Goldenhar syndrome: symptoms, causes and treatments

This rare disease causes various types of malformations and, usually, deafblindness.

Goldenhar syndrome is a rare medical condition in which the patient suffers from malformations in which the patient suffers malformations in various parts of the body, especially the external ear, the face and the vertebrae of the neck.

The exact causes are not known, but it is believed to be due to an interaction of environmental and genetic factors, and the degree of severity is highly variable. Let's take a look at what this rare disease entails.

What is Goldenhar syndrome?

Goldenhar syndrome, also called facio-auriculo-vertebral dysplasia or oculo-auriculo-vertebral dysplasia, is a very rare medical condition in which several malformations occur.. These originate due to problems during fetal development, specifically in the first and second brachial arch, structures which will form the neck and head in the fully developed baby.

Among the main malformations present in the syndrome we find a clear asymmetry of the face, as well as problems in the eyes, ears and spine. The degrees of deformity are very variable from affected to affected, with cases having either a very poorly formed ear or none at all. There may also be benign tumors in the eye and anomalies in the spine.

It does not only affect the face. Patients may have cardiac, pulmonary and renal problems, as well as alterations in the central nervous system.. The cause of the disease is still under investigation, although it points to an interaction between genetics and environment. Treatment is variable, depending on the age, severity of the case and whether the patient has had previous operations.

Goldenhar syndrome is part of the group of hemifacial microsomia diseases, medical conditions in which there are alterations in the face and associated structures.medical conditions in which there are alterations in the face and associated structures. It is not yet known whether the diseases categorized within this group are all different conditions or whether they form part of the same pathological spectrum, in which there would be different degrees of severity.

Symptomatology

This syndrome presents different degrees of severity, although it must be said that in the mildest cases the symptoms and signs can be considered highly disabling. The symptoms are already present at birth, and it is on the list of medical conditions that can cause deafblindness.. Between 70% and 90% of the cases only affect one side of the face (unilateral involvement), being usually the right side the most affected, being approximately 60% of the cases.

Among the symptoms of Goldenhar syndrome we can find all kinds of malformations, especially in the face. In practically all cases there are malformations in the external ears, which may involve the following symptoms:

• Preauricular appendages: skin and cartilage located in front of the ear.
• Microtia: very small ear.
• Anotia: absent ear.
• Deafness.

As we were already commenting, in this syndrome there is asymmetry between the two sides of the face.This is usually due to an underdevelopment of one side of the face. The defects that can be found in the malformed part of the face are:

• Small and flat maxillae, mandible and temporal bone (85% of cases).
• Ocular dermoid cysts: non-cancerous tumors in, usually, one eye.
• Exaggeratedly large mouth on one side of the face.
• Small palate and tongue on the affected side.
• Especially small facial muscles on the affected side.
• Cleft lip and palate.

In the eyes, apart from the cysts, other malformations can occur. Among which we can find:

• Blepharophimosis: very small palpebrae.
• Microphthalmia: small eye.
• Anophthalmia: absence of eye.
• Retinal abnormalities.
• Blindness.

There are alterations in the vertebrae, mainly in the cervical vertebrae.. The following conditions may occur:

• Absence of vertebrae.
• Presence of hemi-vertebrae (vertebrae that only formed on one side).
• Fused ribs.
• Curvature of the spine: kyphosis and scoliosis.

But although this syndrome is also known as facio-auriculo-vertebral dysplasia, it does not mean that there can only be alterations in the face, ears and vertebrae. Deformities can be found in the entire skull, such as having a very small head and encephalocele, i.e., a brain deformation in the skull.that is, a brain deformity in which the cranial lining and protective fluid are left outside, forming a protuberance of different size. Because of this, between 5% and 15% of cases present intellectual disability.

In addition, there may be damage to other parts of the body, such as abnormalities in the lungs, kidneys and heart. Among the cardiac anomalies we find, mainly, ventricular septal defects and tetralogy of Fallot. There may also be deformities in the bones of the extremities, involving problems such as club feet, anomalies in the arms and fingers.

Possible causes

It is estimated that The incidence of this syndrome is estimated to be 1 in 25,000 live births.although the genetic disorder associated with this sporadic condition occurs in 1 in 3,500-5,000 births. It affects mostly males, with a V/M ratio of 3/2.

The exact cause of Goldenhar syndrome is not known, but in the cases that have been described in the literature several factors have been proposed, grouped in four: environmental, hereditary, multifactorial and unknown, being this fourth and last group the label where most of the cases are found.

Environmental causes

Among the environmental causes, it has been proposed as the main one, the use of drugs during pregnancy that contain teratogenic agents, i.e., that induce the development of the disease.that is, they induce malformations in the fetus. Among them would be:

• Ibuprofen.
• Aspirin.
• Ephedrine.
• Tamoxifen.
• Thalidomide.
• Retinoids.
• Mycophenolate.

It should be noted that ibuprofen, aspirin and ephedrine, although it has been suggested that they could have something to do with the appearance of the syndrome, recent studies indicate that this should not necessarily be the case. As for thalidomide, its action as a congenital malformation-inducing agent is well known. of thousands of newborns between the 1950s and 1960s.

