Hemifacial Microsomia in Pediatric Patients: Asymmetric Abnormal  Development of the First and Second Branchial Arches

AbstractHemifacial microsomia and Treacher Collins syndrome are two entities which arise as a consequence of abnormal development of first and second branchial arches in utero. As a result, these dentofacial deformities present with abnormal facies especially the maxilla and mandible. They may also occur as part of other syndromes and may involve other structures of the body. In this chapter, we have discussed the etiology, clinical features, radiological assessment and treatment planning of such cases. Special emphasis should be made on early diagnosis, challenges of airway management and feeding and parental counselling. Since the two deformities are largely considered to be non-progressive, early distraction plays an important role in correction of the dentofacial deformity in these patients.

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

Neonatology surgery and perinatal medicine ◽

10.24061/2413-4260.xi.2.40.2021.10 ◽

2021 ◽

Vol 11 (2(40)) ◽

pp. 64-67

Author(s):

I.V. Lastivka ◽

A.G. Babintseva ◽

V.V. Antsupova ◽

А.І. Peryzhniak ◽

І.V. Koshurba ◽

...

Keyword(s):

Clinical Case ◽

Septal Defect ◽

Neonatal Period ◽

Hemifacial Microsomia ◽

Internal Factors ◽

Vascular Abnormalities ◽

Branchial Arches ◽

The Face ◽

The Right

Hemifacial Microsomia (HFM) is a term used to identify facial deformities associated with the development ofthe first and second pairs of branchial arches, characterized by underdevelopment of one half of the face. One typeof hemifacial microsomia is oculo-auriculo-vertebral dysplasia or Goldenhar syndrome.The incidence of HFM is 1:3500-1:7000 of live births and occurs in 1 case per 1000 children with congenitaldeafness. The ratio of boys to girls is 3:2. The etiology and type of inheritance is studied insufficiently. There are threepossible pathogenetic models: vascular abnormalities and hemorrhages in the craniofacial region, damage of Meckel'scartilage, and abnormal cell development of the cranial nerve crest. Environmental factors, maternal internal factors,and genetic factors (OTX2, PLCD3, and MYT1 mutations) may also cause the development of hemifacial microsomia.The article demonstrates a clinical case of hemifacial microsomia in a newborn boy from a mother with Z-21 inthe form of deformation of the left auricle with atresia of the auditory canal and "false" ears on the right, combinedwith 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 thispatient both in the neonatal period and in the system of subsequent follow-up.

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Goldenhar Syndrome Associated with Extensive Arterial Malformations

Case Reports in Pediatrics ◽

10.1155/2015/954628 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Renee Frances Modica ◽

L. Daphna Yasova Barbeau ◽

Jennifer Co-Vu ◽

Richard D. Beegle ◽

Charles A. Williams

Keyword(s):

Main Pulmonary Artery ◽

Abnormal Development ◽

Goldenhar Syndrome ◽

Iliac Arteries ◽

Vascular Abnormalities ◽

Ct Angiogram ◽

Branchial Arches ◽

The Common ◽

Vertebral Defects ◽

Left Thyroid Lobe

Goldenhar Syndrome is characterized by craniofacial, ocular and vertebral defects secondary to abnormal development of the 1st and 2nd branchial arches and vertebrae. Other findings include cardiac and vascular abnormalities. Though these associations are known, the specific anomalies are not well defined. We present a 7-month-old infant with intermittent respiratory distress that did not improve with respiratory interventions. Echocardiogram suggested a double aortic arch. Cardiac CT angiogram confirmed a right arch and aberrant, stenotic left subclavian artery, dilation of the main pulmonary artery, and agenesis of the left thyroid lobe. Repeat echocardiograms were concerning for severely dilated coronary arteries. Given dilation, a rheumatologic workup ensued, only identifying few weakly positive autoantibodies. Further imaging demonstrated narrowing of the aorta below the renal arteries and extending into the common iliac arteries and proximal femoral arteries. Given a physical exam devoid of rheumatologic findings, only weakly positive autoantibodies, normal inflammatory markers, and presence of the coronary artery dilation, the peripheral artery narrowings were not thought to be vasculitic. This case illustrates the need to identify definitive anomalies related to Goldenhar Syndrome. Although this infant’s presentation is rare, recognition of specific vascular findings will help differentiate Goldenhar Syndrome from other disease processes.

