Otocephaly

Otocephaly, also known as agnathia–otocephaly complex, is a very rare and lethal cephalic disorder characterized by the absence of the mandible (agnathia), with the ears fused together just below the chin (synotia). It is caused by a disruption to the development of the first branchial arch. It occurs in every 1 in 70,000 embryos.
Signs and symptoms.
The disorder is characterised by the absence of the mandible (agnathia), with the ears fused together just below the chin (synotia). In addition to agnathia and synotia, other symptoms that may manifest in otocephaly include:
Grades.
Sewall Wright described twelve grades of otocephaly in guinea pigs. Grades 1 to 5 were isolated agnathia with no neurological defects. Grades 6 to 9 featured severe holoprosencephaly. Grades 10 to 12 featured aprosopus (absence of the face and most of the head) with absence of the prosencephalon and mesencephalon. One human case corresponding to a high Wright grade has been reported in .
Cause.
Otocephaly is generally a result of a de novo mutation in the gene "PRRX1" on the long arm of chromosome 1. Autosomal trisomies, while prevalent in related conditions like cyclopia, are uncommon in otocephaly.
Development.
During early embryogenesis, many different organ systems begin development. Any disruption in these processes results in complex malformation that usually results in death. The first branchial arch will normally develop around the 23rd to 26th day of gestation, also known as Carnegie stage 10. Usually, failure of this will result in isolated agnathia, but otocephaly may occur in exceptional circumstances. After agenesis of the first branchial arch, no cure is possible.
Prognosis.
In almost all cases, fetuses with otocephaly are naturally or electively aborted before birth. If the offspring is carried to term, death usually occurs in minutes to hours after birth.
History.
Otocephaly was first described in 1717 by Dutch scientist Theodor Kerckring. In 1933, evolutionary biologist Sewall Wright performed a study on otocephaly on guinea pigs and gave otocephaly its name. The name comes from the Greek-derived New Latin prefix "oto-" ("ear") and the suffix "-cephaly" ("head").
In 2018, Indian neonatologist Kanwar Singh and his associates described a severe case of otocephaly with cyclopia, agnathia, complete astomia and synotia. They termed this severe presentation Kanwar syndrome.