Quality of life and phonatory and morphological outcomes in cognitively unimpaired adolescents with Pierre Robin sequence: a cross-sectional study of 72 patients

Pierre Robin sequence (PRS) is a rare and complex facial malformation that occurs in approximately 1 in 10,000 births. It associates retro(or micro)gnathia, glossoptosis, airway obstruction and frequently posterior U-shaped cleft palate (CP) [1]. The pathophysiological origin of the embryonic sequence of events leading to the disorder seems heterogeneous [2, 3]. A family history of PRS is present in 10% to 15% of cases, possibly involving mutations upstream of the SOX9 gene, which participates in embryonic mandible development among other roles [4, 5]. Neonates with PRS exhibit breathing and feeding issues, including upper airway obstruction due to the posterior position of the tongue and to glossopharyngeal/laryngeal hypotonia; sucking and swallowing difficulties; and gastroesophageal reflux [6, 7]. Because of these functional disorders, the first year for an infant with PRS is marked by many burdensome medical necessities, such as prolonged hospitalization, mother/child separation, nasogastric or gastrostomy tube feeding and management of upper airway obstruction. In the Paris hospital protocol, this latter management comprises prone positioning, continuous positive airway pressure, nasopharyngeal tube insertion, or tracheostomy according to case severity [8, 9]. Patients usually improve progressively during the first 2 years of life. In PRS with CP, one or two-stage primary surgery, according to the surgical team and the CP width, is performed between age 6 and 18 months.

Nearly half of children with PRS also have associated malformations resulting in syndromic PRS often affecting their cognitive development. In contrast, those with isolated PRS or PRS associated with Stickler syndrome have good cognitive prognosis. However, in a previous prospective longitudinal study spanning 12 years, we showed that about half of such children had good cognitive development but retained phonatory disorders, especially hypernasality [10].

A number of teams have looked at the negative impact of cleft lips/palates on quality of life (QoL), particularly in terms of self-esteem [11‐14]. In contrast, only two studies have been published on QoL in PRS patients [15, 16]. The authors of the first study, concerning younger children (age 4–11 years), reported that self-esteem was comparable in the PRS and control group but underlined that this dimension should be evaluated in adolescents. Results of the more recent second study demonstrated a satisfactory generic QoL in 17 adolescents with PRS. Nonetheless, both families and health providers report self-esteem issues, inhibitions, and social integration difficulties in some teenagers affected by PRS, even those with normal cognitive and scholastic capacities. The hypernasality and face morphology issues they may still carry could contribute to these issues because the voice and face are major elements of social communication.

The primary objective of our study was to analyse generic and specific (vocal and oral) QoL in cognitively unimpaired adolescents with PRS, and identify determinants of any differences between QoL in this series and the general population. Those determinants were defined as current, particularly phonatory or facial morphology sequelae still present; or early, particularly PRS type (isolated or not), neonatal anatomic characteristics (cleft width, retrognathia degree), neonatal functional impairment severity (respiratory, orodigestive) and CP surgery procedure (one- or two-stage).

Our secondary objectives were to describe phonatory and morphological outcomes in a large monocentric cohort of PRS patients as they pass through the important period of adolescence and analyse early determinants of any phonatory or morphological sequelae that they may still have.

Finally, we also compared two surgical protocols for cleft repair (in one- or two-stage primary surgery) to assess the incidence of complications (palatal fistulae) and functional results in terms of facial morphology and phonation. Indeed, in our series, two protocols for CP repair were used. The first consisted of uranostaphylorrhaphy as per the Veau-Wardill technique [17] performed in a single intervention at age 9 months regardless of cleft width (Necker Hospital) and the second, intravelar veloplasty as per Sommerlad [18] performed at 6–8 months with closure of the hard palate during the initial surgery for narrow clefts or during a second surgery at 12–18 months (median age 15 months), for wider clefts (Trousseau Hospital). These two techniques and the results they confer have never been compared in patients with PRS, and their use in other types of cleft lip/palate remains controversial [19‐24].

We present here an analysis of the current situation for 91% of the now-adolescents who, at birth, were treated for PRS in two tertiary hospitals (merged today) in Paris, France. Our study benefits from a high participation rate of adolescents, who were neonates at a time when follow-up was shorter and less strict than it is today.

Overall, our results show that adolescents who were born with PRS but without cognitive impairment had a normal QoL, on average. We confirm that children with non-visible malformations have less difficulties regarding self-esteem and mood than those with visible craniofacial malformations or scars [14]. Nevertheless, in more detail, the comparison of our series to a pooled series of control patients of the same age showed worse generic QoL for our adolescents than control patients in dimensions regarding physical health and relations to others. Having non-isolated PRS was the main factor reducing generic QoL for our adolescents. Dimensions evaluating self-confidence (“self-perception,” “autonomy”) and social relations (“parent relations and home life,” “social support and peers”) were affected in adolescents for whom the medical issue remained present (non-isolated PRS). The “self-perception” and “social support and peers” dimensions reflected best what adolescents expressed in interviews with psychologists (i.e., that they have been and/or are targets of mockery from their fellow students). Also “anxiety” and “self-esteem” were the most frequently affected depression aspects of the MDI-C dimensions.

Contrary to our initial hypothesis, neither facial aesthetic nor phonatory sequelae directly affected generic QoL in our adolescents. These findings may reflect the perception of these sequelae as minor by the patients although professionals noted them. It may illustrate a good capacity for resilience, surely the result of good medical outcomes and pertinent familial and medical support. This capacity for resilience may also be reflected in the KIDSCREEN “moods and emotions” dimension, in which our adolescents scored higher than the norm.