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MON-LB120 MODY3 With Insulin Coding Gene Mutation and Craniofacial Microsomia: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2136 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Chenxiang Cao ◽

Xueyao Han ◽

Yumin Ma ◽

Victor Joseph Bernet ◽

Jianzhong Xiao

Keyword(s):

Insulin Therapy ◽

Gene Mutation ◽

Internal Auditory Canal ◽

Gene Mutations ◽

Maternal Diabetes ◽

Abnormal Development ◽

Hemifacial Microsomia ◽

Coding Region ◽

Chromosome 11 ◽

C Peptide

Abstract Background: Maturity onset diabetes in young 3 (MODY 3) is caused by mutation of the hepatic nuclear factor 1 alpha (HNF-1A) gene. Craniofacial macrosomia (CFM) is associated with an abnormal development of craniofacial structures during the embryonic period. Maternal diabetes and genetic predisposition have been associated with CFM1. There are rare reports about an association of MODY 3 and CFM. Clinical case: An 11-year-old male patient presented with right side CFM (mild mandibular hypoplasia, internal auditory canal absence, severe pinna hypoplasia, abnormal orbital size and location, O3.M0.E3.N0.S02) noted at 8 months of age. Preoperative examination revealed A1c at 10.9%. After short term intensive insulin therapy, he had standard bread meal test: fasting glucose 8.11 mmol/L, insulin 13.9 mIU/L (3-25), C-peptide 1.25 ng/ml (0.81-3.85); 1 hour glucose 10.05 mmol/L, insulin 27 mIU/L, C-peptide 2.42 ng/ml; 2 hour glucose 8.17 mmol/L, insulin 16.09 mIU/L, C-peptide 2.11 ng/ml. GADA, IAA and ICA were negative. The mother was diagnosed diabetes at age 27years, when the patient was 8-month-old, and received insulin therapy. The mother was blind by age 35years due to diabetic retinopathy and died of DKA at 38-years-old. The patient’s 16-year-old brother had left side CFM (O2.M1.E2.N0.S0) and his OGTT was normal. The father was diagnosed with impaired glucose tolerance. The family had whole genome sequencing by Sanger technique, and resequenced the mutation with side primers. The CGA to CAA mutation was present at the 686 loci of exon 3 of HNF1A gene in the patient and mother. The HNF1A exon 3 mutation of CGA to CAA resulted in the change of arginine to glutamine which by the HGMA database is recognized as a reported MODY3 gene mutation. There was a mutation of G to A in the 4 loci of exon 1 of the insulin coding region in chromosome 11 in both the patient and elder brother. Neither elder brother nor father had the CGA mutation of HNF1A. Conclusion: There has not been a previous report of a relationship between HNF1A and CFM. In this case, the elder brother had CFM without a HNF1A mutation which does not support a connection between CFM and HNF1A. The two brothers both had CFM and insulin coding gene mutations which would represent a new association not previously described. Further testing is needed to confirm a relationship between the two. Reference: 1. Chen Q, Zhao Y, Shen G, Dai J. Etiology and Pathogenesis of Hemifacial Microsomia. J Dent Res 2018; 97(12): 1297-305. 2. Gougoutas AJ, Singh DJ, Low DW, Bartlett SP. Hemifacial microsomia: clinical features and pictographic representations of the OMENS classification system. Plast Reconstr Surg 2007; 120(7): 112e-20e.

