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Table of Contents

Magill’s Medical Guide, 9th Edition

Wolf-Hirschhorn Syndrome

by Christine M. Carroll, RN, BSN, MBA

Category: Disease/Disorder

Key terms:

chromosomes: Found in the nucleus of every cell in the body. They carry the genetic material that determines the characteristics of each person.

translocation: It is a swapping of the short arm from one chromosome to another chromosome.

hypotonic: Hypotonic refers to the quality of a person’s muscles. Hypotonic muscles are weak, and may appear to be absent.

scoliosis: This is the abnormal curvature of the thoracic spine (chest). Usually the curvature is visible, and curves to the right or the left.

kyphosis: This is the abnormal curvature of the lumbar spine (the lower part of the spine).

cleft palate: is a congenital abnormality where the roof of the upper mouth is split.

cleft lip: is a congenital abnormality where there is a split of the upper lip into include the upper lip up to the nose.

mutations: A change in the chromosomes and genes that occurs spontaneously.

bands: Bands refer to the genes on the chromosomes.

phenotype: This term refers to the appearance or condition of a person due to their specific genes that are active.

Wolf-Hirschhorn Syndrome (WHS) is a rare genetic mutation that is expressed as a wide range of symptoms. The changes include physical changes on the outside of the body, and internal changes to the structure and function of the body. In WHS, there is a mutation of the short arm of chromosome 4, which is referred to as 4p-. There are several bands on the short arm of chromosome 4p-, and the symptoms expressed depend on the bands (genes) that are missing from chromosome 4.

WHS is twice as common in females, as it is in males. The incidence of WHS is roughly one in 50,000 persons. Pitt-Rogers-Danks (PRD) syndrome appears to be related to WHS. The symptoms of Pitt-Rogers-Danks syndrome are similar to some of the symptoms of WHS, but they are less severe. Researchers think that a shorter piece of chromosome 4p- is missing in PRD. This would indicate that fewer bands are missing in persons with PRD.

CAUSES AND SYMPTOMS

Eighty to ninety percent of cases of WHS occur due to a random mutation on chromosome 4p- during the development of the embryo. These cases do not have similar changes in their parent’s genes. There is no way to prevent WHS. The remaining 10% of cases of WHS have one parent with a balanced translocation. This parent has another short arm of a chromosome in place of the 4p- arm, and the 4p- arm is located on the chromosome that gave up its short arm. This is called a balanced translocation of genes. It appears to be a random mutation. The affected parent has no symptoms of WHS. There is no family history of this genetic change.

Infants with WHS are very fragile when they born, and are often stillborn. Others die within the perinatal period. Infants with WHS may die during their first year of life. WHS causes an infant or child to be susceptible to various heart defects, lung infections, and seizures, which can impact their survival. Once a child with WHS, reaches 2 years of age, they are less likely to die. There is relatively little information about the life expectancy of persons with WHS. Many may die during childhood. The data is difficult to assess because samples are quite small, and because many WHS persons die in utero or early in their lives. It is thought that some persons with WHS could live 20-30 years

The symptoms of WHS are determined by the number and type of genes missing from the 4p- arm of chromosome 4. These children have characteristic facial abnormalities. Their bodies are physically much smaller than the normal baby, and they have very slender extremities. They appear to have no muscles. Some of the facial abnormalities include: a beaked nose, wide eyes, a short forehead with an unusual lump above their noses, downturned mouth, drooping eyelids, deformity of the iris of their eyes, slanted eyelids, and eyebrow defects. Some WHS children have strabismus or crossed eyes. They tend to have dry and mottled skin, and a short upper lip with small jaw. As they develop they may have missing teeth. Some infants may have a cleft lip or a cleft palate, making it difficult for them to take in formulait without aspirating. Their hands are small, and they have several parallel creases on the palms of their hands, like a person with Downs Syndrome. Their fingerprints are not fully developed and they have abnormal finger nails. They may appear like a baby doll.

Internally, infants or children with WHS often have underdeveloped bones of the head, the pelvis, the spine, and the chest wall. Often, they have either scoliosis or kyphosis. These conditions can decrease the space within their bodies for their organs. This lack of space impairs the function of the heart and lungs. They often have heart malformations and frequent lung infections. The whole body’s muscle mass is hypotonic. Many persons with WHS have brain abnormalities. They include: a seizure disorder, mental disability, a hearing disorder, and delayed development of basic motor skills such as sitting, standing, and talking. Their mental disability can vary from mild to severe. These children are often unable to feed themselves. Their verbal skills are limited and they may not speak, or they may speak with grunts or single words. Often they have deformed urinary systems. Boys may have undescended testicles or hypospadias. Both boys and girls can have deformed urinary systems, and they can be incontinent and untrainable. Their kidneys can be affected by the lack of space in their pelvis.

