Goldenhar Syndrome (GS) was described for the first time in 1952 by Prof. M. Goldenhar. It is a polymalformation syndrome and it is characterised by ocular anomalies, uni- or bilateral microtia, mandibular region hypoplasia, hemifacial microsomy, oral anomalies, respiratory organs anomalies, genito-urinary anomalies, heart anomalies, nervous apparatus anomalies, skeleton vertebral anomalies and cranio-facial anomalies.

GS has a variable frequency from 1:3500 to 1:26000 born children and more often occurs on the right hemiface (right:left=3:2) and with a male predominance (m:f=3:2). GS aetiology is still unknown and genetic and environmental patterns were advanced as causes. Though most of GS cases are sporadic, both autosomal dominant and autosomal recessive patterns were described.

Nowadays it is commonly accepted as origin of this syndrome a vascular sufferance of cephalic mesoderm because of an anomaly of stapedius artery, and a consequent alteration of the development of the first and second branchial arches. An element that enforces this theory is the presence of the syndrome in only one of monozygotic twins.

underdevelopment of tissues in a part of the face, underdevelopment of the upper and lower jaw. The ramus can either be short or absent and the chin tends to lean on that side. The cheek tissue is often underdeveloped giving asymmetry in the face along with the mandibular problem. Condyles anomaly and connected dental problems.

defects in the auricular region represented by the presence of cartilage tags in the preauricular area as well as the absence of malformation of the auricle, presence of the pre-auricular tags, stenosis-atresia of the meatus acusticus, transmission or neurosensorial deafness, hearing deficits for injuries both in the medium and inner ear.

epibulbar dermoid cyst, sub-conjunctiva or upper orbital dermoids, coloboma of the upper eyelid, blepharoptosis, lagrymal glands anomalies, epibulbar tumors, micro-anophtalmia, retina anomaly, strabismus.

in a high percentage of cases hemispondyls and lumbar hemivertebrae at lumbar, thoracic dorsal and cervical level, scoliosis, occipital atlas, spina bifida are present. In some cases it is associated with Arnold-Chiari Syndrome. Skull malformations are present on the part interested by the syndrome, very small orbit, smaller zygoma and temporal bone.

macrostomia, tracheo-oesophageal fistulae, oesophageal atresy, structural and functional malformations of pharynx and larynx that can contribute in increasing the risk of obstruction of breathing system, deficiencies in communication and mobility. GS can cause severe obstructive apnoea during sleep, if it is not treated apnoea can lead to growth and mental retardation. Cleft lip, cleft lip and palate, ogival palate.

uni- or bilateral kidney agenesis, kidney hypoplasia hectopy, orchis ectopy, cryptorchidism.

hypoplasia of the encephalic pons, agenesy of the corpus callosum, hydrocephalus, microcephaly, encephalocele. Mental retardation is present in 5%-15% of patients.

some children affected by GS had to suffer tracheotomy soon after their birth. In some cases jaws were so malformed that the tongue obstructed breath during sleep (tracheotomy). Cases of lung aplasia and hypoplasia.

It is not yet availabe as pecific genetic exam to diagnose - before the actual birth - if foetus is affected by the Goldenhar Syndrome.

But still being orientative, echography scan can visualise facial asymmetry, auricular anomalies, ocular defects, vertebral anomalies.

• What is the oculo-auricolo-vertebral spectrum?

The oculo-auricolo-vertebral spectrum is a mainly unilateral condition that may involve various parts of the body; the incidence is estimated to be about 1/6,000 born-alive children, but the manifestation of the syndrome varies greatly giving problems in clearly defining its frequency among the population.

• Which are the most visible signs?

The main characteristics of the syndrome are:

 FACIAL ASYMMETRY: often connected to mandible asymmetry; temporal, malar and mascellare bones may also be involved.

 AURICULAR ANOMALIES: mainly unilateral; the structures of the outer, medium and/or inner ear may be anomalous. The most frequent alteration is the small and malformed, if not completely absent, ala auris (microtia/anotia); many patients may also have skin and cartilaginous, pre-auricular appendages, along the ideal line from the ear to the angle of the mouth. All ear anomalies that are signalled may justify transmission (the most frequent) and/or neurosensorial deafness.

