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Wolf Hirschhorn Syndrome

Synonyms of Wolf Hirschhorn Syndrome

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

Disorder Subdivisions

  • No subdivisions found.

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.

Related Disorders

Syndromes involving deletions of other chromosomes may be similar to Wolf- Hirschhorn syndrome. Comparisons may be useful for a differential diagnosis:

Chromosomal disorders that involve extra chromosomes (trisomy) may also be similar to Wolf-Hirschhorn syndrome. (For more information on these disorders, choose "Trisomy," "Trisomy 13," and "Trisomy 18" as your search terms in the Rare Disease Database.)

Cri-du-chat syndrome is a congenital chromosomal disorder that involves a partial deletion of chromosome 5. It is similar to the Wolf-Hirschhorn syndrome, with additional features such as a high, shrill cry. Patients may also have defects in the urinary and reproductive organs (urogenital tract), curvature of the spine (scoliosis), shortened bones in the feet, premature graying, and severe breathing (respiratory) and feeding problems. (For more information on this disorder, choose "Cri du Chat" as your search term in the Rare Disease Database.)

Down syndrome is a congenital chromosomal disorder involving three copies of chromosome 21. Hypotonia, small stature with awkward gait, and mental deficiency are major symptoms. There also may be inner epicanthic folds around the eyes, iris deformities, small ears with no lobes, and tooth defects. A small nose, flat face, short neck, small hands and fingers, and simian creases of the hands may also occur. Heart defects, dry skin, sparse hair, small penis, and infertility are common symptoms. Seizures, protruding eyes, low placement of ears, and undescended testicles are less frequent symptoms. (For more information on this disorder, choose "Down" as your search term in the Rare Disease Database.)

Pitt-Rogers-Danks syndrome (PRDS) is now thought to represent the lower end of a spectrum of severity of symptoms associated with Wolf-Hirschhorn syndrome. This disorder is characterized as well by fetal growth delays, short stature, a small head (microcephaly), characteristic facial features, mental retardation and seizures. It was discovered that Pitt-Rogers-Danks syndrome was caused by a microdeletion at the distal end of the short arm of chromosome 4, almost exactly the same as seen in cases of WHS. Thus, it appears that PRDS and WHS may represent different points on the spectrum of a single syndrome.

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 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

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

Wolf Hirschhorn Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at

Other Organizations:


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Zollino M, Lecce R, Selicorni A, et al. A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf-Hirschhorn syndrome. Eur J Hum Genet. 2004;12:797-804.

Van Borsel J, De Grande S, Van Buggenhout G, et al. Speech and language in Wolf-Hirschhorn syndrome: a case study. J Commun Disord. 2004;37:21-33.

Sharathkumar A, Kirby M, Freedman M, et al. Malignant hematological disorders in children with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2003;119:194-99.

Zollino M, Lecce R, Fischetto R, et al. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining new critical reason, WHSCR-2. Am J Hum Genet. 2003;72:590-97.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Wolf-Hirschhorn Syndrome; WHS. Entry Number; 194190: Last Edit Date; 11/18/2004.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Wolf-Hirschhorn Syndrome Candidate 1; WHSC1 Entry Number; 602952: Last Edit Date; 7/30/2003.

Battaglia A, Carey JC, Wright TJ. Wolf-Hirschhorn Syndrome. GENEReviews. Last Update: 6 April 2004. 17pp.

Wieczorek D. Wolf-Hirschhorn syndrome. Orphanet. September 2003. 4pp.

Quarrell O. Wolf-Hirschhorn Syndrome. Contact a Family. Last updated February 2004. 2pp.

Chromosome 4p deletion syndrome. Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. nd. 5pp.

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

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/04/07 00:00:00 GMT+0

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