Ultimate Guide to Rare Diseases

Updated September 3, 2019

This article was scientifically reviewed by YourDNA

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

What is a rare disease?

A disease or disorder is defined as rare in the United States when it affects less than 200,000 Americans at any given time.

In Europe, a rare disease is defined as a condition that affects fewer that 1 in 2000 people 1. In some instances, rare diseases are referred to as orphan diseases 2.

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. Read More...

In all, it is estimated that there are more than 7,000 existing rare diseases. About 80% of these have genetic origins 3.

The others are a result of bacterial or viral infections, allergies, environmental causes or they are degenerative or grow or multiply by rapidly producing new tissue, parts, cells, or offspring.

It’s also estimated that about 75% of rare diseases affect children 4.

On a global basis, a disease can be rare in one region, but common in another.

For example, thalassemia is a genetic anemia which is rare in Northern Europe, but it is frequent in the Mediterranean region.

Periodic disease is rare in France, but common in Armenia 5. There are also many common diseases whose variants are rare.

One of the big challenges in attempting to diagnose and treat rare diseases is that because affected populations are relatively small, it is difficult to sometimes gather quality information or obtain key scientific knowledge.

This can result in a delay of a diagnosis or in pushing treatments forward. Misdiagnosis is also a common problem as well, partly because common symptoms may cause health care providers to believe that a condition is another affliction.

Rare diseases also create challenges in providing adequate and quality healthcare, resulting in significant social and financial burdens on patients.

Part of this is because symptoms differ not only from disease to disease, but also from patient to patient suffering from the same disease as well.

Because of the rarity and diversity of so many diseases, research and treatment tends to be international in nature.

This does allow for the pooling of resources to combat various conditions, but it can also lead to communication problems when cross-border research is not conducted effectively.

Most rare diseases have no cure, so living with a rare disease is an ongoing learning experience for patients and families.

In many cases, these rare diseases have not been the focus by the pharmaceutical industry because it provides little financial incentive for the private sector to make and market new medications to treat or prevent it.

An rare disease can also be a common disease that has been ignored, such as tuberculosis, cholera, typhoid, and malaria because it is far more prevalent in developing countries than in the developed world.

How many rare diseases are there?

It’s impossible to state an exact number of how many rare diseases there are but best estimates place the number at around 7,000 or more.

Part of this is because rare diseases encompass such a broad spectrum of disorders and symptoms that not only vary from disease to disease, but from patient to patient.

The other problem is that common symptoms that are present in many different kinds of diseases may lead to a misdiagnosis.

Because most rare diseases are not tracked, it is hard to determine the exact number of rare diseases or how many people are affected.

Another issue that affects the number of rare diseases at any given time is that, by definition, if a cure cannot be administered on a rare disease, it can turn into a defined common disease.

Conversely, when an effective cure for a common disease takes place, that common disease can become a rare disease.

In the United States, only a few types of rare diseases are tracked when a person is diagnosed.

These include certain infectious diseases, birth defects, and cancers. It also includes the diseases tracked on state newborn screening tests.

The National Institutes of Health (NIH) maintains the Genetic and Rare Diseases (GARD) Information Center which oversees a database of rare diseases and related terms.

This list includes the main name for each condition, as well as alternate names.

Inclusion on this list does not serve as official recognition by the NIH that a disease is rare. Some conditions that are not considered rare are on this list and are labeled accordingly.

They are included as a matter of public interest.

If you are looking for statistics on a specific disease, check to see if the disease is listed in Genetics Home Reference, GeneReviews, or Medscape Reference.

What percentage of people have a rare disease?

A rare disease is a condition that affects fewer than 200,000 people in the United States at any given time.

But because there are more than 7,000 rare diseases, combined they affect an estimated 25 million to 30 million Americans.

The equates to about 9% of the population. This number continues to rise as more rare diseases are discovered every year.

By comparison, it’s estimated that rare diseases affect more than 350 million people worldwide, which is more than cancer and AIDS combined 6.

