• Familial pulmonary arterial hypertension (FPAH) is a type of pulmonary arterial hypertension (PAH) that’s partly caused by gene mutations (changes) that can run in families. It’s also called heritable PAH.
• The symptoms and treatments for FPAH are generally the same as for PAH.
• If someone in your family has a gene mutation linked to FPAH, talking to a genetic counselor about testing can help you learn more about your risk for the condition.

Although the cause of PAH is often unknown (also called idiopathic), sometimes there is a genetic link. This may indicate familial pulmonary arterial hypertension, a type of PAH diagnosed in two or more members of the same family. The condition is also referred to as heritable pulmonary arterial hypertension.

PAH is a rare disorder known for causing high blood pressure in the blood vessels of the lungs, potentially leading to right heart failure and possibly death. If PAH runs in your family, it’s important to tell your health care provider. They can help you better understand your risk of developing PAH.

Causes of Familial Pulmonary Arterial Hypertension

The most common cause of FPAH is a mutation in a gene called bone morphogenetic protein receptor 2 (BMPR2). Gene mutations have been linked to different diseases and cancers, and these mutations can be passed down through families.

BMPR2 mutations are found in about 80 percent of people with FPAH. They are also seen, but not as much, in related diseases like idiopathic pulmonary arterial hypertension (IPAH) and congenital heart disease. Although mutations of the BMPR2 gene are the most common cause of FPAH, the condition has also been associated with mutations in other genes, such as TBX4, CAV1, ACVRL1, and ALK1.

Each person inherits one copy of a gene from each of their parents. If one copy of the BMPR2 gene is mutated, then that person is at risk for developing PAH. However, FPAH displays incomplete penetrance, meaning that even if a person inherits a mutated BMPR2 gene, it doesn’t guarantee they will develop PAH. In fact, of all the people who inherit a mutated copy of BMPR2, only 20 percent will develop PAH.

Who Should Get Genetic Testing?

If you’re diagnosed with PAH, your doctor might suggest genetic testing to see if you have certain genetic changes that could be causing it. Family members should also undergo genetic testing for FPAH if these mutations are found. If no FPAH-related mutations are found, genetic testing of family members isn’t necessary.

Annual genetic testing is recommended for family members who don’t have PAH symptoms but are known carriers of FPAH-related gene mutations or whose related gene mutation status is unknown.

Genetic testing should come with genetic counseling. Genetic counseling is recommended before and after someone undergoes genetic testing to ensure family members understand the test results and what they mean.

Symptoms of Familial Pulmonary Arterial Hypertension

Symptoms of FPAH are the same as other forms of PAH. The most common symptoms include:

• Chest pain
• Dyspnea (shortness of breath), especially during physical activity
• Fatigue
• Heart palpitations or irregular heartbeat
• Edema (swelling) around the hands and feet
• Fainting spells

Consult your primary care doctor or a cardiology specialist right away if you notice persistent symptoms of PAH. If you think you may have a family history of PAH, more testing may be recommended for your family members even if they don’t have any symptoms.

Familial Pulmonary Arterial Hypertension Diagnosis

To explore a diagnosis of PAH, a health care provider will start by looking at your symptoms and medical history. Doctors use different tests to confirm a diagnosis, and they also look into whether there’s a family history of the condition.

Genetic Testing and Family History

Your doctor might ask for a genomic sequencing test, which is like reading a detailed map of your DNA. This test helps them look for changes in genes like BMPR2 related to FPAH. They’ll also check your family history to see if anyone in your family has had PAH. Although gene changes don’t always mean you’ll get PAH, having a family member with PAH is a clue that helps tell if it’s familial or idiopathic.

Laboratory Tests

Routine laboratory tests will measure blood cell counts and the amount of antibodies in your blood, which are special proteins that help your body fight germs and infections. Lab tests can also detect other risk factors for pulmonary hypertension, including HIV infection, blood clotting disorders, and autoimmune disease (when your body’s defense system mistakenly attacks healthy cells).

Echocardiogram

One of the main tests required for diagnosing PAH is an echocardiogram. An echocardiogram uses sound waves to make pictures of your heart. Doctors use it to check if your heart is larger than it should be, which could mean potential heart problems. An echocardiogram can also estimate pulmonary arterial pressure and determine if there is any strain on the heart.

