Figure 1

Congenital malformations associated with VANGL2 coding sequence missense mutations. (A) Regions associated with abnormal development in patients carrying heterozygous coding sequence mutations in VANGL2. (B) Anencephaly, failure of anterior neural tube closure during primary neurulation, leading to loss of cerebellum and open cranial cavity. (C) Different forms of spina bifida arising due to failure of primary neurulation which can result in an open or closed spinal column. VANGL2 patients also display failures in secondary neurulation: tethered cord, where free movement of the spinal cord within the column is restricted, and lipoma at the base of the spinal cord (filum terminus). (D) Caudal agenesis (also known as caudal regression syndrome or sacral agenesis) is defined by the loss of the sacrococcygeal bone (brown), associated with dysplastic lower limbs and impacts other caudally located organs. (E) Diastematomyelia is the splitting of the spinal cord. (F) Failure of division of the embryonic forebrain results in holoprosencephaly.