What are the other Names for this Condition? (Also known as/Synonyms)

• Glossoptosis, Micrognathia, and Cleft Palate
• Pierre-Robin Syndrome

What is Pierre-Robin Sequence? (Definition/Background Information)

• Pierre Robin Sequence is a condition present at birth, in which the infant has a smaller than normal lower jaw (micrognathia), a tongue that is placed further back than normal (glossoptosis), and an opening in the roof of the mouth (cleft palate)
• This combination of features can lead to difficulty breathing and problems with eating early in life. Pierre Robin Sequence may occur alone (isolated) or be associated with a variety of other signs and symptoms (described as syndromic). In about 20 to 40 percent of cases, the condition occurs alone
• The exact causes of Pierre Robin Syndrome are unknown. Changes (mutations) in the DNA near the SOX9 gene are the most common genetic cause of isolated cases of Pierre Robin Sequence
• Treatment is focused on the specific needs of each patient, but may include surgery to assist with breathing and feeding modifications to prevent choking

(Source: Pierre-Robin Sequence; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Pierre-Robin Sequence? (Age and Sex Distribution)

• Pierre-Robin Sequence is a congenital disorder, estimated to occur at an incidence of 1 in 10,000 births
• The onset of symptoms may occur at birth
• Both males and females may be affected
• Individuals belonging to all races and ethnicities may be affected worldwide

What are the Risk Factors for Pierre-Robin Sequence? (Predisposing Factors)

The risk factors for Pierre-Robin Sequence may include:

• A positive family history 
• Low amniotic fluid volume during gestation

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pierre-Robin Sequence? (Etiology)

The exact causes of Pierre Robin sequence are presently unknown.

• Possible mechanisms for the sequence include
  • Genetic causes
  • Low volume of amniotic fluid (oligohydramnios), which may limit chin growth
  • Weakness of the facial muscles (myotonia)
  • Connective tissue disease
• The genetic causes for some of the isolated cases (Pierre Robin Sequence without any associated malformations) may include mutations or deletions of parts of the DNA neighboring the SOX9 gene located in chromosome 17 (17q24)
• This gene provides instructions for making a protein (protein SOX9) that plays an important role in the formation of many different tissues and organs during embryonic development
• The SOX9 protein regulates the activity of other genes, especially those involved in the development of the skeleton, including the jaw
• In about 37% of cases, Pierre Robin occurs as part of a syndrome with multiple malformations
• Pierre Robin Sequence has been reported as occurring in association with Stickler syndrome (20%-25% of these cases), campomelic dysplasia, trisomy 11q syndrome, deletion 4q syndrome, CHARGE association, velocardiofacial syndrome, and Treacher-Collins syndrome

(Source: Pierre-Robin Sequence; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Pierre Robin Sequence may follow an autosomal recessive mode of inheritance

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Pierre-Robin Sequence?

The signs and symptoms of Pierre-Robin Sequence may include:

• Cor pulmonale
• Feeding difficulties in infancy

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Cleft palate 
• Glossoptosis
• Micrognathia postaxial hand polydactyly

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the pharynx
• Neonatal respiratory distress
• Upper airway obstruction

(Source: Pierre-Robin Sequence; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Pierre-Robin Sequence Diagnosed?

Pierre-Robin Sequence is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Prenatal diagnosis, if retrognathism is detected at ultrasound

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pierre-Robin Sequence?

The complications of Pierre-Robin Sequence may include:

• Failure to thrive
• Choking

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Pierre-Robin Sequence Treated?

There is no cure for Pierre-Robin Sequence, since it is a genetic condition.

• The treatment is usually given to manage the signs and symptoms and any complication that develops
• Treatment methods may include surgery to correct cleft palate and speech therapy

How can Pierre-Robin Sequence be Prevented?

Currently, Pierre-Robin Sequence may not be preventable, since it is a congenital disorder.

• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Pierre-Robin Sequence? (Outcomes/Resolutions)

• The prognosis of Pierre-Robin Sequence that occurs by itself is good, if treatment to is undertaken within the first year of life
• If the condition occurs as part of a syndrome (such as velocardiofacial syndrome and Treacher-Collins syndrome), the outcomes may be determined by the severity of signs, symptoms, and complications associated with the syndrome
• In most cases, the prognosis may be only assessed on a case-by-case basis

Additional and Relevant Useful Information for Pierre-Robin Sequence:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/