Pierre Robin Sequence 

Updated: Oct 30, 2018
Author: Marie M Tolarova, MD, PhD, DSc; Chief Editor: Ravindhra G Elluru, MD, PhD 

Overview

Background

Pierre Robin sequence (PRS; also referred to as Pierre Robin malformation, Pierre Robin malformation sequence, Robin sequence, Pierre Robin syndrome, and Pierre Robin anomalad) consists of three essential components[1] :

  • Micrognathia or retrognathia
  • Cleft palate (usually U-shaped but sometimes V-shaped)
  • Glossoptosis, often accompanied by airway obstruction

PRS is a series of anomalies all initiated by one developmental problem. Other definitions have been suggested, based on a combination of mandibular deficiency, presence of U-shaped or V-shaped cleft palate, and airway obstruction.

PRS is not only causally heterogenous but also pathogenetically and phenotypically variable.[2] Each of the three symptoms can occur along a wide spectrum of severity. On the basis of the combination of symptoms, newborn babies and infants suffer from airway obstruction and feeding problems. An approach dividing this condition into three grades of severity has been recommended.[3]

PRS occurs as an isolated defect, as part of a recognized syndrome, or as part of a complex of multiple congenital anomalies. Diagnosis of a possible syndrome is very often critically important for correct management of a newborn affected with PRS.[4, 5]

The condition is named after the French dental surgeon Pierre Robin (1867-1950). His first paper described only micrognathia, glossoptosis, and respiratory distress[6] ; a decade later, he included cleft palate in the list of symptoms.[7] His main interest was glossoptosis; over a 30-year period, he published more than 20 articles and monographs on the embryology, anatomy, complications, and management of this disorder.[8]

Pathophysiology

PRS is etiologically heterogenous. This etiologic heterogeneity suggests pathogenetic heterogeneity and phenotypic variability, which include various causes of malformations and deformations and connective tissue dysplasia (see Etiology). A major distinction should be made between isolated occurrences of PRS and cases in which PRS is part of a recognized syndrome, part of a complex of multiple anomalies, or part of an unrecognized syndrome.

Isolated PRS is often a deformation resulting from intrauterine forces acting on the mandible, which restrict its growth and impact the tongue between the palatal shelves. Some deformational cases of PRS have been associated with oligohydramnios. Because micrognathia results from intrauterine molding, mandibular catchup growth is expected after birth once intrauterine forces are removed. The most severe cases of micrognathia are unlikely to be isolated PRS caused by deformation. Therefore, catchup growth is unlikely.

In patients with PRS, 13-27.7% of other family members are affected with cleft lip with or without cleft palate.[9, 10] Jakobsen et al compared data in several databases and proposed genes that might participate in the etiology of PRS, including GAD67 on 2q31, PVRL1 on 11q23-q24, and SOX9 on 17q24.3-q25.1.[11] Melkoniemi et al detected disease-associated mutations in COL11A1 and COL11A2 genes in some patients with nonsyndromic PRS.[12]

Jacobsen et al screened 10 unrelated patients affected with PRS for SOX9 and KCNJ2 mutations and suggested that nonsyndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.[13] Several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9, have been reported by Benko et al.[14]

The proportion of cases that are isolated PRS varies in different studies. Hanson and Smith found that 25% of PRS cases had specific syndromes, another 35% had multiple anomalies without a specific recognized syndrome, and only 40% had isolated PRS.[15] Another study found that 74% of cases were isolated PRS.[16]

Among syndromic varieties of PRS, the most common is Stickler syndrome, which accounts for 20-25% of all cases. The second most common PRS syndrome is velocardiofacial syndrome, which accounts for about 15% of all PRS cases.[17] Treacher Collins syndrome (mandibulofacial dysostosis), Nager syndrome, spondyloepiphyseal dysplasia congenita (SEC), and other recognized syndromes account for the rest of the syndromic PRS cases.

Cohen listed 46 conditions associated with PRS (see the image below).[18] Although this list is representative, it is not complete. PRS may be present with other conditions and various other anomalies, especially those involving the eye, ear, heart, and limb.[19]

Pierre Robin sequence in some recognized and unrec Pierre Robin sequence in some recognized and unrecognized syndromes.