However, more attention is needed for PRS cases with associated malformations (Stickler or others). This remains true for patients with no cognitive disability or grade retention/schooling delay because potential suffering in this population may go undetected. We feel that psychological support through childhood and adolescence is important for these patients.

Our results agree with those reported by Basart et al. in 2017 [16], the only other team to have evaluated generic QoL in adolescents with PRS. However, that study involved only 17 adolescents who completed the Pediatric Quality of Life Inventory over the Internet. Because of the lack of a psychologist to guide and deepen responses, the responses they gathered may not reflect the full breadth of their patients' perceptions. Parental presence may also have affected the responses gathered, thus reducing their value. The authors also reported a tendency toward lower values in adolescents with non-isolated than isolated PRS.

Oral QoL remains an important issue in adolescents with PRS. Indeed, the generic QoL of our adolescents was well-correlated with their oral QoL, which underlines the impact of dental and orthodontic problems on QoL and self-confidence in this setting. As in generic QoL, non-isolated PRS was a risk factor for poor oral QoL, even though the objective, professional evaluations of facial morphology, orthodontic state and phonation were not worse with non-isolated than isolated PRS. Here too, it appears that the simple awareness of having a chronic disease may have a larger impact as compared with certain objective elements describing current PRS sequelae. The oral QoL results we report here cannot be compared to other series of adolescents with PRS. They can be compared to those of an Australian study [33] of children with various types of clefting because the authors used the same tool than we did. Their children had poorer oral QoL than ours, but the proportion of children with PRS in the Australian study is not known. As we do, the previous authors underlined the link between oral and generic QoL. This shared observation calls for vigilance as to the management of oral issues in PRS patients.

Although two-thirds of our patients retained mild to moderate phonation troubles, their vocal QoL was within the norm, and was higher than those of adults with voice pathologies. Of note, in our series, children with significant phonatory sequelae had already undergone surgery. The only determinant for vocal QoL was the intensity of current phonation issues. Our results seem better than but nonetheless are in the same direction as those of studies that specifically investigated effects of velopharyngeal insufficiency (VPI) on QoL with the new VPI Effects on Life Outcomes (VELO) instrument (estimation from the child and the parent[s] themselves) [57, 58]. The VELO is not yet translated or validated in French. Correlations between VELO results and objective speech assessment by a speech therapist remain controversial [59].

Residual phonation disorders of children with PRS and CP is a major issue, with incidences ranging from 13 to 47% across series (interviewer's observations, ages at time of the assessment, specialized examinations by a speech therapist, assessment techniques, voice-correction surgery rate, etc.). Our results confirm this high frequency. Unfortunately, we identified neither early (e.g., PRS type, cleft size, surgery type) nor current (particularly socioeconomic status of the family) risk factors for these phonation disorders. Importantly, the hyperlaxity present in certain patients with Stickler syndrome did not seem to affect velopharyngeal insufficiency. We could not evaluate the quality of any speech therapy our participants may have had. Of note, results were similar for adolescents with and without secondary velopharyngeal surgery. We did not collect perioperative data on palatal muscles, the characteristics of which may play a predictive role in later phonation disorders. However, our colleagues from Trousseau hospital did so and found no predictors for phonological outcomes [26]. The difficulties we encountered for predicting velopharyngeal insufficiency or phonation disorders are shared with other authors. Those who compared phonatory sequelae in children with PRS to those with isolated CP showed a higher rate of disorders in the former but were unable to identify determinants [23, 26, 60‐64]. Recently, Logjes et al. [65] showed that the only determinant for speech sequalae in Robin sequence, as in isolated CP, was the width of the cleft. Differences across these results may be due to variable ways of measuring the type and size of the CP. The standardization of evaluation methods would be of great interest for comparing results among studies.

Facial growth may be assessed in several ways, including simple clinical observation by an experienced specialist, orthodontic examination or X-rays and angle measurements. In PRS, this aspect is essential for two reasons. The first is a question of pathophysiology. A neonatal retrognathia with an origin in bone anatomy should persist more than one with a functional origin secondary to a defect in foetal oral mobility. Thus, the course of mandible growth in these children is a retroactive diagnostic element. The second is a question of therapy. If the bone anomaly is the sequence starting point, early mandibular distraction is more justified than if not. In our assessments, 13.5% of adolescents were considered candidates for esthetical surgery, particularly for boys, because the chin plays a role in the perception of virility. However, we found no correlations between the morphological aspects in adolescence and neonatal retrognathia degree, respiratory impairment severity, or PRS type. Thus, from our findings, we are not able to identify infants who will need genioplasty at adolescence. These results suggest no anatomical justification for early mandibular distraction, and, additionally, genioplasty at adolescence is both a simple surgery and free of side effects on dentition.

The only predictor of better facial morphological results at adolescence was the two-stage surgical protocol. However, intravelar veloplasty with closure of the hard palate resulted in a higher rate of residual fistulas as compared with uranostaphylorrhaphy. In the literature, the frequency of residual fistulas after palatal surgery varies from several percentage points to 36% [26, 60, 62, 63, 66]. These secondary surgeries are sufficiently frequent to merit early parental information.

Morphological or phonatory impairments remain non-rare in adolescents with PRS, whether isolated or associated with bone or collagen disorders, but do not appear to be directly responsible for altered QoL. These adolescents show self-confidence and social-relations fragilities, especially those with non-isolated PRS, who find themselves circumscribed within the status of chronic disease. Building upon the past, when the neurological and cognitive sequelae resulting from neonatal airway obstruction were reduced, the medical community must now turn its attention to bettering long-term functional and psychological results for PRS patients by improving therapy protocols and follow-up, notably for those affecting the oral aspects of the disease.