P i e r re R o b i n Se q u e n c e

Sun T. Hsieh, MS, MDa, Albert S. Woo, MDb,*

KEYWORDS
 Pierre Robin sequence  Cleft palate  Micrognathia  Glossoptosis  Distraction

KEY POINTS
 Pierre Robin sequence (PRS) consists of the clinical triad of micrognathia, glossoptosis, and airway
compromise with variable inclusion of cleft palate.
 Management of airway obstruction in PRS consists of nonsurgical maneuvers, such as prone posi-
tioning and nasopharyngeal stenting; surgical management includes mandibular distraction and
tongue-lip adhesion.
 Diagnostic evaluation of patients with PRS includes nasoendoscopy and bronchoscopy for the
airway and a multidisciplinary approach for multisystemic anomalies in syndromic patients.

Video content accompanies this article at http://www.plasticsurgery.theclinics.com.

INTRODUCTION HISTORICAL PERSPECTIVE

Pierre Robin sequence (PRS) consists of the clinical In 1835, Von Siebold described a case of micro-
triad of congenital micrognathia, glossoptosis, and gnathia, microglossia, and glossoptosis in an in-
airway obstruction with variable inclusion of a cleft fant who ultimately succumbed to asphyxia.1
palate (Fig. 1). When this constellation of findings Nearly a century later, French stomatologist Pierre
occurs in the absence of other congenital anoma- Robin’s2 seminal 1923 paper described the same
lies, it is termed isolated PRS; however, PRS often- constellation of findings, namely glossoptosis in
times finds itself a component of a more complex the presence of micrognathia, highlighting the
syndromic picture. This phenotypic heterogeneity dire consequences to the airway. The historical
arises from a permutation of mechanical, genetic, literature is littered with various authors who sepa-
and environmental derangements. The variable rately encountered and described this set of find-
complexity of the patient presentation lends itself ings, including St. Hillaire in 1822, Fäsebeck in
to a multidisciplinary approach in uncovering the 1842, Fairbairn in 1846, and Shukowski in 1911.3
diagnosis, managing the airway obstruction, opti- Ultimately, these collections of findings assumed
mizing the feeding, and addressing the multisyste- the eponymous title of Pierre Robin sequence.
mic abnormalities intrinsic to the syndromic
patient. Although nearly a century has passed since
EPIDEMIOLOGY
the description of Robin’s eponymous triad, incon-
gruities remain regarding treatment protocols The incidence of PRS ranges from 1 in 8000 to 1 in
among different centers. This lack of consensus re- 14,000.4,5 Mortality for infants with PRS ranges
flects the high degree of difficulty in the manage- from 1.7% to 11.3%; the rate increases to 26%
ment of such a diverse patient population, a when examining only the subset of syndromic pa-
challenge that cannot be overstated. tients.6 Although cleft palate is not a strict criterion
plasticsurgery.theclinics.com

Disclosure Statement: The authors have nothing to disclose.

a
Department of Plastic Surgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University,
2 Dudley Street, Suite 500, Providence, RI 02905, USA; b Pediatric Plastic Surgery, Craniofacial Program, Rhode
Island Hospital, The Warren Alpert Medical School of Brown University, 2 Dudley Street, Suite 180, Providence,
RI 02905, USA
* Corresponding author.
E-mail address: [email protected]

Clin Plastic Surg 46 (2019) 249–259

https://doi.org/10.1016/j.cps.2018.11.010
0094-1298/19/Ó 2018 Elsevier Inc. All rights reserved.
250 Hsieh & Woo

descend from the roof of the nasopharynx causes

a physical blockade to palate formation, prevent-
ing appropriate elevation, medialization, and
fusion of the palatal shelves.8

