INTRODUCTION:

Oculo-auriculo-vertebral spectrum (OAVS) which is a craniofacial developmental disorder affecting the development of the structures derived from the 1st and the 2nd branchial arches during embryogenesis. Its etiology is still poorly understood. Oculo-auriculo-vertebral spectrum (OAVS) encompasses of rare disorders that many clinicians believe to be intimately related to one another and which represent the range of severity of the same disorder. These disorders are apparent at birth (congenital).As the name suggests, they involve malformations of the eyes, ears and spine.

In most cases OAVS appears to occur randomly, with no apparent cause (sporadic). A multidisciplinary approach is adopted as to obtain comprehensive caring for the child.

DEFINITION:

Oculo-auriculo-vertebral spectrum:

Oculo auriculo vertebral spectrum, or OAVS (Oculo refers to the eye, auriculo to the ear, and vertebral to the spine.) As the name suggests, this spectrum involves the eye, ear, and spine. OAV spectrum encompasses both hemifacial microsomia and Goldenhar syndrome. It is thought that Goldenhar Syndrome may be a more complicated version of OAV while hemifacial microsomia may be a milder version. It is possible that someone with just a small ear, and no other problems, may be at the very mildest end of this spectrum ^[1]

Hemifacial microsomia (HFM):

Hemifacial means one side of the face. Microsomia means small. Hemifacial microsomia means that one side of the face is smaller than the other side, fig: [1]. Hemifacial microsomia tends to affect the right side of the face about 60% of the time. The reason why this side is more often affected than the left is not known. The jaw on the affected side may be smaller, as well as the eye. The cheekbones may not be as well developed, making the cheek on the affected side look a little flatter. The corner of the mouth on the affected side may be extended. The outer ear may be smaller (microtia), or in some cases absent (anotia). There may be extra bits of skin, called skin tags, or dimples called pits, in front of the ear. It is possible to have some hearing loss. A person with hemifacial microsomia may have all or just a few of these features. Most people with hemifacial microsomia have normal intelligence. Just having a small ear may be at the very mild end of this condition^[1]

Classification:

Pruzanksky classified Hemifacial Microsomia patients into three different types:

· Type I: Mild hypoplasia of the ramus, and the body of the mandible is slightly affected.

· Type II: The condyle and ramus are small, the head of the condyle is flattened, the glenoid fossa is absent, the condyle is hinged on a flat, often convex, infratemporal surface, and the coronoid may be absent.

^·Type III: The ramus is reduced to a thin lamina of bone or is completely absent. There is no evidence of a TMJ(Temporomandibular joint).^[2]

Goldenhar Syndrome:

People with this syndrome can have all the same features as those with hemifacial microsomia, but somewhere between 10 and 33% of people with Goldenhar syndrome have both sides of the face affected. One side is usually more affected than the other fig: [2]

· In addition to the features of hemifacial microsomia, with Goldenhar syndrome the muscles in the mouth and tongue may be weaker and speech therapy is often advisable.

· Teeth may erupt later than usual and some may be missing.

· A cleft lip, a cleft palate, or a cleft lip and palate may be present. Cleft palate alone is more common than cleft lip or cleft lip and cleft palate together.

· About 35% have a dermoid (cyst on the eye), which is usually not harmful and does not impair vision. If a dermoid is going to occur it will be present from birth.

· There may also be a small notch in the upper eyelid called a coloboma.^[1]

Fig. 1: Child with hemifacial microsomia^[3]

Fig. 2: Child with goldenhar syndrome ^[4]

Prevalence:

On the basis of largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990–2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths.

· In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies.

· There was a high rate (69.5%) of associated anomalies of other organs/systems.

· The most common were congenital heart defects present in 27.8% of patients.

· The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.^[5].

Etiology of OAVS

· Although knowledge of the genetic basis of human disease and its effect on embryonic development has greatly expanded in recent years, the causes of OAVS are still largely unknown, and the involvement of both genetic and environmental factors have been suggested.

