Which Rare Diseases Are the Most Common?

Updated October 23, 2019

This article was scientifically reviewed by YourDNA

We take the information we share seriously. Review our Editorial Policy Here.

A list of references is also included at the bottom of this article.

Rare diseases around the world are disorders like Huntington’s disease, Angelman syndrome, cystic fibrosis, and others.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

Most rare diseases show an unusual epigenetic structure across the genome but a small percentage of them come from infectious diseases, rare cancers, and unusual autoimmune disorders.

However, since rare disorders are both scarce and complex, much research still needs to be done to diagnosis, prognosis, and treatment.

In this article, we will give you an overview of the current state of medical knowledge about rare diseases, as well as explain how a lack of public awareness makes it difficult for patients to get accurate medical treatment and for caregivers to get community support and help from health care organizations.

What Are Rare Diseases?

Rare diseases are usually hereditary and have severely debilitating and life-threatening symptoms. 

For instance, a recessive disorder can cause a debilitating and life-threatening rare disease like cystic fibrosis (CF) 1.

Since someone with CF has mutations in both copies of their CFTR gene, their body creates so much thick mucus that it clogs their lungs.

Eventually, this mucus buildup causes breathing obstructions that shorten their lives.

Because the Orphan Drug Act of 1983 was enacted by Congress to encourage pharmaceuticals to develop drugs and bio-products for these extremely rare genetic disorders, you’ll also hear a rare disease referred to as an orphan disease.

How rare is a medical rare disease, disorder, or syndrome? Different health systems around the world classify the rarity of these diseases in different ways.

For instance, in the United States, the U.S. Food and Drug Administration defines it as a disorder that affects fewer than 200,000 people while in Europe, the Amsterdam-based European Medicines Agency defines it as a disorder that affects fewer than 1 in 2,000 people.

Characteristics of Rare Diseases

Besides their low rate of incidence, rare diseases and their symptoms often follow unpredictable patterns.

The signs and symptoms of a rare disease syndrome are erratic. For instance, some show up in one patient and not another, some show up earlier, and some progress faster.

This random nature of symptoms in a rare disease makes it difficult for researchers to define a clear clinical description, for doctors to predict complications, and for drug makers to develop effective treatments.

However, early detection in children by a rare disease specialist and the availability of a palliative treatment option has allowed many patients to live relatively normal lives.

Causes of Rare Diseases

Diverse factors cause rare diseases, but most directly stem from changes in genes and chromosomes. Families genetically pass some rare diseases down each generation while others occur randomly, with someone becoming the first person in their family with a condition.

Still, not all rare diseases are genetic anomalies. Some are infectious diseases, birth defects, rare cancers, autoimmune diseases, and other non-genetic causes.

Although researchers have not been able to identify all the causes of rare diseases, each year they discover more causes and identify more symptoms.

Are Rare Diseases Genetic?

Since many rare conditions have genetic components, there appears to be a strong correlation between genetics and rare diseases.

Still, not all such disorders are rare genetic diseases. Many environmental factors can cause rare conditions, such as infectious diseases.

Prevalence and Incidence of Rare Diseases

In the United States, an estimated 25 to 30 million Americans have a rare disease. One reason for estimates rather than more exact figures is because of poor tracking of these conditions. 

Few diagnosed rare diseases are tracked, including those diagnosed on state newborn screening tests.

Researchers base documentation of the prevalence and incidence of rare diseases on rough estimations.

For instance, the prevalence and incidence of Huntington’s disease are restricted to the Caucasian population and is estimated at 1/20,000 to 1/10,000 2

This lack of accurate statistics is not just because rare diseases affect a slice of the population, but also because researchers have only discovered a small sample of case studies since doctors frequently misdiagnose rare diseases. 

Misdiagnosis occurs for three main reasons. 

  1. Unfamiliarity with rare diseases. Doctors may never have seen a rare disorder before. 
  2. Symptoms mimic well-known diseases. Doctors with some knowledge and experience with rare diseases might still mistake the symptoms for a more common disease. 
  3. Arbitrary diagnosis of a disease. While doctors sometimes misdiagnose a rare disease because some symptoms closely mimic those of a better-understood disorder, at other times the symptoms don’t even match the profile of the disease.

Here are some examples of rare disease mistakes:

  • Anti-NMDA receptor encephalitis has been mistaken for a mental disorder
  • Autoimmune Hemolytic Anemia has been mistaken for cancer and organ failure
  • Neurodegeneration with Brain Iron Accumulation (NBIA) has been mistaken for Attention Deficit Hyperactivity Syndrome (ADHD). 

How Many Rare Diseases Are There?

There may be far more rare diseases than most people realize. Researchers estimate that there are 7,000 rare diseases 3 and discover about 250 more each year.

While some rare diseases arise from infections, birth disorders, rare cancers, or autoimmune diseases, most of the 7,000 rare diseases on a genetic disorder list occur for one of four reasons:

Point mutation — which is an insertion or deletion inside a gene.

Deletion — of one or more genes.

Chromosome abnormality — like an extra chromosome, a missing chromosome, or both an extra chromosome and a missing chromosome. 

Trinucleotide repeat disorder — which is a gene with an extended length.

The Most Common Rare Diseases

Researchers have compiled a long list of rare diseases by prevalence.