 EYE ANOMALIES: the most frequent anomalies are whitish masses visible on the eye globe (epibulbar dermoid cysts); these small, monolateral or bilateral, masses may sometimes interfere with sight.

 MOUTH ANOMALIES: they range from true malformations (cleft palate and lip) to mastication problems caused by malocclusion.

 SKELETON ANOMALIES; the bones that are more often involved are vertebrae (fused, butterfly, hypoplasic vertebrae, hemivertebrae, spina bifida, scoliosis), involving cervical vertebrae in particular. Ribs, skull bones, upper limbs (radium and thumb anomalies) and lower limbs (clubfoot) may also reveal anomalies.

• How do children affected by this pathology grow and develop?

Height and weight growth are usually normal. Psychomotor development of the affected children is mostly normal, even if acquisition retardation during the main steps of development affects about 10% of patients.

• How is it diagnosed?

The diagnosis is clinical, and therefore based on the comparison of a number of similarities among the clinical characteristics of the patients and the ones that are most frequently identified among the affected subjects. The defect causing the pathology is still unknown.

• Is the oculo-auricolo-vertebral spectrum an hereditary disease?

The aetiology (i.e. the cause) of Goldenhar syndrome is not totally clear; patients anomalies seem to be caused by an anomalous embryo development. Most Goldenhar cases are sporadic, in other words, transmission instances are isolated in the same family. Among those families described in scientific literature, cases found among siblings, or parents-to-children transmission are rare. Association between Goldenhar Syndrome and chromosome anomalies are rarely found.

• Do parents with a child affected with the syndrome risk having another child with the same pathology?

Parents who have already had a child affected with Goldenhar syndrome have a slightly higher probability in having another affected child than the general population.

• Is it suggested to have a genetic advice?

For a couple who has a Goldenhar child or for grown up people with the syndrome, a genetic advice can be useful: any questions may be asked to clear all doubts about the pathology (i.e. medical consequences of the disease, possibilities to prevent or to cure it, transmission probabilities).

• Is a pre-birth diagnosis of Goldenhar syndrome possible ?

No exam can give a sure diagnosis of the pathology during pregnancy: as a matter of fact, if foetal malformations are absent, pregnancy criteria appear to be normal. The identification of severe malformations of organs that are typically involved in Goldenhar syndrome during an echography scan might be the evidence of the syndrome. In these cases it is useful to have an evaluative a foetal scan in three dimensions in a specialised centre and, above all, a genetics doctor advice.

How can a Goldenhar patient be helped?

Treatment and assistance strategies are complex both for the great variability among the patients, and for the involvement of various body parts that consequently need a competence in many sciences. In general, an accurate otorhinolaryngology evaluation (in particular hearing) may be useful, as well as an oculist examination, an orthopaedic examination with the radio exam of the backbone, an accurate study to plan the possible correction of craniofacial anomalies by a plastic surgeon, a possible orthodontic treatment, an analysis of the psycho-intellectual development of the child, and other examinations. They should be planned singularly, if inner organs are suspected to be malformed.

