Micrognathia

Journal Pre-proof Micrognathia Beryl R. Benacerraf, MD, Bryann S. Bromley, MD, Angie C. Jelin, MD PII:

S0002-9378(19)31021-X

DOI:

https://doi.org/10.1016/j.ajog.2019.08.019

Reference:

YMOB 12841

To appear in:

American Journal of Obstetrics and Gynecology

Please cite this article as: Benacerraf BR, Bromley BS, Jelin AC, Micrognathia, American Journal of Obstetrics and Gynecology (2019), doi: https://doi.org/10.1016/j.ajog.2019.08.019. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.

SMFM Fetal Anomalies Consult Series #1: Facial Anomalies smfm.org 1

Micrognathia

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Beryl R. Benacerraf, MD; Bryann S. Bromley, MD; Angie C. Jelin, MD

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Introduction

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Micrognathia is a condition in which the mandible is undersized for the fetal face, giving the

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fetus the appearance of a small jaw and overbite on profile facial views.

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Definition

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Micrognathia and retrognathia both refer to an abnormal mandible. Micrognathia is an

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abnormally small mandible while retrognathia is a mandible that is displaced posteriorly

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(although not necessarily small) with respect to the maxilla. Most fetuses diagnosed with

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micrognathia by prenatal ultrasound have a combination of these 2 disorders (1). Agnathia

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(otocephaly) is complete or almost complete agenesis of the mandible, with the temporal bones

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rotating medially; this results in the ears being horizontal and adjacent to each other or even

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fused in the expected location of the mandible. This extreme form of micrognathia is very rare

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(1).

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Ultrasound Findings

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The midsagittal view of the face is necessary to evaluate the size of the mandible, taking care to

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avoid a flexed neck or chin-tuck fetal position that makes it difficult to see the size and position

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of the mandible. The chin and mandible are normally easily subjectively assessed and should be

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aligned with the upper lip and nose in the midsagittal view of the fetal face. The fetus with

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micrognathia or retrognathia will appear to have an overbite due to the small and/or posteriorly

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displaced mandible. Measurement tables are available but are often unnecessary when the 1

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finding is clear on inspection of the fetal profile view (2-4). The diagnosis of micrognathia can

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be suspected in the first trimester (12–14 weeks of gestation) on the midsagittal view of the fetal

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face. The sagittal profile must be done carefully to ensure that the plane of section is truly

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midline. It is easy to create the impression of micrognathia if the view is not truly midline, while

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a normal profile cannot be visualized when micrognathia is present. The retronasal triangle view

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is also useful in the first-trimester evaluation of suspected micrognathia. There is normally a gap

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where the 2 mandibular rami come together on the coronal plane of the fetal face displayed in the

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retronasal triangle view. The absence of this mandibular gap is a useful early sign of

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micrognathia in the first and early second trimesters (5). Overcalling this anomaly may lead to

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unnecessary testing, and micrognathia should not be diagnosed subjectively unless it is clearly

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seen (Figures 1 and 2).

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Associated Abnormalities

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Although mild micrognathia can be familial, it can also be associated with genetic disorders such

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as skeletal or neuromuscular diseases. Associated abnormalities include cleft palate, central

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nervous system (CNS), spine, limb and hand anomalies. Micrognathia may appear to be isolated

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sonographically when associated with Pierre Robin sequence, although there is a cleft palate in

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most cases. Cleft palate is difficult to detect sonographically in the absence of a cleft lip but can

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be seen in the third trimester using a three-dimensional and flip-face view, where the palate is

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seen en-face looking cephalad from a plane inside the mouth (6, 7). It is also important to search

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for outer ear anomalies when micrognathia is suspected, as this finding suggests Treacher Collins

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or Goldenhar syndrome. When micrognathia is part of a fetal syndrome, anomalies of additional

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organ systems (cardiac or lymphatic) can aide in identifying a recognizable pattern of

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malformations.

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Differential Diagnosis

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It is important to distinguish between isolated and syndromic micrognathia. Primary mandibular

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syndromes include Pierre Robin sequence (micrognathia leading to glossoptosis, which affects

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palate formation and results in a cleft palate; this is sometimes diagnosable in the third

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trimester); Nager syndrome (acrofacial dysostosis with associated abnormal radii); Treacher

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Collins syndrome (ear anomalies), and orofacial digital syndromes (CNS and hand anomalies).

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Skeletal and neuromuscular diseases that result in micrognathia include multiple skeletal

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dysplasias (achondrogenesis, campomelic dysplasia, diastrophic dysplasia, and others);

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craniosynostosis syndromes (Shprintzen-Goldberg syndrome); and Roberts pseudothalidomide

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syndrome. Micrognathia is a feature of many chromosomal abnormalities, including trisomies 9,

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13, and 18; triploidy; and others. These aneuploidies typically have many associated anomalies,

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such as cardiac defects, anterior abdominal wall defects, CNS anomalies, and limb

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malformations; detection of these can lead to the correct diagnosis. DiGeorge (22q11.2

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microdeletion) syndrome is also associated with micrognathia. Other syndromes that can include

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micrognathia are too numerous to list but include Smith-Lemli-Opitz syndrome (genital and limb

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anomalies); Goldenhar syndrome (hemifacial microsomia with microphthalmia, ear tags, facial

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cleft, asymmetry, and hemivertebrae); Noonan syndrome (cystic hygroma, hydrops, heart

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defect); Meckel-Gruber syndrome (cystic kidneys, occipital encephalocele, polydactyly); Fryns

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syndrome (diaphragmatic hernia, heart defect); Pena-Shokeir syndrome (limb contractures,

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growth restriction); and Joubert syndrome (Dandy-Walker malformation) (1).

