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Holoprosencephaly
Thursday, 09 December 2004
Thursday, 09 December 2004

What

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.

Who

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.

Signs and Symptoms

There are many signs and symptoms due to the abnormally structured brain and children usually have some, but not all of these findings. • 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 (increased amount of fluid within the brain spaces) • Anosmia (inability to smell) Facial defects are characterized by under-development of the center part of the face. • 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) • Ethmocephaly (tube-shaped nose between close-set eyes, least common defect) • Cebocephaly (small flat nose with one nostril below incompletely formed eyes) • Single central incisor (front tooth)

Possible Causes

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.

Diagnosis

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).

Treatment

There is no specific treatment for holoprosencephaly. The goal of management is treatment of any associated symptoms and defects, such as medication for seizures or shunting for hydrocephalus. Advising parents about future pregnancies is important, as the recurrence rate is higher compared to the average population, especially those with inherited syndromes. Genetic counseling and prenatal ultrasounds performed at experienced centers may help to detect fetal problems early on in pregnancy.

Prognosis

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.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Carter Centers for Research in Holoprosencephaly http://www.stanford.edu/group/hpe Website for a group of research centers dedicated to studying holoprosencephaly and creating an international registry of patients. Site includes latest research developments, a helpful list of support and resource links for parents, and information in Spanish. The Holoprosencephaly Support Site http://hpe.home.att.net/ Parent support group site, including email groups and conference information.

Google Search for Holoprosencephaly

References and Sources

Kinsman SL, Plawner LL and Hahn JS (2000). Holoprosencephaly: recent advances and new insights. Current Opinion in Neurology. 13: 127-132. The National Institute of Neurological Disorders and Stroke (2003). NINDS Holoprosencephaly Information Page. www.ninds.nih.gov/health_and_medical/disorders/holoprosencephaly.htm