GENETIC FINDINGS
There is no classic causal relationship between
PRS and a single genetic mutation, but rather a
wide swath of genetic errors that have been asso-
ciated with a variety of phenotypic presentations.
Box 1 contains a list of associated syndromes.
Approximately 26% to 83% of PRS diagnoses
are part of a syndrome, most commonly Stickler
syndrome, 22q11.2 Deletion Syndrome, Treacher
Collins syndrome, and Campomelic Dysplasia,
among others.10,11 Approximately 11% to 18%
of patients with PRS are diagnosed with Stickler
syndrome, a connective tissue disorder impacting
Fig. 1. Lateral view of infant with PRS, which consists collagen metabolism.8 Ocular findings are most
of the clinical triad of retromicrognathia, glossoptosis, prominent, presenting as myopia, vitreous abnor-
and airway compromise with variable inclusion of a malities, glaucoma, retinal detachment, and cata-
cleft palate.
racts. Skeletal sequelae, hearing loss, and
craniofacial anomalies may be present. Velocar-
for the diagnosis of PRS, 85% of these patients diofacial syndrome accounts for approximately
present with a concomitant cleft.4 The incidence 11% of patients with PRS.10 Now known as
of these patients presenting with an associated 22q11.2 Deletion Syndrome, findings include
syndrome is 38% to 44%. Male and female indi- learning disability, micrognathia, cleft palate, long
viduals are affected at an equal rate.4,5,7 philtrum, conductive hearing loss, hypoparathy-
roidism, and thymic aplasia.
INTRAUTERINE DEVELOPMENT
Craniofacial morphogenesis begins with delami- DIAGNOSIS AND INITIAL MANAGEMENT
nation of neural crest cells from the dorsal neural Patients with PRS frequently have other systemic
tube into ventral pharyngeal arches.8,9 The anomalies that warrant a multidisciplinary
first pharyngeal arch forms the maxilla and approach to their diagnosis and management.12
mandible through intramembranous ossification. A comprehensive evaluation may require involve-
The Meckel cartilage serves as the initial scaffold ment of specialties such as maternal-fetal medi-
onto which mandibular intramembranous ossifica- cine, genetics, neonatology, pulmonary and
tion occurs, orienting mandibular growth in a sleep medicine, developmental pediatrics, plastic
proximo-distal configuration. surgery, oral surgery, orthodontics, dentistry,
Maxillary development occurs concomitantly otolaryngology, ophthalmology, pediatric surgery,
with mandibular outgrowth. Lateral palatal shelves cardiology, speech pathology, feeding specialists,
extend from the maxillary arches at approximately audiology, and neurology.
the seventh week of gestation and begin to grow in
a sagittal plane adjacent to the tongue.8 PRENATAL IMAGING
As mandibular outgrowth continues, the tongue
is flattened and distracted anteriorly by the Diagnostic workup may start in the prenatal
genioglossus, originating on the lingual surface of period with ultrasound or MRI.12 Micrognathia
the mandible.8 This facilitates reorientation of may be difficult to diagnose via ultrasound, with
sagittal palatal shelves into a transverse plane. sensitivity of 72.7%.13 Normalization of the
The medial edge epithelia fuse in coordinated mandibular anteroposterior length by the biparie-
fashion in an anterior-to-posterior direction on tal skull width creates a jaw index, which im-
the eighth week, as illustrated in Fig. 2. proves ultrasound sensitivity to 100% and
Classically, the inciting insult in PRS is a micro- specificity to 98.1%.14 The positive predictive
gnathic mandible that obligates retropositioning of value for diagnosing PRS versus isolated micro-
the tongue base, predisposing the infant to glottic gnathia correlates directly with the maxillo-
airway compromise. Inability of the tongue base to mandibular discrepancy.13,15 Polyhydramnios is
 251

Fig. 2. Normal intrauterine development of primary and secondary palate with reorientation of the palatal
shelves from a vertical to horizontal position. A retrognathic mandible leads to retropositioning of the tongue,
which impedes this fusion process. (From https://discovery.lifemapsc.com/library/review-of-medical-embryology/
chapter-55-development-of-the-palate. Accessed May 1, 2018.)
252 Hsieh & Woo

