Holoprosencephaly

Holoprosencephaly

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Holoprosencephaly is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • HPE
  • alobar holoprosencephaly
  • holoprosencephaly sequence
  • lobar holoprosencephaly
  • middle interhemispheric fusion
  • semilobar holoprosencephaly

Disorder Subdivisions

  • None

General Discussion

Holoprosencephaly (HPE) is the failure of the prosencephalon, or forebrain, to develop normally. The forebrain is a region of the brain in the fetus that develops into parts of the adult brain, including the cerebral cortex. Instead of the normal complete separation of the left and right halves of the forebrain, there is an abnormal continuity between the two sides.

There are several different types of holoprosencephaly. In the alobar form, there is no separation between the right and left halves at all. In semilobar HPE, at least some of the brain has separated into different halves. In the lobar form, most of the brain has separated into right and left sides, though there is incomplete division into the two halves.

Symptoms

Holoprosencephaly is a malformation sequence with a very variable degree of severity for both the brain and facial abnormalities. Intellectual disability is associated with HPE and seizures are often present.



Children diagnosed with this disorder may have a small head (microcephaly), excessive fluid in the brain (hydrocephalus), facial abnormalities, tooth abnormalities (single central incisor), cleft lip and/or palate, epilepsy, and/or endocrine abnormalities. The most severely affected individuals may have cyclopia, a single central eye that is the most severe eye finding seen in holoprosencephaly, though this is very rare. Abnormalities in the formation of the nose may also occur.



Holoprosencephaly may also affect other systems in the body. Defects in the pituitary gland can cause an abnormally low level of sugar in the blood (hypoglycemia), low levels of sodium in the blood, or genital abnormalities.

Causes

Holoprosencephaly is a birth defect that arises during the first few weeks of the pregnancy. Diabetes in the mother during the pregnancy can increase the risk of holoprosencephaly in the fetus. However, for most children, there is no known intrauterine exposure that can be related to holoprosencephaly.



Some children will have an identifiable genetic cause of holoprosencephaly. Approximately one-third of children born with holoprosencephaly have an abnormality of the chromosomes, which contain the genetic material (DNA). The most common chromosomal abnormality associated with HPE is when there are 3 copies of chromosome 13 (trisomy 13), although a number of other chromosomal changes can also cause holoprosencephaly.



In other children, holoprosencephaly is due to a change in a specific gene. These changes cause the genes and their proteins to function abnormally, and this affects the development of the brain, resulting in holoprosencephaly. Some of these genes are SHH, SIX3, TGIF, ZIC2, PTCH1, FOXH1, NODAL, and GLI2. Holoprosencephaly can also occur in certain genetic syndromes in which there are other medical issues besides those mentioned in this report that affect organs in addition to the brain and face (e.g., Smith-Lemli-Opitz syndrome).



Despite the above understanding of the causes of holoprosencephaly, the exact cause of the condition is not identified for many individuals. There are likely to be additional genetic causes other than those already known and mentioned above.

Affected Populations

Holoprosencephaly affects males and females in equal numbers before birth and has been reported in many ethnic groups. The incidence of holoprosencephaly has been estimated at 1 in 250 during early embryonic development, and approximately 1 in 16,000 live births.

Standard Therapies

The diagnosis of holoprosencephaly is usually made by MRI or CT of the brain. Holoprosencephaly can sometimes be detected prenatally through ultrasound or MRI, though more mild forms may not be reliably detected prenatally.



Treatment and care for the issues associated with holoprosencephaly are supportive and based on the specific medical issues present for an individual child.



An endocrinology evaluation should be performed to assess for pituitary abnormalities. A neurologist should also be involved in the child's care and will treat seizures if they are present. Plastic reconstructive surgery of cleft lip and palate or other facial features may be needed if indicated. A developmental pediatrician can help direct developmental therapies. Other treatments can be instituted as appropriate.



A clinical genetics evaluation and genetic counseling should be obtained for patients and their families once the diagnosis is made. Relatives of a child with holoprosencephaly may have an increased risk of having a child with holoprosencephaly, and this should be assessed and discussed by the child's physicians, especially the neurologist and/or clinical geneticist. There are specific features that suggest an increased risk for having another child with holoprosencephaly (e.g., a single central upper incisor), and these should be carefully assessed in parents and family members. A chromosome analysis and gene testing is often performed.



Pediatricians, neurologists, dentists, special education teachers, surgeons, therapists, psychologists, developmental pediatricians, and others must systematically and comprehensively plan the child's treatment for holoprosencephaly.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOK

Muenke M, Beachy PA. Holoprosencephaly. In: Scriver CR, Beaudet AL, Valle D, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:6203-6230.



JOURNAL ARTICLES

Kauvar EF, Muenke M. Holoprosencephaly: recommendations for diagnosis and management. Curr Opin Pediatr. 2010; 22:687-95.



Cohen MM Jr. Holoprosencephaly: clinical, anatomic, and molecular dimensions. Birth Defects Res A Clin Mol Teratol. 2006;76:658-73.

Resources

National Foundation for Facial Reconstruction

333 East 30th Street, Lobby Unit

New York, NY 10016

Tel: (212)263-6656

Fax: (212)263-7534

Internet: http://www.nffr.org



NIH/National Institute of Child Health and Human Development

31 Center Dr

Building 31, Room 2A32

MSC2425

Bethesda, MD 20892

Fax: (866)760-5947

Tel: (800)370-2943

TDD: (888)320-6942

Email: NICHDInformationResourceCenter@mail.nih.gov

Internet: http://www.nichd.nih.gov/



Carter Centers for Brain Research in Holoprosencephaly and Related Malformations

Texas Scottish Rite Hospital for Children

Department of Neurology

2222 Welborn Street

Dallas, TX 75219-3993

USA

Tel: (214)559-8411

Fax: (214)559-8383

Tel: (800)421-1121

Email: hpe@tsrh.org

Internet: http://www.carterdatabase.org/hpe



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.