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Hemifacial Microsomia: A Mini Review

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2019/v30i730208 ◽

2019 ◽

pp. 1-7

Author(s):

Shilpa Ashok Sharma ◽

Sayali Vikram Pagar Patil ◽

Anupama Mudhol ◽

Jyothi Shashidhar

Keyword(s):

Well Being ◽

Psychological Development ◽

Facial Appearance ◽

Hemifacial Microsomia ◽

Long Term Effects ◽

Medical Treatments ◽

Mandibular Hypoplasia ◽

Branchial Arches ◽

Derivatives Of

Hemifacial Microsomia (HFM) is a congenital anomaly involving embryological derivatives of the first and second branchial arches and characterized mainly by mandibular hypoplasia and unilateral or bilateral microtia; although, other facial structures may be affected. It may have long-term effects on psychological development and social well-being, due to unaesthetic facial appearance, functional disturbances and complex medical treatments.

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Anomalies of branchial cleft: our experience and review of literature

International Surgery Journal ◽

10.18203/2349-2902.isj20174108 ◽

2017 ◽

Vol 4 (10) ◽

pp. 3234

Author(s):

Neha Sisodiya Shenoy ◽

Charu Tiwari ◽

Suraj Gandhi ◽

Pankaj Dwivedi ◽

Hemanshi Shah

Keyword(s):

Clinical Presentation ◽

Abnormal Development ◽

Review Of Literature ◽

Complete Excision ◽

Duration Of Symptoms ◽

Incision And Drainage ◽

Branchial Arches ◽

Branchial Cleft ◽

Definitive Surgery

Background: Anomalies of branchial arches are uncommon anomalies of embryonic development and may present as cysts, sinus tracts, fistulae or cartilaginous remnants. We describe our experience with 30 children with branchial cleft anomalies.Methods: Case records of all patients were retrospectively reviewed and analysed with respect to age, sex, clinical presentation, duration of symptoms, investigations, management and follow up. All patients underwent complete excision of the tract/cyst.Results: There were 15 males and 15 females (ratio of 1:1). The average age of presentation was 5 years. Majority of the patients presented with discharging sinuses (n=26). Twenty-six patients had branchial sinuses, three patients had branchial cysts and one had pyriform fistula. The anomalies were lateralized to left side in 17 patients (56.66%), right side in 11 patients (36.66%) and bilateral in 2 patients (0.066%). Complete excision was done in all patients. Four patients presented with abscesses and required incision and drainage. Definitive surgery was done after 6 weeks. There were no complications.Conclusions: Abnormal development of branchial apparatus lead to formation of different anomalies which remain asymptomatic and present later in life as cysts, sinuses or fistulae in neck. Diagnosis is mostly clinical and complete excision provides definitive cure.

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Craniofacial Microsomia: Goldenhar Syndrome in Association with Bilateral Congenital Cataract

Case Reports in Ophthalmological Medicine ◽

10.1155/2015/435967 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

U. D. Shrestha ◽

S. Adhikari

Keyword(s):

Congenital Cataract ◽

Multidisciplinary Approach ◽

Goldenhar Syndrome ◽

Hemifacial Microsomia ◽

Pediatric Ophthalmology ◽

Pupillary Reflex ◽

Craniofacial Microsomia ◽

Branchial Arches ◽

Vertebral Anomalies ◽

Bilateral Congenital Cataract

Craniofacial microsomia (CFM) includes a spectrum of malformations primarily involving structures derived from the first and second branchial arches. Patients with hemifacial microsomia and epibulbar dermoids are said to have Goldenhar syndrome (GHS). Four-month-old boy with whitish pupillary reflex presented with the features of GHS in pediatric ophthalmology clinic. The child had ocular and auricular manifestations. There were no vertebral anomalies, but he had bilateral congenital cataract. The peculiarity of this case is the presence of the bilateral total congenital cataract, in association with CFM. There is absence of epibulbar dermoid or lipodermoid in the eyes, although the child had features of GHS. In addition to it, anesthetic intubation was smooth in this case. Any case diagnosed with CFM and/or GHS needs treatment through multidisciplinary approach, consultation in ophthalmology department is one of them.