Cardiac Catheterization

Although pulmonary arterial pressure can be estimated with an echocardiogram, it’s more accurately measured by right heart catheterization, a minimally invasive procedure in which a catheter is inserted into the heart and pulmonary arteries. Right heart catheterization measures the pressure in the pulmonary arteries and the level of oxygen in the blood and can identify ventricular dysfunction — when the heart ventricles don’t work properly — caused by PAH.

Familial Pulmonary Arterial Hypertension Treatment Options

Many therapies can be prescribed to manage PAH, including FPAH. Many commonly used drugs act as vasodilators — they widen the blood vessels to help blood flow more easily.

Prostacyclin Analogs

Prostacyclin is a compound naturally produced in the body that makes blood vessels widen to increase blood flow. Prostacyclin analogs are often prescribed to treat pulmonary arterial hypertension. Prostacyclin analogs include epoprostenol (sold as Flolan and Veletri), treprostinil (sold as Orenitram, Remodulin, and Tyvaso), and selexipag (sold as Uptravi).

Soluble Guanylate Cyclase Stimulators

Soluble guanylate cyclase stimulators work by making blood vessels wider. They do this by boosting the activity of a protein called guanylate cyclase. Doctors might prescribe these stimulators to treat long-term thromboembolic pulmonary hypertension, which is a type of PH where blood clots block the arteries in the lungs for a long time. A commonly prescribed stimulator is riociguat (Adempas).

Endothelin Receptor Antagonists

Endothelin receptor antagonists are medicines that help decrease the action of endothelins, which are molecules that make blood vessels tighten up. By doing this, the medication helps to widen the blood vessels, making it easier for blood to flow through.

Drugs that fall into this class include:

• Ambrisentan (Letairis)
• Bosentan (Tracleer)
• Macitentan (Opsumit)

Phosphodiesterase Type 5 Inhibitors

Phosphodiesterase type 5 (PDE5) is like a switch in your body that can tighten blood vessels, just like endothelins do. But when we use PDE5 inhibitors, they work to open up those blood vessels instead. This helps to lower blood pressure and improve blood flow throughout the body. This class of drugs includes tadalafil (Adcirca) and sildenafil (Revatio).

Anticoagulants

Anticoagulants, also known as blood thinners, help prevent blood cells from sticking together and forming clots. By doing this, they lower the chance of clots forming in your blood vessels, which can help reduce the risk of serious health issues like strokes or heart attacks. The most common anticoagulant drug used in the treatment of pulmonary hypertension is warfarin (Coumadin).

Diuretics

Also called water pills, diuretics are often prescribed to treat high blood pressure. This kind of drug works by getting rid of sodium and water through urination, thereby lowering pulmonary blood pressure. Common diuretics include:

• Furosemide (Lasix)
• Metolazone (sold under brands including Mykrox and Zaroxolyn)
• Spironolactone (sold as Aldactone and CaroSpir)

Calcium Channel Blockers

Calcium channel blockers help these blood vessels relax and widen, making it easier for blood to flow through. At the same time, they also help reduce the force with which your heart pumps blood. This can help manage high blood pressure or certain heart problems.

Types of calcium channel blockers include:

• Amlodipine (sold as Katerzia and Norvasc)
• Diltiazem (sold under brands such as Cardizem)
• Nifedipine (sold under brands including Adalat CC and Nifedical XL)

Read more about specific medications in this list of treatments for pulmonary hypertension.

Outlook for Familial Pulmonary Arterial Hypertension

Although many people can manage FPAH with treatments, there is currently no cure for FPAH. The prognosis (outlook) for PAH is generally considered poor without treatment, but outcomes are improved if the condition is detected earlier and treated. Your doctor will perform regular risk assessments to help monitor disease progression and how well your body responds to treatments.

If a known or suspected genetic cause for PAH runs in your family, genetic counseling is generally recommended to understand your risk of developing PAH. Talking to a genetic counselor will help you understand the process of genetic testing and decide whether it’s the right option for you. This step can help find the problem early and start treatment quickly, which can improve the long-term outlook for FPAH.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 53,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Have you learned if familial pulmonary hypertension runs in your family? How have you managed with diagnosis and treatment? Share your experience in the comments below, or start a conversation by posting on your Activities page.