HFM is a predominantly unilateral malformation of craniofacial structures that develop from the first and second branchial arches.3
As similar malformations may be present on both sides, the more comprehensive term facioauriculovertebral spectrum or sequence (FAVS) has been suggested.4
Cases are characterised by hypoplasia of the malar, maxillary and/or mandibular region, macrostomia and hypoplasia of facial musculature. The patients have abnormalities of the auricles, even microtia and preauricular tags and/or fistulae. They may be deaf because of middle or inner ear defects. Sometimes there may be accompanying ocular and/or vertebral defects. This pattern of anomalies has been designated as Goldenhar syndrome. Patients who have Goldenhar syndrome, the most severe form of HFM, may have eye tumours (epibulbar dermoid, coloboma) and fused spines in addition to the characteristic facial asymmetry. The present case adds to the variable clinical presentation of the oculoauriculovertebral spectrum (OAVS). OAVS refers to three rare disorders that many clinicians believe to be intimately related to one another and that represent the range of severity of the same disorder.3–5
Oculoauriculovertebral disorder (OAVD) represents the mildest form of the disorder, while Goldenhar syndrome presents frequently as the most severe form. HFM appears to be an intermediate form. The vertebral anomalies are known to range from hypoplasia of atlas, block vertebrae or spina bifida occulta, hemivertebra or butterfly vertebrae to complete sacral agenesis. The child in the present report did not have any limb or vertebral defects but had pulmonary hypoplasia. The other genetic syndromes to be considered in the differential diagnosis are: Nager acrofacial dysostosis, Treacher Collins–Franceschetti syndrome, Townes–Brocks syndrome, Beckwith–Weidemann syndrome (BWS) and Russell–Silver syndrome (RSS).6–9
Nager acrofacial dysostosis combines the facial anomalies of mandibulofacial dysostosis (Treacher Collins–Franceschetti) with hypoplastic/aplastic or triphalangeal thumbs. Characteristic features of Nager acrofacial dysostosis are absent/hypoplastic thumb, radial hypoplasia or radioulnar synostosis, which were absent in this case. The main features of Townes–Brocks syndrome (TBS) are triphalangeal thumb, imperforate anus/anal anomaly, overfolded helices of ear, sensorineural deafness and pes planus; preauricular pits/tags may also be present. In the index case, no thumb anomaly or anal anomaly existed, which excluded the diagnosis of TBS. Characteristic features of Treacher Collins–Franceschetti syndrome are symmetrical facial anomaly, malformed ear, malar hypoplasia, coloboma of lower eyelid, mandibular hypoplasia, cleft palate and sensorineural deafness. Since in the index case there is facial asymmetry with unilateral abnormalities, Treacher Collins–Franceschetti syndrome is untenable. BWS and RSS can also be associated with facial asymmetry, but the associated manifestations help in making a correct diagnosis. BWS is an overgrowth syndrome and RSS a syndrome associated with prenatal onset growth retardation, asymmetry and skeletal defects. In any case of microtia, or preauricular ear tags, it is necessary to look for associated defects such as cardiac defect, anal anomalies, digital/limb abnormalities. Ultrasonography and x-rays should be performed to rule out vertebral and renal anomalies. Echocardiography delineates the type of cardiac defect. Hearing assessment is required on follow-up, since conductive deafness is common in cases with external ear anomalies.
In the present report, the index case had pulmonary involvement. David et al7
describe a child with Nager acrofacial dysostosis, Mullerian abnormalities, renal agenesis/ectopy and cervicothoracic somite dysplasia (MURCS) anomaly (Klippel–Feil anomaly, vertebral synostoses, left renal agenesis) and left pulmonary agenesis. A case of HFM in association with rare cardiac, lung and laryngeal abnormalities that included atrial and ventricular septal defects, hypoplasia of the right lung and the larynx was reported 20 years ago.10
Hodes et al11
described a patient with Goldenhar syndrome with plagiocephaly, abnormalities of the left ear, facial asymmetry, cleft lip and palate, bifid tongue, left torticollis, hemivertebrae, left radial hypoplasia, absent thumb, patent ductus arteriosus, narrowing of the thoracic aorta and hypoplastic right pulmonary artery. The present case is somewhat similar to that of the case reported by Hodes et al
as he has cardiac defect and pulmonary hypoplasia, but there are no limb anomalies. Other external malformations should be looked for in cases of pulmonary agenesis.12
While the exact aetiology of HFM has not yet been determined, there are many theories based on embryological, clinical and laboratory studies. Laboratory studies suggest that an early loss of neural crest cells may be the specific factor responsible for the clinical presentation of HFM. The extent of the neural crest cell loss is reflected in the severity of the facial deficiency and, therefore, is thought to dictate the severity of the clinical phenotype.13
Infants of diabetic mothers are at increased risk for a diagnosis of OAVS.14
Poorly controlled diabetes may interfere with neural crest migration. This is akin to other malformations associated with maternal diabetes such as several forms of caudal regression.
Most patients affected with HFM spectrum represent sporadic cases. However, an autosomal dominant trait with variable expressivity has been reported. The observation of affected siblings with normal parents suggests autosomal recessive inheritance. Patients with autosomal dominant inheritance of OAVS are more often bilaterally affected than sporadic patients, and hearing loss, absent or narrow external auditory canal, anomalies of the mouth and epibulbar dermoids appear to occur less frequently in patients with autosomal dominant inheritance than in sporadic patients. Eye involvement may be less marked in the dominant form. Concordance in monozygotic twins has also been described. Detailed examinations of relatives of HFM patients, if possible including x-rays and sonography, are indispensable for ascertaining the possible risk of recurrence. If there is no evidence from clinical examination and family history is of one of the above-listed types of HFM, the statistical risk of recurrence is 2%.15
In the index case there was no family history of similar illness and the child had atypical features. Therefore, this most likely represents the sporadic nature of the condition. Genetic analysis rarely shows chromosomal anomalies in the HFM spectrum such as trisomy 22, unbalanced translocation t5,8
(p15.31;p23.1) resulting in monosomy for 5pter-p15.31 and trisomy for 8pter-p23.2, 5pter-p15.33 deletion, complex translocation resulting in deletion of 5pter-p15.3, deletion of 21q22.3-qter, and duplication of 21q22.11-q22.12. Thus in selected cases, cytogenetic analysis may delineate the underlying abnormality.
- Hemifacial microsomia (HFM) is a common genetic condition presenting with preauricular tag with microtia, with or without cardiac defect, and other malformations.
- The diagnostic investigation of each patient must establish the extent of the anatomical deformity, degree of functional impairment, and associated anomalies are to be looked for proper management.
- Accurate diagnosis facilitates proper genetic counselling.