What is Wolf-Hirschhorn syndrome?

What is Wolf-Hirschhorn syndrome?

Do you know about Wolf-Hirschhorn syndrome (4p deletion syndrome, WHS)? This disease is a chromosomal abnormality that has been designated as an intractable disease.
In this issue, I would like to provide an easy-to-understand overview of the disease, its symptoms, diagnosis, and treatment for those of you who are interested in learning more about this disease.

What is Wolf-Hirschhorn syndrome?

Disease Overview

Wolf-Hirschhorn syndrome is a rare chromosome disorder caused by a deletion of the distal portion of the short arm of chromosome 4 (including 4p16), also known as 4p deletion syndrome or 4p-syndrome WHS. The size of the deletion varies from person to person, but larger deletions are known to cause more severe mental retardation and physical disabilities. NSD2, LETM1, and MSX1 are the most commonly defective genes. The specific roles of these genes are not yet clear. However, it is becoming clear that these genes play an important role in the developmental process. It is now believed that defects in the NSD2 gene may cause characteristic facial features and developmental delays. Defects in the LETM1 gene are thought to be associated with seizures and other abnormal electrical activity, while defects in the MSX1 gene have been suggested to cause abnormal tooth formation and cleft lip and palate. Scientists are currently investigating an additional gene located at the end of the short arm of chromosome 4.

Disease frequency

The frequency of Wolf-Hirschhorn syndrome is 1 in 5,000, making it an incurable disease. The male-to-female ratio is 1:2, with the disease slightly more common in women than in men.

About Genetic Forms

85-90% of all cases of Wolf-Hirschhorn syndrome are not hereditary. This is because of random chromosome deletions that occur during germ cell formation or early embryogenesis. Random chromosome changes occur in Wolf-Hirschhorn syndrome with no family history, although more complex chromosome rearrangements can also occur. some individuals with Wolf-Hirschhorn syndrome have ring chromosomes. A ring chromosome is created when a chromosome breaks in two places and the ends of each chromosome fuse together. In the process, genes at the ends of the chromosomes are lost, resulting in various disorders.

Some cases of Wolf-Hirschhorn syndrome may inherit a copy of chromosome 4 with a defective portion. In such cases, one of the parents has a chromosome rearrangement between chromosome 4 and the other chromosome. This condition is called an equilibrium translocation. Since an equilibrium translocation is a balanced translocation, there is no new increase or decrease in genetic material. Therefore, it does not cause health problems under normal circumstances. However, it is possible for the equilibrium translocation to become unbalanced when passed on to the next generation. In this case, a child born without both parents may develop Wolf-Hirschhorn syndrome.

What are the actual symptoms of Wolf-Hirschhorn syndrome?

A wide variety of symptoms are seen, including a broadly prominent face from the forehead to the nasal area (Greek-Warrior Appearance), hypotonia, mental retardation, growth retardation beginning in the fetal period, epilepsy, feeding difficulties, microcephaly, protruding eyebrows, shortening of the midsection, congenital heart disease, and hearing impairment. Epileptic seizures, in particular, occur in almost 100% of infants with Wolf-Hirschhorn syndrome before the age of one year, and it is considered important to avoid epilepsy in order to improve quality of life. The patterns of epileptic seizures vary from clonic, tonic-clonic, and tonic-clonic seizures. These epilepsies are believed to be triggered by fever. Both growth retardation and mental retardation occur in this disorder. Specifically, weight gain is poor and intrauterine growth retardation occurs even with proper protein and energy intake; severe mental retardation occurs in Wolf-Hirschhorn syndrome. It is generally considered to be an inability to speak and a lack of communication skills. In recent years, however, some cases have been observed in which the patient can speak two syllables under special circumstances.

Is there a way to diagnose Wolf-Hirschhorn syndrome?

The first step in the diagnosis process is to perform the usual chromosome examinations. This is done to check for large deletions or translocations. Genetic testing is also useful in diagnosing Wolf-Hirschorn syndrome. Screening for deletions in subtelomeric regions by the FISH method is both sensitive and specific. The majority of translocation cases involve subtelomeric regions. In addition to FISH, array CGH may also be used. When using conventional cytogenetic testing, it is necessary to find an additional portion attached to 4p. In such cases, the SKY or M-FISH methods are used for identification.

What does the treatment for Wolf-Hirschhorn syndrome do?

Since Wolf-Hirschhorn syndrome is caused by a congenital genetic abnormality, there is no curative treatment. Therefore, it is important to provide individualized treatment for each symptom.

I will now give the typical diseases of Wolf-Hirschhorn syndrome and look at the individual treatments.

Mental Retardation

Training to develop motor development, cognition, language, and social skills is useful. Furthermore, it is important to properly assess the individual and set up a rehabilitation program. In the past, there was concern that heavy use of gestures would further slow down the emergence of language, but it is now known that gestures can increase a child's motivation to communicate. Therefore, it is better to actively use gestures and other forms of communication. It is also important to obtain appropriate services using the physical disability certificate or rehabilitation certificate, which can be obtained by all patients except infants under one year of age. and home-visit services, which should be used as needed.

Eating Disorder

Feeding training.

Feeding devices such as the Haberman Feeder are available for children without cleft palates or before surgery. Tube feeding may be used for children with weak swallowing ability.

If gastroesophageal reflux disease complicates the procedure, a reduction of the fundoplication and gastrostomy are performed.


In children with Wolf- Hirschhorn syndrome, the key issue is how to control the epilepsy. Generally, the antiepileptic drugs valproate and diazepam are used, but in recent years, oral sodium bromide has been found to be effective. Antiepileptic drugs may be discontinued if there have been no apparent epileptic seizures for at least 5 years, even if the electroencephalogram is not normal.

For other congenital malformations, congenital heart disease, and hearing impairment, surgery is performed based on individual circumstances.


  • Journal of the Japanese Society of Red Cross Nursing - Kahoru Kitagawa, Michiko Okazaki, A Study on Self-Help Functions of Family Social Meetings for Children with Disabilities
  • NIH  U.S. National Library of Medicine - Wolf-Hirschhorn syndrome