case to case.


Introduction
Goldenhar syndrome (GS) is also known as oculoauriculo-vertebral (OAV) dysplasia. It is considered a variant of hemifacial macrosomia [1]. In 1881, the first observation of oculo-auriculo-vertebral (OAV) dysplasia was reported by Von Arlt and in 1952, Dr. Maurice Goldenhar, a renowned Swiss ophthalmologist classified the clinical features and named the malformation complex as Goldenhar Syndrome and described it as a congenital defect characterized by constellation of malformations classically involving the face, eyes and ears [2,3].
Reported incidence of this syndrome is 1:3500 to 1:5600 with a male to female ratio of 3:2 [4]. Although most cases are sporadic, autosomal dominance inheritance has also been described. Though, the aetiology of Goldenhar Manuscript received: 26 th December 2019 Reviewed: 7 th January 2020 Author Corrected: 12 th January 2020 Accepted for Publication: 17 th January 2020 syndrome is not well established, it is thought to be due to exposure to various viruses or chemicals during pregnancy. Some researchers also suggested gestational diabetes mellitus as one of the causes. The MSX homeobox genes play a crucial role in the pathogenesis [5,6].
Unilateral macrostomia (lateral facial cleft). Back: Pilonidal dimple, kyphoscoliosis, Sprengel's deformity, Hands / Fingers: clubbing, polydactyly, clinodactyly, single palmar crease, and Vertebral column anomalies (atlas occipitalization, synostosis, hemivertebrae, fused vertebrae, scoliosis, and bifid spine) [7]. The multifactorial etiopathogenesis includes nutritional and environmental factors that result in blastogenesis disorders. Information to identify these etiological factors do not exist [8]. The anomalies of 1 st and 2 nd branchial arcs have been observed in children born from mothers who were exposed to thalidomide, primidone and retinoic acid, in addition to diabetic mothers [9,10]. Embryologically, the ocular-auricle-vertebral defect has been considered an anomaly of 1 st branchial arc, but this alteration does not explain the anomalies in the brain, heart, kidneys or dorsal spine [11].
Principal deformities of the Goldenhar syndrome are often combined with various malformations, like Cleft lip and/or palate, tongue cleft, unilateral tongue hypoplasia, and parotid gland aplasia, Rib anomalies, Congenital heart disease (ventricular septal defects), anomalies of the urogenital and gastrointestinal system, mental retardation, Venous anomalies, associated juvenile glaucoma in Turner's syndrome, Congenital Facial nerve palsy and Growth hormone deficiency [7].

Case Report
A 12-year-old female patient diagnosed with Goldenhar syndrome at secondary care Regional Hospital Bilaspur, Himachal Pradesh. She was diagnosed with a case of Goldenhar syndrome on clinic-radiological investigations. The patient reported to ophthalmology OPD of the hospital with the chief complaint of soft tissue structure in left eye with decreased vision. On examination limbal dermoid was observed. With a syndromic suspicion, patient was referred to Pediatrics department for further clinical examination.

Fig-1: Image showing limbal dermoid
On physical examination in pediatrics department, it was found that the patient was having pre-auricular tissue tag on both sides, hemifacial micrognathia and microstomia There was no family history of any genetic abnormality or infections. The parents were healthy and their marriage was nonconsanguineous. Correlating the history and physical findings a provisional diagnosis of Goldenhar Syndrome was made with differential diagnosis of Franschetti syndrome or Treacher -Collins syndrome, Nager syndrome or acro-facial dysostosis and Townes-Brocks syndrome. On investigations patient was showing normal ECHO, USG Abdomen & KUB, audiometry & blood investigation while there was refractive error with astigmatism.
On NCCT face with screening whole spine with 3D construction, following observations were made:  Right sided mandible is hypoplastic predominantly in region of ramus as well as mandibular condyle.  Mandibular condyle is located anteromedially compared to left side and shows ill formed temporomandibular joint.  Bilateral preauricular tags and blind fistula in front of preauricular tag on one side.  Screening spine with intervertebral discs showing grossly normal study. Based on the clinical and radiographic findings a diagnosis of Goldenhar syndrome was made. The genetic analysis was planned but couldn't be done due to affordability issues to the family. (All other blood investigations are done at regional hospital Bilaspur free of cost under RBSK scheme and radiological investigations were done free of cost). The patient was referred to tertiary care hospital for multidisciplinary management.

Discussion
A number of case reports of Goldenhar syndrome have been described in literature. In 1997, Araneta et al. described the occurrence of Goldenhar syndrome among children of Persian Gulf War veterans and found that 7 infants out of an estimated 75,414 infants had Goldenhar syndrome [12]. As similar to previously reported cases, our patient had marked right facial hypoplasia Tsai and Tsai reported a family in which seven members in three successive generations were diagnosed with Goldenhar syndrome [13]. Clinical features in all were highly suggestive of Goldenhar syndrome [7]. Anderson and David reported spinal anomaly in seven patients with wide range of abnormalities including butterfly vertebrae, hemivertebrae, kyphosis and rib anomalies [14]. Ozdemir et al. reported a case of 12-year-old male with postaxial polydactyly, congenital heart disease, vertebral anomaly and facial asymmetry [15]. Berker, Acaroglu, and Soykan reported a patient with congenital facial nerve paralysis in conjunction with Goldenhar syndrome [16]. Kumar et al. reported polydactyly and hydrocephalus as rare associations with Goldenhar syndrome [17]. Zaka-ur-Rab and Mittal reported a case where drusen of the optic nerve head was found in association with this syndrome [18]. Our patient was provisionally diagnosed as Goldenhar syndrome but a number of other first and second arch syndromes were considered in the differential diagnosis [19]. A recent study detected multiple congenital anomalies in ecography findings in 20 cases. The gestational age in the diagnosis varied from 15 to 35 weeks and in more than half of the cases it was associated to the polyhydramnios or oligohydramnios.
The characteristics observed were: face malformations present in 52% of the cases, as microphtalmy, auricular abnormalities, face asymmetry and face cleft; amongst the neurological alterations, occiptal encephalocele, hydrocephaly and cerebellar hypoplasia were observed, which occurred in 47% of the findings; cardiac defects, radial aplasia and renal agenesia were seen less frequently [20,21].
Preauricular tags can be associated with several genetic conditions such as: Oculoauriculovertebral dysplasia, Chromosome arm 11q duplication syndrome, Chromosome arm 4p deletion syndrome and Chromosome arm 5p deletion syndrome but our case doesn't have classical findings of these syndromes and fit only in Goldenhar syndrome phenotype. Both laboratorial and image tests are important for the diagnosis, once they are directly related to provoked alterations. The Xray of the zigomatic bones shows a macroscopic deficiency of bone symmetry development.
Also a possibility of agenesia of these bones exists, with defect of fusing of the zigomatic arc and agenesia of the palatine bones. Palatine cleft must radiographically be observed. Ophthalmological and otorhinolaryngological examinations are also important for the final diagnosis [22].  [26] reported Goldenhar in association with agenesis of septum pellucidum.
Vinay and others [4] reported Goldenhar syndrome based on clinical and radiographic findings with no systemic involvement.

Conclusion
Severe cases of GS can affect the routine and social life of the patient. Early detection can help avoid complications at a later stage of life. Such patients will have an increased risk for psychosocial difficulties.
The study of this condition is still controversial because the symptoms and the physical features may vary greatly in range and severity from case to case.

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