Wolf-Hirschhorn Syndrome

Wolf-Hirschhorn Syndrome (WHS) is a rare genetic condition that leads to various structural abnormalities including facial and cardiac malformations. Read and know all about the causes, symptoms, diagnosis and treatment of this syndrome.

What is Wolf-Hirschhorn Syndrome?

It is a rare chromosomal disorder that occurs due to a partial deletion of the short arm of chromosome 4.

The condition is also known by various other names, like:

  • WHCR
  • 4-P Syndrome
  • 4-P deletion Syndrome
  • Monosomy 4-p Syndrome

Wolf-Hirschhorn Syndrome Incidence

The male to female ratio of the occurrence of the syndrome is 1:2 and it occurs in almost 1 out of 50,000 births.

History of Wolf-Hirschhorn Syndrome

The disease was first explained in the year 1961by two scientists Herbert L. Cooper and Kurt Hirschhorn. They published a lot of articles related to the syndrome in a German magazine, Humangenetik. Thereafter, WHS received worldwide attention and many other scientists also started researching about this rare syndrome.

Causes of Wolf-Hirschhorn Syndrome

As aforementioned, this disease occurs due to the deletion of the short arm of the chromosome 4. In 90% of the cases, there is de-novo deletion which means that the parents of patients do not have any abnormal chromosomal arrangement. In the remaining 10 % cases, a suffering child is found to inherit the chromosomal disorder from parents. If the parents of a sufferer are found to be carriers of balanced dislocation, they should be offered genetic counseling. The amount of missing genetic material determines the intensity of the symptoms. Research has also proved that WHSC1, LETM1 and MSX1 genes are also involved with the syndrome. For instance, the absence of WHSC1 gene is thought to be responsible for the distinctive facial features resulting from this disorder. The deletion of LETM1 is associated with increased occurrence of seizures and MSX1 gene is related to dental problems.

Symptoms of Wolf-Hirschhorn Syndrome

WHS is characterized by various symptoms like heart problems, seizures, breaked nose, wide eyes and mental retardation. The missing genetic material, in case of this condition, results in a number of complications. Although the symptoms may vary from one patient to another, the common ones are:

Picture of Wolf-Hirschhorn Syndrome

Picture 1 – Wolf-Hirschhorn Syndrome


  • Slow body growth, before and after birth
  • Seizures
  • Strabismus, which refers to the crossed eyes resulting from this disorder. Widely spaced eyes are also possible due to this condition.
  • Heart problems
  • Underdeveloped bones of the head and pelvis
  • Cranial asymmetry
  • Malformation of the organs of the urinary system
  • Malformation of bones in chest and spine
  • Distinctive facial features, such as broad nose and short head, which are collectively referred to as “Greek Warrior Helmet” feature.
  • Compromised muscle development and mental growth
  • Skin changes, which are mainly manifested through changes in the color of the skin.

Diagnosis of Wolf-Hirschhorn Syndrome

The distinctive facial features in patients act as strong indicators for this disease. If WHS is suspected, it should be immediately reported to a doctor who can confirm the condition based on advanced techniques like genetic testing.

The techniques commonly used for the diagnosis of WHS include:

Fluorescent in situ Hybridization (FISH)

It is used for specifically analyzing the 4p16.3 region of chromosome. The technique is used for analysis of genetic material that is too small to be viewed under a microscope. FISH helps detected the chromosomal abnormalities that are unseen by the routine chromosome analysis.

Prenatal Diagnosis

It is also very important in terms of providing proof for the disease. The prenatal analysis makes use of the techniques like anomaly ultrasound scan, chromosomal analysis and umbilical blood sampling. The ultrasound allows the recognition of distinctive facial characteristics and thereafter the technique of karyotyping is used.

Other tests

Immunoglobulin and T-cell numbers and functions are also evaluated as they are related to immunodeficiency. EEG can also be used to study the types of seizures occurring in the patient. Imaging studies of urinary tract provide information about the condition of urinary organs (which are generally malformed in WHS sufferers). MRI and CT scans may be used to study the condition of the brain.

Differential Diagnosis of Wolf-Hirschhorn Syndrome

WHS is often confused with Pitt-Rogers-Danks Syndrome due to identical symptoms. Thus, a differential diagnosis is necessary to distinguish one disorder from the other. The FISH test is usually sufficient for this purpose as it shows the deletion of 4p that occurs only in WHS patients. A differential diagnosis is also required to distinguish WHS from Proximal 4p Syndrome and Seckel’s Syndrome.

Treatment of Wolf-Hirschhorn Syndrome

The treatment of WHS differs from one patient to another. This is due to the fact that each patient exhibits different symptoms which require different approach. For instance, in cases where a cleft lip or palate is found surgery might be required. However, operative cure is unnecessary in case of patients who do not have any such abnormality.

The treatment of WHS commonly revolves around the following techniques:

Image of Wolf-Hirschhorn Syndrome

Picture 2 – Wolf-Hirschhorn Syndrome Image

1)   Following confirmation of existence of the disease, proper antiepileptic medicines should be prescribed to patients to control seizures. Valproic acid is one of the commonly used anti-epileptic drugs for the treatment of this syndrome.

2)   If affected children exhibit loss of hearing, they should be treated with suitable medication. Ocular abnormalities (defects of the eye) should be brought to the attention of an ophthalmologist.

3)   In case of severe heart problems, surgery might be required.

The management and cure of WHS requires consulting different specialists as different body parts are affected by this chromosomal disorder.

Wolf-Hirschhorn Syndrome Life Expectancy

Most patients of WHS die within 2-3 years of the onset of this syndrome. However, an affected individual may survive till adulthood in exceptional cases. Some people with the disorder can be found in good health in their second or even fourth decade of life.


Patients of WHS should be provided full support and encouragement by their parents and family members. Parents should fully cooperate with the doctors during the treatment to ensure best possible cure for and increased lifespan of their children.








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