Pierre Robin Sequence (PRS) is a rare condition characterized by the triad of micrognathia, glossoptosis, and cleft palate. It occurs due to restricted growth of the mandible in utero, which causes the tongue to obstruct palatal fusion and the airway. Management requires a multidisciplinary approach and may include interventions like nasopharyngeal intubation, mandibular advancement, or tracheostomy to address airway and feeding issues. Long term care involves monitoring for catch-up mandibular growth and treating dentofacial abnormalities, with some studies finding persistence of mandibular deficiencies in PRS versus isolated cleft palate. Genetic assessment is also important as PR

1. Pierre Robin Sequence
Table of Contents
Pierre Robin Sequence.............................................................................................................1
Introduction..........................................................................................................................1
The typical features of PRS ................................................................................................2
Aetiology ...............................................................................................................................2
Subtypes ...............................................................................................................................3
Incidence ...............................................................................................................................2
Differential diagnosis ...........................................................................................................2
Investigations........................................................................................................................5
Management .........................................................................................................................5

2. Introduction
 Related conditions - these may display features of the malformation: Stickler's syndrome, velocardiofacial syndrome, Catel-Manzke syndrome,
Treacher Collins' syndrome, Nager syndrome, spondyloepithelial dysplasia congenita, campomelic dysplasia.
 Pierre Robin, a French dental surgeon (1867-1950), is identified with the sequence/syndrome due to his role in the early part of the twentieth
century, describing the typical triad of features and his many articles on its management.
 It is called a sequence because the mandibular abnormality sets off a sequence of events in the uterus, leading to the other deformities. The term
“sequence” (currently favoured over the previously reported “syndrome” and “anomalad”) reflects the prevailing concept that the mandibular
micrognathia is the primary pathogenetic event, subsequent to which, the tongue, because of restricted space, interferes with fusion of the palatal
shelves prenatally and obstructs the upper airway in the immediate postnatal and neonatal period (Vig 1988)
Incidence
• PRS is a rare condition.
• A German prospective study reported an incidence of 12.4 per 100,000 live births (Bush 1983)
Differential diagnosis
1. Fetal alcohol syndrome.
2. Stickler's syndrome: PRS plus severe myopia, retinal detachment and blindness with abnormal epiphyseal development due to alpha-1 collagen II
polypeptide mutation (Ross 2005
3. Velocardiofacial syndrome: 22q deletion with neuropsychiatric impairments and cardiac abnormalities (Kobrynski 2007)
4. Other rare syndromes that display the malformation.

3. Aetiology
Several theories have attempted to explain why growth and development of the mandible is so restricted in PRS among these are:
1. Oligohydramnios or a increased amniotic fluid pressure compressing the chin against the sternum and therefore restricting mandibular
development (Poswillo, 1968). If this theory is accurate, it would appear logical to expect some rebound growth of the mandible shortly after birth,
reducing the facial convexity and perhaps allowing the mandible to catch up with the maxilla. A number of cephalometric studies have attempted
to investigate this catch-up growth issue:
• Pruzansky (1969) found the facial profiles of 21 patients with PR sequence to be nearly identical to those of patients with isolated cleft lip by the
age of 10.5 years, although they had been much more convex at infancy. Hotz and Gnoinski (1982) reported that by the age of 5 years no difference
in mandibular length existed between 7 patients with PR sequence and 7 patients with isolated cleft palate (CP).
• Figueroa et al (1991) followed 17 infants with PR between 3 months and 2 years of age and compared them with 26 infants with isolated CP
and 23 healthy infants of similar ages. Their finding of increased rate of growth in the PR group, as compared with the 2 other groups, was
interpreted as partial mandibular catch-up growth, because the mandibular length in the
2. A lack of mandibular movement during embryogenesis (secondary to muscle weakness or hypotonia);
3. Genetic:
• Recent studies have indicated that genetic dys-regulation of SOX9 gene prevents the SOX9 protein from properly controlling the development
of facial structures, which leads to isolated PRS.
• PR also has been linked with deletions on chromosome 2 that are known to be associated with palatal abnormalities and some cases may have a
Mendelian genetic basis that is, as yet, unclear.
The typical features of PRS are:
1. Glossoptosis (implying a relatively large tongue). In reality, the tongue may be normal size or small, so upper airway obstruction may be

