Wolf-Hirschhorn syndrome (4p16.3)


Wolf-Hirschhorn syndrome is a congenital chromosome abnormality in which part of the short arm of chromosome 4 is missing. Severe mental retardation, growth retardation, intractable epilepsy and multiple malformations are the main symptoms.

In addition, they have asymmetrical facial features and microcephaly, which results in short stature in most people with this disorder.


The prevalence of Wolff-Hirschhorn syndrome is estimated at 1 in 50 000 births. However, this may be an underestimate, as some affected individuals are likely to go undiagnosed.

The disease occurs in about twice as many women as men, but the cause is unknown.


It is caused by the loss of several genes on the short arm of chromosome 4. The genes missing in people with typical signs and symptoms of this disorder are NSD2, LETM1 and MSX1, with loss of the NSD2 gene thought to be associated with many of the features of Wolf-Hirschhorn syndrome, such as characteristic facial features and developmental delay; loss of the LETM1 gene is associated with brain seizures or other abnormal electrical activity; the loss of the MSX1 gene may be responsible for the dental abnormalities, cleft lip or cleft palate that are common in this condition.


Wolff-Hirschhorn syndrome usually causes malformations of the heart, brain, skeleton, urinary tract, eyes and immune system. People with the syndrome usually also have severe mental retardation. However, symptoms and their severity vary from person to person. Some people are born with cleft lip, cleft jaw or cleft palate.


Chromosomal abnormalities are confirmed by FISH and microarray chromosome testing. Additional tests for complications are also added as appropriate.


For mental retardation, this includes training to develop motor development, cognitive, language and social skills, while for convulsions, anticonvulsants are administered.

Children with this syndrome also often have difficulty sucking, swallowing and taking in adequate nutrition and therefore need to be fed through a tube that passes through the nose, throat and oesophagus.

Tests of palate and palatal function are carried out at an early stage, as even a small cleft palate can make eating difficult for the child.


The prognosis of life depends mainly on the coexistence of intractable epilepsy and concomitant cardiac disease.