· OAVS involves primarily the derivatives of the first and second pharyngeal arches, so it has been proposed that the etiology and mechanisms of OAVS are related to the development of these structures. The pharyngeal arches, which start to develop in the 4th week of embryonic development, are composed of mesenchymal cells and give rise to various facial structures, including skeletal, muscular and neural elements, through a complex but poorly characterized signaling network. The morphogenesis of the pharyngeal arch derivatives depends on continuous and reciprocal tissue–tissue interactions.

· One of the key features of craniofacial development is the formation of cranial neural crest cells, which migrate ventrolaterally as they populate the craniofacial regions. Disturbances in the specification, migration, proliferation, survival and ultimate fate determination of the cranial neural crest cells have been proposed as a possible mechanism for OAVS.

· The phenotypic characteristics of OAVS and severity of the defects probably depend on how the expression and activation of certain developmental genes and proteins have been disrupted during facial development.

· Microtia is a common phenotype in OAVS, which may arise as a consequence of neural crest cell defects and/or vascular disruption. This clinical feature can occur as an isolated defect or in association with other anomalies, although the role of these genes in external ear development is not clearly defined, it does show that single gene defects can cause this phenotype by interfering in the genetic pathways necessary for normal development of mesenchymal tissues during fetal development. Inheritance is more likely in familial cases of OAVS, sporadic cases may have polygenic or multifactorial causes.

· Environmental factors, such as maternal diabetes during pregnancy, thalidomide, vasoactive drugs, smoking and multiple pregnancy may also play a part in causation of this condition.

· One of the most favored hypotheses is that of vascular disruption of insufficiency in utero. In fact, disruption of embryonic blood flow during development, maternal vasoactive medication use, diabetes and twinning are predisposing factors to a number of structural congenital anomalies. Moreover, a great number of case reports on concordant and discordant twins with OAVS suggest that there might be an association between reproductive abnormalities, twinning and OAVS. ^[6]

Etiology of hemifacial microsomia (HFM)

· Vascular problems that affect blood flow during pregnancy. Due to interrupted or faulty blood flow to the facial areas, the fetus begins to develop its face irregularly, with some areas growing at a slower pace. The specific cause of this vascular problem may be genetically informed, though research still has not determined any concrete links between genes and Hemifacial Microsomia.^[7]

Etiology of goldenhar syndrome

· Goldenhar syndrome its etiology is multifactorial, but familial cases have been described, with autosomal recessive, autosomal dominant, variable expressivity and incomplete penetrance. Several chromosomal abnormalities have also been described, associated with the syndrome, and the chromosomes most frequently involved are chromosome 22 (Deletion (Del) and duplication (dup) and trisomy of the long arm), chromosome 5 (Del short arm and translocation between chromosomes 5 and 8) and chromosome 18 (Del, and recombinant trisomy).

· Goldenhar syndrome was associated with risk factors such as vasoactive drugs during pregnancy, bleeding in the second trimester, maternal diabetes, and multiple pregnancies.

· Microtia, hemifacial microsomia and Goldenhar syndrome phenotypes characterizes oculoauriculo vertebral spectrum (OAV), within the group of syndromes developing first and second arches. For others, the OAV spectrum understand Goldenhar syndrome with changes in other organs or systems, the most common, cardiovascular (50%), central nervous system or mental impairment (5 to 10%) and renal / respiratory (5%). The risk of recurrence of the OAV spectrum, for first-degree relatives, is 6%. ^[6]

Signs & Symptoms:

There are many ways to describe and classify the appearance and function in HFM (hemifacial microsomia); one such system is the OMENS classification. The letters in OMENS stand for:

· Orbit (or eye socket): the cavity in the skull that contains the eye

· Mandible: the jawbones

· Ear

· Nerve

· Soft tissues (in anatomy, this refers to skin, muscle, fat, tendons and ligaments – amongst other tissues that are not bone).

Common features of hemi facial microsomia include:

Orbit:

· Normal

· Small orbit and eye with normal vision

· Small, underdeveloped eye (microphthalmos) with impaired vision

· Absence of the eye (anophthalmic orbit)

· Benign growths on the eye (epibulbar dermoids)