Robin sequence

Definition and epidemiology

Robin sequence is a clinical triad consisting of glossoptosis, retro- or micrognathia, and airway obstruction. The term “glossoptosis” refers to a posteriorly displaced tongue that obstructs the airway and does not refer to an enlarged tongue. A cleft palate is not obligatory for the diagnosis, although a high degree of concordance has resulted in the erroneous substitution of cleft palate into the diagnostic triad of RS in several studies. Cleft palate in RS patients may be U- or V-shaped and is reported in 65% to over 90% of cases ( Fig. 28.2 ). Robin sequence can be an isolated entity or found in the clinical setting of a syndromic child. Between 30% and 60% of patients with RS have an associated syndrome.

The incidence of RS is estimated to be from 1:8500 to 1:20,000 live births. There are no gender differences in incidence, except in extremely rare X-linked syndromic associations.

Pathophysiology

The etiology of RS remains unclear and is likely multifactorial. Before any etiological considerations, a clear understanding of the difference between a syndrome and clinical sequence is important. A syndrome refers to a group of signs and symptoms that vary in degree of expression but ultimately result from a single pathological insult. A sequence describes a series of anomalies that may be instigated by varying disease processes, but ultimately converge in the same phenotypic findings. This differentiation is germane, as a portion of patients with RS will also be syndromic, such as Stickler syndrome. The converse does not hold true, as not all patients with Stickler syndrome have the phenotypic findings of RS ( Fig. 28.3 ).

The etiology of RS is likely multifactorial. Shprintzen classified etiology as “malformational” or “deformational”. “Malformational” refers to a mandibular predisposition to be retrognathic, such as in Nager or Stickler syndromes. “Deformational” refers to an intrauterine growth restriction that places the child’s chin in a flexed position into the chest, restricting growth. He hypothesized that restriction could be caused by a multigravid pregnancy, oligohydramnios, or a uterine anomaly.

Chiriac and colleagues postulated three theories regarding the etiology of RS. In the “mechanical theory”, the inciting event is mandibular hypoplasia that occurs in the 7th to 11th week of gestational life from various etiologies. The effect is a tongue that rides high in the oral cavity and interferes with the movement of the lateral palatine processes as they progress from a vertical to horizontal orientation ( Fig. 28.4 ). Experimental animal models support this sequence of events. Imaging of human fetuses has shown tongue malposition against the posterior pharyngeal wall in RS fetuses while in utero , providing additional support for the “mechanical theory”. Some hypothesize a U-shaped palatal cleft is more common in RS due to this wide blockage by the tongue; however, clinically, both U- and V-shaped clefts have been noted. In the “neurological maturation theory”, a neuromuscular delay occurs in the musculature to the tongue, pharyngeal pillars, and palate. The delay has been noted on electromyogram in RS. In the “rhombencephalic dysneuralation theory”, motor and regulatory organization of the rhombencephalon is related to a major complication in development.

Cohen also described several distinct mechanisms of etiopathogenesis: malformation, deformation, and connective tissue dysplasia. This final mechanism describes a link between diseases of “connective tissue dysplasia” such as Stickler syndrome and RS. Many authors also agree upon the potential influence of intrauterine teratogen exposure in the formation of RS, including alcohol, trimethadione, and phenytoin.

Historical perspective

The earliest account of a presentation of RS dates back to 1822 by St. Hilaire, followed by Fairbain in 1846. Later in the nineteenth century, Taruffi attempted to subclassify the clinical entity into those with “hypomicrognathus” and those with “hypoagnathus.” These descriptions demonstrate that as early as the nineteenth century clinicians understood that a major component of this entity was the mandible. In 1891, Lanneloague and Monard described four cases, two of which had an associated cleft of the palate. In 1902 Shukowsky presented a case of a hypoplastic mandible causing respiratory distress.

Despite earlier descriptions, the condition bears the name of the French stomatologist Dr. Pierre Robin. Dr. Robin lived from 1867 to 1949 and was a professor in the French School of Stomatology as well as editor of the periodical Stomatologie . His main contribution to the body of knowledge regarding RS was its dissemination. Beginning in 1923, he wrote 17 articles on the problems of “glossoptosis” and is credited with introducing the term. He highlighted the severity of the potential respiratory complications and the difficulty these children have with feeding and weight gain. Robin felt that the more severe cases were quite dire and wrote, “I have never seen a child live more than 16–18 months who presented with hypoplasia such as the lower maxilla [mandible] was pushed more than 1 cm behind the upper.” To combat the airway compromise Robin preferred a “monobloc” dental orthopedic appliance to keep the mandible forward to restore the normal maxillomandibular relationship. Unfortunately, Robin drew many extraneous associations to this cohort and overestimated the incidence of the clinical entity at 3 out of 5 live births ( Fig. 28.1 ).

In 1902, Shukowsky performed the first tongue–lip adhesion (TLA) by simply suturing the tongue to the lip, but the description was not published until 1911. This was successful in one patient, but another patient died of asphyxia when the suture pulled through the tongue. The use of TLA was not widely accepted during these initial descriptions. For the next four decades, primary treatment for respiratory distress in this cohort consisted of external traction devices placed on the mandible. One such device consisted of a pediatric back brace with a halo from which traction was applied. This was maintained for 4 weeks and was usually successful in alleviating the airway compromise. This modality, however, led to a significant amount of temporomandibular joint ankylosis. Then, in the 1940s, Douglas published a refined technique of TLA and a resurgence in the technique occurred.

