Pierre Robin Sequence – Causes, Symptoms, Treatment

Pierre Robin sequence is related to several other craniofacial anomalies and may appear in conjunction with the findings characteristic of several different syndromes. Stickler syndrome, an autosomal dominant condition, is characterized by a short mandibular ramus, antegonial notching of the mandibular body, myopia, and joint problems.^[rx] Velocardiofacial syndrome is characterized by a retrognathic mandible, palatal abnormalities, hypotonia, impaired thymus development, and cardiac malformations.^[rx,rx] Craniofacial microsomia (or oculoauriculovertebral spectrum) results in anomalies of the external and middle ear, mandible, zygoma, maxilla, temporal bone, facial muscles, and palate.^[rx] Treacher Collins syndrome is notable for dysplasia affecting the zygoma, temple, ear, and mandible. It is further characterized by down slanting palpebral fissures, lower lid colobomas, facial bone hypoplasia, malformation of the external ear, macrostomia, and a high-arching palate.

Pierre-Robin Syndrome (PRS), also known as Pierre Robin sequence, is a congenital? condition that affects the lower jaw and palate. The three main features that characterize PRS are:

• cleft palate (opening in the roof of the mouth)
• severe underdevelopment of the lower jaw (retrognathia)
• glossoptosis (airway obstruction caused by backwards displacement of the tongue base)

This condition occurs in approximately 1 in 8,500 to 14,000 births, and it’s equally common in males and females. There is a higher incidence in twins, which may be due to crowding in the uterus, restricting growth of the mandible (lower jaw). PRS may occur in isolation, but it is can be part of an underlying disorder or syndrome. The most common is Stickler Syndrome.

The condition is called a sequence because it is believed the underdeveloped mandible begins a sequence of events, which leads to the abnormal displacement of the tongue and subsequent formation of a cleft palate.

Causes of Pierre Robin Sequence

An exact cause of PRS is not known. It is believed that any external factor crowds the fetus and interferes with the growth of the lower jaw. Certain neurological conditions, which lead to decreased jaw movement in utero, can also restrict jaw growth. In addition, some studies demonstrate there may be genetic anomalies at chromosomes 2, 11 or 17.

Normally, between 9 to 11 weeks of gestation, the tongue moves down and away from the roof of the mouth. This allows space for the sides of the palate to shift to the midline and close. However, in PRS the small mandible keeps the tongue positioned higher in the mouth than normal, thereby interfering with the normal closure of the palate. This typically results in a wide U-shaped cleft of the soft and part of the hard palate.

Mechanical basis

The physical craniofacial deformities of PRS may be the result of a mechanical problem in which intrauterine growth of certain facial structures are restricted, or mandibular positioning is altered.^[rx] One theory for the etiology of PRS is that, early in the first trimester of gestation, some mechanical factor causes the neck to be abnormally flexed such that the tip of the mandible becomes compressed against the sternoclavicular joint. This compression of the chin interferes with development of the body of the mandible, resulting in micrognathia. The concave space formed by the body of the hypoplastic mandible is too small to accommodate the tongue, which continues to grow unimpeded. With nowhere else to go, the base of the tongue is downwardly displaced, which causes the tip of the tongue to be interposed between the left and right palatal shelves. This in turn may result in failure of the left and right palatal shelves to fuse in the midline to form the hard palate.^[rx] This condition manifests as a cleft palate. Later in gestation (at around 12 to 14 weeks), extension of the neck of the fetus releases the pressure on the mandible, allowing it to grow normally from this point forward. At birth, however, the mandible is still much smaller (hypoplastic) than it would have been with normal development. After the child is born, the mandible continues to grow until the child reaches maturity.