		Name GOLDENHAR SYNDROME Synonyms · oculo-auriculo-vertebral dysplasia · facio-auriculo-vertebral syndrome (FAV) · oculo-auriculo-vertebral syndrome (OAV) · hemifacial microsomy · first and second branchial arch syndrome Signs and Symptom Goldenhar Syndrome (GS) was described for the first time in 1952 by Prof. M. Goldenhar. It is a polymalformation syndrome and it is characterised by ocular anomalies, uni- or bilateral microtia, mandibular region hypoplasia, hemifacial microsomy, oral anomalies, respiratory organs anomalies, genito-urinary anomalies, heart anomalies, nervous apparatus anomalies, skeleton vertebral anomalies and cranio-facial anomalies. GS has a variable frequency from 1:3500 to 1:26000 born children and more often occurs on the right hemiface (right:left=3:2) and with a male predominance (m:f=3:2). GS aetiology is still unknown and genetic and environmental patterns were advanced as causes. Though most of GS cases are sporadic, both autosomal dominant and autosomal recessive patterns were described. Nowadays it is commonly accepted as origin of this syndrome a vascular sufferance of cephalic mesoderm because of an anomaly of stapedius artery, and a consequent alteration of the development of the first and second branchial arches. An element that enforces this theory is the presence of the syndrome in only one of monozygotic twins. Mandibular hypoplasia - hemifacial microsomia: underdevelopment of tissues in a part of the face, underdevelopment of the upper and lower jaw. The ramus can either be short or absent and the chin tends to lean on that side. The cheek tissue is often underdeveloped giving asymmetry in the face along with the mandibular problem. Condyles anomaly and connected dental problems. Uni- or bilateral microtia: defects in the auricular region represented by the presence of cartilage tags in the preauricular area as well as the absence of malformation of the auricle, presence of the pre-auricular tags, stenosis-atresia of the meatus acusticus, transmission or neurosensorial deafness, hearing deficits for injuries both in the medium and inner ear. Ocular anomalies: epibulbar dermoid cyst, sub-conjunctiva or upper orbital dermoids, coloboma of the upper eyelid, blepharoptosis, lagrymal glands anomalies, epibulbar tumors, micro-anophtalmia, retina anomaly, strabismus. Skeleton vertebral anomalies and cranio-facial anomalies: in a high percentage of cases hemispondyls and lumbar hemivertebrae at lumbar, thoracic dorsal and cervical level, scoliosis, occipital atlas, spina bifida are present. In some cases it is associated with Arnold-Chiari Syndrome. Skull malformations are present on the part interested by the syndrome, very small orbit, smaller zygoma and temporal bone. Oral abnormalities: macrostomia, tracheo-oesophageal fistulae, oesophageal atresy, structural and functional malformations of pharynx and larynx that can contribute in increasing the risk of obstruction of breathing system, deficiencies in communication and mobility. GS can cause severe obstructive apnoea during sleep, if it is not treated apnoea can lead to growth and mental retardation. Cleft lip, cleft lip and palate, ogival palate. Kidney and genito-urinary abnormalities: uni- or bilateral kidney agenesis, kidney hypoplasia hectopy, orchis ectopy, cryptorchidism. Cardiac anomalies: tetralogy of Fallot, defect of the interventricular sect, restriction of aorta. Nervous apparatus anomalies - cerebral anomalies: hypoplasia of the encephalic pons, agenesy of the corpus callosum, hydrocephalus, microcephaly, encephalocele. Mental retardation is present in 5%-15% of patients. Respiratory system abnormalities: some children affected by GS had to suffer tracheotomy soon after their birth. In some cases jaws were so malformed that the tongue obstructed breath during sleep (tracheotomy). Cases of lung aplasia and hypoplasia. Pre-birth diagnosis: It is not yet availabe as pecific genetic exam to diagnose - before the actual birth - if foetus is affected by the Goldenhar Syndrome. But still being orientative, echography scan can visualise facial asymmetry, auricular anomalies, ocular defects, vertebral anomalies. Signs -Anomalies vein carries - preauricular tags (very frequent) - partial absence / hypoplasia of mandibula(very frequent) - epibulbar dermoid cysts (very frequent) - narrow face (very frequent) - macrostomia / large mouth (very frequent) - atresy / absence of outer meatus acusticus (very frequent) - parrot jaw (very frequent) - retrognatia / micrognatia (very frequent) - cleft palate (very frequent) - transmission / conduction deafness (very frequent) - vertebrae: dimension / shape anomalies (very frequent) - hearing anomalies / deafness (frequent) - astigmatism (frequent) - coloboma of the eyelid (frequent) - cheeks with tags (frequent) - microphtalmia (frequent) - retroflected ears (frequent) - facial paralysis (frequent) - lateral cleft lips (frequent) - flattened zygoma / malar hypoplasia (frequent) - kidney agenesy / mono- / bilateral hypoplasia (sporadic) - pharynx anomalies / anomalies in deglutition (sporadic) - thumb anomalies (excluded hypoplasia) (sporadic) - absence of the ear / small ear (sporadic) - aplasia / hypoplasia of