Focal dermal hypoplasia

Focal dermal hypoplasia is caused by mutations in the PORCN gene and is inherited in an X-linked dominant manner. Many cases of focal dermal hypoplasia result from a new mutation and occur in people with no history of the disorder in their family ^[1] For a woman affected with focal dermal hypoplasia, the theoretical risk of passing the mutation to each of her offspring is 50%; however, many males with this condition do not survive. In addition, there are cases in which a woman may have the focal dermal hypoplasia mutation in some but not all of her egg cells, a condition known as germline mosaicism. In this case the risk of passing along the mutation may be as high as 50% depending on the level of mosaicism. Males with focal dermal hypoplasia typically have the mutation in some but not all of their cells. The risk that a male with FDH will pass the condition on to his daughters may be as high as 100%; men do not pass this condition on to their sons.^[2] We recommend discussing specific concerns with a genetics professional, who can help you understand how this condition might be inherited in your family. Click on the following link for resources for finding a genetics professional.

Females have two X chromosomes, while males have one X chromosome and one Y chromosome. Early in female embryonic development, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg cells). This process, known as X-inactivation, ensures that both females and males have only one active copy of the X chromosome in each body cell. As a result, in each somatic cell, the X chromosome that contains the focal dermal hypoplasia mutation may be turned on or turned off. Usually, X-inactivation occurs randomly. When X-inactivation does not occur randomly, it is called skewed X-inactivation. ^[1] Researchers suspect that the distribution of active and inactive X chromosomes may play a role in determining the severity of focal dermal hypoplasia.^[1][2] As X-inactivation occurs in somatic cells, it does not affect the inheritance of a condition.^[1][3][4]