Other environmental causes include the use of drugs during pregnancy, especially cocaine, is another environmental cause.. The possibility of presenting Goldenhar syndrome has also been related in case the mother has been exposed to insecticides and herbicides during pregnancy.

Other environmental factors, in this case not associated with substances, are that the mother has Diabetes mellitus, has had multiple pregnancies or has resorted to assisted reproduction.

Genetic causes.

In most cases, the onset of the syndrome is sporadic.. This means that no other cases have been reported in the family. However, the possibility of genetic alterations inducing the syndrome, especially abnormalities on chromosome 14, has been raised.

Between 1% and 2% have the syndrome through autosomal dominant inheritance, although there are rare cases of autosomal dominant inheritance.although there are rare cases in which the inheritance is autosomal recessive.

Inherited cases are more frequent when the syndrome affects both sides of the face. Deafness, abnormalities of the mouth and ocular dermoid cysts usually occur in sporadic cases.

Cases in which the cause is solely genetic or solely environmental are rare. In most cases there must be an interaction between the two factors, although, as mentioned above, in most cases the exact cause is unknown.

Diagnosis

It is possible to try to diagnose this condition before the baby is born. For this purpose, fetal ultrasound is used to diagnose the condition before the baby is born. fetal ultrasound, nuclear magnetic resonance and genetic studies are used for this purpose.. However, in many cases the diagnosis is established once the baby is born, since it is much easier to see the facial involvement with the naked eye.

Although the involvement is highly variable, in most cases there are combinations of symptoms, which are not at all discrete, involving facial asymmetry, facial asymmetry, asymmetry of the face, facial asymmetry and facial asymmetry.These include facial asymmetry, mandibular hypoplasia and preauricular appendages, as well as small ears and dermoid cysts in the eyes. The presence of ear abnormalities is considered necessary for diagnosis.

Treatment

There is no cure for Goldenhar syndrome. Treatment is focused on increasing the sufferer's well-being, as well as opting for the most appropriate corrective measures to ensure that he/she can perform daily tasks, especially focused on improving vision and hearing. to ensure that he/she can perform daily tasks, especially focused on improving vision and hearing. Treatment depends on age, especially on how the affected bones grow and form.

Professionals recommend taking a series of preventive measures to avoid other associated medical problems, to plan treatment and to know if there is a risk of another person being born with the syndrome.

Among these measures, the most important is to take a detailed history of the pregnancy, in order to know if there is maternal diabetes mellitus, bleeding during pregnancy, multiple gestation or if assisted reproduction was used. It is also important to know if the mother has been exposed to teratogenic agents or has consumed drugs, especially cocaine.

Another good measure is to take a family history of at least three generations, paying special attention to family members who may have had any type of malformation.. It is very important to know if there have been cases of facial asymmetry, ear malformations, deafness, cardiac or vertebrae problems, no matter how slight these conditions may seem.

As for the newborn, it is advisable to perform a complete physical examination and perform a karyotype study.. Hearing tests should also be performed, combined with spinal x-rays, echocardiogram and cervical renal ultrasound, as well as a CT scan of the temporal bone, one of the cranial areas that is often affected. This is especially recommended after the age of five.

Given the large number of symptoms, and that they affect various parts of the body, it is important that affected children are observed by several specialists. Among those who should not be missed are:

• Medical geneticists.
• Plastic surgeons specialized in cranial malformations.
• Otorhinolaryngologists.
• Oculists.
• Dermatologists.
• Dentists and orthodontists.

In newborns, respiratory and nutritional support is necessary in case of malformations, especially in the mouth, which make breathing and feeding difficult.malformations, especially in the mouth, that make breathing and swallowing difficult. Jaw defects are corrected with surgical interventions. The external ear is reconstructed and the cheeks are filled to give a greater symmetry to the face.

Prognosis

Depending on the malformations of the infant with Goldenhar syndrome, the prognosis is very variable, the prognosis is very variable.

Surprisingly, most children diagnosed with this syndrome have a normal life expectancy, but this is especially true if the malformations do not severely affect the individual's organs or systems. In case the patient lacks any internal organ, an uncommon symptom but still present in this syndrome, and usually translating into problems in the heart, kidneys or central nervous system, the prognosis is usually less favorable.

Bibliographic references:

• González Calvete, Laura, Ramos Pérez, Alfonso, Lozano Losada, Sara, Salazar Méndez, Raquel, & López Quintana, Calixto. (2016). Goldenhar syndrome: apropos of a case. Pediatría Atención Primaria, 18(69), 49-53. Retrieved March 02, 2020, from http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1139-76322016000100010&lng=es&tlng=es.
• Touliatou V, Fryssira H, Mavrou A, Kanavakis E, Kitsiou-Tzeli S (2006). Clinical manifestations in 17 Greek patients with Goldenhar syndrome. Genet. Couns. 17 (3): 359–70. PMID 17100205
• Kokavec, R ( 2006). "Goldenhar syndrome with various clinical manifestations". The Cleft Palate-Craniofacial Journal. 43 (5): 628–34. doi:10.1597/05-094