Information on the following diseases can be found in the Related Disorders section of this report:

• Cleft Lip and Cleft Palate

Holoprosencephaly is a malformation sequence that can be mild or severe. Children diagnosed with this disorder may have a small head, excessive fluid in the brain, facial deformities, variable degrees of mental retardation, epilepsy, endocrine abnormalities, or abnormalities of other organ systems.

Individuals affected mildly with Holoprosencephaly may have closely set eyes (hypotelorism), missing front teeth (incisors), and an abnormally small head (microcephaly). Cleft lip and/or palate may also occur. Mental retardation also occurs.

Rarely, the most severely affected individuals may have cebocephaly or cyclopia. Cebocephalic individuals have a deformed or absent nose, and either closely set eyes or cyclopia. Cyclopia is the most severe and rarest finding in Holoprosencephaly and is characterized by the fusion of the eyes together.

Holoprosencephaly may also affect other systems in the body, including absence of the pituitary gland. An abnormally low concentration of glucose (sugar) in the blood (hypoglycemia) may then occur. Interruption of normal breathing (apnea) and seizure disorders may also be present. Males may have an abnormally small penis (micropenis).

Holoprosencephaly is a birth defect that occurs during the first few weeks of intrauterine life. It is a disorder in which the fetal brain does not grow forward and divide normally. The resulting brain malformation and associated conditions can range from mild to severe.

The exact cause of Holoprosencephaly is not known. This birth defect occurs alone in the majority of cases; however, certain chromosomal abnormalities including Trisomy 13, 18p- and 13q- Syndromes, and Meckel-Gruber Syndrome, should be considered. A higher incidence of Holoprosencephaly has been reported in children of diabetic mothers. Cytomegalovirus (CMV) infection in the fetus has also been associated with Holoprosencephaly. Several reported cases have involved parents who were related to each other. Finally, Holoprosencephaly can be inherited. However, there is disagreement as to whether it is transmitted through autosomal dominant or autosomal recessive genes. (For more information on these disorders, choose "Trisomy 13", "18p", "13q", "Meckel-Gruber" or "Cytomegalovirus" as your search terms in the Rare Disease Database).

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Holoprosencephaly is a very rare disorder affecting males and females in equal numbers before birth. The incidence of Holoprosencephalic children with normal chromosomes has been estimated at between 1 in 16,000 and 1 in 53,394 live births.

Holoprosencephaly usually includes mental retardation and cleft lip or palate. There are many birth defects in which mental retardation is a symptom. (For more information, choose "Mental Retardation" as your search term in the Rare Disease Database.)

Cleft lip and cleft palate are among the most common birth defects found in newborn infants. A cleft occurs when the roof of the mouth is not completely closed at birth. This opening or fissure is due to a failure of the upper jaw bones (maxillae) to properly fuse together during development of the embryo. This deformity may affect the entire roof of the mouth (palate), the lip, or both. The severity of the cleft may range from a barely visible notch to complete non-closure and deformity of the lip and palate. It may be inherited as an autosomal dominant trait, it can be a symptom of other birth defects, or it may involve a complex genetic pattern not understood as of yet. (For more information on this disorder, choose "Cleft" as your search term in the Rare Disease Database.)

The presence of Holoprosencephaly can be detected prenatally through ultrasound. Prenatal chromosomal examination of subsequent pregnancies may be indicated. Computerized tomography may be used to determine the severity of the Holoprosencephaly.

Pediatricians, dentists, special education teachers, surgeons, speech pathologists, psychologists and others must systematically and comprehensively plan the child's treatment for Holoprosencephaly. Plastic reconstructive surgery of the face may be considered in some cases.

Genetic counseling may be of benefit for patients and their families. Family members of children with Holoprosencephaly should be carefully examined for mild symptoms such as a single front tooth (incisor) instead of two, and closely-set eyes (hypotelorism). Other treatment is symptomatic and supportive.

Through the Carter Centers for Brain Research in Holoprosencephaly and Related Malformations, a collaborative effort has been launched to gather, store, organize, analyze, and share information about holoprosencephaly. Participating institutions are: the Texas Scottish Rite Hospital for Children in Dallas; Kennedy Krieger Institute in Baltimore; Stanford University Medical Center in California; Rutgers, the State University of New Jersey; and the Children's Hospital of Philadelphia.

The Carter Centers are creating an International HPE (holoprosencephaly) Registry of patients that will enable scientists to study the prevalence of HPE and share research information. In addition, specialized clinics will be conducted for children diagnosed with HPE, and an ongoing database will be maintained to provide information on the incidence, signs and symptoms, and current treatments.

For additional information about the registry or other activities of the collaborating centers, visit the web site at www.stanford/edu/group/hpe or contact the national project director, Nancy Clegg, RN, PhD, at (214) 559-8411 or hpe@tsrh.org.

SMITH'S RECOGNIZABLE PATTERNS OF HUMAN MALFORMATION, 4th ed.: Kenneth L. Jones; W.B. Saunders Co., 1988. Pp.546-7.

MENDELIAN INHERITANCE IN MAN, 8th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 987.

SONOGRAPHY OF FACIAL FEATURES OF ALOBAR AND SEMILOBAR HOLOPROSENCEPHALY: J.P. McGahan, et al.; AJR Am J Roentgenol (January, 1990, issue 154(1)). Pp. 143-8.

HOLOPROSENCEPHALY: A DEVELOPMENTAL FIELD DEFECT: V.P. Johnson; Am J Genet (October, 1989, issue 34(2)). Pp. 258-64.