Pierre Robin Syndrome 

Updated: Sep 07, 2017
  • Author: Ted L Tewfik, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Background

Lannelongue and Menard first described Pierre Robin syndrome in 1891 in a report on 2 patients with micrognathia, cleft palate, and retroglossoptosis. In 1926, Pierre Robin published the case of an infant with the complete syndrome. Until 1974, the triad was known as Pierre Robin syndrome; however, the term syndrome is now reserved for those errors of morphogenesis with the simultaneous presence of multiple anomalies caused by a single etiology. The term sequence has been introduced to include any condition that includes a series of anomalies caused by a cascade of events initiated by a single malformation.

Breugem and Courtemanche, in a 2009 article, illustrated the confusion regarding the classification of Robin sequence. [1] They surveyed (via questionnaires) numerous aspects, among them, the difference between "retrognathia" and "micrognathia" and whether the cleft type (ie, "U-shaped" versus "V-shaped") had any influence in the decision-making process. A Pubmed literature review of the 50 most recent articles about Robin sequence was also included. The results were confusing. The questionnaires revealed 14 different definitions, and the Pubmed review of 50 publications gave 15 different opinions regarding Robin sequence.

An image depicting Pierre Robin syndrome can be seen below.

A 5-month-old baby with Pierre Robin sequence and A 5-month-old baby with Pierre Robin sequence and severe micrognathia. Used with permission from Tewfik TL, Der Kaloustian VM, Congenital Anomalies of the Ear, Nose, and Throat. New York, NY: Oxford University Press; 1997:517.
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Etiology and Pathogenesis

Frequency

This heterogeneous birth defect has a prevalence of approximately 1 per 8500 live births. The male-to-female ratio is 1:1, except in the X-linked form.

Etiology

Autosomal recessive inheritance is possible. An X-linked variant has been reported involving cardiac malformations and clubfeet.

Pathogenesis

Three pathophysiological theories exist to explain the occurrence of Pierre Robin sequence.

  • The mechanical theory: This theory is the most accepted. The initial event, mandibular hypoplasia, occurs between the 7th and 11th week of gestation. This keeps the tongue high in the oral cavity, causing a cleft in the palate by preventing the closure of the palatal shelves. This theory explains the classic inverted U-shaped cleft and the absence of an associated cleft lip. Oligohydramnios could play a role in the etiology since the lack of amniotic fluid could cause deformation of the chin and subsequent impaction of the tongue between the palatal shelves.
  • The neurological maturation theory: A delay in neurological maturation has been noted on electromyography of the tongue musculature, the pharyngeal pillars, and the palate, as has a delay in hypoglossal nerve conduction. The spontaneous correction of the majority of cases with age supports this theory.
  • The rhombencephalic dysneurulation theory: In this theory, the motor and regulatory organization of the rhombencephalus is related to a major problem of ontogenesis.
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Otolaryngologic Manifestations

Micrognathia is reported in the majority of cases (91.7%). It is characterized by retraction of the inferior dental arch 10-12 mm behind the superior arch. The mandible has a small body, obtuse genial angle, and a posteriorly located condyle. The growth of the mandible catches up during the first year; however, mandibular hypoplasia resolves and the child attains a normal profile by approximately age 5-6 years. The jaw index is defined as the alveolar overjet multiplied by the maxillary arch divided by the mandibular arch. This index can be used to objectify mandibular growth. The alveolar overjet is the distance between the most anterior points of the upper and lower alveolar arches. The maxillary arch is the measurement between the 2 tragi via the subnasal point, and the mandibular arch is the distance from the right to the left tragus passing through the pogonion.

Glossoptosis is noted in 70-85% of reported cases. Macroglossia and ankyloglossia are relatively rare findings, noted in 10-15% of reported cases.

The combination of micrognathia and glossoptosis may cause severe respiratory and feeding difficulty in the newborn. Godbout et al (2013) published a study comparing anatomical cleft parameters between isolated cleft palate patients and Pierre Robin syndrome patients. [2] They concluded that cleft palate Pierre Robin syndrome patients present statistically significant different cleft characteristics. They demonstrated a significant correlation between the width of the cleft of the soft palate and the severity of the respiratory symptoms and feeding difficulties in Pierre Robin syndrome patients. Obstructive sleep apnea may also occur. In reported series, the prevalence of cleft palate varies from 14-91%. It can affect the soft and hard palates and is usually U shaped (80%) or V shaped. Occasionally, it may present as a bifid or double uvula or as an occult submucous cleft.