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Genetic Evaluation

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Diagnostic testing with chromosomal microarray analysis (CMA) should be offered when

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significant micrognathia is detected, particularly if there are additional features suggestive of a

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syndromic diagnosis. If a common aneuploidy syndrome is suspected, karyotype or fluorescence

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in situ hybridization, with reflex to CMA, is a reasonable approach. Micrognathia can be

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inherited; however, a de novo variant is common with severe micrognathia. If there are

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additional anomalies, consanguinity, or a family history of a specific condition, gene panel

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testing or exome sequencing is sometimes useful, as CMA does not detect single-gene

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(Mendelian) disorders. If exome sequencing is pursued, appropriate pretest and posttest genetic

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counseling by a provider experienced in the complexities of genomic sequencing is

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recommended (8). After appropriate counseling, cell-free DNA screening is a reasonable option

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for patients who decline diagnostic evaluation if a common aneuploidy syndrome is suspected. If

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micrognathia is isolated, evaluation of both parents is indicated because mild micrognathia can

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be a constitutionally inherited variant.

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Pregnancy and Delivery Management

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In addition to a detailed ultrasound examination, careful evaluation of the fetal cardiac anatomy

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is important, and a fetal echocardiogram should be considered. Fetal magnetic resonance

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imaging may be useful if the palate is not clearly visualized or if there is concern for cerebral

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anomalies. The patient should be referred for pediatric consultation to as neonatology, a

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craniofacial clinic, and others as appropriate based on sonographic findings. Consultation with an

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ear, nose, and throat specialist (ENT) may be helpful if airway obstruction is suspected. The

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patient should be counseled about potential neonatal difficulties with breathing and feeding.

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Pregnancy termination is an option that should be discussed with all patients in whom a fetal

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anomaly is detected, although with isolated, mild micrognathia, the prognosis can be excellent. A

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third-trimester growth ultrasound examination with re-evaluation of the mandible, fetal growth,

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and amniotic fluid index is recommended. No change in route of delivery is needed, although

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delivery at a tertiary care center is recommended with pediatrics and potentially ENT specialists

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present and ready to intubate if needed. A lactation consultation should be requested, and a

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breast pump should be prescribed.

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Prognosis

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The prognosis depends on the final syndromic diagnosis. Isolated micrognathia is often

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associated with Pierre Robin sequence with glossoptosis, and airway obstruction should be

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anticipated at delivery. In some cases, the growth of the mandible can accelerate and normalize

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into adulthood. Prognostic counseling should be guided by the suspected diagnosis based on

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sonographic findings and diagnostic testing.

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Summary Paragraph

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Prenatally detected micrognathia is often one finding of an associated syndrome. A detailed

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ultrasound examination with additional imaging should be performed to appropriately

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characterize the prenatal phenotype. Diagnostic testing is recommended and should be directed

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by the composite sonographic findings. Delivery at a tertiary care center with the capability for

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rapid neonatal intubation is preferable in the majority of cases.

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Figure <05->1. A fetus with Pierre Robin syndrome at 18 weeks of gestation. Note the small and

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appearance of an overbite.

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Figure <05->2. A third-trimester fetus with micrognathia. Note the recessed chin due to the small

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size of the mandible and the posterior location of the tongue inside the mouth.

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References 1. Paladini D. Fetal micrognathia: almost always an ominous finding. Ultrasound Obstet Gynecol

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2010 Apr;35(4):377-84.

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2. Paladini D, Morra T, Teodoro A, Lamberti A, Tremolaterra F, Martinelli P. Objective

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diagnosis of micrognathia in the fetus: the jaw index. Obstet Gynecol 1999 Mar;93(3):382-6.

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3. Otto C, Platt LD. The fetal mandible measurement: an objective determination of fetal jaw

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size. Ultrasound Obstet Gynecol 1991 Jan 1;1(1):12-7.

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4. Rotten D, Levaillant JM, Martinez H, Ducou le Pointe H, Vicaut E. The fetal mandible: a 2D

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and 3D sonographic approach to the diagnosis of retrognathia and micrognathia. Ultrasound

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Obstet Gynecol 2002 Feb;19(2):122-30.

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5. Sepulveda W, Wong AE, Vinals F, Andreeva E, Adzehova N, Martinez-Ten P. Absent

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mandibular gap in the retronasal triangle view: a clue to the diagnosis of micrognathia in the first

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trimester. Ultrasound Obstet Gynecol 2012 Feb;39(2):152-6.

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6. Platt LD, Devore GR, Pretorius DH. Improving cleft palate/cleft lip antenatal diagnosis by 3-

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dimensional sonography: the "flipped face" view. J Ultrasound Med 2006 Nov;25(11):1423-30.

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7. Benacerraf BR, Sadow PM, Barnewolt CE, Estroff JA, Benson C. Cleft of the secondary

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palate without cleft lip diagnosed with three-dimensional ultrasound and magnetic resonance

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imaging in a fetus with Fryns' syndrome. Ultrasound Obstet Gynecol 2006 May;27(5):566-70.

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8. International Society for Prenatal Diagnosis, Society for Maternal Fetal Medicine, Perinatal

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Quality Foundation. Joint Position Statement from the International Society for Prenatal

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Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality

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SMFM Fetal Anomalies Consult Series #1: Facial Anomalies smfm.org 155

Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn 2018

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Jan;38(1):6-9.

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