Auriculocondylar syndrome

Description

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.

Frequency

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

Causes

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

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.

Autosomal dominant inheritance with a new (de novo) mutation. Credit: U.S. National Library of Medicine.

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.

Autosomal recessive inheritance. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• Auriculo-condylar syndrome
• Dysgnathia complex
• Question-mark ear syndrome

Where this page came from

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