Otocephaly

Otocephaly
Other names	Agnathia-otocephaly complex,[1] dysgnathia complex,[1] holoprosencephaly–agnathia,[1] Kanwar syndrome[2]
Female infant with otocephaly
Specialty	Medical genetics
Symptoms	Absence of mandible (agnathia), small or absent mouth (microstomia), fused ears below chin (synotia), holoprosencephaly
Usual onset	23rd–26th day of gestation (Carnegie stage 10)
Causes	Genetic
Diagnostic method	Prenatal ultrasound
Differential diagnosis	Treacher Collins syndrome, Goldenhar syndrome, Möbius syndrome
Prognosis	Stillbirth or miscarriage
Frequency	1:70,000

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[]

Otocephaly with cyclopia and a proboscis

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:^[2]

• Facial/musculoskeletal
  • Small (microglossia) or absent (aglossia) tongue
  • Small (microstomia) or absent (astomia) mouth
  • Cyclopia with proboscis
  • Median cleft lip and cleft palate
• Neurological
  • Holoprosencephaly
  • Agenesis of the corpus callosum
  • Anencephaly or other neural tube defects
• Organ systems
  • Situs inversus (full rotation of the internal organs)
  • Cardiac anomalies
  • Ambiguous genitalia
  • Absence of glands

Grades[]

Sewall Wright described twelve grades of otocephaly in guinea pigs.^[3] 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 modern history.^[4]

Cause[]

Otocephaly is generally a result of a de novo mutation in the gene PRRX1 on the long arm of chromosome 1.^[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.^{[citation needed]} If the offspring is carried to term, death usually occurs in minutes to hours after birth.^{[citation needed]}

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.^[3] 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.^[2]

References[]

External links[]

• NINDS Overview