Goldenhar syndrome: symptoms, causes and treatments

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

The causes are not exactly 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 see what this rare disease means next.

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What is Goldenhar syndrome?

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

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 deformation are very variable from affected to affected, there being cases in which either they have a very poorly formed ear, or there is not even one. Benign eye tumors and spinal abnormalities can also occur.

It does not only affect the face. Patients may have heart, lung, and kidney problems, as well as central nervous system disorders. The cause of the disease is still being investigated, although it points to an interaction between genetics and the environment. The treatment is variable, depending on the age, the seriousness of the case and if you have received the pertinent operations previously.

Goldenhar's syndrome It is part of the group of hemifacial microsomia diseases., medical conditions in which there are alterations in the face and associated structures. It is not yet known if the diseases classified within these groups are all different. conditions or if they would 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 from birth, and it is on the list of medical conditions that can cause deafblindness. Between 70% and 90% of cases only affect one side of the face (involvement unilateral), usually the right side being the most affected, being approximately close to 60% of the cases.

Among the symptoms of Goldenhar syndrome we can find all kinds of malformations, especially on 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 being due, usually, to a poor development of a part of it. The defects that can be found in the malformed part of the face are:

• Small and flat jaws, 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.
• Facial muscles especially small 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 eyelids.
• Microphthalmia: small eye.
• Anophthalmia: absence of eye.
• Retinal abnormalities.
• Blindness.

Alterations occur in the vertebrae, mainly in the cervical. The following conditions may occur:

• Absence of vertebrae.
• Presence of hemivertebrae (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. Deformations can be found in the entire skull, such as having a very small head and encephalocele, that is, a brain deformation in which the cranial lining and protective fluid are extruded, forming a bulge of different sizes. Because of this, between 5% and 15% of cases have 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, abnormalities in the arms and fingers.

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Possible causes

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

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

environmental causes

Among the environmental causes, it has been proposed, as the main one, the use of drugs during pregnancy that contain teratogenic agents, 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 would not have to be So. As for thalidomide, its action as an agent that induces congenital malformations is well known. of thousands of newborns between the decades of the fifties and sixties.

Another environmental cause is drug use during pregnancy, especially cocaine. 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 the fact that the mother has diabetes mellitus, has had multiple pregnancies or has resorted to assisted reproduction.

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genetic causes

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

Between 1% and 2% have the syndrome through 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 both factors, although, as we have already mentioned, in most cases the exact cause is unknown for the specific case.

Diagnosis

There is the possibility of trying to diagnose this condition before the baby is born. For it fetal ultrasound, nuclear magnetic resonance and genetic studies are used. However, in many cases the diagnosis is established once the baby has been born, since it is much easier to observe facial involvement with the naked eye.

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

Treatment

Goldenhar syndrome has no cure. The treatment focuses on increasing the well-being of the sufferer, in addition to opting for the most appropriate corrective measures. to make sure you can perform everyday 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 problems associated doctors, plan treatment and 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 reproduction was used assisted. It is also important to know if the mother has been exposed to teratogenic agents or has used drugs, especially cocaine.

Another good measure is to do the family history of at least three generations, paying special attention to relatives who may have had some type of malformation. It is very important to know if there have been cases of facial asymmetry, ear malformations, deafness, heart or vertebrae problems, however slight these conditions may seem.

As for the newborn it is advisable to perform a complete physical examination and perform a karyotype study. Tests to see hearing should also be done, combined with x-rays of the spine, echocardiogram, and cervical renal ultrasound, in addition to computed tomography of the temporal bone, one of the cranial areas where there is usually affectation. This is especially recommended to do after five years.

Given the large number of symptoms, and that these affect various parts of the body, it is important that affected children are observed by several specialists. Among those that cannot be missing we have:

• Genetic doctors.
• Plastic surgeons specialized in cranial malformations.
• otolaryngologists.
• eye doctors
• Dermatologists.
• Dentists and orthodontists.

In newborns, respiratory and alimentary support is necessary in case there are malformations, especially in the mouth, that make breathing and swallowing difficult. Defects in the jaw are corrected with surgical interventions. The external ear is reconstructed and the cheeks are filled in to give the face greater symmetry.

Forecast

Depending on the malformations that the baby with Goldenhar syndrome presents, the prognosis is highly variable.

Surprisingly, most children diagnosed with this syndrome have a normal life expectancy, but This is especially so in the event that the malformations do not affect, in a very serious way, organs or systems of the individual. In case the patient lacks any internal organ, a rare symptom but still present in this syndrome, and which usually result in 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: about a case. Primary Care Pediatrics, 18(69), 49-53. Retrieved on March 2, 2020, from http://scielo.isciii.es/scielo.php? script=sci_arttext&pid=S1139-76322016000100010&lng=en&tlng=en.
• Touliatou V, Fryssira H, Mavrou A, Kanavakis E, Kitsiou-Tzeli S (2006). Clinical manifestations in 17 Greek patients with Goldenhar syndrome. Genet. Counts. 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