Brain Malformations

Brain malformations affect children worldwide. Usually, they form congenitally, have no effective means of prevention or treatment, and are associated with poor prognoses. Anencephaly is the absence of a major portion of the brain, skull, and scalp, and results from failure of the neural tube to close. (The neural tube is the primitive structure from which develops the central nervous system.) Children born with anencephaly are essentially headless, and, therefore, death is certain. In America, 1,000 to 2,000 children are born with anencephaly every year. Females are more likely to be affected than males, and insufficient maternal intake of folic acid also increases the likelihood of this and other neural tube defects.

Colpocephaly is the enlargement of the occipital horns, the part of the brain located at the posterior end of the lateral ventricles, because of insufficient development of the posterior cerebrum. The precise cause of colpocephaly is unknown, but is believed to result from some intrauterine disturbance between the second and sixth months of pregnancy. Children with this malformation present with microcephaly, mental retardation, muscle spasms, and seizures. The prognosis with colpocephaly is directly correlated with the degree of abnormality.

Holoprosencephaly results from the failed development of the prosencephalon (embryonic forebrain). The prosencephalon fails to divide and form the two cerebral hemispheres, and this failure results in defects in both the brain and face. About one-half of holoprosencephaly cases are caused by chromosomal defects, such as trisomy 13 (Patau syndrome) and 18 (Edwards syndrome). The clinical presentation of this disorder falls along a broad spectrum, with defects as minor as a cleft lip or as severe as cyclopia (one eye). One risk factor for the development of holoprosencephaly is birth to a diabetic mother.

Hydranencephaly is a form of porencephaly, characterized by a brain with absent cerebral hemispheres, replaced instead with cerebrospinal fluid (CSF)-filled sacs. This condition is caused by vascular insult (i.e., stroke), injuries, or infections after week 12 of pregnancy. Although the infant may appear normal at birth, after a few weeks, he or she demonstrates irritability and increased muscle tone followed by seizures and hydrocephalus after several months. Death typically occurs during the first year of life, although reports exist of patients surviving into their 20s.

Iniencephaly is a combination of retroflexion (backward bending) of the head and severe spinal defects. Like anencephaly, iniencephaly is a neural tube defect. Affected infants are born looking upward because of the retroflexion, and the skin of the face is connected directly to the skin of the chest, while the skin of the scalp is connected to the skin of the back. Thus, patients appear to have no neck. Females are affected more than males. These patients tend to survive only for a few hours after birth.

Lissencephaly means “smooth brain” and is an umbrella term that encompasses several disorders, including Miller-Dieker syndrome, isolated lissencephaly sequence, and Walker-Warburg syndrome. The normal brain has many folds and grooves (gyri and sulci), but brains affected by lissencephaly do not. Lissencephaly is caused by defective neuronal migration, which itself is thought to be caused by viral infections, inadequate blood supply to the embryonic brain, or genetic disorders (namely X- or chromosome 17 linked). Symptoms of lissencephaly include abnormal facies, difficulty swallowing, failure to thrive, and psychomotor retardation.

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