THE CLINICAL CASE OF HEMIFACIAL MICROSOMIA IN THE NEWBORN BOY FROM MOTHER WITH Z-21 Summary Hemifacial

Introduction Hemifacial Microsomia (HFM) is a term used to identify facial deformities associated with impaired development of the first and second pairs of branchial arches, characterized by underdevelopment of one half of the face. Alternative names: otocraniostenosis, craniofacial microsomia, lateral facial dysplasia, syndrome of the first and second pair of branchial arches, Goldenhar syndrome or oculo-auriculovertebral dysplasia. Historically, if a patient is diagnosed with epibulbar dermoid among the symptoms, the disease is called Goldenhar syndrome (GS), and if it is not – Hemifacial Microsomia [1-3]. Firstly HFM was described by Cant (1861) and later by Von Arlt (1881), but this went unnoticed. In 1952, the Swiss ophthalmologist Goldenhar described three cases of eye and ear dysplasia with two characteristic abnormalities: epibulbar dermoid and preauricular growths. These abnormalities were accompanied by coloboma in the middle of the eyelid, microphthalmia, aplasia or hypoplasia of the auditory canal, preauricular fistula and macrostomy. Gorlin and Pindborg (1963) reported their observations under the general name "oculo-auriculo-vertebral dysplasia", thus pointing to changes in the spine: hemivertebrale, occipitalisatio atlantis, spina bifida occulta and others. Since then, GS has been defined as dysplasia of the eyes, ears and spine in the clinical atlas of congenital anomalies of the face [1, 2, 4, 5, 6]. The wide range of anomalies associated with HFM complicates systematic and inclusive classification. In 1991, Vento et al., proposed a system in which each letter of the abbreviation O.M.E.N.S. indicates one of the five main manifestations of HFM: O – orbital distortion; M – mandibular hypoplasia; E – ear anomaly; N – nerve involvement; S – soft tissue deficiency. O.M.E.N.S. the system is easily adapted for data storage, retrieval and statistical analysis. The retrospective study of 154 patients with HFM classified according to O.M.E.N.S. confirmed the concept that mandibular deformity is the "cornerstone" of this anomaly [3, 7]. According to statistics, the incidence of HFM is 1:3500-1:7000 live births and occurs in 1 case per 1000 children with congenital deafness. The ratio of boys and girls is 3:2. The probability of giving birth to the next child with this disease is about 2%, the probability of transmitting the disease to children – less than 3 % [2, 5]. The etiology and type of inheritance are insufficiently studied. Currently, 8 genes have been identified in which mutations can cause HFM. The orthodontic homeobox 2 gene (OTX2) is identified more often than the other seven genes. It also determines the genetic code of the transcription factor. The GSC gene, which determines the clinical manifestations of HFM, is mapped on the long arm of chromosome 14, at locus 14q32 [3, 8, 9]. Most cases of HFM are sporadic due to reduced penetrance, somatic mosaicism and epigenetic changes. There are reports of familial inheritance, which thus requires consideration of autosomal dominant (AD), autosomal recessive (AR) or multifactorial inheritance. The etiology of the disease does not exclude the role of adverse obstetric and gynecological history of the mother: previous abortions, diabetes, overweight, malnutrition, smoking and alcohol use; and the influence of teratogenic factors in early pregnancy, НЕОНАТОЛОГІЯ, ХІРУРГІЯ ТА ПЕРИНАТАЛЬНА МЕДИЦИНА Т. ХI, No 2(40), 2021 NEONATOLOGY, SURGERY AND PERINATAL MEDICINE VOL. ХI, No 2(40), 2021


