Goldenhar syndrome is a rare congenital disease that manifests itself with multiple malformations, pronounced clinical polymorphism. Occurs due to mutation of genes localized in chromosomes 5, 14, 20. The syndrome is characterized by various anomalies of the facial skeleton, pathologies of the sensory organs, often the disease is accompanied by a delay in mental development. The examination plan includes genetic testing to verify the diagnosis, laboratory and instrumental methods taking into account the leading clinical signs. The treatment is supportive, many patients require hearing replacement, complex neurorehabilitation.
Q87.0 Syndromes of congenital anomalies affecting mainly the appearance of the face
The syndrome is named after the American scientist Maurice Goldenhar, who described its typical clinical manifestations in 1952. In 1963, R.J. Gorlin and his colleagues reported their own observations of patients, giving the disease the second name “oculo-auriculo-vertebral dysplasia”. The condition is detected with a frequency from 1:3500 to 1:7000 live births, the ratio of boys and girls is 3:2. If there is a sick child in the family, then the probability of Goldenhar syndrome in the following children is no more than 3%.
The disease occurs when there is a violation of the differentiation of the 1-2 gill arches, which is provoked by a mutation in the GSC and TCOF1 genes. In 98% of cases of the syndrome, the role of heredity cannot be traced. However, about 2% of patients have relatives with similar clinical symptoms. The literature describes cases of autosomal dominant and autosomal recessive inheritance.
The main predisposing factors are:
- exposure to teratogenic factors in the early stages of gestation;
- the presence of diabetes mellitus in the mother, overweight;
- previous artificial abortions of pregnancy and miscarriages.
The mechanisms of formation of phenotypic changes characteristic of Goldenhar syndrome continue to be studied. To date, the leading theory is the theory of disorders of facial structures in early gestational periods (from the 3rd to the 8th week of embryogenesis). Presumably, during this period, as a result of the combined effects of adverse external factors and genetic anomalies, the differentiation of paired first-second gill arches is disrupted.
As a consequence, the frontal, mandibular and maxillary ectodermal processes originating from the first gill arch, and the auricles formed by the 1st and 2nd gill arches develop asymmetrically. After the birth of a child, this is manifested by specific changes in the upper and lower jaws, eyes and eye sockets, facial and chewing muscles, structures of the outer and middle ear, malocclusion, soft tissue deficiency.
The main signs of Goldenhar syndrome are anomalies of the facial structure, which in 70% of cases are right—sided. All patients have asymmetry, underdevelopment of the lower jaw, reduction in size, deformation or absence of auricles. Pathologies of the hearing organ are more often unilateral, accompanied by atresia of the auditory canal, preauricular outgrowths. Sometimes an additional rudimentary auricle is formed.
Also characterized by a decrease in the size of the eyeballs (microphthalmia), strabismus, iris atresia, cataract. About 50% of patients with Goldenhar’s disease have a high Gothic palate, a wide mouth (macrostomy), cleavage of the tongue, abnormal bite, missing part of the teeth. In 40% of cases, clubfoot, spinal anomalies (scoliosis, spina bifida), curvature of the ribs are noted. In 30% of patients, congenital pathologies of internal organs occur: heart defects, hypoplasia of the lungs, dysplasia of the kidneys.
The most dangerous consequence of Goldenhar syndrome is mental retardation, which is caused by bilateral hearing loss, decreased visual acuity. At the same time, most children have normal functioning of the nervous system, but sensory deprivation creates difficulties with speech and psychomotor development. The complicated course of the syndrome occurs with severe congenital heart, lung, and kidney defects.
In most cases, a preliminary diagnosis is established on the basis of characteristic phenotypic signs: deformity of the ears, facial asymmetry, pathology of the development of the lower jaw. To confirm Goldenhar syndrome, a geneticist’s consultation is required, a set of diagnostic measures is carried out:
- Genetic analysis. Testing for a specific mutation of the genes 14q32, 5p15, MYT1 allows 100% confirmation of the diagnosis. The study is carried out in special genetic laboratories using methods of exon sequencing, fluorescent hybridization.
- Audiometry. Dynamic hearing assessment is necessary for all patients in order to identify conductive hearing loss in time, to provide measures for its correction. An extended examination by an otolaryngologist may include impedance measurement, assessment of the stapedial muscle reflex.
- Neurological examination. Consultation of a pediatric neurologist is required to determine the causes of delayed psychomotor development, assess the functioning of the central and peripheral nervous system. If there are indications, the patient is sent for further examination to a psychiatrist.
- Instrumental visualization. In order to confirm or exclude somatic defects, chest x-ray, echocardiography, ultrasound of the abdominal cavity are performed in Goldenhar syndrome. CT or MRI of the brain is used to study the central nervous system.
Since the main problem is hearing loss, hearing replacement is recommended at an early age in order to prevent deafness and the resulting delay in psychorechological development. Also, the patient is examined by a plastic surgeon in order to correct, if possible, the typical external manifestations of the syndrome, correct asymmetry, and harmonize facial features.
Patients diagnosed with Goldenhar’s disease are subject to lifelong dynamic monitoring. They are assigned regular examinations by an ophthalmologist, an otolaryngologist, a neurologist and other specialists to monitor their health. The courses of supportive treatment include several areas of care, the main of which are:
- Metabolic therapy. For the proper development of the central nervous system, improving cognitive skills, nootropics, B vitamins are used.
- Neurorehabilitation. In order to improve speech development, long courses of classes with speech therapists and surdologists are recommended. According to the indications, psychological correction is carried out.
- Special training. Patients with signs of ZPR need to continue their studies in correctional classes with speech pathologists, sign language teachers.
Prognosis and prevention
In the absence of congenital somatic defects in the patient and a sufficient level of intelligence, the prognosis is favorable, most patients live to adulthood and old age. Cases of Goldenhar syndrome that are accompanied by cardiological, pulmonological or nephrological defects are of concern, and an unfavorable prognosis is also established for severe mental retardation.
The basis for the prevention of the syndrome is the antenatal protection of the fetus. The critical period is the first trimester, since it is at this time that characteristic bone anomalies occur. Pregnant women are advised to avoid contact with chemicals, X-rays, and to observe anti-epidemic measures to protect against viral infections.