Overview

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure (hypertension) in the arteries of the lungs (pulmonary artery) for no apparent reason. The pulmonary arteries are the blood vessels that carry blood from the right side of the heart through the lungs.The exact cause of PAH is unknown and although treatable, there is no known cure for the disease. PAH usually affects women between the ages of 30-60.

Symptoms

PAH symptoms are those that are normally associated with not having enough oxygen in the blood. In most cases, the initial symptom is severe shortness of breath following exertion. Additional symptoms include excessive fatigue, weakness, chest pain, dizzy spells, and fainting episodes.

Affected individuals may also have a cough, sometimes with blood (hemoptysis), an enlarged heart and liver, low blood pressure (hypotension), and hoarseness due to compression of a nerve in the chest by an enlarged pulmonary artery.

In some cases, affected individuals may experience puffiness or swelling of the face, ankles, abdomen and feet due to abnormal accumulation of fluid (edema) within fascial tissues.

In approximately 10 percent of cases, individuals experience Raynaud’s phenomenon, a condition characterized by painfully cold fingers and toes caused by widening (dilation) or narrowing (constriction) of small blood vessels in the hands and feet in response to cold.

Individuals with advanced stages of PAH may have abnormal bluish discoloration of the skin due to low levels of circulating oxygen in the blood (cyanosis). In addition, in severe cases of PAH, the right chamber (ventricle) of the heart is abnormally enlarged (hypertrophy), resulting in diminished functioning of the right portion of the heart and, potentially, right heart failure. Some patients with PAH do not seek medical advice until they are no longer able to continue with their normal activities. At this time, the disease may have progressed to a point where the patient is completely bedridden from shortness or breath or other symptoms.

Causes

The exact cause of PAH is unknown. Researchers believe that injury to the layer of cells that line the small blood vessels of the lung, perhaps then causing or in concert with changes in the smooth muscle cells in the vessel wall, initiates blood vessel disease. This injury, which occurs for unknown reasons, results in the contraction of smooth muscle and therefore narrows the vessel. Researchers also think that most people who develop PAH have blood vessels that are particularly sensitive to certain internal or external factors and constrict, or narrow, when exposed to these factors.

Approximately 15-20% of patients with PAH have heritable PAH. Heritable PAH is an autosomal dominant genetic condition caused by mutations in the BMPR2 gene most commonly, though recently other genes and pathways have been identified. In approximately 20% of families with PAH, we do not yet know the underlying gene mutations. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation in the affected individual. Approximately 80% of individuals who have a mutated (abnormal) BMPR2 gene will not develop PAH, so other genes or environmental triggers must be necessary for PAH to develop. The risk of passing the abnormal gene from parent to offspring is 50% for each pregnancy and the risk is the same for males and females. Of note, there now exist several publications associating PAH with mutations in other genes in a small number of subjects (e.g. CAV1, KCNK3, etc), although many of those genes are closely linked to BMPR2 in terms of biologic signaling (SMAD9, ALK1, endoglin).

Diagnosis

It can often be hard to detect PAH in a routine clinical examination, even if the disease has progressed. Symptoms of PAH are not unique and may be confused with many other diseases that cause a lack of oxygen in the blood. The diagnosis of PAH is also one of exclusion, meaning that PAH is only diagnosed when other causes of pulmonary hypertension have been ruled out and there seems to be no known cause of the hypertension. The tests that are commonly performed to diagnose PAH and rule out other diseases are blood tests, pulmonary function tests, X-rays of the chest, electrocardiography (ECG), and the “6-minute walk test”, which essentially measures how far an individual can walk in that time period. Ultimately, the majority of subjects undergo echocardiographic testing, followed by confirmation by cardiac catheterization with and without vasodilator testing.

Heritable PAH is confirmed if two or more family members have PAH or if a BMPR2 gene mutation is identified in the affected person. Molecular genetic testing is available for mutations in the BMPR2 gene, but should only be performed in concert with genetic counseling.

Clinical Testing and Work-Up

Patients suspected to have PAH should be referred to a referral center specializing in PAH diagnosis and treatment. The Pulmonary Hypertension Association website can provide contact information for these centers.

Genetic counseling is recommended for affected individuals and their families.

Resources

Clinical Trials

ClinicalTrials.gov
An online database of publicly and privately supported clinical studies conducted around the world. ClinicalTrials.gov currently lists thousands of studies with locations in all 50 states and in 191 countries.