Unfortunately, because diagnosis is difficult and pharmaceutical companies are not able to profit from developing rare disease drugs as much as with other more common diseases, the percentage of rare diseases with an FDA-approved treatment is only 5%.

Prior to the passage of the Orphan Drug Act (ODA) of 1983, fewer than a dozen drugs were approved in the 1970s to treat rare diseases.

Since passage, almost 400 drugs have been approved with several hundred more in development.

The ODA provides a system of tax credits, government grants, assistance for clinical research, and seven years marketing exclusivity, treating over millions of patients worldwide.

Similar legislation has been adopted in Japan, Australia and the UK

Venture capital funding for rare disease development has also continued to climb at a rapid rate.

It is estimated that U.S. venture capital funding of companies developing rare-disease drugs in 2003 was $268 million. By 2013, that amount had risen to $557 million.

What causes rare diseases?

Because estimates place the number of rare diseases at 7,000 or more, it is impossible to say in a simple way what causes rare diseases.

However, the vast majority, as many as 80%, share the fact that they can be traced to gene mutations.

Many of these rare diseases are passed on from one generation to the next, explaining why rare diseases can often run in families.

Environmental factors are also a cause of rare diseases as well.

This can include influences such as smoking, diet, exposure to chemicals and other factors that may directly cause a disease, or mingle with genetic factors to cause a disease or increase its severity.

Some rare diseases caused by mutations in single genes include cystic fibrosis, Huntington's disease, and muscular dystrophies.

Single genes are also responsible for some inherited types of cancer. For example, the BRCA1 and BRCA2 genes sometimes mutate and increase the risk for hereditary breast and ovarian cancers.

Another example is the FAP gene. When it mutates, it can increase the risk for hereditary colon cancer.

Rare diseases related to environmental factors include uncommon types of anemia caused by vitamin-deficient diets or certain medications.

A rare cancer caused by environmental factors is mesothelioma which affects the cells lining the chest cavity.

It is estimated that more than 90% of mesothelioma cases are caused by exposure to asbestos that was once commonly used in fireproofing and insulation materials.

Genetic origins and characteristics of rare diseases

There are a number of different causes of rare diseases. About 80% are thought to be genetic and caused by changes in genes or chromosomes.

In some cases, genes that cause the disease are passed from one generation to the next.

They can also occur randomly when a person is the first in a family to be diagnosed. The other 20% are caused by things such as infections, autoimmune issues or cancers that are not inherited.

Chromosomes are packages of DNA that are found inside cells in a body. DNA contains genes that tell your body how to develop and function.

Humans normally have 23 pairs of chromosomes (46 total), inheriting one of each of the chromosome pairs from each parent.

There are two different types of chromosomes. They are the sex chromosomes and autosomal chromosomes.

Sex chromosomes determine a person’s gender and are known as either X or Y chromosomes.

Mothers always contribute and X chromosome and fathers can contribute either an X or a Y, which determines the gender of the child.

Females have two X chromosomes and males have one X and one Y chromosome.

The remaining 22 pairs of chromosomes are called autosomal chromosomes and contain the balance of a person’s genetic information.

When chromosome disorders take place, it can lead to genetic mutations that can result in the manifestation of rare diseases.

These disorders can either be classified as numerical or structural.

Numerical disorders take place when there is a change in the number of chromosomes that can either be more or less than the normal number of 46.

Examples of numerical disorders include trisomy, monosomy and triploidy. Probably the most well-known numerical chromosome disorder is Down syndrome (trisomy 21).

Other common types of numerical disorders include trisomy 13, trisomy 18, Klinefelter syndrome and Turner syndrome.

Structural disorders happen when there is a breakage inside a chromosome.

When this happens, it can result in there being more or less than two copies of a gene. The difference in the number of copies is what can cause genetic diseases.

There are a number of different types of structural breakages that can occur. According to NIH, those breakages include:

  • Chromosomal deletions, sometimes known as partial monosomies, occur when a piece or section of chromosomal material is missing. Deletions can occur in any part of any chromosome.

