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Understanding Familial Pulmonary Arterial Hypertension

Posted on July 28, 2022
Medically reviewed by
Steven C. Pugliese, M.D.
Article written by
Aminah Wali, Ph.D.

  • Familial pulmonary arterial hypertension (FPAH) is a type of pulmonary arterial hypertension (PAH) that has a genetic component.
  • The symptoms and treatments for FPAH are generally the same as for PAH.
  • If you have one or more family members with a gene mutation related to FPAH, you can speak with a genetic counselor about genetic testing to better understand your risk for the condition.

While the cause of pulmonary arterial hypertension is often unknown, in some cases 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 or HPAH.

PAH is a rare disorder characterized by 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 familial PAH 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 present in approximately 80 percent of people with familial PAH. They are also observed, but to a lesser degree, in related diseases like idiopathic pulmonary arterial hypertension and congenital heart disease.

While mutations of the BMPR2 gene are the most common cause of familial PAH, the condition has also been associated with mutations in other genes, such as TBX4, CAV1, ACVRL1, or 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 actually develop PAH.

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 a primary care doctor or a cardiology specialist right away if you notice persistent symptoms of PAH. If a family history of PAH is suspected, additional 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. Several clinical tests are used to confirm a diagnosis, along with checking for a familial link.

Genetic Testing and Family History

A physician will order a genomic sequencing test to look for any mutations or abnormalities in the BMPR2 gene, or other related genes involved in FPAH. They will also look into your family history to see if you have family members who have been diagnosed with PAH. Gene mutations don’t always predict that you’ll develop PAH, but the evidence of a family history of PAH is the key observation that distinguishes familial PAH from idiopathic PAH (PAH from an unknown cause).

Laboratory Tests

Routine laboratory tests will measure blood cell counts and antibody levels. Lab tests can also detect other risk factors for pulmonary hypertension, including HIV infection and coagulation (blood clotting) disorders.

Echocardiogram

One of the primary tests required for diagnosing PAH is an echocardiogram. An echocardiogram is an ultrasound that looks at the heart to see if it’s abnormally enlarged. 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 is 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.

Familial Pulmonary Arterial Hypertension Treatment Options

Many therapies can be prescribed to manage PAH, including familial PAH. Many commonly used drugs act as vasodilators, meaning 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. Commonly used prostacyclin analogs include epoprostenol (sold as Flolan and Veletri) and treprostinil (sold as Orenitram, Remodulin, and Tyvaso).

Soluble Guanylate Cyclase Stimulators

Soluble guanylate cyclase stimulators widen blood vessels by stimulating activity of a protein called guanylate cyclase. The stimulators may be used to treat chronic thromboembolic pulmonary hypertension, a type of PH in which blood clots block the arteries in the lungs for long periods of time. A commonly prescribed stimulator is riociguat (Adempas).

Endothelin Receptor Antagonists

Endothelin receptor antagonists reduce the function of endothelins, molecules that cause constriction of the blood vessels. Drugs that fall into this class include:

Phosphodiesterase Type 5 Inhibitors

Phosphodiesterase type 5 (PDE5) is an enzyme that plays a role in constricting blood vessels, similar to endothelins. PDE5 inhibitors dilate blood vessels and reduce blood pressure. This class of drugs includes tadalafil (Adcirca) and sildenafil (Revatio).

Anticoagulants

Anticoagulants, also called blood thinners, reduce the clumping of blood cells, thereby reducing the risk of clots. 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 class of drugs works by eliminating 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 open the arteries and decrease the force with which the heart pumps. This can relieve high blood pressure and chest pain. 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)

Outlook for Familial Pulmonary Arterial Hypertension

Although many people are able to manage the condition with treatments, there is currently no cure for familial PAH. The prognosis (outlook) for PAH is generally considered poor without treatment, but outcomes are improved if the condition is detected earlier and treated.

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 can allow for early detection and prompt treatment, ultimately leading to a more favorable long-term outlook for familial PAH.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 46,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Are you or a loved one living with familial pulmonary hypertension? How do you manage the condition? Share your experience in the comments below, or start a conversation by posting on myPHteam.

All updates must be accompanied by text or a picture.
Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here.

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