Genetic Testing

Genetics Home Reference
An online resource from the National Institutes of Health. The website provides easy-to-understand information about genetic conditions and a range of topics. You’ll find basic explanations of how genes work and how mutations cause disorders. It also includes current information about genetic testing, gene therapy, and the Human Genome Project.

National Society of Genetic Counselors
Provides a helpful, easy-to-use online directory to help connect physicians, patients, and other genetic counselors. Search by state, city, counselor’s name, institution, work setting, type of specialty, or zip code.

Resources for Families and Caregivers

Rare Share
A unique social hub building communities for patients, families, and healthcare professionals affected by rare disorders.

Caregiver Action Network (CAN)
The nation’s leading family caregiver organization working to improve the quality of life for the more than 90 million Americans who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. CAN (formerly the National Family Caregivers Association) is a nonprofit organization providing education, peer support, and resources to family caregivers across the United States free of charge.

Center for Parent Information & Resources
A central resource of information and products to the community of Parent Training Information Centers and the Community Parent Resource Centers so they can focus their efforts on serving families of children with disabilities.

Cyberbullying Research Center
Dedicated to providing up-to-date information about the nature, extent, causes, and consequences of cyberbullying, it is intended to be a resource for parents, educators, law enforcement officers, counselors, and others who work with youth. You will find facts, figures, and detailed stories from those who have been directly affected by online aggression. In addition, the site includes numerous resources to help you prevent and respond to cyberbullying incidents.

Family Caregiver Alliance (FCA)
A community-based nonprofit organization that that aims to illuminate the caregivers’ daily challenges to better the lives of caregivers nationally, provide them the assistance they need, and champion their cause through education, services, research and advocacy. FCA offers programs at national, state, and local levels to support and sustain caregivers.

Family Voices
Family Voices aims to achieve family-centered care for all children and youth with special health care needs and/or disabilities. Throughout their national grassroots network, they provide families resources and support to make informed decisions, advocate for improved public and private policies, build partnerships among families and professionals, and serve as a trusted resource on health care.

OurKids
An email list of family of parents, caregivers and others who are working with children with physical and/or mental disabilities and delays.

Parent to Parent USA
Programs offering parent-to-parent support as a core resource for families with children who have a special health care need, disability, or mental health issue. Through a one-to-one “match,” experienced support parents provide emotional support to families and assist them in finding information and resources.

Sibling Support Project
A national program dedicated to the lifelong and ever-changing concerns of the millions of brothers and sisters of people with special health, developmental and mental health concerns.

Stopbullying.gov
A website providing information from various government agencies on what bullying is, what cyberbullying is, who is at risk, and how you can prevent and respond to bullying.

The Bully Project
Inspired by the award-winning film BULLY, this social action campaign includes tools for educators to spark meaningful conversations about bullying.

The Parent Advocacy Center for Educational Rights (PACER Center)
PACER Center is a parent training and information center for families of children and youth with all disabilities from birth to young adults. Parents can find publications, workshops, and other resources to help make decisions about education, vocational training, employment, and other services for their children with disabilities. PACER’s National Bullying Prevention Center provides resources designed to benefit all students, including those with disabilities.

The Washington State Fathers Network (WSFN)
The Washington State Fathers Network (WSFN) connects men with other dads, resources, information and education, plus opportunities for “all family” celebrations. Focus is on assisting fathers as they become more competent and compassionate caregivers for their children with special needs. WSFN is the only regional program in the US and Canada fully devoted to fathers of children with special health care needs and developmental disabilities. Since 1986 it has opened new doors of hope for thousands of men and their families, providing them with support and resources to be effective, nurturing dads.

General Health Resources

Agency for Healthcare & Research Quality (AHRQ)
Aims to provide evidence to make health care safer, higher quality, more accessible, equitable and affordable, and to work with the US Department of Health and Human Services and with other partners to ensure that the evidence is used and understood.

Health Hotlines (National Library of Medicine)
A community service to help the public locate health-related information.

Social Security Administration Compassionate Allowances Program
Provides a way of quickly identifying diseases and other medical conditions that may qualify for financial assistance.

Center on Technology & Disability
Designed to increase the capacity of families and providers to advocate for, acquire, and implement effective assistive and instructional technology practices, devices, and services for those who suffer from disabilities.

National Human Genome Research Institute
Developed with the goal of mapping the human genome, the group provides a list of resources for financial assistance with genetic testing.

National Library of Medicine
Provides guidance on how to find reliable information online regarding human genetics.

Patient Advocate Foundation
Provides professional case management services to individuals facing barriers to healthcare access for chronic and disabling disease, medical debt crisis, and employment-related issues at no cost.