Genetic basis

Alternatively, PRS may also be caused by a genetic disorder. In the case of PRS which is due to a genetic disorder, a hereditary basis has been postulated, but it usually occurs due to a de-novo mutation. Specifically, mutations at chromosome 2 (possibly at the GAD1 gene), chromosome 4, chromosome 11 (possibly at the PVRL1 gene), or chromosome 17 (possibly at the SOX9 gene or the KCNJ2 gene) have all been implicated in PRS.^[5] Some evidence suggests that genetic dysregulation of the SOX9 gene (which encodes the SOX-9 transcription factor) and/or the KCNJ2 gene (which encodes the Kir2.1 inward-rectifier potassium channel) impairs the development of certain facial structures, which can lead to PRS.^[rx][rx]

PRS may occur in isolation, but it is often part of an underlying disorder or syndrome.^[rx] Disorders associated with PRS include Stickler syndrome, DiGeorge syndrome, fetal alcohol syndrome, Treacher Collins syndrome, and Patau syndrome.^[rx]

Symptoms of Pierre Robin Sequence

PRS is commonly characterized by:

• An unusual small lower jaw (micrognathia)
• Posterior displacement or retraction of the tongue (glossoptosis), which may cause upper airway obstruction

Symptoms of this condition include:

• Cleft palate
• High-arched palate
• The jaw that is very small with a small chin
• A jaw that is far back in the throat
• Repeated ear infections
• A small opening in the roof of the mouth, which may cause choking or liquids coming back out through the nose
• Teeth that appear when the baby is born
• Tongue that is large compared to the jaw

Incomplete closure of the roof of the mouth (cleft palate) is present in the majority of patients, and is commonly U-shaped tongue that is large compared to the jaw

Diagnosis? of Pierre Robin Sequence

There’s no specific diagnostic test for PRS. Consulting with a genetic specialist can rule out other problems linked to this syndrome.

A diagnosis? is made by precise physical examination of the infant, generally right after birth. A CT scan? and sleep study may be required.

PRS can be detected while the fetus is still in the womb. Trained medical personnel may visualize characteristic features of PRS using ultrasound? imaging. If not diagnosed previously, craniofacial abnormalities are typically detected at birth on physical exam. Infants with severe airway obstruction may present with respiratory distress at birth, and may require medical intervention.

There is no one standard test that is routinely used to diagnose isolated PRS, though molecular genetic testing can be used to identify DNA changes involving the SOX9 gene.

If syndromic PRS is suspected, consultation with a geneticist is highly recommended. This healthcare professional may carry out a laboratory workup in support of the suspected condition.

The diagnosis? is most often made when your doctor sees the symptoms described above during an exam. Those findings are confirmed with further testing, which may include:

• CT (computed tomography) scan
• Sleep study
• In some cases an airway evaluation by Otolaryngology / ENT

Treatment of Pierre Robin Sequence

A multidisciplinary team approach is highly recommended for the proper management of PRS. The goal of treatment is to focus on breathing and feeding and optimizing growth and nutrition despite the predisposition for breathing difficulties. If there is evidence of airway obstruction (snorting breathing, apnea, difficulty taking a breath, or drops in oxygen), then the infant should be placed in the side or prone position, which helps bring the tongue base forward in many children.

In moderate cases, the patient will need to have a tube placed through the nose and into the airways to avoid airway blockage. In severe cases, surgery is needed to prevent a blockage in the upper airway. This is often done by distraction osteogenesis of the lower jaw, which stretches the tissue and grows new bone to make a larger jaw. In rare cases, patients need surgery to make a hole in the windpipe (tracheostomy) because the breathing problems are so severe.

Surgery will be needed to repair the cleft palate and this is done between 9 and 12 months of age, depending on the overall health of the child.

Living & Managing

Children affected with PRS usually reach full development and size. Infants with this condition should NOT be put on their back, to prevent the tongue from falling back into the airway.

Most children have normal speech after palate repair, but some will require speech therapy or a second operation later on to improve speech.

Feeding must be done very carefully to avoid choking and aspirating liquid into the airway.

Some complications that may occur are:

• Breathing difficulties, especially when the child sleeps
• Choking episodes
• Feeding difficulties
• Low blood oxygen and brain damage (due to difficulty breathing)

References