Microcephaly occurs in many conditions. Smith’s book on recognizable patterns of human malformation lists microcephaly as a frequent finding in 42 syndromes and as an occasional finding in 33 more. The differential diagnosis of congenital microcephaly can be approached by categorizing each patient in one of the following groups: (1) neonates with dysmorphic facial features and normal karyotype; (2) neonates with dysmorphic facial features and abnormal karyotype; (3) neonates with normal facial features and elevated serum IgM; and (4) neonates with normal facial features and normal serum IgM.

Neonates with dysmorphic facial features and normal karyotype include those exposed to teratogenic physical or chemical agents during pregnancy and those with genetic abnormalities that are not detected by chromosomal studies.

Teratogenic Microcephaly
Microcephaly due to teratogenic physical or chemical agents results from exposure of the fetus to a noxious agent at a vulnerable period of brain development. Physical agents include radiation. Microcephaly due to radiation is very rare since the introduction of low-dose ionizing radiation for diagnostic radiological evaluations, the shielding of the pelvis for chest radiographs, and the avoidance of pelvic radiographs if pregnancy is remotely suspected. Hyperthermia was once considered a significant factor in the production of microcephaly based on experimental animal studies and an initial medical report. However, hyperthermia is no longer considered a significant factor in the production of microcephaly. Chemical agents that may cause microcephaly include phenylalanine, alcohol, and anticonvulsant drugs.