Isolated Pierre Robin syndrome (ORPHA:718)
A rare, congenital head and neck malformation characterized by the association of retrognathia and glossoptosis, with or without cleft palate, and respiratory obstruction.
Epidemiology
The prevalence of this syndrome has been estimated at 1 in 10 000 births. However, precise values are difficult to obtain because historically the definition varied and studies often included cases which occurred as part of a recognised syndrome.
Clinical description
.Isolated Pierre Robin sequence (PRS), occurring without any other associated malformation, constitutes about 50% of cases presenting with these orofacial malformations. At birth and during the first weeks of life, the main troubles are functional and include upper airway obstruction, difficulties in respiration, poor sucking and swallowing, reflux, oesophageal motor anomalies, and vagal syncope.
Etiology
This condition is referred to as a sequence because the posterior cleft palate is a secondary defect associated with abnormal mandibular development and glossoptosis. Mandibular hypoplasia, occurring early in gestation, causes the tongue to be maintained high-up in the oral cavity, preventing normal fusion of the palatal shelves (secondary palate). The mandibular growth defect can be either the consequence of antenatal orofacial hypomobility (usually related to a brainstem dysfunction, or from peripheral origin), or the consequence of a primary growth defect from tissue origin (bone, connective tissue). Molecular identification of isolated PRS is rare. Only mutations in regulatory elements upstream from SOX9 were identified in families with PRS.
Diagnostic methods
Pierre-Robin sequence is usually diagnosed at birth based on clinical presentation. It is more and more often evoked during prenatal life.
Differential diagnosis
PRS often occurs as part of a complex malformation syndrome. The nature of these anomalies is heterogeneous but they are most commonly collagenopathies, first arch anomalies, various chromosomal disorders (including microdeletion 22q11), phenocopy syndromes associated with toxic agents (alcohol, sodium valproate) and other more complicated associations.
Antenatal diagnosis
Prenatal diagnosis is possible if the retrognathia is detected on the strict profile of the fetus at ultrasound. Several angle measures may help discern retrognathia, leading to screening of the cleft palate and the tongue position (posterior and high-up in the oral cavity). An excess of amniotic fluid is a good diagnostic indicator.
Genetic counseling
The majority of cases occur sporadically; however, approximately 10% cases are familial (mainly dominant). Genetic counselling is subtle and should be offered to all families, even in the event of sporadic cases, by expert teams.
Management and treatment
Most of the time, respiratory and feeding problems resolves during the first year of life. The growth of the mandible leads to correction of retrognathia and tongue position within the first years. In cases of mandibulofacial dysostosis, surgery of the mandible may be necessary. The cleft palate is corrected by surgical intervention (one or two steps) before the age of one year. However, the persistent risk of otitis, transmission hearing loss and phonation difficulties necessitate follow-up by an ear, nose and throat specialist, and speech therapist.
Prognosis
For patients with isolated PRS, the prognosis is very favourable.

                            Last update: 
                            June 2020


                            - Expert reviewer(s): 
                            Pr Véronique ABADIE