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Oculoauriculofrontonasal Dysplasia Syndrome with Additional Clinical Features

The Cleft Palate-Craniofacial Journal ◽

10.1597/15-078 ◽

2017 ◽

Vol 54 (6) ◽

pp. 749-753 ◽

Cited By ~ 3

Author(s):

Turan Tunc ◽

Adem Polat ◽

Bilal Altan ◽

Abdul Kerim Yapici ◽

Mehmet Saldir ◽

...

Keyword(s):

Inguinal Hernia ◽

Clinical Features ◽

Clinical Entity ◽

Abnormal Development ◽

Frontonasal Dysplasia ◽

Branchial Arches

Oculo-auriculo-vertebral spectrum and frontonasal dysplasia are two well-known examples of dysmorphology syndromes. Oculoauriculofrontonasal syndrome (OAFNS) is a clinical entity involving the characteristics of both OAVS and FND and is thought to be a result of the abnormal development of structures in the first and the second branchial arches, including the abnormal morphogenesis of maxillary processes. Herein we report a case of OAFNS with cliteral hypertrophy, premaxillary teeth, and inguinal hernia, features not previously reported in the literature.

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A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme

Development ◽

10.1242/dev.125.16.3005 ◽

1998 ◽

Vol 125 (16) ◽

pp. 3005-3014 ◽

Cited By ~ 10

Author(s):

T. Thomas ◽

H. Kurihara ◽

H. Yamagishi ◽

Y. Kurihara ◽

Y. Yazaki ◽

...

Keyword(s):

Neural Crest ◽

Regulatory Elements ◽

Branchial Arch ◽

Limb Bud ◽

Abnormal Development ◽

Cardiac Defects ◽

Endothelin 1 ◽

The Third ◽

Branchial Arches ◽

Catch 22

Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived branchial arches and branchial arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the branchial arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second arches are hypoplastic secondary to programmed cell death and the third and fourth arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the branchial arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null branchial arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal branchial arch. Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome.

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Validity of the HfmTransgenic Mouse as a Model for Hemifacial Microsomia

The Cleft Palate-Craniofacial Journal ◽

10.1597/1545-1569_2002_039_0081_vothtm_2.0.co_2 ◽

2002 ◽

Vol 39 (1) ◽

pp. 81-92 ◽

Cited By ~ 2

Author(s):

Richard Cousley ◽

Hiroyuki Naora ◽

Minesuke Yokoyama ◽

Minoru Kimura ◽

Hiroki Otani

Keyword(s):

Facial Asymmetry ◽

External Auditory Meatus ◽

Cranial Base ◽

Hemifacial Microsomia ◽

Loss Of Function ◽

Conventional View ◽

Facial Defects ◽

Branchial Arches ◽

Craniofacial Features ◽

Ear Anomalies

Objective Our comprehension of hemifacial microsomia (HFM) has been hindered by its diverse phenotype and unclear etiopathogenesis. The conventional view has been that HFM's facial defects result from embryonic hemorrhages in the region of the first and second branchial arches. A more recent model based on a transgenic mutation of a locus termed Hfm (B1 to B3 on chromosome 10) appears to provide an insight into HFM causation. This study investigated the validity of this model by examining the Hfm craniofacial phenotype and histological development of the embryonic head (E13.5 to 17.5). Results The results confirmed that although the loss-of-function mutation was transmitted in an autosomal dominant manner, the penetrance rate was significantly reduced and only Hfm heterozygotes were viable. The observations here extend the Hfm phenotype beyond microtia and jaw asymmetry to include structural and positional anomalies affecting the external auditory meatus, middle ear, cranial base, maxilla, and pharyngeal structures. Temporo-mandibular joint (TMJ) development and palatal shelf fusion were also affected in a small number of cases. In addition, some Hfmembryos displayed a novel finding: transposition of the developing inner ear between the tubotympanic recess and cranial base. Conclusions These craniofacial features, especially the ear anomalies and facial asymmetry indicate that the Hfm transgenic mouse represents a useful model for the HFM-microtia spectrum. In particular, it supports the hypothesis that at least a proportion of HFM anomalies has a genetic causation mediated via mesenchymal disruptions and possibly embryonic hemorrhages.

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