Box 1 the apnea-hypopnea index (AHI) is limited by the

List of syndromes most frequently associated lack of standardized neonatal normative values.13
with Pierre Robin sequence Sleep studies differentiate between obstructive
and central sleep apnea, the latter prompting
Associated Syndromes greater consideration before surgical intervention.
Stickler syndrome Polysomnography as a diagnostic tool is not uni-
formly adopted. Opponents highlight the absence
22q11.2 Deletion syndrome
of an objective threshold with which to gauge the
Treacher Collins syndrome clinical severity of the airway obstruction.13 Syn-
Campomelic dysplasia dromic patients may be longitudinally assessed
Marshall syndrome through serial polysomnography, nasopharyngo-
scopy, and physical examination as they mature.
Nager syndrome
Miller syndrome FEEDING
Kabuki syndrome
Feeding may be dysfunctional secondary to the
Catel-Manske syndrome cleft palate (if present), hypoplastic mandible,
Congenital myotonic dystrophy and dynamic exacerbation of airway obstruction.
Carey-Fineman-Ziter syndrome Speech pathology monitors feeding sessions for
signs of dysphagia, such as coughing, choking,
Fetal alcohol syndrome
or feeding refusal.13 Videofluoroscopy, nasoendo-
Maternal diabetes scopy, and swallowing studies aid in evaluating
Spondyloepiphyseal dysplasia congenita dynamic function.
Hemifacial microsomia Supplemental feeding is required in 38% to 62%
of patients with PRS.6,13 Temporary nasogastric
Glass syndrome
tube feeding may suffice; however, syndromic
Mandibulofacial dysostosis patients may develop chronic feeding difficulty,
requiring placement of a gastrostomy tube.
Tongue-lip adhesion has a nearly threefold risk of
associated with impaired swallowing secondary
eventual gastrostomy tube placement when
to glossoptosis.
compared with mandibular distraction.19 Average
weight gain of 20 to 30 g/d is considered satisfac-
AIRWAY EVALUATION tory for the neonate.20,21 Consistent weight gain
Airway obstruction is life-threatening for the allows for transitioning of continuous nasogastric
neonate. Prolonged obstruction results in hypoxia, tube feeding to bolus feeds, and eventual oral
apnea, respiratory tract infections, aspiration, intake.19 Oral feeding and swallowing training
compromised feeding, and failure to thrive.16 should be implemented to limit oral aversion. The
Chronic hypoxia leads to increased pulmonary pediatric gastroenterologist may longitudinally
vascular resistance, cor pulmonale, heart failure, follow the patient to ensure appropriate growth
and cerebral hypoxia.16 and development.
Robin2 attributed neonatal airway compromise
to posterior displacement of the tongue base. MANAGEMENT
This decreases the cross-sectional area of the Treatment of PRS may be divided into nonsurgical
oropharynx, limiting mass flow rate of oxygen dur- and surgical methodologies. Protocols vary across
ing respiration and predisposing the upper airway different centers and may be a function of individ-
to collapse during inspiration.17 ual surgeons’ training and experience, each with
Physical examination provides a clinical gestalt their own criteria for pursuing surgical versus
of the patient’s respiratory effort through observa- nonsurgical intervention.
tions of stridor, positional retraction of the chest
and neck, positional desaturation, cyanosis, and NONSURGICAL MANAGEMENT
feeding difficulty (Video 1).6 Nasopharyngoscopy
may reveal synchronous lesions, such as subglot- Airway obstruction is initially addressed via prone
tic stenosis, laryngomalacia, tracheomalacia, or lateral positioning with a success rate of
bronchomalacia, choanal atresia, tracheal steno- 70%.22 Should the obstruction prove recalcitrant,
sis, and aspiration bronchitis.18 a nasopharyngeal stent may be placed to mitigate
Polysomnography quantifies obstruction events the retroglottic obstruction (Fig. 3). Custom stents
and gas exchange disturbances, although utility of tailored to the infant’s weight may minimize dead
 Pierre Robin Sequence 253

