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We do not know precisely ‘why’ TBX4 mutations cause PH. But, scientists and clinicians are making progress. We know that TBX4 mutations disrupt key cellular actions that may ultimately cause lung changes at the microscopic level which cause the blood pressure to rise (PH to occur).
PH may occur in a person with a TBX4 mutation at any age. Or, it may never occur. We are still working to understand why some people get PH but others never get PH.
How Might PH Present in Childhood?
While every person is different, the presentation of PH in a person with a TBX4 mutation has some common features.
- Some children may present with a profound, prolonged, unexplained persistence of pulmonary hypertension within a few hours to days of birth (in the neonatal period), known as persistent pulmonary hypertension of the newborn (PPHN). However, it is important to know that PPHN is rather common (0.5 to 5 people with PPHN per 1000 live births)--the vast majority of cases of PPHN are not associated with a TBX4 gene mutation.
- Some children may have neonatal onset of PPHN that does not remit, and turns into a more chronic, ongoing PH condition.
- Some children may present in infancy with PH in concordance with other features of a developmental lung disorder. In this case, the child’s condition may look like PPHN with features of a developmental lung disorder; or, the PH may present later than the neonatal period.
- Some children may have no problems during infancy, but present later in childhood with PH not obviously associated with another medical condition.
As best we currently know, unless there are other factors aggravating the lungs and/or heart, the condition is a ‘precapillary PH’ condition.
How Might PH Present in Adulthood?
While every person is different, the presentation of PH in a person with a TBX4 mutation has some common features. When presenting in an adult, unless there are other factors aggravating the lungs and/or heart, the condition is a ‘precapillary PH’ condition. In this case, a person may present with PH that upon work up has no obvious cause initially; however, upon workup features of TBX4 Syndrome may be discovered.