When Robin sequence is diagnosed, a full genetic evaluation (including fluorescent in situ hybridization [FISH] for 22q deletion and testing for mutation in the Treacle [TCOF1] gene) is appropriate, together with diagnostic tests for other suspected syndromes (eg, bone radiographs and ophthalmologic examination).

Among 47 patients with PRS who were monitored by Sheffield et al, 12 patients were diagnosed as syndromic.[20] Out of 52 cases reported by Sher, 15 patients had Stickler syndrome and only five had nonsyndromic PRS.[21]

Distinguishing between micrognathia (ie, a small mandible) and retrognathia (ie, an essentially normal-sized mandible in an abnormal position) is important. In micrognathia, the mandible is small; in retrognathia, the mandible is essentially normal in size but is retrognathic in position because the cranial base angle is larger than normal. Most PRS conditions are either micrognathic or retrognathic.[22]

In velocardiofacial syndrome, the mandible is retrognathic. Because the cranial base is altered, the mandible grows downward instead of forward. This gives the appearance of a small mandible, but the bone mass is normal. Retrognathia rarely produces severe airway distress.

In the vast majority of other syndromes, the mandible is micrognathic. The bone mass is decreased, and the mandible is disproportionately small. Severe airway obstruction is more common with these syndromes.

One of the most severe problems with airway obstruction may occur in patients affected with SEC. Cleft palate or PRS is often present in this autosomal dominant condition that has a mutation in the COL2A1 gene, located on chromosome 12 (12q13.11-q13.2), the same as that found in Stickler syndrome type I (hereditary progressive arthro-ophthalmopathy).

The respiratory compromise in SEC is caused by multiple mechanisms, including a small abnormal chest, a tracheobronchomalacia, and a central apnea caused by compression of cervical spinal cord or medulla oblongata from cervical instability.[23] Furthermore, the upper respiratory obstruction of PRS may worsen the respiratory condition of the patient with SEC (see the image below).

Pierre Robin sequence and complexes. Pierre Robin sequence and complexes.

The mandible in PRS is often compared with the mandible in Treacher Collins syndrome (see the image below). When comparing two newborn babies with these two conditions, one can see that the mandible is short in both.

Robin sequences and complexes. Robin sequences and complexes.

Because the severity of the defects varies widely in both conditions, the defects in PRS may initially seem much greater than those in Treacher Collins syndrome; however, a significant difference between these conditions becomes very apparent as the infant develops. In deformational PRS, so-called catchup growth occurs, though it may be incomplete.[24] In Treacher Collins syndrome, mandibular growth remains severely affected.

Etiology

Suggested causes of PRS and Robin complexes include malformation, deformation, and connective tissue dysplasia.[25]  Because of differences in pathogenetic causes and phenotypes, various forms of PRS or Robin complexes can occur (see the image below).

Pierre Robin sequence and complexes. Pierre Robin sequence and complexes.

For example, a pure exogenous factor such as oligohydramnios causing mandibular constraint leads to a failure of the tongue to descend and starts a sequence that ends as PRS. However, intrinsic intrauterine mandibular hypoplasia that may be part of a complex of anomalies (syndrome) caused by a chromosomal aberration can cause the same problem (ie, failure of tongue descent) and end in exactly the same way as the previous example; yet the former is a deformation sequence and the latter is a malformation sequence.

Epidemiology

The reported birth prevalence of PRS ranges from 1 in 2000 to 1 in 30,000.[26] Bush and Williams suggested 1 in 8500.[27] The case definition of PRS still varies, and differences in definition lead to differences in the reported birth prevalence.[28] In studies with the highest birth prevalence of PRS, syndromic cases are most likely included.

A study of a population-based sample of 4433 patients with orofacial cleft (ascertained from 2,509,881 California births) reported the birth prevalence of nonsyndromic PRS to be 1 in 18,730 (0.05 cases per 1000 births).[29]

Most nonsyndromic PRS cases are sporadic. In the older literature, several authors reported a familial occurrence[30, 31, 32] ; some of these cases were probably syndromic. The authors' recommend that Stickler syndrome be considered first when a familial occurrence of PRS is found. Stickler syndrome is the most common syndrome among PRS cases, and PRS is the most constant feature of Stickler syndrome. When correctly diagnosed, myopia is detected early; this can prevent retinal detachment and possibly blindness.