The most common otic anomaly is otitis media, occurring 80% of the time, followed by auricular anomalies in 75% of cases. Hearing loss, mostly conductive, occurs in 60% of patients, while external auditory canal atresia occurs in only 5% of patients. Temporal bone computerized planigraphs demonstrate inadequate pneumatization of the mastoid cavities in many patients with Pierre Robin sequence.

Gruen et al (2005) studied 13 temporal bones by light microscopy and identified multiple architectural anomalies involving the entire ear, including abnormal auricles, and anomalies of the ossicles, including abnormal stapes footplates. [3] All specimens showed signs of middle ear infection. Anomalies of the inner ear included aplasia of the lateral semicircular canals, a large vestibular aqueduct, and unusually large otoconia. In the mastoid process there were islands of cartilage in the expected position of Reichert's cartilage and dehiscence of the fallopian canal. Loss of cochlear hair cells was seen in children who had antemortem hypoxia.

Nasal deformities are infrequent and consist mostly of anomalies of the nasal root. Dental and philtral malformations occur in one third of cases. Laryngomalacia occurs in approximately 10-15% of patients with Pierre Robin sequence. Gastroesophageal reflux and esophagitis has also been described.

Speech defects occur frequently in patients with Pierre Robin sequence. Velopharyngeal insufficiency is usually more pronounced in these patients than in those with isolated cleft palate.

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Systemic Manifestations

In general, systemic anomalies are documented in 10-85% of reported cases. Ocular anomalies are reported in 10-30% of patients. The higher frequency is usually observed when an ophthalmologist is consulted. The following lesions occur in decreasing order of frequency: hypermetropia, myopia, astigmatism, corneal sclerosis, and nasolacrimal duct stenosis.

Cardiovascular findings such as benign murmurs, pulmonary stenosis, patent ductus arteriosus, patent foramen ovale, atrial septal defect, and pulmonary hypertension have all been documented. Their prevalence varies in the literature from 5-58%.

Anomalies involving the musculoskeletal system are the most frequent systemic anomalies (noted in 70-80% of cases). They include syndactyly, dysplastic phalanges, polydactyly, clinodactyly, hyperextensible joints, and oligodactyly in the upper limbs. In the lower extremities, foot anomalies (clubfeet, metatarsus adductus), femoral malformations (coxa varus or valgus, short femur), hip anomalies (flexure contractures, congenital dislocation), anomalies of the knee (genu valgus, synchondrosis), and tibial abnormalities have been reported. Vertebral column deformities include scoliosis, kyphosis, lordosis, vertebral dysplasia, sacral agenesis, and coccygeal sinus.

Central nervous system (CNS) defects such as language delay, epilepsy, neurodevelopmental delay, hypotonia, and hydrocephalus may occur. The incidence of CNS defects is around 50%.

Genitourinary defects may include undescended testes (25%), hydronephrosis (15%), and hydrocele (10%).

Associated syndromes and conditions include Stickler syndrome, trisomy 11q syndrome, trisomy 18 syndrome, velocardiofacial (Shprintzen) syndrome, deletion 4q syndrome, rheumatoid arthropathy, hypochondroplasia, Möbius syndrome, and CHARGE association.

Evans et al (2006) from the Massachusetts Eye and Ear Infirmary reviewed 115 patients with PRS. [4] They found that 54% (N=63) of patients were nonsyndromic. Syndromic patients included: Stickler syndrome (18%), velocardiofacial syndrome (7%), Treacher-Collins (5%), facial and hemifacial microsomia (3%), and other defined (3.5%) and undefined (9%) disorders.

A retrospective study by Costa et al of 181 infants indicated that isolated Pierre Robin syndrome does not increase mortality risk, with the risk being increased in patients with cardiac or central nervous system anomalies or with anomalies of two or more organ systems. [5]

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Conservative Management

In the majority of patients, conservative management with close observation and follow up is successful. The natural history shows that with normal growth, airway compromise resolves without immediate surgical intervention. Isolated Pierre Robin syndrome (PRS) patients usually respond more favorably to the conservative approach.

