Isolated Pierre Robin sequence

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Pierre Robin sequence is a set of abnormalities affecting the head and face, consisting of a small lower jaw (micrognathia), a tongue that is placed further back than normal (glossoptosis), and blockage (obstruction) of the airways. Most people with Pierre Robin sequence are also born with an opening in the roof of the mouth (a cleft palate). This feature is not generally considered necessary for diagnosis of the condition, although there is some disagreement among doctors.

Some people have the features of Pierre Robin sequence as part of a syndrome that affects other organs and tissues in the body, such as Stickler syndrome or campomelic dysplasia. These instances are described as syndromic. When Pierre Robin sequence occurs by itself, it is described as nonsyndromic or isolated. Approximately 20 to 40 percent of cases of Pierre Robin sequence are isolated.

This condition is described as a "sequence" because one of its features, underdevelopment of the lower jaw (mandible), sets off a sequence of events before birth that cause the other signs and symptoms. Specifically, having an abnormally small jaw affects placement of the tongue, and the abnormally positioned tongue can block the airways. In addition, micrognathia and glossoptosis affect formation of the palate during development before birth, which often leads to cleft palate.

The combination of features characteristic of Pierre Robin sequence can lead to difficulty breathing and problems eating early in life. As a result, some affected babies have an inability to grow and gain weight at the expected rate (faltering weight). In some children with Pierre Robin sequence, growth of the mandible catches up, and as adults these individuals have normal-sized chins.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Changes in the DNA near the SOX9 gene are the most common genetic cause of isolated Pierre Robin sequence. It is likely that changes in other genes, some of which have not been identified, are also involved in the condition. Doctors speculate that nongenetic factors, for example conditions during pregnancy that restrict growth of the jaw, may cause some cases of isolated Pierre Robin sequence.

The SOX9 gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX9 protein regulates the activity of other genes, especially those that are important for development of the skeleton, including the mandible.

The genetic changes near the SOX9 gene that are associated with isolated Pierre Robin sequence are thought to disrupt regions of DNA called enhancers, which normally regulate the activity of the SOX9 gene. These changes reduce SOX9 gene activity. As a result, the SOX9 protein cannot properly control the genes essential for normal development of the lower jaw, causing micrognathia, and consequently, glossoptosis, airway obstruction, and, often, cleft palate.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Isolated Pierre Robin sequence is usually not inherited. It typically results from new (de novo) genetic changes and occurs in people with no history of the disorder in their family. When the condition is inherited, it follows an autosomal dominant pattern, which means one copy of the DNA alteration in each cell is sufficient to cause the disorder.

Syndromic Pierre Robin sequence is inherited in the same pattern as the condition it is associated with.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Isolated Pierre Robin sequence affects an estimated 1 in 8,500 to 14,000 people.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Cleft palate · Very frequent (99-80%)

Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Glossoptosis · Very frequent (99-80%)

Posterior displacement of the tongue into the pharynx, i.e., a tongue that is mislocalised posteriorly.

Micrognathia · Very frequent (99-80%)

Developmental hypoplasia of the mandible.

Failure to thrive · Frequent (79-30%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Feeding difficulties in infancy · Frequent (79-30%)

Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.

Hypoxemia · Frequent (79-30%)

An abnormally low level of blood oxygen.

Neonatal respiratory distress · Frequent (79-30%)

Respiratory difficulty as newborn.

Polyhydramnios · Frequent (79-30%)

The presence of excess amniotic fluid in the uterus during pregnancy.

Other findings in the same source

From: Orphanet

Additional reported features include Upper airway obstruction (Frequent (79-30%)); Bronchomalacia (Occasional (29-5%)); Choanal atresia (Occasional (29-5%)); Cor pulmonale (Occasional (29-5%)); Cyanosis (Occasional (29-5%)); Dysphagia (Occasional (29-5%)); Elevated pulmonary artery pressure (Occasional (29-5%)); Laryngomalacia (Occasional (29-5%)); Sleep apnea (Occasional (29-5%)); Stridor (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Isolated Pierre Robin sequence is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Isolated Pierre Robin sequence. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.