Introduction
Hemifacial Microsomia (HFM) is a term used to identify facial deformities associated with impaired development of the first and second pairs of branchial arches, characterized by underdevelopment of one half of the face. Alternative names: otocraniostenosis, craniofacial microsomia, lateral facial dysplasia, syndrome of the first and second pair of branchial arches, Goldenhar syndrome or oculo-auriculovertebral dysplasia. Historically, if a patient is diagnosed with epibulbar dermoid among the symptoms, the disease is called Goldenhar syndrome (GS), and if it is not -Hemifacial Microsomia [1][2][3].
Firstly HFM was described by Cant (1861) and later by Von Arlt (1881), but this went unnoticed. In 1952, the Swiss ophthalmologist Goldenhar described three cases of eye and ear dysplasia with two characteristic abnormalities: epibulbar dermoid and preauricular growths. These abnormalities were accompanied by coloboma in the middle of the eyelid, microphthalmia, aplasia or hypoplasia of the auditory canal, preauricular fistula and macrostomy. Gorlin and Pindborg (1963) reported their observations under the general name "oculo-auriculo-vertebral dysplasia", thus pointing to changes in the spine: hemivertebrale, occipitalisatio atlantis, spina bifida occulta and others. Since then, GS has been defined as dysplasia of the eyes, ears and spine in the clinical atlas of congenital anomalies of the face [1,2,4,5,6].
The wide range of anomalies associated with HFM complicates systematic and inclusive classification. confirmed the concept that mandibular deformity is the "cornerstone" of this anomaly [3,7].
According to statistics, the incidence of HFM is 1:3500-1:7000 live births and occurs in 1 case per 1000 children with congenital deafness. The ratio of boys and girls is 3:2. The probability of giving birth to the next child with this disease is about 2%, the probability of transmitting the disease to children -less than 3 % [2,5].
The etiology and type of inheritance are insufficiently studied. Currently, 8 genes have been identified in which mutations can cause HFM. The orthodontic homeobox 2 gene (OTX2) is identified more often than the other seven genes. It also determines the genetic code of the transcription factor. The GSC gene, which determines the clinical manifestations of HFM, is mapped on the long arm of chromosome 14, at locus 14q32 [3,8,9].
Most cases of HFM are sporadic due to reduced penetrance, somatic mosaicism and epigenetic changes. There are reports of familial inheritance, which thus requires consideration of autosomal dominant (AD), autosomal recessive (AR) or multifactorial inheritance.
The etiology of the disease does not exclude the role of adverse obstetric and gynecological history of the mother: previous abortions, diabetes, overweight, malnutrition, smoking and alcohol use; and the influence of teratogenic factors in early pregnancy, The article demonstrates a clinical case of hemifacial microsomia in a newborn boy from a mother with Z-21 in the form of deformation of the left auricle with atresia of the auditory canal and "false" ears on the right, combined with congenital anomaly of heart (atrial septal defect) and brain (hypoplasia of the corpus callosum).
Emphasis is placed on the need of involving a multidisciplinary team of specialists in the management of this patient both in the neonatal period and in the system of subsequent follow-up.
such as drugs cocaine, thalidomide, retinoic acid, herbicides [2,6,9,10,11]. Posvillo (1976), using an animal model, suggested that fetal hypoxia, maternal hypertension, anticoagulants can lead to hematoma in the ear or jaw of the fetus. Hematomas can cause impaired tissue differentiation, which, in turn, can lead to dysplasia of the branching arch in the process of early ontogenesis. Gomes et al. (1984) hypothesized the role of radiological intervention in the 4th or 6th week of pregnancy as a causative factor of the syndrome. Now it is believed that when the source of blood supply changes in the area 1 and 2 of the branchial arches of the embryo, hemorrhage occurs. Rupture of a blood vessel in this place leads to mitotic cell division and incorrect formation of the basic anatomical structures of the human body. Callen et al. (2004) believe that HFM and CHARGE syndrome combine a single pathogenetic mechanism, namely the violation of the tab of the nerve roller [1,9].
Unilateral lesions were observed in 85% of HFM abnormality cases, the bilateral lesions were observed in 10-33% of cases; and right side is affected more often. Combined conductive and sensorineural hearing loss occurs in 50% of cases.

Clinical case
We present our own clinical case of HFM in a newborn boy. The study was approved by the BSMU Research Ethics Committee.
The child was born from the second pregnancy and the second birth at 37 weeks of gestation. This pregnancy took place against the background of the mother's underlying disease Z-21. Childbirth took place by elective caesarean section, without complications from the mother. Mother's heredity is complicated by diabetes and cardiovascular disease in close relatives, and thyroid disease from her father.
The boy's body weight at birth was 2550 g, body length -49 cm, head circumference -35 cm, chest circumference -35 cm. Apgar score at the end of the first minute of life was 8 points, the fifth minute -8 points; resuscitation measures were not performed.
The condition at birth is regarded as vitally compensated. Somatic and neurological statuswithout pathological manifestations. But at external inspection of the child the asymmetrical face due to underdevelopment of the left lower third has been noted; underdeveloped auricle on the left; on palpation -displacement of the height of the branch of the lower jaw on the left and the absence of the masticatory muscle on the left (Fig.).