outward movement. The ventral tongue is coapted

to the lower lip mucosa and the contact area is
identified. A rectangular inferiorly based lower lip
musculo-mucosal flap and a congruent superiorly
based ventral tongue flap are developed,
measuring approximately 2  1 cm each (Fig. 4).
Attention must be paid to avoid injury to the sub-
mandibular and sublingual ducts.27 The leading
edge of the lip flap is sutured to the inferior edge
of the tongue wound, the exposed labial muscle
is sutured to the lingual muscles, and the leading
edge of the tongue flap is sutured to the superior
edge of the lip wound, in sequential fashion. Appo-
sition of the muscular planes is critical to mini-
mizing risk of dehiscence. Retention sutures
secure the tongue base to the lingual surface of
the mandible, exiting through the submenton and
tied over a button to preserve the underlying skin
(Fig. 5).27,28 Endoscopic evaluation of the airway
Fig. 3. A nasopharyngeal stent may be used to main-
tain the retroglottic airway should prone and lateral
confirms resolution of the retroglottic obstruction.
positioning prove insufficient in relieving retroglottic Nasopharyngeal stenting is performed for 2 to
airway obstruction. 3 days to account for postoperative edema.28
Nasogastric feeds should be administered for a
space and permit delivery of supplemental oxygen week to prevent contamination of the wound dur-
via nasal cannulas.23 Positioning and nasopharyn- ing the acute healing phase.28 Muscular adhesion
geal stenting alone may be sufficient in infants who occurs over 2 weeks, after which the retention su-
maintain a weight above the 25th percentile and tures are released. Division of the TLA occurs be-
have an AHI less than 19.2 events per hour.24 Sup- tween 12 and 18 months postoperatively either
portive stenting may last 2 to 4 months and can concomitantly or in sequence with palate repair.26
continue at home. TLA has a success rate of 71% to 89% in relieving
Noninvasive continuous positive airway pres- the airway obstruction.26,29
sure (CPAP) can obviate the need for surgical Complications from TLA include dehiscence,
intervention in a subset of infants with moderate abnormal eruption of deciduous incisors, infection,
obstruction who can breathe spontaneously while lip scarring, and tongue edema.26 The former has
possessing an AHI greater than 10.25 Once initi- largely been mitigated through modifications by
ated, CPAP is weaned to use only during sleep pe- Rutledge in the 1960s, with dehiscence rates at
riods over a period of 1 to 2 weeks, and may be 4.2% to 17.2%. Mucosa-only adhesions have re-
applied for up to 6 months.25 ported dehiscence rates of 41.6%.30 Persistent
Should a noninvasive airway prove inadequate, airway obstruction following TLA on up to 20%
the patient may undergo endotracheal intubation of cases likely stems from a failure of elucidating
or placement of a laryngeal mask airway. the complete etiology of airway obstruction
beyond the tongue base.
AHI can be improved from 30.8 to 15.4 events
SURGICAL MANAGEMENT
per hour following TLA.31 TLA has been shown to
Tongue-Lip Adhesion
improve mean lowest oxygen saturation from
Tongue-lip adhesion (TLA) acts to increase the 75.8% to 84.4% and mean oxygen saturation
cross-sectional area of the oropharyngeal airway from 90.8% to 95%. Feeding outcomes remain
by anteriorly tethering the posteriorly displaced disparate with 0% to 54% of infants requiring
tongue base to the hypoplastic mandible. Its indi- eventual gastrostomy tube placement depending
cation is limited to when upper and lower airway on the study.18,26,32
evaluation has excluded additional subglottic,
synchronous lesions. Some view TLA as a first-
Floor of Mouth Release
line surgical treatment for those who fail nonoper-
ative management. Subperiosteal floor of mouth release (FMR) is
The procedure begins with placement of ante- based on the assertion that airway obstruction oc-
rior traction sutures at the lateral aspects of the curs due to a posterior rotation of the tongue sec-
tongue.26 The frenulum is released if found to limit ondary to abnormally tight attachments of lingual
254 Hsieh & Woo

Fig. 4. TLA acts to increase the cross-sectional area of the oropharyngeal airway by anteriorly tethering the pos-
teriorly displaced tongue base to the hypoplastic mandible. A rectangular inferiorly based lower lip musculo-
mucosal flap (A, B) and a congruent superiorly based ventral tongue flap (C, D) are developed and approximated
to each other (E). (From Qaqish C, Caccamese J. The tongue-lip adhesion. Operat Tech Otolaryngol Head Neck
Surg 2009;20(4):274–7; with permission.)

musculature onto the lingual mandible.33 Release Caouette-Laberge and colleagues34 reported an
of anterior belly of the digastric, myohyoid, genio- 84% success rate in infants developing indepen-
hyoid, and genioglossus insertions facilitates de- dence from nasopharyngeal stenting following
rotation of the tongue. FMR and a decrease in the AHI from 46.5 to

