Genetic disorders

Pierre Robin Sequence

Georgia Christakis

Florida State University College of Medicine, Daytona Beach

Kendall Riley, MD

University of Florida College of Medicine, Gainesville

Paul Christakis, MD

Christakis Pediatrics, Boca Raton, Florida

Lea Parsley, MD

Florida State University College of Medicine, Tallahassee

A 32-year-old gravida 1 mother delivered a girl at 40 weeks’ gestation via normal spontaneous vaginal delivery after an uncomplicated pregnancy. At birth, the neonate was noted to have micrognathia, cleft palate, pectus excavatum, and metatarsus varus. 

There was no history of illness or teratogenic exposure during pregnancy. Fetal ultrasonograms showed a small chin but no other abnormalities. Amniocentesis results were normal. Family histories were noncontributory, and there is no history of consanguinity. 

Results of a brain ultrasonogram were normal, and the infant passed her newborn hearing screening test. The infant struggled to gain weight due to poor feeding secondary to micrognathia, and discharge was delayed until day of life 11, after she had shown adequate weight gain.

Blood chromosome analysis revealed a variant on chromosome 20, 46,XX,var(20)(q11.2). Chromosomal microarray analysis was recommended in order to assess whether this variant was pathogenic or benign. The girl received a tentative diagnosis of Pierre Robin sequence pending the results of a workup for a genetic syndrome.


Pierre Robin sequence is described as a triad of glossoptosis, mandibular hypoplasia, and cleft palate.1 It is believed to occur as a result of mandibular hypoplasia initiating a series of events by interfering with placement of the tongue and formation of the palate during prenatal development. The ultimate result of this is glossoptosis (the tongue set far back in the mouth) and cleft palate.2 These craniofacial abnormalities often lead to poor suck and occlusion of the larynx, which may be life-threatening.3

Related Genetic Conditions

Pierre Robin sequence can occur as an isolated event from a de novo mutation; however, 60% to 80% of cases are associated with known genetic mutations.2 These mutations most commonly are autosomal dominant and associated with collagen development, and they may have other manifestations in addition to craniofacial abnormalities.

Stickler syndrome: In addition to glossoptosis, respiratory obstruction, and mandibular hypoplasia, patients with Stickler syndrome have myopia, retinal detachment, hearing loss, and mild short stature. The face may appear flattened due to hypoplasia of the bones of the middle of the face. An autosomal dominant mutation is present on the COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 genes that coding for collagen development.4

Campomelic dysplasia: This disorder is due to an autosomal dominant inheritance of the SOX9 gene, leading to a loss of cartilage development. It typically manifests as short stature, campomelia, hearing loss, and scoliosis, in addition to Pierre Robin sequence.1

Velocardiofacial syndrome: This condition, also called DiGeorge syndrome, results from a deletion in band 22q11 and involves congenital heart defects, hypocalcemia and seizures, thymic hypoplasia, and distinctive craniofacial features including mild microcephaly and/or cleft palate.5

Trisomy 18 syndrome: Also called Edward syndrome, trisomy 18 is one of the most common trisomies, affecting 1 in 8,000 live births. It often is apparent early in pregnancy. In addition to micrognathia, infants are born with a prominent occiput, microcephaly, low-set ears, and renal and cardiac defects. Survival rates are very low, and many pregnancies do not reach term.6

Numerous other genetic conditions have been identified that may present with Pierre Robin sequence. It is critical to obtain a genetic consultation when meeting a patient with this triad. Other diagnoses to consider include spondyloepiphyseal dysplasia congenita, Kniest dysplasia, Marshall syndrome, Catel-Manzke syndrome, Toriello Carey syndrome, and Treacher Collins syndrome.1

Pierre Robin Sequence Management

Complications stem largely from the infant’s inability to maintain a patent airway or produce a strong suck.

In mild cases, prone positioning alone may be sufficient to maintain patency of the airway by allowing the tongue to move forward and out of the way. If this is not effective or sufficient, continuous positive airway pressure, tongue-lip adhesion, and the use of a nasopharyngeal airway may improve patency. Tracheotomy should be reserved for cases in which all other respiratory interventions have failed.7 Surgical distraction of the mandible, or distraction osteogenesis, eventually can be performed to move the jaw forward and enhance the patency of the airway.

Feeding difficulties for infants with Pierre Robin sequence include poor suck due to the presence of a cleft palate, and special care must be taken to ensure adequate caloric intake and growth. Special bottle-feeding nipples can be employed to bypass the cleft palate and deposit formula to the back of the mouth, where it is more likely to reach the esophagus. Home health care providers can assist in feedings and ensure formula is deposited in the mouth beyond the cleft palate. Nevertheless, failure to thrive and malnutrition still are common problems due to the great amount of energy expended with breathing and feeding. Therefore, high-calorie formula should be employed and, if necessary, nasogastric feedings should be used.

In the case described here, results of fluorescence in situ hybridization testing were negative for 22q11 deletion, ruling out DiGeorge syndrome. The infant received a definitive diagnosis of Pierre Robin sequence, and plans were made for craniofacial correction procedures to advance the jaw forward. A full ophthalmologic examination was to be completed before the infant’s first birthday to evaluate for evidence of retinal pathology. In the meantime, physical therapists and occupational therapists worked with the patient and family to assist with feedings and ensure proper weight gain.


1. Tan TY, Kilpatrick N, Farlie PG. Developmental and genetic perspectives on Pierre Robin sequence. Am J Med Genet C Semin Med Genet. 2013;163C(4):295-305.

2. Tan TY, Farlie PG. Rare syndromes of the head and face—Pierre-Robin sequence. Wiley Interdiscip Rev Dev Biol. 2013;2(3):369-377.

3. Albanese CT, Sylvester KG. Pediatric surgery. In: Doherty GM, ed. Current Diagnosis and Treatment: Surgery. 13th ed. New York, NY: McGraw-Hill; 2010:chap 43.

4. Stickler syndrome. Genetics Home Reference. Reviewed January 2013. Accessed September 9, 2014.

5. Tsai AC-H, Manchester DK, Elias ER. Genetics and dysmorphology. In: Hay WW Jr, Levin MJ, Deterding RR, Abzug MJ, Sondheimer JM, eds. Current Diagnosis and Treatment: Pediatrics. 21st ed. New York, NY: McGraw-Hill; 2012:chap 37.

6. Genetics. In: Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY, eds. Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010:chap 12.

7. Daniel M, Bailey S, Walker K, et al. Airway, feeding and growth in infants with Robin sequence and sleep apnoea. Int J Pediatr Otorhinolaryngol. 2013;77(4):499-503.