TREATMENT AND THERAPY

Wolf-Hirschhorn Syndrome can be identified in utero during the first trimester of pregnancy. If a physician suspects that a mother is carrying an infant with Wolf-Hirschhorn Syndrome, they can try to verify this by performing an ultrasound, and removing some umbilical cord blood. The blood will have cells so that they can perform a microassay of the fetus’ DNA to look for the missing 4p- arm of chromosome 4. There is another test that can be done, called Fluorescent in situ Hybridization (FISH). It is a test that can read the chromosomal abnormalities of the fetus within the uterus. At this time, the chromosomes of the fetus are quite small. It is 60-70% accurate. Once the infant is born, the presence of genetic abnormalities can be verified with additional radiological tests. The purpose of the tests is to look at the scope of the infant’s genetic changes in the brain, bones and organs. The tests are an EEG (brain scan), ultrasounds, CT scans and MRIs.

The treatment for an infant with WHS is individual based on the infant’s particular needs. Surgery is usually performed on heart defects, cleft lip or palate, disorders of the urinary system, and eye malformations. These children may be treated for contracted wrists or flexed soles of their feet. The physical care of an infant with WHS can be fairly complex, including breathing assistance, tube feeding, drug therapy for seizures, and a multi-disciplinary team of medical specialists. Genetic counseling should be performed and the parents of a WHS infant or child, should be counseled as to the cause of the genetic mutations. The parents of a child with WHS will most likely require assistance to care for this child.

PERSPECTIVE AND PROSPECTS

WHS was first described in 1961 by 2 Americans, Herbert L. Cooper and Kurt Hirschhorn. They published several studies in the German journal, Humangenetik. More cases of WHS have been identified each year since then. This may be due to better genetic testing which can point out the genetic mutations causing WHS. More WHS infants are surviving due to advances in medical care. Currently, 34% of infants with WHS die within the first 3 years of life. Those that survive this period can live into their twenties or thirties.

A child or adult with WHS is severely disabled and requires custodial care for the rest of their life. Only 10% of them are able to control their sphincters, so they require diapers for much of their life. They need assistance to eat, to bathe and to dress themselves. They often speak a few words or grunts, so it can be difficult to communicate with them. Some fetus’ with WHS are aborted due to the extreme care that they will require all of their lives.

For Further Information:

1 

WebMD. (26 September 2016) What is Wolf -Hirschhorn Syndrome? Retrieved on August 4, 2017 from www.webmd.com/children/wolf-hirschhorn-syndrome?print=true. This article has pictures of children with WHS, and an example of the genes responsible for WHS.

2 

Zanelli, Santina A.,MD, Chief Editor: Rohena, Luis O., MD, FAAP, FACMG, et al. (15 May 2017) Wolf-Hirschhorm Syndrome. Retrieved on August 4, 2017 from emedicine.medscape.com/Article/950480-overview#showall. This article includes more information about the diagnosis of WHS.

3 

Medical Substance. (25 June 2012) Wolf-Hirschhorn Syndrome. Retrieved on August 4, 2017 from www.Medicalsubstance.com/wolf-hirschhorn-syndrome/This article includes some history concerning WHS and diagnosing it.

4 

Genetics Home Reference. (August 2, 2017) Wolf-Hirschhorn Syndrome. Retrieved on August 4, 2017 from ghr.nlm. nih.gov/condition/wolf-hirschhorn-syndrome#sources forpage. This article describes symptoms of WHS and the genetic causes of the condition.

5 

Shannon, N.L., Maltby, E.L., Rigby, A.S., Quarrell, O.W., (2017) Epidemiological Study of Wolf-Hirschhorm-syndrome: life expectancy and cause of mortality. Retrieved on August 6, 2017 from bmj.com/content/38/10/674. This British article reported on a study of the statistics on life expectancy for persons with Wolf-Hirschhorn Syndrome.

Citation Types

Type
Format
MLA 9th
Carroll, Christine M. "Wolf-Hirschhorn Syndrome." Magill’s Medical Guide, 9th Edition, edited by Anubhav Agarwal,, Salem Press, 2022. Salem Online, online.salempress.com/articleDetails.do?articleName=MMG2022_1473.
APA 7th
Carroll, C. M. (2022). Wolf-Hirschhorn Syndrome. In A. Agarwal, (Ed.), Magill’s Medical Guide, 9th Edition. Salem Press. online.salempress.com.
CMOS 17th
Carroll, Christine M. "Wolf-Hirschhorn Syndrome." Edited by Anubhav Agarwal,. Magill’s Medical Guide, 9th Edition. Hackensack: Salem Press, 2022. Accessed September 16, 2025. online.salempress.com.