International Journal of Infertility & Fetal Medicine

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VOLUME 12 , ISSUE 2 ( May-August, 2021 ) > List of Articles


Otocephaly: Agnathia-Microstomia-Synotia Syndrome

Tanya T Kitova, Borislav D Kitov

Citation Information : Kitova TT, Kitov BD. Otocephaly: Agnathia-Microstomia-Synotia Syndrome. Int J Infertil Fetal Med 2021; 12 (2):40-43.

DOI: 10.5005/jp-journals-10016-1195

License: CC BY-NC 4.0

Published Online: 29-07-2021

Copyright Statement:  Copyright © 2021; The Author(s).


The aim of the study is to present otocephaly, which is a rare congenital lethal malformation. Until this moment, only a little bit more than 100 cases worldwide were reported, and only 22 cases of prediagnosed otocephaly. Background: Otocephaly or agnathia-microstomia-synotia syndrome (SAMS) is characterized by agenesis of mandible (agnathia), disposition or fusion of the auricle (synotia), microstomia, and complete or partial lack of language (aglossia), which often ends up lethal. Case description: A 499.7 g male fetus was obtained after a therapeutic abortion during the 23rd gestational week at the Center for Maternity and Neonatology, Embryo-fetopathology Clinic, Tunis, Tunisia. The mother is an 18-year-old with close relative marriage with first-degree incest, primigravida. Examination of the fetus revealed microcephaly with craniosynostosis, hypertelorism, closed eyelid exophthalmos, one nostril, point microstomia, mandibular agenesis, bilateral, and auditory cysts of neck. The ears are located at the level of the neck. A study of the brain and the base of the skull revealed holoprosencephaly and sphenoid bone agenesis. There are no internal organ abnormalities. Conclusion: In cases where, at the end of the second trimester of pregnancy, polyhydramnios is detected, inability to visualize the mandible, and malposition of ears, otocephaly should be suspected. In these cases, the decision to interrupt pregnancy should be taken by a multidisciplinary team, after an magnetic resonance imaging, which is much better in visualizing location of the ears and other facial malformations and the presence of other associated anomalies. Clinical significance: Otocephaly (SAMS) is usually incompatible with life, which is why it is important to perform prenatal diagnosis in order to make prognosis for pregnancy.

  1. Hwang K-S, Ding D-C, Chang Y-K, et al. Otocephaly. Chin Med Assoc 2007;70(7):298–301. DOI: 10.1016/S1726-4901(07)70009-6.
  2. Gekas J, Li B, Kamnasaran D. Current perspectives on the etiology of agnathia-otocephaly. Eur J Med Genet 2010;53(6):358–366. DOI: 10.1016/j.ejmg.2010.09.002.
  3. Krassikoff N, Sekhon GS. Familial agnathia–holoprosencephaly caused by an inherited unbalanced translocation and not autosomal recessive inheritance. Am J Med Genet 1989;34(2):255–257. DOI: 10.1002/ajmg.1320340227.
  4. Faye-Petersen O, David E, Rangwala N, et al. Otocephaly: report of five new cases and a literature review. Fetal Pediatr Pathol 2006;25(5):277–296. DOI: 10.1080/15513810601123417.
  5. Ibba RM, Zoppi MA, Floris M, et al. Otocephaly: prenatal diagnosis of a new case and etiopathogenetic considerations. Am J Med Genet 2000;90(5):427–429. DOI: 10.1002/(SICI)1096-8628(20000228)90:5<427::AID-AJMG13>3.0.CO;2-5.
  6. Sergi C, Kamnasaran D. PRRX1 is mutated in a fetus with agnathia–otocephaly. Clin Genet 2011;79(3):293–295. DOI: 10.1111/j.1399-0004.2010.01531.x.
  7. Çelik T, Simsek P, Sozen T, et al. PRRX1 is mutated in an otocephalic newborn infant conceived by consanguineous parents. Clin Genet 2012;81(3):294–297. DOI: 10.1111/j.1399-0004.2011.01730.x.
  8. Dasouki M, Andrews B, Parimi P, et al. Recurrent agnathia–otocephaly caused by DNA replication slippage in PRRX1. Am J Med Genet A 2013;161A(4):803–808. DOI: 10.1002/ajmg.a.35879.
  9. Hisaba WJ, Milani HJF, Júnior EA, et al. Agnathia-otocephaly: Prenatal diagnosis by two- and three-dimensional ultrasound and magnetic resonance imaging. Case report. Med Ultrason 2014;16(4):377–379.
  10. O’Neill BM, Alessi AS, Petti NA. Otocephaly or agnathiasynotia-microstomia syndrome: report of a case. J Oral Maxillofac Surg 2003;61(7):834–837. DOI: 10.1016/S0278-2391(03)00160-5.
  11. Blaas HGK, Eriksson AG, Salvesen KÅ, et al. Brains and faces in holoprosencephaly: pre and postnatal description of 30 cases. Ultrasound Obstet Gynecol 2002;19(1):24–38. DOI: 10.1046/j.0960-7692.2001.00154.x.
  12. Jagtap SV, Saini N, Jagtap S, et al. Otocephaly: agnathia- microstomia-synotia syndrome– a rare congenital anomaly. J Clin Diagnos Res 2015;9(9):ED03–ED04. DOI: 10.7860/JCDR/2015/13636.6444.
  13. Hide T, Hatakeyama J, Kimura-Yoshida C, et al. Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice. Development 2002;129:4347–4357.
  14. Kajiwara K, Tanemoto T, Nagata C, et al. Prenatal diagnosis of isolated agnathia-otocephaly: a case report and review of the literature. Case Rep Obstet Gynecol 2016. 8512351. DOI:
  15. Chen C-P, Chang T-P, Huang J-K, et al. Early second-trimester diagnosis of fetal otocephaly. Ultrasound Obstet Gynecol 2007;29(4):470–471. DOI: 10.1002/uog.3956.
  16. Rotten D, Levaillant JM. Two- and three-dimensional sonographic assessment of the fetal face. A systematic analysis of the normal face. Ultrasound Obstet Gynecol 2004;23(3):224–231. DOI: 10.1002/uog.984.
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