4. substituted for this feature.
2. Cleft palate (classically U-shaped but V-shaped may occur, usually without cleft lip).
3. Micrognathia or retrognathia
4. Dento-skeletal feature (Mastuda 2006)
• Reduction the gonial angle and mandibular body length
• Smaller SNA and SNB angles
• Significantly steep mandibular planes.
• Significant labial tipping of the lower incisors
Subtypes are recognised
1. Isolated PRS (iPRS) - 40%
2. Unique PRS (unique anomalies plus PRS) - 35%
3. Syndromic PRS (a syndrome plus PRS) - 25% such as:
a. 22q11 (Velocardiofacial/Di George) – 11% PR
 One of most common syndromes associated with CP without a CL (although CL can occur)
 CP, cardiac anomalies (tetralogy of fallot=Pulmonary stenosis, Overriding aorta, Ventricular Septal Defect, Right ventricular hypertrophy),
learning difficulties, Behavioural problems
 Characteristic Facial appearance: long face, prominent nose, squared nasal tip, narrow palpebral fissures, ‘hooded’ eyelids, small mouth, small
ears with attached lobes
b. Sticklers – 35%
 Connective tissue disorder

5.  Eyes – myopia. Associated with eye abnormalities therefore need to test all at birth as risk of detached retina
 Joints – hyper-extensibility, pain, stiffness,
 Facial appearance - midface hypoplasia; flat nasal bridge; anteverted nares; prominent eyes
Investigations
1. Pulse oximetry, arterial or capillary blood gases
2. Bone radiographs
3. Genetic assessment
4. Ophthalmological/auditory assessment
Management
1. Prenatal: with the increasing routine use of antenatal ultrasound, diagnosis is frequently before birth - based on identification of micrognathism or
retrognathism and glossoptosis. This may be complimented by MRI
2. Neonatal and postnatal: The multidisciplinary team involved is often large (incorporating paediatricians, ENT and plastic surgeons, dentists,
orthodontists, nurses, speech therapists, audiologists and social workers) but ensures the most comprehensive care plan.
a) Breathing
• Neonates with severe micrognathia present as emergencies at birth with significant respiratory obstruction, requiring a nasopharyngeal airway or
intubation.
• Affected babies are at risk of obstructive sleep apnoea.
• Unrecognised or untreated airways obstruction may lead to chronic hypoxia and cerebral impairment, failure to thrive and corpulmonale.
• Patients commonly exhibit upper airway obstruction and concomitant feeding difficulty that may be severe enough to necessitate:

6. i. Tracheostomy in the neonatal period.
ii. Other suggested types of management include
• sideling or prone position, which helps bring the tongue base forward in many children
• mandibular traction and advancement appliances,
• nasopharyngeal intubation
• tongue-lip adhesion
• Release of the musculature of the floor of the mouth.
• By the age of 3, most children with PRS are taking an oral diet and do not have significant airways obstruction (smith 2006)
b) Feeding
• The most common early problem is feeding difficulties, as the cleft palate prevents enough negative pressure to feed effectively.
• Feeding can be problematic due to the cleft palate and posterior tongue. Where nursing is not possible, formula or breast milk can be provided via
a bottle with a nipple cut to a large hole to make delivery effortless. Positioning (in the prone position) is also vital.
• If feeding is problematic, a feeding tube may be required.
• Gastroesophageal reflux (GERD) seems to be more prevalent in children with Robin sequence (Dudkiewicz, March 2000, CPCJ). Because reflux
of acidic contents in the posterior pharynx and upper airway can intensify the symptoms of Robin sequence, specifically by worsening airway

7. obstruction, it is important to maximize treatment for GER in children with PRS and reflux symptoms. Treatment may include upright positioning
on a wedge (a tucker sling may be needed if the baby is in the prone position), small and frequent feedings (to minimize vomiting), and/or
pharmacotherapy (such as proton pump inhibitors).
• Babies with a cleft palate will need a special cleft feeding device (such as the Haberman Feeder). The feeder's design enables the feeder to be
activated by tongue and gum pressure, imitating the mechanics involved in breastfeeding, rather than by sucking.
c) Eye
i. Careful examination for other somatic abnormalities, including examination of the eyes and ears, may indicate the presence of the malformation

