Incomplete fusion of the neural tube and overlying bone, soft tissue, or skin leads to several defects varying from mild anomalies (e.g., spina bifida occulta) to severe anomalies (e.g., anencephaly). Anencephaly is a fatal autosomal recessive neural tube defect characterized by the absence of scalp, calvarium, and normal brain, which is replaced by an angiomatous mass. Central nervous system (CNS) findings include absence of the cerebral hemispheres, the spinal cord pyramidal tracts and the cerebellum. Pathological studies reveal hypoplastic pituitaries and small adrenals, deficient in a fetal zone. The thyroid, gonads, and the number of pancreatic islets are normal, but P-cell hypertrophy is often seen. Two thirds of the anencephalic fetuses die in utero, and those that are alive at birth rarely survive more that a week. The anomaly is twice as common in females as compared to males.
Some studies concluded that the recurrence of anencephaly in families are best explained by a persistent environmental factor. Recently, a homozygous missense mutation in the TRIM36 gene was identified by whole-exome sequencing in a fetus with anencephaly, where the mutation was suspected to have an impact on neural cell proliferation causing anencephaly.