the lugs (sporadic) - artesia of oesophagus / tracheo-oesophageal fistulae (sporadic) - congenital cardiopathy (sporadic) - heart in unusual position / dextrocardia (sporadic) - ectopy of kidney / horseshoe kidney (sporadic) - ectoy of orchis / cryptorchidism (sporadic) - hypo- / a-plasic mammal gland (sporadic) - hydrocephalus (sporadic) - hypertelorism (sporadic) - pectus carinatum (sporadic) - mental / psychomotor retardation (sporadic) - scoliosis (sporadic) - uterus / vagina / anomaly of tubae (sporadic) Taken from: www.orpha.net and www.malattierare.pediatria.unipd.it • What is the oculo-auricolo-vertebral spectrum? The oculo-auricolo-vertebral spectrum is a mainly unilateral condition that may involve various parts of the body; the incidence is estimated to be about 1/6,000 born-alive children, but the manifestation of the syndrome varies greatly giving problems in clearly defining its frequency among the population. • Which are the most visible signs? The main characteristics of the syndrome are:  FACIAL ASYMMETRY: often connected to mandible asymmetry; temporal, malar and mascellare bones may also be involved.  AURICULAR ANOMALIES: mainly unilateral; the structures of the outer, medium and/or inner ear may be anomalous. The most frequent alteration is the small and malformed, if not completely absent, ala auris (microtia/anotia); many patients may also have skin and cartilaginous, pre-auricular appendages, along the ideal line from the ear to the angle of the mouth. All ear anomalies that are signalled may justify transmission (the most frequent) and/or neurosensorial deafness.  EYE ANOMALIES: the most frequent anomalies are whitish masses visible on the eye globe (epibulbar dermoid cysts); these small, monolateral or bilateral, masses may sometimes interfere with sight.  MOUTH ANOMALIES: they range from true malformations (cleft palate and lip) to mastication problems caused by malocclusion.  SKELETON ANOMALIES; the bones that are more often involved are vertebrae (fused, butterfly, hypoplasic vertebrae, hemivertebrae, spina bifida, scoliosis), involving cervical vertebrae in particular. Ribs, skull bones, upper limbs (radium and thumb anomalies) and lower limbs (clubfoot) may also reveal anomalies. • How do children affected by this pathology grow and develop? Height and weight growth are usually normal. Psychomotor development of the affected children is mostly normal, even if acquisition retardation during the main steps of development affects about 10% of patients. • How is it diagnosed? The diagnosis is clinical, and therefore based on the comparison of a number of similarities among the clinical characteristics of the patients and the ones that are most frequently identified among the affected subjects. The defect causing the pathology is still unknown. • Is the oculo-auricolo-vertebral spectrum an hereditary disease? The aetiology (i.e. the cause) of Goldenhar syndrome is not totally clear; patients anomalies seem to be caused by an anomalous embryo development. Most Goldenhar cases are sporadic, in other words, transmission instances are isolated in the same family. Among those families described in scientific literature, cases found among siblings, or parents-to-children transmission are rare. Association between Goldenhar Syndrome and chromosome anomalies are rarely found. • Do parents with a child affected with the syndrome risk having another child with the same pathology? Parents who have already had a child affected with Goldenhar syndrome have a slightly higher probability in having another affected child than the general population. • Is it suggested to have a genetic advice? For a couple who has a Goldenhar child or for grown up people with the syndrome, a genetic advice can be useful: any questions may be asked to clear all doubts about the pathology (i.e. medical consequences of the disease, possibilities to prevent or to cure it, transmission probabilities). • Is a pre-birth diagnosis of Goldenhar syndrome possible ? No exam can give a sure diagnosis of the pathology during pregnancy: as a matter of fact, if foetal malformations are absent, pregnancy criteria appear to be normal. The identification of severe malformations of organs that are typically involved in Goldenhar syndrome during an echography scan might be the evidence of the syndrome. In these cases it is useful to have an evaluative a foetal scan in three dimensions in a specialised centre and, above all, a genetics doctor advice. How can a Goldenhar patient be helped? Treatment and assistance strategies are complex both for the great variability among the patients, and for the involvement of various body parts that consequently need a competence in many sciences. In general, an accurate otorhinolaryngology evaluation (in particular hearing) may be useful, as well as an oculist examination, an orthopaedic examination with the radio exam of the backbone, an accurate study to plan the possible correction of craniofacial anomalies by a plastic surgeon, a possible orthodontic treatment, an analysis of the psycho-intellectual development of the child, and other examinations. They should be planned singularly, if inner organs are suspected to be malformed.