Other soft-tissue procedures were described for RS that have not been continued. Oecononopoulas described the use of a heavy silk suture through the base of the tongue that is affixed to the cartilaginous portion of the mandible about 1 cm lateral to the midline. Hadley and Johnson also devised a technique where the tongue is pulled anteriorly, then a Kirschner wire is driven through the mandible from angle to angle in order to maintain tongue position. Lewis et al . described a tensor fascia lata sling for treatment. In this technique, a long strip of tensor fascia lata is harvested and passed posteriorly through the substance of the tongue through a submental incision. The graft is then tensioned and sutured to the periosteum of the mandibular symphysis. Bergoin and colleagues describe a procedure termed “Hyomandibulopexie”. In this technique the ventral anterior surface of the tongue and mandible is anchored to the hyoid bone with 3-0 braided nylon sutures. Lapidot and Ben-Hur describe passing 18-gauge steel wire into the most posterior midline portion of the tongue base and tensioned around the hyoid bone. In the Duhamel procedure, heavy nylon suture was passed across the most posterior aspect of the body of the tongue, exiting laterally through the cheeks or oral commissures, and then tied over buttons.

Skeletal techniques have transitioned from traction procedures to distraction procedures over time. Traction applied to mandible as a treatment for RS is mainly of historical note, but is still practiced in some institutions. Circummandibular wires are placed, and these wires are attached to a pulley that applies traction to the mandible. One major drawback of this technique is that the circummandibular wires at the parasymphysis can cut through the thin bone in neonates. One method affixes an acrylic plate to the mandible by circummandibular wires and the tension is distributed evenly, decreasing cut-through. The traction is released for feeds after 1–2 weeks. Over time, the counterweight is decreased. The wires may remain in place for up to 5 weeks. Some centers have had success with this technique on an outpatient basis.

Robin Sequence has evolved in name since the early descriptions as the understanding of the etiopathogenesis has advanced. Initially, the clinical constellation was termed “Pierre Robin syndrome”. In 1976 Gorlin, Pinborg, and Cohen created the term “Pierre Robin anomalad”, noting that this entity was not a syndrome. The term “anomalad” was used to describe an etiologically nonspecific complex that could occur with various syndromes of known or unknown origin or in isolation. Some authors began to use the phrase “Robin complex” but this was shortly replaced by “Pierre Robin sequence” or “Robin sequence” (RS) by Pasyayan and Lewis in 1984. Purists feel that eponyms should not include first names and prefer “Robin sequence”.

Clinical presentation

Robin sequence varies widely in clinical presentations and severity of symptoms. Most patients will have respiratory and/or feeding difficulties among other anomalies. Respiratory disturbances range from mild, with subtle findings on polysomnogram, to profound, requiring emergent intubation at birth. In severe cases, periodic desaturations may occur along with retractions, stridor, or hypoxia and hypoxemic neurological injury. Untreated, these children can progress to develop cor pulmonale. Children with RS consistently have an obstruction localized to the level of the base of the tongue due to glossoptosis. However, synchronous airway lesions are common in RS in up to 28% of patients. The most common of these is laryngomalacia with loss of support of supraglottic structures, present in 10% to 15% of infants with RS. Furthermore, central nervous system abnormalities may exacerbate the impact of existing anatomic airway abnormalities on respiratory function.

Infants with RS may also present with feeding difficulties and failure to thrive. Poor feeding, long feeding times, hypoxia during feeding, gagging, vomiting, aspiration, frequent pneumonia, and gastroesophageal reflux disease are possible. The failure to thrive in this cohort has dual causality from both the poor intake and from the increased metabolic demand from increased respiratory effort. Feeding difficulties in RS are multifactorial. Airway compromise can lead to gastroesophageal reflux through decreased intrathoracic pressure which can exacerbate respiratory issues. Additionally, children with RS have abnormal oroesophageal motility, and syndromic RS patients often have abnormal oral and/or facial muscle innervation.

Cardiac abnormalities are also commonly associated with RS, with congenital heart defects detected in 14%–30% of cases. Cardiac findings can be isolated or result from syndromic association. The presence of cardiac abnormalities is associated with increased mortality in the population of RS patients initially admitted to an intensive care unit. Mortality rates have improved as both the understanding of and treatment options for RS have evolved. As noted above, Robin painted a bleak picture for any child with RS. In 1946 Douglas reported greater than 50% mortality with conservative treatment. The major cause of mortality was felt to be secondary to aspiration. In 1994, Caouette-Laberge et al . stratified mortality into three groups. For patients with adequate respiration in prone position and the ability to bottle-feed, the mortality was 1.8%, increasing to 10% if gavage feeds were required. Mortality increased further to 41% in those with respiratory distress necessitating endotracheal intubation and gavage feeds. More recently, Costa et al . describe an 11-year series of 181 patients, with an overall 16.6% mortality rate. Concomitant cardiac and neurologic malformations were the greatest predictors of mortality. There were no deaths in isolated nonsyndromic RS patients.