For most individuals, the diagnosis of PHO is based on the clinical features. It is recognized more often in males than females, as males have more noticeable and severe features. PHO can be inherited, but a non-genetic form has also been described.
Genetic conditions can be inherited in different ways. Individuals typically inherit one copy of a gene pair from their mother, and the other from their father. Genes provide instructions to tell the body how to function. When there is a harmful change (mutation) in a gene it may not function normally leading to unusual features and/or conditions. Autosomal dominant and autosomal recessive inheritance patterns have been reported for PHO.
There are two genes that have been associated with PHO: HPGD and SLCO2A1. Mutations in HPGD are associated with autosomal recessive inheritance and this condition is sometimes abbreviated PHOAR1 or Touraine-Solente-Gole syndrome.
Recessive genetic conditions occur when an individual inherits one non-working gene for the same condition from each parent. If an individual receives one normal gene and one gene with a mutation, the person will be a carrier for the condition and will usually not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have a child with that condition is 25% with each pregnancy. The chance to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal working genes from both parents is 25%. The chance is the same for males and females.
Parents who are closely related by blood (consanguineous) have a higher chance than unrelated parents to both carry the same non-working gene, which increases the chance to have children with a recessive genetic disorder.
PHO caused by mutations in SLCO2A1 can be dominant or recessive. The recessive form is called PHOAR2. The dominant form is called PHOAD. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to see symptoms of the condition. The non-working gene can be inherited from either parent or can be the result of a new mutation (gene change) in the individual with the condition. The chance of passing the non-working gene from an affected parent to child is 50% for each pregnancy. The risk is the same for males and females. However, with PHOAD, males are more commonly and often more severely affected.