Fig. 5. (A) Anteroposterior and (B) lateral view of a transcutaneous retention suture that may aid in apposing the
tongue base to the lingual surface of the mandible. The button dissipates the chronic stress of the suture and
minimizes injury to the skin.
 Pierre Robin Sequence 255

17.4. Gastrostomy feeding was able to be avoided periosteum is incised and a subperiosteal plane
in 73% of cases, with half of patients being orally is developed, exposing the coronoid and antego-
fed within 11 days postoperatively. nial notch as reference. Distraction vector may
be sagittal, vertical oblique, or obtuse depending
Mandibular Distraction Osteogenesis on the degree of vertical deficiency and occlusal
McCarthy and colleagues35 published their experi- relationship.
ence with mandibular distraction osteogenesis A 270 osteotomy is completed of the anterior,
(MDO) on a series of patients with congenital posterior, and buccal cortices with a conventional
mandibular hypoplasia in 1992, introducing the or piezoelectric saw, taking care to spare the infe-
technique to the field of craniofacial surgery. In rior alveolar nerve. The internal distraction device
the decades since, MDO has experienced wider is secured with monocortical screws, and the
acceptance among the craniofacial community lingual osteotomy is completed. Initial activation
for treatment of mandibular hypoplasia.35 of the distractor confirms bony separation and
Distraction devices are available in external or the bony edges are then returned to their original
semi-buried internal forms. External devices allow positions. The soft tissue is closed.
for multiple vectors of distraction that can be Osteotomy design may be aided by virtual surgi-
adjusted following the initial osteotomy and cal planning to minimize injury to developing tooth
greater distraction length (Fig. 6).36 Disadvantages buds and the inferior alveolar nerve.37 Configura-
include buccal scarring, risk of pin dislodgement, tions include linear oblique, inverted-L, and multi-
decreased precision, greater relapse, patient angular. The inverted-L osteotomy is frequently
discomfort, and pin site infections.36 advocated because it proceeds distal to the tooth
Alternatively, distraction can be performed by buds, better preserving these structures.37 While
placement of internal devices. By their nature, in- damage to deciduous teeth can be minimized
ternal distractors are less conspicuous with lower with imaging and planning, injury to permanent
scar burden; however, they provide only uni- dentition is difficult to predict.
vector distraction and require precise preoperative In neonatal MDO, our institution begins the pro-
planning. Nonresorbable devices require a second cess of distraction the day after surgery at a rate
surgery for removal. Advantages include patient of 2 mm/d. Older patients are allowed a latency
comfort, prolonged retention period for optimal period of 2 to 5 days followed by distraction rate
ossification, and decreased risk of pin site of 1 mm/d. The former accelerates the process
infection.36 of distraction, allowing extubation within approxi-
A brief description of the distractor placement mately 1 week postoperatively. The patient is
is given. Illustrative photos are shown in Fig. 7. closely monitored during the distraction phase
A submandibular Risdon incision is made. with a goal of moderate prognathism. In the
Dissection continues through the platysma, neonate, it is the common practice of Dr Woo
avoiding injury to the facial vessels and marginal AS to attempt 25 to 30 mm of distraction. Once
mandibular branch of the facial nerve. The distraction is completed, the externalized portion
of the distractor is removed. A bony consolidation
phase of 6 to 8 weeks ensues, followed by
removal of the internal device. The patient is longi-
tudinally followed to track mandibular growth
(Fig. 8).
Success rate of MDO for relieving airway
obstruction is 94%.38 A systematic review con-
ducted by Master and colleagues39 compiled
complication rates from MDO, including relapse
64.8%, tooth injury 22.5%, hypertrophic scarring
15.6%, nerve injury 11.4%, infection 9.5%, inap-
propriate distraction vector 8.8%, device failure
7.9%, fusion error 2.4%, and temporomandibular
joint injury 0.7%. Predictors of failure include pre-
operative intubation, gastroesophageal reflux, low
birth weight, syndromic diagnosis, neurologic
Fig. 6. External distraction allows for multivector anomalies, intact palate, airway anomalies other
changes to the mandible, although having multiple than laryngomalacia, and late surgery.38 Transition
pieces of exposed hardware poses a chronic infectious to oral feeding occurs in 82% of distracted pa-
burden. tients within 12 months postoperatively; however,
256 Hsieh & Woo