Prognosis

All neonates with significant PRS are at risk for sudden death. The sudden infant death syndrome (SIDS) data show that the risk of SIDS is increased when infants sleep in the prone position. Neonates with PRS already have a compromised airway, and they also typically require prone positioning. Accordingly, monitoring of these neonates should be strongly considered.

Infants with PRS deserve to be treated with a multidisciplinary approach that involves a knowledgeable and experienced team capable of providing a comprehensive assessment, a realistic plan of treatment, and appropriate follow-up. Engaging the family in the early stages of the evaluation, the ongoing medical investigations, the issues regarding the child's care, and future planning generally leads to satisfaction, even in the most difficult of medical scenarios.

In a study of 103 patients followed for a median of 8.6 years (range, 0.1-21.9 years), Logjes et al documented a 10% mortality (n = 10) at a median patient age of 0.8 years (range, 0.1-5.9 years).[33] Of the 10 infants who died, nine had syndromic PRS; seven of the nine died of respiratory insufficiency due to various causes, and the other two died of arrhythmia due to hypernatremia and of West syndrome with status epilepticus. The infant with nonsyndromic PRS died of brain ischemia after mandibular distraction osteogenesis.

Patient Education

Children with PRS have difficulties with feeding.[34]  A cleft palate prevents production of the negative pressure necessary for sucking during breastfeeding. In addition, because of an abnormal jaw position, a baby with a small mandible usually has difficulties contracting its orbicularis oris muscle and squeezing the mother's nipple. In cleft palate, a wide communication between the oral and nasal cavities creates a risk of aspiration, nasal regurgitation, choking, and other feeding problems.

Consultation with a feeding specialist is advised. In many cases, when carefully instructed, a mother is able to manage bottle feeding while her baby is in a semisitting position. Special cleft palate nipples and squeezing bottles are helpful (see Cleft Lip and Palate). In patients with severe problems, gavage feeding may be necessary in the beginning of the baby's life.

Verifying that the mother of the baby with PRS is familiar with emergency techniques for the prevention of suffocation by food, such as the Heimlich maneuver, is important.

 

Presentation

History and Physical Examination

Pierre Robin sequence (PRS) consists of the following three essential components (see the images below):

  • Micrognathia or retrognathia
  • Cleft palate (usually U-shaped but sometimes V-shaped)
  • Glossoptosis, often accompanied by airway obstruction - The tongue is not actually larger than normal, but because of the small mandible, the tongue is large for the airway and therefore causes obstruction; rarely, the tongue is smaller than normal
Three-week-old baby boy affected with nonsyndromic Three-week-old baby boy affected with nonsyndromic Pierre Robin sequence.
One-month-old baby affected with nonsyndromic Pier One-month-old baby affected with nonsyndromic Pierre Robin sequence.
U-shaped and V-shaped cleft palates. U-shaped and V-shaped cleft palates.

PRS is a series of anomalies all initiated by one developmental problem. Other definitions have been suggested, based on a combination of mandibular deficiency, presence of U-shaped or V-shaped cleft palate, and airway obstruction.

Airway obstruction with PRS, if very severe or not properly managed, may lead to hypoxia, cor pulmonale, failure to thrive, and cerebral impairment. Syndromic cases and Robin complexes are usually more severe than nonsyndromic PRS and have worse prognoses. Mortality has been reported to be as high as 30%.[35]  Neonates with PRS should be carefully monitored because a significant airway obstruction may develop during the first 1-4 weeks of life.

PRS occurs as an isolated defect, as part of a recognized syndrome, or as part of a complex of multiple congenital anomalies. Diagnosis of a possible syndrome is very often critically important for correct management of a newborn affected with PRS.[4, 5]  Among syndromic varieties of PRS, the most common is Stickler syndrome, which accounts for 20-25% of all cases (see the images below).

Eight-year-old boy with Stickler syndrome. Note fl Eight-year-old boy with Stickler syndrome. Note flat, hypotonic face and small mandible. Patient also has U-shaped, wide cleft palate (CP). His mandible does not show catchup growth. Patient is mouth-breather and snores and is using CP as airway. Closing of CP without preparation would compromise airway passage. Authors recommend placing an obturator (perhaps with speech bulb) for couple of hours daily at first, then gradually increasing time. After few months, when child will have changed breathing pattern, palate can be closed.
Eight-year-old boy with Stickler syndrome. Note fl Eight-year-old boy with Stickler syndrome. Note flat, hypotonic face and small mandible. Mandible does not show catchup growth.
Eight-year-old boy with Stickler syndrome. Note U- Eight-year-old boy with Stickler syndrome. Note U-shaped, wide cleft palate.
 

