Auriculocondylar syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Auriculocondylar syndrome is a condition that affects facial development, particularly the development of the ears and lower jaw (mandible). The features seen in people with this condition can vary, even among members of the same family.

A hallmark of this condition is an ear abnormality called a question mark ear, in which the ears have a distinctive question mark shape that is caused by a split that separates the upper part of the ear from the earlobe. Other ear abnormalities that can occur in people with auriculocondylar syndrome include cupped ears, ears with fewer folds and grooves than usual, narrow ear canals, small skin tags in front of or behind the ears, and ears that are rotated backward. Some affected individuals also have hearing loss.

Affected individuals often have a small lower jaw (micrognathia), which is caused by the underdevelopment of the upper portion of the mandible (condyle). These abnormalities can impair the function of the temporomandibular joint (TMJ), which connects the lower jaw to the skull. Problems with the TMJ affect how the upper and lower jaws fit together and can make it difficult to open and close the mouth. Because micrognathia often causes problems with breathing, many infants with auriculocondylar syndrome will need a breathing tube.

Other features of auriculocondylar syndrome can include prominent cheeks, an unusually small mouth (microstomia), a tongue that is placed further back in the mouth than normal (glossoptosis), differences in the size and shape of facial features between the right and left sides of the face (facial asymmetry), and an opening in the roof of the mouth (cleft palate). In rare cases, people with auriculocondylar syndrome have developmental delays and intellectual disabilities.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in several genes, including the GNAI3, EDN1, and PLCB4 genes, can cause auriculocondylar syndrome. These genes provide instructions for making proteins that are involved in chemical signaling. These proteins help transmit information from the outside of the cell to the inside of the cell. This information helps the cell to grow, divide, or take on specialized functions.

Studies suggest that the proteins produced from the GNAI3, EDN1, and PLCB4 genes are involved in a signaling pathway that regulates the movement (migration) and maturation (differentiation) of cells called neural crest cells. During early development, the neural crest cells that are regulated by this signaling pathway form the first and second pharyngeal arches, which ultimately become the jawbones, the muscles that create facial expressions, the inner and outer ears, and other bones and tissues of the head and face.

The GNAI3, EDN1, and PLCB4 gene variants that cause auriculocondylar syndrome cause cells to produce proteins that do not function properly. These altered proteins impair the migration and differentiation of neural crest cells, leading to abnormalities of the structures that are formed from the first and second pharyngeal arches.

Variants have not been found in everyone who has the characteristic features of auriculocondylar syndrome. In these cases, the cause of the condition is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Auriculocondylar syndrome is typically caused by variants in the GNAI3 or PLCB4 gene that are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some cases of auriculocondylar syndrome result from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Some people who have one of the gene variants that are associated with auriculocondylar syndrome never develop features of the condition. This is known as reduced penetrance. It is not clear why some people with an altered gene develop the signs and symptoms of auriculocondylar syndrome, while other people with an altered gene do not.

This condition can also be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. Typically, the parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they do not show signs and symptoms of the condition. Cases of auriculocondylar syndrome that are caused by changes in the EDN1 gene and some cases that are caused by changes in the PLCB4 gene are inherited in an autosomal recessive pattern.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Auriculocondylar syndrome appears to be a rare disorder. Fewer than 100 affected individuals have been described in the medical literature.

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.

Abnormal pinna morphology · Very frequent (99-80%)

An abnormality of the pinna, which is also referred to as the auricle or external ear.

Cleft helix · Very frequent (99-80%)

A notched form of the helix of the ear. That is, a defect in the continuity of the helix, which may occur at any point along its length.

Mandibular condyle hypoplasia · Very frequent (99-80%)

Abnormal pinna morphology · Frequent (79-30%)

An abnormality of the pinna, which is also referred to as the auricle or external ear.

Abnormality of the crus of the helix · Frequent (79-30%)

An abnormality of the crus of the helix, which is the horizontal piece of cartilage located outside the ear canal that divides the upper and lower parts of the ear.

Abnormality of the temporomandibular joint · Frequent (79-30%)

An anomaly of the temporomandibular joint.

Aplasia/Hypoplasia of the external ear · Frequent (79-30%)

The presence of aplasia or developmental hypoplasia of all or part of the external ear.

Bifid uvula · Frequent (79-30%)

Uvula separated into two parts most easily seen at the tip.

Other findings in the same source

From: Orphanet

Additional reported features include Cleft palate (Frequent (79-30%)); Dental crowding (Frequent (79-30%)); Dental malocclusion (Frequent (79-30%)); Facial asymmetry (Frequent (79-30%)); Full cheeks (Frequent (79-30%)); Glossoptosis (Frequent (79-30%)); Micrognathia (Frequent (79-30%)); Narrow mouth (Frequent (79-30%)); Obstructive sleep apnea (Frequent (79-30%)); Periauricular skin pits (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Auriculocondylar syndrome 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 Auriculocondylar syndrome. 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.