Recently, Abel et al (2012) reported on long-term outcomes in 104 children with PRS and airway obstruction. In most children (86.5%), airway obstruction was managed by conservative measures or with a nasopharyngeal airway (NPA) for a few months. [6]

Prone positional therapy has proved to be highly efficient in airway management. Oral airway placement, laryngeal mask, nasopharyngeal stenting, and short-term intubation (< 2 wk) are other options in case positioning is inadequate. Intubation is often difficult owing to the micrognathia and should be performed by someone specialized in problematic pediatric airway management.

Feeding difficulties can be alleviated by upright feeding techniques, modification of the nipple for bottle feeding, temporary use of nasogastric or orogastric feeding tube, and the placement of a gastrostomy. Palatal plates such as the pre-epiglottic baton plate, which have a velar extension, pull the base of the tongue forward. This can be helpful in the relief of airway obstruction, and it also facilitates the swallowing mechanism during feeds.

A retrospective study by Rathé et al of 48 patients with Pierre Robin sequence found that the need for resuscitation and invasive treatment were higher in those with Pierre Robin syndrome or nonsyndromic associated anomalies than in patients with isolated Pierre Robin sequence. [7]

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Surgical Management

Infants with pronounced micrognathia may experience severe respiratory distress or failure to thrive. Treatment is prioritized according to the severity of airway compromise followed by the extent of feeding difficulties. [8] Lidsky et al (2008) reviewed 67 Pierre Robin syndrome (PRS) patients from their multidisciplinary cleft team at a tertiary pediatric hospital. [9] They found that delaying airway intervention may necessitate feeding assistance via a g-tube. Surgical intervention is necessary in these cases.

Although many different surgical procedures have been described, tracheostomy remains the most widely used technique. Other surgical procedures, such as subperiosteal release of the floor of the mouth (see the image below), and different types of glossopexy, such as the Routledge procedure or other forms of tongue-lip adhesions, can be used. Any glossopexy should be released before significant dentition develops (age 9-12 mo). Mandibular lengthening by gradual distraction may be used for severe mandibular hypoplasia that causes obstructive apnea. Published articles by Hong and others on the use of mandibular distraction osteogenesis in PRS patients have described significant improvements in both airway obstructive symptoms and feeding abnormalities. Patients showed clinical and objective improvements in reflux and swallowing function after surgery. [10, 11, 12]

Paes et al (2013) compared the outcome and cost-effectiveness of tracheotomy versus mandibular distraction. [13] They demonstrated that tracheostomy was 3 times more expensive and indirect costs were almost 5 times higher. They also reported 4 times more complications with tracheostomy.

A study by Khansa et al indicated that airway obstruction and feeding difficulties in Pierre Robin sequence can be effectively addressed through adoption of a comprehensive treatment approach that incorporates conservative management, mandibular distraction osteogenesis, and tongue-lip adhesion, with requirement for postprocedure tracheostomy minimized via careful selection of which patients should undergo surgery and which procedure is best employed in the specific patient. [14]

Diagram illustrating the surgical technique for su Diagram illustrating the surgical technique for subperiosteal release of the floor of mouth in patients with Pierre Robin sequence.

As the therapy of choice to correct the conductive hearing loss and prevent middle ear complications, tympanostomy tubes are usually inserted when the palatoplasty is performed.

Surgical procedures to repair the cleft palate, details of which are not included herein, fall into 1 of 2 categories. The first category comprises all the one-stage procedures, and the second includes all multistage approaches in which the velum is initially closed and hard palate repair is delayed. The most common procedure is the single-stage palate (hard and soft) closure, performed when the child is aged 6-18 months.

Bütow et al (2009) analyzed data from 188 patients with Robin Sequence defined by the clinical triad of glossoptosis, retrognathia/micrognathia, and cleft or agenesis of the palate. [15] They analyzed different aspects such as incidence, risk factors, associated syndromes, airway and feeding difficulties, and outcome management. They also evaluated a protocol of different surgical and nonsurgical management options.

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