DDx

Diagnostic Considerations

The first diagnostic consideration should be to determine whether Pierre Robin sequence (PRS) is an isolated condition. The most common syndrome with PRS is autosomal dominant Stickler syndrome. In this syndrome, mutations in the COL2A1 or COL11A1 genes cause connective tissue dysplasia that results in a short ramus and antegonial notching of the mandibular body and subsequent micrognathia.

Different forms of Robin complexes also occur. Cohen gave the following two examples[36] :

In the 22q11.2 deletion syndrome, retrognathia and cleft palate are present. Pharyngeal obstruction is caused by hypotonia, not by a flat cranial base angle and retrognathia. Thus, PRS is not present. Rather, in this form of Robin complex, all manifestations are causally, but not sequentially, related.[25]

Differential Diagnoses

 

Workup

Imaging Studies

When Pierre Robin sequence (PRS) is diagnosed, diagnostic tests such as bone radiographs are appropriate to assess for other suspected syndromes.

Other Tests

When PRS is diagnosed, a full genetic evaluation (fluorescent in situ hybridization [FISH] for 22q deletion, test for mutation in Treacle [TCOF1] gene) is appropriate. An ophthalmologic examination is also appropriate to assess for suspected syndromes.

Given the small jaw and therefore the predispostion to upper-airway obstruction, children with suspected PRS should undergo polysomnography, as well as an airway evaluation with bedside nasopharyngoscopy.

Finally, children with PRS may have feeding problems and should be evaluated by a feeding specialist (speech pathologist).

 

Treatment

Approach Considerations

The newborn affected with Pierre Robin sequence (PRS) is of serious concern to neonatologists, pediatricians, and other health care providers.

PRS has three essential components: micrognathia/retrognathia, cleft palate, and relative glossoptosis. Immediately after delivery, because of the micrognathia and, therefore, relative glossoptosis, many children have airway distress. This may necessitate emergency treatment. Because the body will always prioritize breathing over eating, many infants have difficulty in achieving adequate caloric intake. A cleft palate further adds to the feeding difficulties.

Neonatal Care

The primary concern in airway compromise is its life-threatening aspect. Most neonates with PRS have an isolated defect that is not part of a syndrome, for which the airway and feeding complications are usually greater. The great majority of neonates can be treated in the prone position (face down). Devices or procedures such as oral airways, palatal prostheses, continuous positive airway pressure or endotracheal intubation, mechanical ventilation, and tracheostomy can be avoided.

These neonates also need to be fed in a prone position, but they can be fed by mouth. Again, very few infants need long-term gavage feeding tubes or other devices. Multidisciplinary care that includes a neonatologist, a neonatal nurse specialist, members of the craniofacial team, and the parents is the best approach in the complex care of neonates affected with PRS and Robin complexes.

The vast majority of neonates with nonsyndromic PRS, those who are breathing without assistance and orally feeding while prone, can be discharged home after a few days. It is expected that the mandible will eventually grow and, thus, that the severe airway obstruction and feeding issues will decrease. Feeding and speech assessments continue to be needed, and breathing capacity must be monitored. Eventually, the cleft palate must be closed, and long-term orthodontic care is required; however, some neonates have much more severe immediate or long-term medical problems.

Postneonatal Care

Airway

Secondary to the micrognathia/retrognathia, airway obstruction may be mild or severe. Severe obstruction may require immediate intervention with a very difficult intubation. In many infants, airway difficulties may seem mild at birth but progress during the first 4-8 weeks. This may be because a newborn's respiratory needs are relatively small. As an infant grows, the requirements increase, making the obstruction more severe.

Mild obstruction can normally be handled in a very conservative manner with positional changes. Obstruction of the airway results from a small mandible and a normal-sized tongue. Putting a baby in the prone position causes gravity to pull the tongue forward and results in a larger airway passage. Infants with a nonsyndromic etiology will often outgrow this type of obstruction.