Fig. 7. (A) Operative markings of the mandible including the zygomatic arch, mandibular condyle, angle, and
proposed submandibular incision, which should be placed at least 1 cm caudal to the inferior mandibular border
to avoid injury to the marginal mandibular facial nerve branch. (B) Facial artery and vein may be encountered
during the soft tissue dissection and exposure of the mandible. (C) Completion of the bicortical mandibular os-
teotomies with mobilization of the distal and mesial segments. (D) Application of a uni-vector, semi-buried
mandibular distractor to the osteotomized mandible. (E) Soft tissue closure of the submandibular incision and
application of a universal joint to the extruded distractor arm.

syndromic patients are 5 times more likely to examination with nasoendoscopy and bronchos-
require adjunctive feeding.40 copy to evaluate for synchronous lesions. Those
with subglottic obstruction may have a suboptimal
TREATMENT PROTOCOL response to TLA or MDO and undergo
tracheostomy.
Universal agreement with respect to diagnosis and Tongue-base obstruction is managed with
management of PRS has yet to be achieved. Lack increasing invasiveness. Nonsurgical maneuvers,
of randomized controlled trials, limited patient such as prone and lateral positioning, nasopha-
population, training disparities, suboptimal stan- ryngeal stenting, and noninvasive CPAP, are tri-
dardization of published studies, and individual aled. Should this fail, the senior author performs
biases impede standardization of care. MDO in accordance with certain centers41,42;
Evaluation of the patient with PRS begins with however, others may elect to pursue TLA initially,
history and physical examination by otolaryn- reserving MDO only for those who have failed
gology, pulmonology, neonatology, genetics, and TLA.43
plastic surgery. Patients are monitored in a In a recent survey of surgeon members of the
neonatal intensive care unit with continuous pulse American Cleft Palate-Craniofacial Association,
oximetry recording desaturation episodes, fol- nearly half preferred MDO as first-line treatment
lowed by a formal sleep study to stratify the degree for airway obstruction.44 Some advocate for a
of obstruction. Consideration is placed toward predictive management algorithm as a function
feeding status, weight gain, and desaturation epi- of the maxillo-mandibular discrepancy, severity
sodes with feeding. Feeding difficulty in the of glossoptosis, persistent desaturations
absence of desaturation is addressed by nasogas- with prone positioning, feeding difficulties,
tric feeds and swallow studies. nasogastric tube dependence, concomitant
Desaturation on clinical examination and abnormal airway anomalies, and failure of nonsurgical
polysomnography prompt a comprehensive airway management.44
 Pierre Robin Sequence 257

Fig. 8. Lateral view of patient. (A) Before mandibular

distraction, demonstrating the markedly retrognathic
mandible. (B) After consolidation, with slight progna-
thism and well-healed submandibular incision. (C)
Following years of healing and further mandibular
growth with sustained maxillo-mandibular relationship.

Although some centers argue for stratification of before surgical intervention. Airway interventions
severity of obstruction as a node in the decision must be undertaken only after nasoendoscopy
tree between pursuing TLA versus MDO, others and bronchoscopy to delineate sites of airway
consistently perform TLA as a first-line treatment, compromise beyond the tongue base, as patients
reserving MDO for failure of TLA.43,44 As refer- with subglottic anomalies may be poor candidates
enced earlier, a growing majority of craniofacial for distraction and should undergo tracheostomy.
surgeons view MDO as definitive treatment of Surgical options include TLA, subperiosteal FMR,
airway obstruction, excluding TLA from their man- and MDO. Disagreement remains invariant among
agement algorithm.41,42 In light of the variability in institutions regarding a uniform treatment algorithm
diagnostic criteria and disagreement concerning for this diverse group of patients.
the role of MDO and TLA in the surgical manage-
ment of PRS, further multicenter work should be SUPPLEMENTARY DATA
undertaken toward achieving a standardized treat-
ment protocol. Supplementary data related to this article can be
found online at https://doi.org/10.1016/j.cps.
SUMMARY 2018.11.010.

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