Wolf Hirschhorn Syndrome

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Wolf Hirschhorn Syndrome 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.


  • WHS
  • Wolf Syndrome
  • Wolf-Hirschhorn Chromosome Region (WHCR)
  • WHCR
  • Chromosome 4, Partial Deletion 4p
  • Partial Deletion of the Short Arm of Chromosome 4
  • Chromosome 4, Partial Monosomy 4p
  • 4p- Syndrome, Partial
  • Pitt-Rogers-Danks Syndrome

Disorder Subdivisions

  • None

General Discussion

Wolf-Hirschhorn syndrome is an extremely rare chromosomal disorder caused by a partial deletion (monosomy) of the short arm ("p") of chromosome 4. Major symptoms may include extremely wide-set eyes (ocular hypertelorism) with a broad or beaked nose, a small head (microcephaly), low-set malformed ears, mental and growth deficiency, heart (cardiac) defects, and seizures. Because the amount of genetic material deleted varies, the symptoms of this syndrome vary from case to case.


Individuals with Wolf-Hirschhorn syndrome are recognizable by an unusual bump on the forehead above the nose (prominent glabella) and a beaked nose, giving the appearance of a Greek helmet. Other characteristics include low birth weight, growth retardation and deficiency, delayed bone age, an unusually small head (microcephaly), and undescended testicles (cryptorchidism). Failure to thrive, reduced muscle tension (hypotonicity), mental and psychomotor retardation, seizures, and precocious puberty may also occur.

Children with this syndrome have protruding wide-set eyes and one eye may be angled either inward or outward (strabismus). Droopy eyelids (ptosis), eye defects (coloboma), iris deformity, slanted eyelid slits (oblique palpebral fissures), excess skin over the inner corner of the eyes (epicanthic folds), and defects of the middle half of the eyebrow may also occur.

Cleft lip, cleft palate, a short groove in the midline above the upper lip (philtrum), short upper lip, and downturned "fish-like" mouth may occur. Small jaws (micrognathia) and low-set ears with a dimple may also be present. Underdeveloped fingerprints (dermal ridges), a double loop on thumb, creases across the palms (simian creases), and highly curved upward (hyperconvex) fingernails may occur. WHS patients may have permanently flexed soles so that walking is done on the toes. There may be heart (cardiac) and kidney (renal) defects, and susceptibility to lung (pulmonary) infections. The urethra (the tube leading from the bladder) may open underneath the penis (hypospadias) or the urethra may open into the vagina. The pubic bone (part of the pelvis) may be underdeveloped.


Wolf-Hirschhorn syndrome is an extremely rare chromosomal disorder in which the end (distal) portion of the short arm of chromosome 4 is deleted (monosomic). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q."

The deletion of the distal portion of the short arm of chromosome 4 (4p) is responsible for the symptoms that characterize this chromosomal disorder. It is believed that band 16.3 on chromosome 4p (4p16.3) is the critical region for the disorder, meaning that deletion of this area leads to full expression of Wolf-Hirschhorn syndrome. (In order for researchers to clearly refer to the thousands of genes that may be present on one chromosome, both the long arm (q) and short arm (p) of each chromosome are divided into many bands that are numbered.)

In most documented cases, Wolf-Hirschhorn syndrome is due to a spontaneous (de novo) genetic change very early in embryonic development that occurs for unknown reasons (sporadic). In other cases, the disorder may result if one of the parents has a balanced translocation. A translocation is balanced if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes. Because a person with a balanced translocation has all the necessary genetic material for normal development, balanced translocations usually do not affect the carrier. However, they are associated with a higher risk of abnormal chromosomal development in the carrier's offspring. Genetic testing can determine if a parent has a balanced translocation.

Affected Populations

Wolf-Hirschhorn syndrome is an extremely rare disorder that is apparent at birth. Studies undertaken about 25 years ago suggested that the disorder occurred once in about 50,000 live births with a female to male ratio of 2:1. More recent studies suggest that the disorder is underestimated because of misdiagnosis.

Standard Therapies


In some cases, the diagnosis of Wolf-Hirschhorn syndrome may be determined before birth (prenatally) via ultrasound. If a case is suspected, prenatal diagnosis using conventional genetic techniques on cells from the fetus will detect the disorder in about 60-70% of cases. A more sophisticated technique (FISH) can be used on prenatal or postnatal cells with a 95% chance of a correct finding.


Treatment of Wolf-Hirschhorn syndrome may include surgical repair of malformations. For example, surgery may be performed to correct cleft lip and palate. Other treatment is symptomatic and supportive. A team approach may be helpful in ensuring that affected individuals reach their fullest potential. Such a team approach may include special remedial education, physical therapy, and other medical, social, or vocational services. Genetic counseling will also be of benefit for families of children with Wolf-Hirschhorn syndrome.

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:




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4p Support. Last udated on 28-Apr-04. 10pp.



Chromosome Disorder Outreach, Inc.

P.O. Box 724

Boca Raton, FL 33429-0724


Tel: (561)395-4252

Fax: (561)395-4252

Email: info@chromodisorder.org

Internet: http://www.chromodisorder.org/CDO/

4P- Support Group

131 Green Cook Road

Sunbury, OH 43074

United States

Tel: (740)936-5095

Email: president@4p-supportgroup.org

Internet: www.4p-supportgroup.org

Wolf Hirschhorn Syndrome Trust for the UK and Ireland

1 Hawthorne Villas

Holmes Chapel

Crewe, CW4 7AR

United Kingdom

Tel: 08456035338

Email: enquiries@whs4pminus.co.uk

Internet: http://www.whs4pminus.co.uk

World Health Organization (WHO)

Avenue Appia 20

Geneva 27, 1211


Tel: 41227912111

Fax: 41227913111

Internet: http://www.who.int/en/

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.