If the obstruction does not resolve through positional changes, many practitioners advocate use of the nasopharyngeal airway. The nasopharyngeal airway bypasses the oral pharynx and the obstruction caused by the relative glossoptosis. In the neonatal intensive care unit (ICU), this can be a very effective temporary form of management of the airway obstruction. Most centers do not feel comfortable sending patients home with a nasopharyngeal airway, because dislodgement can result in an acute airway obstruction.

In patients who consistently maintain CO2 levels above 50, a surgical procedure is appropriate. The following three surgical procedures are used to treat PRS[37] :

  • Tongue-lip adhesion/glossopexy
  • Tracheostomy
  • Distraction osteogenesis of the mandible

Tongue-lip adhesion/glossopexy

In tongue-lip adhesion/glossopexy, the tongue is sutured to the lower lip, thereby pulling the tongue forward and providing a larger airway. Later, presumably after the child has demonstrated catchup growth, this bond between the tongue and lip is separated. This results in a very mild cosmetic deformity to the lip and tongue.

With a glossopexy, many surgeons try to pull the base of the tongue forward by attaching it to the mandible. Because the mandible is relatively soft, placing a suture that permanently holds the base of the tongue forward is very difficult; consequently, the tongue-lip adhesion/glossopexy has been the subject of some controversy. Nevertheless, it does have its advocates among maxillofacial surgeons.

Tracheostomy

A tracheostomy tube effectively bypasses the obstruction in the oral pharynx and hypopharynx. When and if the infant's airway obstruction is resolved, the tracheostomy tube can be removed.

Unfortunately, tracheostomy tubes require close monitoring. If the tracheostomy tube becomes occluded or dislodged, the patient could have an acute respiratory arrest. However, a tracheostomy tube rarely remains in place less than a year after being placed in a newborn. Despite the hardship for the family of taking care of a tracheostomy tube, methods of teaching families how to care for it are well established. Tracheostomy remains a criterion standard for children with severe airway obstruction.

Distraction osteogenesis

Distraction osteogenesis, a more recently developed technique for treating airway obstruction in PRS,[38]  was popularized by Sidman, who has the world's widest experience in treating patients with PRS with distraction osteogenesis.[39]

Many centers have acquired expertise in this area. In this technique, the mandible is cut near the angle of the mandible on both sides. A mechanical device distracts the two portions of the mandible approximately 1.5-2 mm a day. As the portions of the mandible are separated, new bone is formed, and the mandible gradually elongates over a period of 2-3 weeks. Distraction can be performed in the newborn to prevent a tracheostomy or can be performed later to remove a tracheostomy tube. (See the images below.)

Child with Pierre Robin sequence before distractio Child with Pierre Robin sequence before distraction osteogenesis.
Distraction osteogenesis is completed, and bone is Distraction osteogenesis is completed, and bone is consolidating.

Because this technique was popularized only during the past couple of decades, the long-term sequelae on mandibular growth and tooth development have not been fully defined; nevertheless, good results have been reported, and distraction osteogenesis is being performed with increasing frequency.

The promising results of distraction osteogenesis notwithstanding, it must be kept in mind that in nonsyndromic PRS, the mandible grows very fast after birth and that catchup growth improves the airway passage (though the extent of such growth has been questioned by some[40] ). It has been argued that mandibular distraction should be reserved only for very severe isolated PRS cases and for syndromic PRS cases in which mandibular catchup growth does not occur.[41]

Feeding

Many children with PRS have feeding difficulties. Because the body chooses breathing over eating, it is expected that a patient with airway difficulties will have feeding difficulties.

If the infant demonstrates catchup growth, feeding may be handled through special techniques, which consist of keeping the child's head more elevated and using special cleft nursing bottles (for more details, see Cleft Lip and Palate). If this is not satisfactory, gavage or feeding tubes can temporarily provide adequate nutrition. If feeding does not improve over a period of months, many infants require gastrostomy tubes. After the child develops the ability to feed orally, these tubes can be removed.

Cleft palate

In the United States, cleft palates are typically repaired in infants aged 10-18 months; however, if airway concerns are expressed, the palate surgery is often delayed until the child is aged approximately 18 months. The current belief is that as a general rule, the earlier the surgery is performed, the better the chance that the child will have completely normal palatal function and, consequently, normal speech. If a child has a tracheostomy tube in place, the palate repair can be performed at any time.