    When there is just one break in the chromosome, the deletion is called a terminal deletion because the end (or terminus) of the chromosome is missing.

    When there are two breaks in the chromosome, the deletion is called an interstitial deletion because a piece of chromosome material is lost from within the chromosome.

    Some examples of more common chromosome deletion syndromes include cri-du-chat syndrome and 22q11.2 deletion syndrome.
  • Chromosomal duplications, sometimes known as partial trisomies, occur when there is an extra copy of a segment of a chromosome.

    A person with a duplication has three copies of a particular chromosome segment instead of the usual two copies.

    Some examples of duplication syndromes include 22q11.2 duplication syndrome and MECP2 duplication syndrome.
  • Balanced translocations occur when a chromosome segment is moved from one chromosome to another.

    In balanced translocations, there is no detectable net gain or loss of DNA.
  • Unbalanced translocations occur when a chromosome segment is moved from one chromosome another.

    In unbalanced translocations, the overall amount of DNA has been altered (some genetic material has been gained or lost).
  • Inversions occur when a chromosome breaks in two places and the resulting piece of DNA is reversed and re-inserted into the chromosome. Inversions that involve the centromere are called pericentric inversions; inversions that do not involve the centromere are called paracentric inversions.
  • Isochromosomes are abnormal chromosomes with identical arms - either two short (p) arms or two long (q) arms.

    Both arms are from the same side of the centromere, are of equal length, and possess identical genes.

    Pallister-Killian syndrome is an example of a condition resulting from the presence of an isochromosome.
  • Dicentric chromosomes result from the abnormal fusion of two chromosome pieces, each of which includes a centromere.
  • Ring chromosomes form when the ends of both arms of the same chromosome are deleted, which causes the remaining broken ends of the chromosome to be "sticky". These sticky ends then join together to make a ring shape. The deletion at the end of both arms of the chromosome results in missing DNA, which may cause a chromosome disorder.

An example of a ring condition is ring chromosome 14 syndrome 7.

What causes chromosome disorders?

There is no single clear answer but scientists know that abnormalities usually take place when a cell divides in two as part of the normal growth process.

At other times, it can happen during the development of an egg or sperm cell or after conception.

Normally, the correct number of chromosomes are supposed to wind up in each cell, but errors can and do occur resulting in cells with too few or too many copies of a whole chromosome or a piece of a chromosome.

Several factors can increase the chance of this happening, such as when a mother is 35 years or older.

In other cases, mosaicism may occur. This is when a person has a chromosome abnormality in some, but not all, cells.

The impacts of mosaicism are difficult to predict because how signs and symptoms manifest depend on which cells have the chromosome abnormality.

How are chromosome disorders diagnosed?

In some cases, medical professionals may suspect a chromosome disorder in someone who has an intellectual disability, exhibits challenging behaviors or is experiencing developmental delays.

Symptoms will vary based on which chromosomes are involved.

However, there will be some degree of learning disability or developmental delay in those who have either a loss or gain of chromosome material in chromosomes 1 through 22.

This is because there are many genes located across all of these chromosomes that provide instructions for normal development and function of the brain

There are several types of genetic tests that can be employed to confirm a suspected diagnosis. These include:

  1. Karyotyping
  2.  Microarray (also called array CGH)
  3. Fluorescence in situ hybridization (FISH)

Progress in the Diagnosis and Treatment of Rare Diseases

The treatment of rare diseases is especially challenging given the number of rare diseases that have been identified and the lack of clinical data readily available to scientists and researchers.

However, things are changing as genetic research continues to change and advance at a rapid pace.

In addition, a number of disease-specific registries have been created, with the list growing more each day.

This makes it much easier for disparate parts of the research and treatment fields to share critical information.

Networks are also launching to share the results of research and to advance diagnosis, treatments and cures more efficiently.

The Orphan Drug Act of 1983 opened the door for drug companies to develop treatments for rare diseases.

