What is Wolf-Hirschhorn Syndrome?

Result of chromosome 4 error

GIPhotoStock/Cultura/Getty Images

https://www.verywell.com/benign-seizures-of-infancy-2488790Wolf-Hirschhorn syndrome is a genetic disorder that affects fetal growth and development. It produces distinctive facial features, short stature, mental retardation, and abnormalities of several organ systems. It is estimated to occur in 1 in 50,000 births.

Wolf-Hirschhorn syndrome results from a genetic error on chromosome 4.

However, in most cases, this is not an inherited genetic error, but a spontaneous mutation. So, in 87% percent of affected individuals, there is no family history of the disorder. Wolf-Hirschhorn syndrome affects females more frequently than males, and occurs in people of all ethnic backgrounds.


Wolf-Hirschhorn syndrome causes malformations in most parts of the body because the genetic error affects the developing fetus.

Symptoms may include:

  • Distinctive facial features - prominent forehead, wideset eyes, and broad-beaked nose, collectively described as "Greek warrior helmet" features
  • Brain and muscles - profound mental retardation, small head, seizures (50% of individuals), low muscle tone, poor muscle development
  • Bones - very short stature, facial deformities, malformations of hands and feet, chest, and spine
  • Heart defects - especially atrial septal defect, ventricular septal defect, and pulmonic stenosis
  • Urinary and genitals - malformations or underdevelopment of organs


Children born with Wolf-Hirschhorn syndrome may be diagnosed by ultrasound in utero or by appearance at birth. The distinctive facial features are an immediate clue to the presence of the syndrome. Genetic testing can confirm the diagnosis.

Additional tests, such as x-rays to look for bone and internal malformations, renal ultrasonography to examine the kidneys, and magnetic resonance imaging of the brain, are important.


Since no treatment exists for the underlying genetic disorder, treatment for Wolf-Hirschhorn syndrome focuses on the symptoms present.

For example, a seizure disorder would be treated with medication, and difficulty eating or swallowing might require a gastrostomy feeding tube. Physical and occupational therapy can help maintain muscle strength and joint mobility. Care by many different specialists may be needed.

The risk of a parent having another child with Wolf-Hirschhorn syndrome is quite unlikely, unless the parent is a carrier for the disorder.


Chen, H. (2003). Wolf-Hirschhorn syndrome. eMedicine http://www.emedicine.com/ped/toppic2446.htm

Hart L, Rauch A, Carr AM, et al. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition. Dis Model Mech 2014; 7:535.

Andersen EF, Carey JC, Earl DL, et al. Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf-Hirschhorn Syndrome. Eur J Hum Genet 2014; 22:464.

Edited by Richard N. Fogoros, MD

Continue Reading