Fig. Phenotypic signs of HFM in the newborn boy
In accordance with national clinical guidelines and protocols, as well as routes of patients of the medical institution, the child was in a joint stay with the mother under the supervision of medical staff, started enteral feeding with an adapted mixture in physiological volumes. Given the mother's diagnosis of Z-21, the child was prescribed appropriate antiretroviral therapy with a combination of three drugs in enteral administration.
During the second day of life, negative dynamics of the child's condition was noted in the form of manifestations of the syndrome of oppression and vegetative-visceral disorders, as well as a decrease in tolerance to enteral nutrition, in connection with which the child was transferred to the intensive care unit of newborns. The conditions of thermal comfort were provided, non-pharmacological and pharmacological anesthesia was carried out, infusion was established to ensure the physiological needs for fluid and its pathological losses. From the third day of life, the boy showed an increase in jaundice, with the level of total bilirubin, which required phototherapy.
On the fifth day of life, the child was transferred to the ward with the mother in the post-intensive care unit, where he was continued enteral feeding with an adapted mixture through a tube with a gradual expansion of daily to physiological needs, treatment of jaundice, implementation of "early intervention", mother training features of care and feeding of the baby. In total, the boy spent 28 days in the hospital.
The child was consulted by a pediatric dental surgeon, who provided recommendations for further examination: X-ray of the head in a direct view and lateral left projection; child care (teaching a child to suck and feed from a bottle. It was also recommended to consult a pediatric maxillofacial surgeon at the Department of National Medical Bogomolets University, when the child reaches the age of three months.
Examination by a pediatric otolaryngologist included external examination, anterior rhinoscopy, otoscopy, mesopharyngoscopy. It was found that the nasal passages are clear, breathing is free, the turbinates and mucous membranes are pink; the right auditory meatus is normal, clean, the eardrum is gray, the shell has an additional rudiment; left -agenesis of the auricle, absence of the cutaneous part of the ear canal; there is a reaction to auditory stimuli; the mucous membrane of the pharynx is clean, pink; deformation of the lower jaw. It was recommended to carry out a planned surgical correction of the external hearing aid on the left.
The children's ophthalmologist established the absence of pathological signs from the patient's visual analyzer.
Echocardiography examination revealed signs of hemodynamically insignificant open ductus arteriosus, atrial septal defect. Neurosonography revealed hypoplasia of the corpus callosum.
After a consular examination of the child with the participation of narrow specialists, including a geneticist, taking into account the results of clinical and instrumental examination, the child was diagnosed with the main clinical: cerebral depression in a newborn (P91.4) concomitant: congenital malformations that affect the appearance of the face: hemifacial microsomia (Q87.0), contact with a patient or the possibility of infection with human immunodeficiency virus (Z03.71), jaundice in a newborn (P59.8).
A multidisciplinary team of specialists has defined a plan for follow-up of the patient, including continuing the practice of "early intervention", accompanying the child in the family, consulting a pediatric cardiologist, magnetic resonance imaging to confirm or rule out spinal abnormalities, determining the timing of hearing prosthetics, classes with a deaf educator, psychological support of the child's parents, as well as long-term support of the child and family by an infectious disease specialist to monitor the effectiveness of antiretroviral therapy, etc.

Conclusion
The article demonstrates a clinical case of hemifacial microsomia in a newborn boy from a mother with Z-21 in the form of deformation of the left auricle with atresia of the auditory canal and "false" ears on the right; combined with congenital anomaly of the heart (atrial septal defect) and of the brain (hypoplasia of the corpus callosum). Emphasis is placed on the need to involve a multidisciplinary team of specialists in the management of this patient both in the neonatal period and in the system of subsequent follow-up.