Micrognathia/retrognathia

Micrognathia may be managed during the perinatal period if airway obstruction is significant and the family opts for distraction osteogenesis of the mandible. Otherwise, most centers wait until the infant achieves full growth of the facial bones before dealing with the functional and aesthetic abnormalities caused by micrognathia. In infants with retrognathia, surgery for the defective dental occlusion is rarely indicated. However, infants with either micrognathia or retrognathia may benefit from some sort of chin enhancement procedure for esthetic reasons.

An extensive description of treatment choices can be found in the review by St-Hilaire and Buchbinder.[42]

Because different types of obstruction, positioning, and traction devices are not always successful, they may not be recommended in most patients with syndromic PRS and Robin complexes. Thus, nasopharyngeal airway, tongue-lip adhesion, and other glossopexy procedures, as well as tracheostomy, are more common in syndromic patients with PRS than in those with isolated deformational PRS.

A multidisciplinary approach is always necessary in choosing the best treatment protocol for each patient. In patients with syndromic as well as nonsyndromic PRS, postponement of palatal closure may be beneficial for the final treatment outcome. One must carefully consider the individual timing and choice of procedures on the basis of a precise diagnosis and the particulars of the individual case, particularly because variability is great both between syndromes and within each clinical condition.

The major problem is airway compromise or obstruction.[43, 44] As mentioned previously (see Pathophysiology), different causes of airway obstruction are noted in PRS and Robin complexes. Therefore, one must accurately diagnose a baby with PRS as soon as possible in order to successfully manage this serious condition.

The vast majority of infants with nonsyndromic PRS and normal tongue size experience airway obstruction due to micrognathia of different degrees. If the baby is in the prone position (face down), gravity pulls the tongue forward and keeps the airway open. In severe cases, this may not be sufficient, and tongue-lip adhesion or glossopexy may be necessary.

Placement of a nasopharyngeal airway can help to avoid airway blockage. Consider it especially when hypotonia is also present (eg, deletion of chromosome band 22q11.2 syndrome), as well as in Robin complexes with neurologic symptoms. Some patients still require a tracheostomy to maintain an open airway.

In extensive studies dealing with airway problems in PRS, Shprintzen demonstrated that different mechanisms of obstruction can occur within the same syndrome and noted that in some patients, glossoptosis is frequently not the cause of the upper airway obstruction.[28, 5]

Infants with PRS also have difficulties with feeding. A cleft palate prevents production of the negative pressure necessary for sucking during breastfeeding. In addition, because of an abnormal jaw position, a baby with a small mandible usually has difficulties contracting its orbicularis oris muscle and squeezing the mother's nipple. In cleft palate, a wide communication between the oral and nasal cavities creates a risk of choking and other feeding problems.

In deformational PRS, the mandible undergoes catchup growth (see the images below) that starts after birth when intrauterine constraint disappears and thus eases airway and feeding problems.

Child with nonsyndromic Pierre Robin sequence at a Child with nonsyndromic Pierre Robin sequence at age 4 years. Profile is almost normal because of catchup growth.
Child with nonsyndromic Pierre Robin sequence at a Child with nonsyndromic Pierre Robin sequence at age 4 years.

Usually, improvement is observed after the first 3 months. Even with partial catchup growth, a child's profile is almost normal at age 4-6 years without any treatment. When, as in some patients, the mandible still lags behind, orthodontic treatment of malocclusion may be required (see Surgical Care).

In PRS that is part of a syndrome or in Robin complexes, initial problems during the neonatal period and early stages of life are similar to those in deformational PRS.

Numerous syndromes occur with PRS.[25, 19] Because postnatal development is different for each of them, a precise diagnosis based on a genetic workup is essential.

A careful analysis of the type of airway obstruction is fundamental. Sher et al studied the mechanism of airway obstruction using flexible fiberoptic nasolaryngoscopy and developed a classification scheme based on four different processes.[21] Identifying a type of airway obstruction and understanding its mechanism is essential for correct management and treatment.

One thing is common for nondeformational PRS: No catchup growth of the mandible occurs. Because growth is altered in the mandible but may not be altered in other parts of the face, a dysmorphism of the features may progress and become more prominent with age if not treated.