Here are the top 10 rare diseases and their causes:

  1. Angelman syndrome — DCP mutation in chromosome 15
  2. Canavan disease — Unknown genetic condition affects chromosome 17p
  3. Charcot–Marie–Tooth disease — Unknown genetic condition affects chromosome 17
  4. Color blindness — P mutation in chromosome X
  5. Cri du chat syndrome — D mutation in chromosome 5
  6. Cystic fibrosis — P mutation in chromosome 7q
  7. DiGeorge syndrome  — D mutation in chromosome 22q
  8. Down syndrome — C mutation in chromosome 21
  9. Duchenne muscular dystrophy — D mutation in chromosome Xp
  10. Familial hypercholesterolemia — P mutation in chromosome 19

Diagnosing Rare Diseases

It can take years for a patient to get an accurate diagnosis. Along the way, patients frequently experience misdiagnosis and costly and erroneous treatments while their families go through persistent anxiety and confusion.

Diagnosis quickly improves once physicians recognize their patients might have a rare disease.

This insight then prompts leads to a suspected a genetic causation as there is a strong correlation between rare diseases and genetic anomalies. 

However, primary care doctors unfamiliar with rare diseases won’t make the intuitive leap to look for a genetic reason cause for the symptoms.

According to the British Journal of General Practice, general practitioners often don’t recognize “the zebras among the horses.” 4

For this reason, more common rare diseases like Angelman Syndrome in children, are often mistaken for an autistic spectrum disorder or cerebral palsy.

Treatment of Rare Diseases

Diagnosis, treatment, and prevention of rare diseases are only now making some progress. Much research broader research is necessary. 

At present, for example, clinical trials are limited to focusing on non-carcinogenic rare diseases.

Rare diseases without a cure are the norm rather than the exception. Still, the Office of Orphan Products Development (OOPD) has helped to create a sea of change for developing rare diseases drugs.

From 1973 to 1983, there were only ten treatments available for rare diseases, but since 1983, there have been 400 treatments developed for rare diseases, which include drugs and bio-products.

The FDA is also providing guidance to manufacturers to help them develop a gene therapy product for treating children and adults with rare diseases.

Living With a Rare Disease

Living with a rare disease 5is extremely difficult in a society that doesn’t know much about the problem. Consequently, many patients and caregivers can’t get the medical help they need from the healthcare system because of this lack of awareness. 

Patients with rare diseases frequently have a poor clinical experience. Doctors often misdiagnose symptoms and patients experience long delays in receiving proper treatment.

However, it’s not accurate to put the blame on doctors who don’t get sufficiently researched information on rare diseases or on children’s hospitals without pediatric rare disease specialists.

Healthcare providers don’t have access to high-quality information about rare diseases.

The real reason that patients and caregivers don’t receive the help they need is the insufficient number of studies and synthesis of findings.

Where to Find Help

Patients and caregivers can find help from one or more of the following rare disease associations: 

Raising Public Awareness

Society’s lack of knowledge about rare diseases makes it difficult for both patients and healthcare providers. 

It is difficult enough for patients and caregivers because of the debilitating symptoms, but what aggravates their situation is the lack of public awareness.

Besides getting inadequate and often inaccurate medical treatment, they also don’t have enough emotional, community, or financial support to manage day-to-day living issues. 

Meanwhile, medical researchers can’t get the support they need for clinical trials and physicians often can’t get the accurate information they need to improve diagnosis and provide more effective treatment plans. 

Dr. Christopher P. Austin, who is the director of the National Center for Advancing Translational Studies (NCATS) at the U.S. National Institutes of Health, believes this lack of awareness is a public health crisis.

Speaking at the 2019 World Orphan Drug Congress USA in Oxon Hill, MD, he explained, “There are currently 7,000 rare diseases, 80% of them genetic, and 250 new ones identified every year,” he continued. “Together, they have the same prevalence as type 2 diabetes — about 8% of the population — yet I would bet no more than one in 1,000 people on the street know that.”

Despite this grim scenario, patient advocacy groups for rare diseases have made enormous progress in raising public awareness, improving public health policies, and increasing scientific and clinical knowledge. 

In fact, the FDA is now offering guidance to manufacturers interested in investing in genetic therapy products and several private and government-sponsored rare disease organizations are disseminating both practical and scientific information on their websites. 

In addition, events like Rare Diseases Awareness Month and Rare Disease Day are raising public awareness.

In fact, Rare Disease Day has been gaining some momentum over the years. In 2008, only 18 countries took part, but in 2019, more than 100 countries were involved.


The definition of a rare disease depends on a country or region’s health care system.

In the U.S., it’s defined as an illness that affects fewer than 200,000 Americans. Meanwhile, the European Union defines it as affecting fewer than 1 in 2000.

About 80% of these diseases are due to genetic conditions, while the remaining 20% can be traced to bacterial or viral infections, allergies, birth defects, environmental factors, and other external causes.

The exact number of rare diseases is unclear because of insufficient tracking, but researchers estimate it is about 7,000.

The characteristics of rare diseases make them difficult to diagnose, and misdiagnosis is common.

Not only is there a wide diversity of symptoms, but people with the same disease may show a different cluster of symptoms.

These symptoms are often chronic, degenerative, and progress to become life-threatening.

Besides difficulties in diagnosis, even a doctor who has arrived at a correct diagnosis can only help his or her patients with palliative care.

No effective cures have available for most rare diseases.

Powered by Froala Editor

Referenced Sources

  1. “Cystic Fibrosis”
    Genetics Home Reference, 2011.
  2. “Orphanet: Huntington Disease”
    Orpha.net, 2011
  3. “FAQs About Rare Diseases | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program.” .
    ‌Nih.gov, 2017.
  4. “Rare Diseases in General Practice: Recognising the Zebras among the Horses.”
    Evans, William RH, and Imran Rafi, October 27, 2016
  5. “Living with a Rare Disorder: A Systematic Review of the Qualitative Literature.” 
    ‌Lippe, Charlotte von der, Plata S. Diesen, and Kristin B. Feragen.July 23, 2017