8. as one of the related syndromes.
d) Micrognathia
• It may improve in 'non-syndromal' PRS as catch-up growth occurs and no intervention beyond positioning is required.
i. It has been suggested that compensatory growth of the mandible may occur during the first 5 years in cases of PRS, but this is controversial. For
instamce, a study by Daskalogiannakis et al in Canada 2000 showed that there is significant differences between PR and isolated cleft patients,
particularly in the size and sagittal position of the mandible, which was consistently shorter in the Pierre Robin group at all 5,10,15 years of ages.
Less severe differences were noted in the inclination of the palatal plane, the facial height proportions, and the midface depth.We conclude that
patients with Pierre Robin sequence have a significantly smaller mandible as compared with patients with isolated cleft palate, and the difference
does not change after the age of 5 years.
ii. In one study, 61% of patients only required positioning. 59% of patients who failed to respond to positioning required a nasopharyngeal airway
and 12% required short-term endotracheal intubation. The remainder required surgical treatment (Glynn 2011)
• Surgical options: These include:
i. Palatal repair is usually carried out at 6-12 months (Argrawal 2009)
ii. The EXIT (ex utero intrapartum therapy) procedure has been developed to treat a number of abnormalities affecting the fetal airway. Basically
this involves performing a caesarean section, leaving the baby attached to the placenta, whilst surgical correction is undertaken.[11]
iii. Distraction osteogenesis of the mandible (where the mandible is progressively elongated).
iv. Tongue-lip adhesion/glossopexy (connecting the tongue to the lower lip to improve the airway - later reversed).
One study found that distraction osteogenesis was superior to tongue-lip adhesion/glossopexy for the treatment of non-syndromic PRS when
judged by the outcomes of oxygen saturation, apnoea/hypopnea index and tracheostomy.[10]

9. e) Hearing
Early audiological assessment is important as tympanostomy tube placement to ensure adequate speech and language development (Glynn 2011)
Prognosis
f) Speech
A degree of palatal dysfunction and speech defect is to be expected in the long term. However, overall, the outlook is good but dependent on the
presence or absence of other syndromes and their complications.
North Thames Cleft Service – Great Ormond Street Hospital (GOSH)
Robin Sequence - A Guide for Hospital Management
MILD/ Suspected MODERATE SEVERE CONSIDERATIONS
Classification 1. Cleftpalate
2. Micrognathia
3. +/- Glossoptosis
4. veryoccasional episodes
of noisybreathing
1. Cleftpalate
2. Micrognathia
3. +/- Glossoptosis
4. Increasedfeedingproblems
5. Several episodesof noisybreathing
- AIRWAYOBSTRUCTION
1. Cleftpalate
2. Micrognathia
3. +/- Glossoptosis
4. Unsafe for oral feeds
5. Continuousepisodesof noisybreathing
- SEVERE AIRWAY OBSTRUCTION
* don’trelyonPhenotype butalso
lookat clinical presentation.
Feeding
Feeding is successful with
softsqueeze bottle as
instructedbycleftclinical
nurse specialist
1. Feedingwithbottleexacerbates
respiratory symptoms
2. Poorweightgain
3. Refluxing/vomiting
4. Aspirationrisk
1. Secretionsaroundmouth
2. No non-nutrativesuck
3. Refluxing/ vomiting
4. Aspirationrisk
* considerRefluxmedication.
Alwaysseekadvice fromthe Clinical
Nurse Specialists(see below)

10. Breathing
Positioningonside relieves
obstructiontoairway.
No distress.
Side or prone positionrelieves
airwayobstruction.
1.  SpO2 inair (intermittent)
2.  SpO2 whenfeeding
3. Tongue makes‘clicky’soundon
the back of the throat (tongue
sittingupincleft)
Onlysafe inProne position
1.  SpO2 inair – desaturations
/prolongedobstruction
2. Tracheal tug, use of accessorymuscles,
rib recession
3. Continuallyvisiblydistressed
4. Breathingdifficultiesexacerbatedby
crying/feeding/sleep
Be aware that symptomscanchange,
between mildandmoderate.
Continual reassessmentisVERY
important.
Action MonitorO2 saturationson
handlingandfeeding.
Continue toobserve overthe
next4-8 weeksassymptoms
can deteriorate.
1. Place NGT for feeds
2. ContinuousO2 monitoring
3. If on O2, checkCO2 bloodgasand
Bicarb.(O2 will maskdesaturations
associatedwithobstruction.
ElevatedCO2/Bicarbmayconfirm
ongoingobstruction)
4. ReferdirecttoRespiratoryTeamat
GOSH for advice andalsoinform
the CNS.
1. Place NGT for feeds
2. ContinuousO2 monitoring
3. If on O2, checkCO2 bloodgasand
Bicarb.(O2 will maskdesaturations
associatedwith obstruction. Elevated
CO2/Bicarbmayconfirmongoing
obstruction)
4. Suctionoral secretionsasrequired
5. URGENT referral toRespiratoryTeamat
GOSH.
6. ConsiderplacingNaso -pharangeal
Prongor start CPAP
7. If unable to stabilise- CATS/Intubation
© North Thames Cleft Service 2010 (M. Sharp)
CONTACTS
Clinical Nurse Specialists
GOSH
Julie Hughes 0207 813 8439
Mel Sharp 0207 813 8439
Sally Wright 0207 813 8439
St Andrews
Jill Bailey 01245 516029
On-call Respiratory Registrar GOSH
0207 405 9200 bleep: 0635/0820