Although treatment in the beginning of an infant's life is similar for all patients with Robin sequences, management of airway obstruction may require a more invasive approach in syndromic PRS and in Robin complexes.

Smith and Senders reviewed 60 patients with PRS.[45] One third of patients who failed positional therapy were temporarily stabilized with a nasopharyngeal airway or endotracheal intubation. The remaining two thirds of patients required a surgical procedure. By age 3 years, most patients were successfully taking an oral diet.

Surgical Care

An extensive description of treatment choices for PRS can be found in the review by St-Hilaire and Buchbinder.[42] Because of the different types of obstruction, positioning and traction devices are not always successful and may not be sufficient for airway management in patients with syndromic PRS and Robin complexes. Thus, nasopharyngeal airway, tongue-lip adhesion, and other glossopexy procedures, as well as tracheostomy, are more common than in patients with deformational PRS.

Most infants with nonsyndromic PRS and normal tongue size experience airway obstruction due to micrognathia of different degrees. If the baby is in the prone position, gravity pulls the tongue forward and keeps the airway open. Placement of a nasopharyngeal airway can help avoid airway blockage. Consider it especially when hypotonia is also present (eg, deletion of chromosome band 22q11.2 syndrome) as well as in Robin complexes with neurologic symptoms. Some cases require a tracheostomy to maintain an open airway in the baby.

One should pay special attention to the timing of cleft palate surgery. Usually, the palatal cleft is shaped like a wide U, with a wide and shallow palate. At the time when surgery is recommended for most children with cleft palate (9-18 months), the lower jaw is still small, and the child may not be gaining weight and thriving properly because of feeding and airway problems.

Furthermore, because of the micrognathic jaw and the normal tongue size, an infant may be using his or her cleft palate as an airway. Closing of the cleft may significantly compromise airway function; therefore, a multidisciplinary team of specialists should carefully evaluate the timing of cleft palate closure. Lehman reported a detailed retrospective analysis of cleft palate repair in 34 patients with Robin sequence.[46] Approximately 24% of patients suffered from complications related to airway management at the time of palatoplasty.

Mandibular distractional osteogenesis offers a definitive structural resolution of micrognathia. After the first cases of mandibular distractional osteogenesis were published,[47] numerous patients underwent this procedure; various modifications of the original technique are now used.

Cohen et al reported performing mandibular distractional osteogenesis in patients aged 14 weeks to 12 years with obstructive sleep apnea caused by craniofacial anomalies.[48] In all patients, significant relief from airway obstruction was observed.

Lam et al, in a retrospective study of 123 patients with severe micrognathia, found that mandibular distractional osteogenesis was highly successful in allowing patients to avoid tracheostomy.[49]

Flores et al, in an outcomes analysis of mandibular distractional osteogenesis versus tongue-lip adhesion in the treatment of nonsyndromic PRS, concluded that the former procedure yielded better outcomes with respect to oxygen saturation, apnea-hypopnea index, and incidence of tracheostomy.[50]

A systematic review by Zhang et al that addressed the literature directly comparing tongue-lip adhesion with mandibular distraction osteogenesis for Pierre Robin sequence found both procedures to be effective alternatives to tracheostomy when conservative management fails.[51]  In this review, mandibular distraction osteogenesis appeared to be be superior to tongue-lip adhesion with regard to long-term resolution of airway obstruction and avoidance of gastrostomy, but it was associated with significant complications.

A retrospective cohort study by Resnick et al found mandibular distraction osteogenesis to be more effective than tongue-lip adhesion for relieving obstructive apnea in infants with Robin sequence.[52]

Complications

Velopharyngeal dysfunction after palatoplasty is rather common. It is more common in patients with nonsyndromic PRS, when the cleft is usually U-shaped, large, and wide, than it is in patients with syndromic PRS.[53]

Consultations

Consultation with a feeding specialist is advised. In many cases, when carefully instructed, a mother is able to manage bottle feeding while her baby is in a semisitting position. In patients with severe problems, gavage feeding may be necessary in the beginning of the baby's life.

 

Medication

Medication Summary

Drug therapy currently is not a component of standard care for Pierre Robin sequence (PRS). See Treatment.