Holoprosencephaly.
Incidence
Holoprosencephaly occurs in 5-12 out of every 100,000 births. This number may be an underestimation since the mildest cases may never be diagnosed. 20-40% of affected children have underlying cytogenetic abnormalities (extra or missing genetic material) and these children tend to be more severally affected.
Clinical Characteristics
Holoprosencephaly is a defect in the structure of the brain that occurs during pregnancy. The brain is normally divided into two sides, also called lobes or hemispheres, and holoprosencephaly occurs when the developing brain fails to divide properly into the right and left lobes. Affected children have a one-lobed brain and this often occurs with defects of the overlying skull and face (usually the eyes, nose, and upper lip). There is a wide degree of severity associated with holoprosencephaly with some cases causing miscarriage to other cases of children with near normal brain development. Holoprosencephaly is divided into three categories based on the degree of division between the two lobes and these are: 1. Alobar: The brain has no division at all and there are usually severe facial deformities. 2. Semilobar: The hemispheres (lobes) are partially divided. 3. Lobar: The least severe form, in which the brain hemispheres are fairly well separated. There are many signs and symptoms due to the abnormally structured brain and children usually have some, but not all of these findings. These symptoms are: Microcephaly (small head), mental retardation, developmental delay, hormone problems due to abnormalities of the hypothalamus and pituitary gland (structures of the brain that produce and control hormones), seizures, abnormal muscle tone, feeding difficulties, constipation. Hydrocephalus may be seen as well as anosmia (inability to smell). Facial defects are characterized by under-development of the center part of the face. These defects include hypotelorism or hypertelorism (eyes are either closer together or father apart than usual), iris coloboma (a defect in the colored part of the eye), flat nose, cleft lip. Cyclopia (single eye, the most severe facial defect) as well as ethmocephaly (tube-shaped nose between close-set eyes, least common defect) or cebocephaly (small flat nose with one nostril below incompletely formed eyes) may be seen, as well as single central incisor (front tooth). There are several known genes associated with holoprosencephaly and others are currently being researched. The first and best understood is a gene named Sonic Hedgehog (SHH). Holoprosencephaly is also a feature of many genetic syndromes, the most common being trisomies 13 and 18. Environmental factors are also involved but not well understood. One environmental factor is maternal diabetes during pregnancy and these children have a three times greater risk of holoprosencephaly. The prognosis for holoprosencephaly varies a great deal depending on the degree of brain and facial deformities. It is currently very difficult for a doctor to predict how a child will do developmentally, especially in milder cases.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
The diagnosis of holoprosencephaly is most clearly made with magnetic resonance imaging (MRI) of the brain, which will show the lack of separation between the two sides of the brain. This study can show even milder forms than is possible with computed tomography (CAT scan).