Handbook of Genetic Counseling/Robin Sequence

Robin Sequence

Introduction

 * Robin sequence was named after the French stomatologist Pierre Robin.
 * It has typically been regarded as the association of micrognathia, wide, U-shaped cleft palate, and upper airway obstruction.
 * Robin sequence is a heterogenous disorder that most often occurs as a sequence of other syndromes.

Incidence

 * Incidence has been estimated to be approximately 1 in 2,000 live births.
 * Some babies with Robin sequence die shortly after birth because of severe airway obstruction or a variety of underlying syndromes incompatible with life (such as trisomy 13).
 * Therefore, population prevalence is slightly lower than birth incidence.

Diagnostic Criteria

 * The large majority of cases of Robin sequence are associated with other multiple-anomaly syndromes.
 * The majority of syndromes that result in Robin sequence are single-gene disorders, often inherited in an autosomal dominant manner.
 * There are also several X-linked recessive disorders and recessive disorders.
 * The most common teratogenic disorder is fetal alcohol syndrome, although phenytoin and retinoic acid have been implicated as well.
 * In one study, only 17% of Robin sequence cases were isolated.
 * Stickler syndrome and velocardiofacial syndrome are the first and second most commonly associated diagnoses.
 * An initial diagnosis of Robin sequence should be regarded as a starting point in the diagnostic search.
 * Robin sequence may be associated with mandibular anomalies other than micrognathia, including retrognathia and mandibular asymmetry.
 * It may also be caused by macroglossia and severe muscle weakness.
 * Most clinicians cite micrognathia, U-shaped cleft palate, and upper airway obstruction as the criteria for Robin sequence, but some may use only two of the features.
 * Many other anomalies may exist with this triad because Robin sequence is most often secondary to another syndrome.

Diagnostic Testing

 * There is no specific testing for Robin sequence other than observation of clinical features
 * Micrognathia and cleft palate can be detected with sonography in the fetus
 * Because Stickler syndrome and VCF account for nearly half of all cases of Robin sequence, it is appropriate to screen all newborns with Robin sequence for these disorders.

Etiology

 * Robin sequence is a sequence, not a syndrome:
 * The term syndrome is used when multiple anomalies in a single individual are caused by a single etiology.
 * The term sequence is used when an individual has multiple anomalies caused secondarily by a single known or presumed structural anomaly or error in morphogenesis; that is, it is a cascade of events.
 * The primary anomaly in Robin sequence which interrupts the normal developmental process is micrognathia or occasionally retrognathia.
 * This mandibular anomaly is present at the time that palate fusion is to begin. As a result, the tongue is not free to descend from between the vertical palatal shelves, preventing them from growing toward fusion.
 * Although the tongue may eventually descend in the oral cavity, it may do so after lateral head growth is too great for the remaining palatal growth to overcome or the period of programmed growth may be over.
 * After birth, micrognathia persists. With the mouth closed and a small or retruded mandible present, the tongue is retrodisplaced in the pharynx (glossoptosis_ which causes airway obstruction and failure to thrive.
 * The most common occurrence of a short mandibular body is in positional mandibular deformation, and extrinsic mechanical force
 * This may occur as a result of fetal crowding caused by the presence of multiple fetuses, abnormal fetal position, or uterine anomalies.
 * Associated deformations may include clubfoot, crumpled ear, or limb contractures.
 * One would not expect to find other anomalies that were not related to mechanical constriction.
 * The most common cause of retrognathia is platybasia, which draws the glenoid fossa and the temporomandibular joint backward away from the maxilla.
 * Platybasia has been observed in a number of craniofacial syndromes, most commonly is VCF.

Management

 * Growth and Feeding:
 * Babies may have marginal airways that permit sufficient respiration to sustain life, but there is difficulty maintaining the airway while feeding.
 * Failure to thrive becomes evident in the neonatal period.
 * Failure to thrive and long-term feeding problems occur in over 50% of babies with Robin sequence.
 * Respiratory sounds should be assessed by stethoscope during feeding.
 * In most cases, resolution of the airway problem results in resolution of the feeding problem.
 * Respiratory:
 * Robin sequence is typically evident at birth because of the potentially life-threatening effects of upper airway obstruction.
 * Apneic events are typically silent because the neonatal lung capacity cannot create the high negative pressures that would prompt loud noises or snoring.
 * Glossoptosis associated with micrognathia is typically suspected to be the cause of airway obstruction and apnea.
 * Other types of upper airway obstruction are hypotonic pharynx, absence of adequate muscle tone, laryngeal anomalies, or tracheomalacia.
 * Treatment depends upon the severity of the airway obstruction, which can be variable in Robin sequence.

Resources & References

 * Pierre Robin Network www.pierrerobin.org
 * American Cleft Palate-Craniofacial Association (ACPA) www.cleft.com
 * www.geneclinics.org
 * Management of Genetic Syndromes (2001) Suzanne B. Cassidy & Judith E. Allanson. pp. 323-336