Current perspectives on the etiology of agnathia-otocephaly

Eur J Med Genet. 2010 Nov-Dec;53(6):358-66. doi: 10.1016/j.ejmg.2010.09.002. Epub 2010 Sep 16.


Agnathia-otocephaly, a rare, sporadic and lethal malformation, is characterized by microstomia (small mouth), aglossia (absence of the tongue), agnathia (absence of the lower jaw) and abnormally positioned ears. It is a principal anomaly derived from the first pharyngeal arch as a consequence of failed mesenchymal migration of the maxillary prominence and atrophy in the development of the mandibular prominences. Unfortunately, these patients have poor prognoses and may succumb to death shortly after birth due to respiratory problems if appropriate airway management is not implemented. Difficulties persist in the prenatal diagnosis of agnathia-otocephalic patients. However, two- and three-dimensional ultrasonography, computed tomography and magnetic resonance imaging technologies now offer significant improvements in refining the resolution of distinctive facial anomalies. This complex disorder can be attributed to both genetic and teratogenic causes, in addition to other unidentifiable factors. Furthermore, studies in model organisms, in particular mice, have unraveled potential genetic pathways that may contribute to the etiology. This article highlights current perspectives on agnathia-otocephaly with a focus on the etiological causes and issues concerning prenatal diagnosis, differential diagnosis, prognosis and genetic counseling. Finally, studies using animal models especially genetically engineered mice are described to comprehend the molecular genetic interactions that may occur during the genesis of this intriguing craniofacial birth defect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / diagnostic imaging*
  • Airway Management
  • Animals
  • Branchial Region / abnormalities
  • Branchial Region / diagnostic imaging*
  • Ear / abnormalities
  • Ear / diagnostic imaging*
  • Face / abnormalities
  • Face / diagnostic imaging*
  • Female
  • Fetal Diseases / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • Mandible / abnormalities
  • Mandible / diagnostic imaging*
  • Maxillofacial Abnormalities / diagnostic imaging*
  • Mice
  • Mice, Transgenic
  • Microstomia / diagnostic imaging*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Syndrome
  • Tomography, X-Ray Computed
  • Tongue / abnormalities
  • Tongue / diagnostic imaging*
  • Ultrasonography, Prenatal