Molecular characteristics

ZFHX4-associated syndrome is caused by one copy of the ZFHX4 gene not functioning properly. This may be due to a change (pathogenic variant) within the gene which disrupts its function, or to the loss (deletion) of the gene or a part of it. Most affected people are the first person in their family to carry the gene change, but a small proportion have inherited it from a parent, who is likely to have features of ZFHX4­-associated syndrome. This condition affects boys and girls, and there are both mildly and more significantly affected individuals of both sexes.

When children are conceived their parents’ genetic material is copied in the egg and sperm that makes a new child. The biological copying method is not perfect and occasionally random, rare changes occur in the genetic code of children that are not seen in the DNA of their parents. ZFHX4-associated syndrome occurs when one of these changes affects the ZFHX4 gene on chromosome 8 (band q21.11). These types of changes happen naturally in all species. The possibility of having another child affected by a rare gene disorder depends on the genetic code of the parents. In most families, the genetic change has happened for the first time in the child with ZFHX4-associated syndrome. This is called a de novo change. When the parents are unaffected, the chances of having another child with the same condition are very low (usually less than 1%). If a parent has ZFHX4­-associated syndrome, the chances of passing the condition on to a child are much higher at 50%, as the parent could either pass on their altered copy of the gene or the unaffected copy. This is called an autosomal dominant inheritance pattern. Each family situation is different, and a clinical geneticist or genetic counsellor can give specific advice for your family.