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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.
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.
Other Names for This Condition
- Auriculo-condylar syndrome
- Dysgnathia complex
- Question-mark ear syndrome
Additional Information & Resources
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Gordon CT, Petit F, Kroisel PM, Jakobsen L, Zechi-Ceide RM, Oufadem M, Bole-Feysot C, Pruvost S, Masson C, Tores F, Hieu T, Nitschke P, Lindholm P, Pellerin P, Guion-Almeida ML, Kokitsu-Nakata NM, Vendramini-Pittoli S, Munnich A, Lyonnet S, Holder-Espinasse M, Amiel J. Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears. Am J Hum Genet. 2013 Dec 5;93(6):1118-25. doi: 10.1016/j.ajhg.2013.10.023. Epub 2013 Nov 21. Citation on PubMed
- Gordon CT, Vuillot A, Marlin S, Gerkes E, Henderson A, AlKindy A, Holder-Espinasse M, Park SS, Omarjee A, Sanchis-Borja M, Bdira EB, Oufadem M, Sikkema-Raddatz B, Stewart A, Palmer R, McGowan R, Petit F, Delobel B, Speicher MR, Aurora P, Kilner D, Pellerin P, Simon M, Bonnefont JP, Tobias ES, Garcia-Minaur S, Bitner-Glindzicz M, Lindholm P, Meijer BA, Abadie V, Denoyelle F, Vazquez MP, Rotky-Fast C, Couloigner V, Pierrot S, Manach Y, Breton S, Hendriks YM, Munnich A, Jakobsen L, Kroisel P, Lin A, Kaban LB, Basel-Vanagaite L, Wilson L, Cunningham ML, Lyonnet S, Amiel J. Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. J Med Genet. 2013 Mar;50(3):174-86. doi: 10.1136/jmedgenet-2012-101331. Epub 2013 Jan 12. Citation on PubMed
- Guion-Almeida ML, Kokitsu-Nakata NM, Zechi-Ceide RM, Vendramini S. Auriculo-condylar syndrome: further evidence for a new disorder. Am J Med Genet. 1999 Sep 10;86(2):130-3. doi: 10.1002/(sici)1096-8628(19990910)86:23.0.co;2-o. Citation on PubMed
- Guion-Almeida ML, Zechi-Ceide RM, Vendramini S, Kokitsu-Nakata NM. Auriculo-condylar syndrome: additional patients. Am J Med Genet. 2002 Oct 1;112(2):209-14. doi: 10.1002/ajmg.10631. Citation on PubMed
- Li Q, Jiang Z, Zhang L, Cai S, Cai Z. Auriculocondylar syndrome: Pathogenesis, clinical manifestations and surgical therapies. J Formos Med Assoc. 2023 Sep;122(9):822-842. doi: 10.1016/j.jfma.2023.04.024. Epub 2023 May 17. Citation on PubMed
- Liu X, Sun W, Wang J, Chu G, He R, Zhang B, Zhao Y. Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report. BMC Pregnancy Childbirth. 2021 Nov 17;21(1):780. doi: 10.1186/s12884-021-04238-x. Citation on PubMed
- Masotti C, Oliveira KG, Poerner F, Splendore A, Souza J, Freitas Rda S, Zechi-Ceide R, Guion-Almeida ML, Passos-Bueno MR. Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity. Eur J Hum Genet. 2008 Feb;16(2):145-52. doi: 10.1038/sj.ejhg.5201955. Epub 2007 Nov 14. Citation on PubMed
- McGowan R, Murday V, Kinning E, Garcia S, Koppel D, Whiteford M. Novel features in auriculo-condylar syndrome. Clin Dysmorphol. 2011 Jan;20(1):1-10. doi: 10.1097/MCD.0b013e32833e56f5. Citation on PubMed
- Rieder MJ, Green GE, Park SS, Stamper BD, Gordon CT, Johnson JM, Cunniff CM, Smith JD, Emery SB, Lyonnet S, Amiel J, Holder M, Heggie AA, Bamshad MJ, Nickerson DA, Cox TC, Hing AV, Horst JA, Cunningham ML. A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. Am J Hum Genet. 2012 May 4;90(5):907-14. doi: 10.1016/j.ajhg.2012.04.002. Citation on PubMed or Free article on PubMed Central
- Romanelli Tavares VL, Zechi-Ceide RM, Bertola DR, Gordon CT, Ferreira SG, Hsia GS, Yamamoto GL, Ezquina SA, Kokitsu-Nakata NM, Vendramini-Pittoli S, Freitas RS, Souza J, Raposo-Amaral CA, Zatz M, Amiel J, Guion-Almeida ML, Passos-Bueno MR. Targeted molecular investigation in patients within the clinical spectrum of Auriculocondylar syndrome. Am J Med Genet A. 2017 Apr;173(4):938-945. doi: 10.1002/ajmg.a.38101. Citation on PubMed
- Storm AL, Johnson JM, Lammer E, Green GE, Cunniff C. Auriculo-condylar syndrome is associated with highly variable ear and mandibular defects in multiple kindreds. Am J Med Genet A. 2005 Oct 1;138A(2):141-5. doi: 10.1002/ajmg.a.30883. Citation on PubMed
- Yanagi K, Morimoto N, Iso M, Abe Y, Okamura K, Nakamura T, Matsubara Y, Kaname T. A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1. J Hum Genet. 2021 Oct;66(10):1029-1034. doi: 10.1038/s10038-021-00915-z. Epub 2021 Mar 15. Citation on PubMed
- Zhang Y, Zhao Y, Dai L, Liu Y, Shi Z. Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature. Mol Genet Genomic Med. 2024 Apr;12(4):e2441. doi: 10.1002/mgg3.2441. Citation on PubMed
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