Case of oculo-auriculo-vertebral spectrum: rare clinical features

Discussion

OAVS presents with heterogeneous manifestations. Craniofacial anomalies such as facial asymmetry, facial clefts, maxillary/mandibular hypoplasia, malocclusion/malalignment, cleft lip/palate and macrostomia are frequently observed. Auricular abnormalities such as microtia (anotia representing its most severe form), aural atresia, preauricular tags/sinus/pit, middle and inner ear defects with/without hearing loss are common. Ocular anomalies such as epibulbar dermoids and lipodermoid are commonly reported. Extracranial skeletal anomalies like vertebral (hemivertebra, scoliosis) and radial anomalies when present along with craniofacial features ease the diagnostic dilemma. Systemic involvement in form of congenital heart defects (ventricular septal defects, tetralogy of fallot, aortic arch anomalies), urogenital (renal agenesis, ectopic kidney, muticystic kidney), neurologic (facial nerve palsy, developmental delay, hydrocephalus, Arnold-Chiari malformation, corpus callosum and septum pellucidum dysgenesis), gastrointestinal (rectal atresia, tracheoesophageal fistula) and pulmonary involvement (lung hypoplasia) can also occur.5

Most reported cases are sporadic in nature, while few of them show autosomal recessive inheritance, but autosomal dominant inheritance of HFM gene on 14q32 is also reported.6 In a recent systematic review conducted to assess the use of high-resolution (HR) karyotype, fluorescence in situ hybridisation, multiplex ligation-dependent probe amplification (MLPA) and microarray-based comparative genomic hybridisation (CGH) for differential diagnosis of OAVS. It was found that a genetic defect was present in only 19.47% (59/303) individuals. They also noted that using HR karyotyping inv 9, t(9;18) and del 22 were most common genetic alterations. Using MLPA and array-based CGH, 22q11 microdeletions were commonly found.7

In our case, the child presented with bilateral microtia with EAC atresia, left-sided preaxial polydactyly of hand (bifid thumb), left-sided LMN facial palsy, right-sided hypoplastic depressor anguli oris, micrognathia, hemivertebra leading to scoliosis, a bifid rib and developmental delay. But there were no cardiovascular, respiratory, genitourinary, gastrointestinal or temporal bone abnormalities. All these features suggest a clinical diagnosis of OAVS as per the minimal diagnostic criteria proposed by Tasse et al.4 In the study by Tasse et al,4 the complete spectrum of Goldenhar syndrome, characterised by the presence of microtia in association with HFM, vertebral anomalies and epibulbar dermoids, was only present in 4 of 53 (7.5%) patients.

Similar cases of OAVS with radial anomalies have been reported in literature. Das et al 8 reported a typical case of OAVS with unilateral microtia and HFM, bilateral epibulbar dermoids with right-sided hypoplastic first metacarpal with deformed floating right thumb. Biswas et al 9 also reported a similar case of Goldenhar syndrome with aplasia of radius, short hypoplastic abnormally curved ulna, absence of first metacarpal and phalanges of the thumb as well as radially placed carpal bones. Preaxial polydactyly with Goldenhar syndrome has been reported by Mishra et al 10 and Taksande and Vilhekar11 The latter case similar to ours had left-sided polydactyly but right-sided LMN facial palsy. Vendramini et al 12 in a case series of OAVS with radial defects found that agenesis of thumb and hypoplasia and/or agenesis of radius were most common defects while triphalangeal thumb, preaxial polydactyly and thumb hypoplasia were not so common. Beleza-Meireles et al 13 in their series observed a higher incidence of HFM and lower incidence of ocular anomalies. In our case also, there were no ocular anomalies.

This case highlights the heterogeneity of this spectrum and calls for a multidisciplinary approach to management. Children presenting with features of external ear abnormalities or HFM or epibulbar dermoids should undergo extensive screening to identify other possible malformations for which timely interventions may be planned. We suggest that such children should undergo a vision, hearing and developmental assessment along with a thorough physical examination to identify other possible malformations and a targeted approach to work up can be planned. Also when planning a genetic work up, a stepwise approach should be followed as suggested by Glaeser et al.7 First exclude structural and numerical changes using HR karyotyping, followed by screening for 22q11 microdeletion by MLPA, and if further required planning an array-based CGH.