Since that time, several hundred new treatments have been approved by the U.S. Food and Drug Administration.

More recently, the National Institutes of Health (NIH) launched a new effort called the Therapeutics for Rare and Neglected Diseases (TRND) program.

The goal is to create an integrated research pipeline to jump start the development of new treatments for rare and neglected disorders.

The NIH Office of Rare Diseases Research (ORDR) handles oversight and governance of TRND.

The laboratory work for TRND is being overseen by the intramural program of the National Human Genome Research Institute (NHGRI).

Conversely, there are still groups of undiagnosed patients to contend with as well. They fall into two categories.

  • ‘Not yet diagnosed’ refers to a patient whose disease has not been diagnosed because the patient has not been referred to the appropriate clinician due to common, misleading symptoms, or an unusual clinical presentation of a known rare condition.
  • ‘Undiagnosed’ (Syndromes Without a Name or SWAN) refers to a disease where a diagnostic test is not yet available. The disease has not been characterized and the cause is not yet identified. This patient can also be misdiagnosed as his/her condition can be mistaken for others.

Some patients live for months, years or often their entire lives with an undiagnosed condition.

Obtaining a diagnosis can be a long and difficult process. Further complicating matters is that often times, patients receive a misdiagnosis, providing a setback in actual effective treatments, if they are available.

A correct diagnosis can unlock access to effective medical and social care.

Getting the right and accurate diagnosis, even when there is no treatment, increases opportunities for patients to plan their future.

In situations where diseases are inherited, many families have several affected siblings.

For these families, the absence of a diagnosis increases the risk and worry of having another child suffering from the same undiagnosed condition.

Medical and Social Consequences of Rare Diseases

There are a number of medical and social consequences of rare diseases to consider.

First, just the sheer number of rare diseases that have been identified means that there is an ongoing balancing act of trying to find cures and advance treatments on an overwhelming number of fronts.

Competition for funding and gaining traction can be a big problem.

Another consequence is that because data and the dearth of research may be limited, there are often misdiagnosed rare diseases.

Without a proper diagnosis, those who are afflicted can’t be property and fully treated in many cases.

Overall, there is a chronic deficit in the amount of knowledge that researchers and scientists have when it comes to rare diseases.

Also, without a clear and easily definable label of what a person suffers from, there can be a social stigma attached when attempting to explain a condition.

In addition, the field of genetic research and diagnosis continues to change at such a rapid pace that some patients may have already been diagnosed and may not be fully aware of the latest advancements for their particular rare disease.

This corresponds closely to the challenge of maintaining networks of information that are current and provide valuable updates that can improve the lives of patients.

Rare diseases are also often serious, chronic and progressive.

With relatively small patient populations, there can be a challenge in finding enough highly qualified medical professionals to properly treat a patient and relieve their ongoing suffering.

Another issue is that more than half of all rare diseases afflict children.

This places an exceptionally large burden on families who must cope with long-term care issues.

Without a high enough level of awareness of specific rare diseases, policymakers and those who control the purse strings related to research and finding treatments and cures and faced with tough challenges about how to allocate funding for thousands of conditions.

There is a constant and ongoing debate as to whether it makes more sense to fund research and treatment for diseases that affect millions of people, or whether to allocate a certain level of funding for a condition where there are only thousands of people who are affected.

Pharmaceutical companies must also weigh the costs of developing medications that will have limited use and have a negative impact on their bottom line with the societal and moral responsibilities they have to improve the human condition.

Some progress has been made with stimulating research and development in the sector of orphan drugs by implementing incentives for health and biotechnology industries.

This started as early as 1983 in the United States with the adoption of the Orphan Drug Act, then in Japan and in Australia in 1993 and 1997.

Europe followed in 1999 by implementing a common EU policy on orphan drugs.

Caring for Patients with Rare Diseases

Care givers face a number of unique challenges in taking care of patients with a rare disease.

These obstacles mirror the challenges that society faces regarding rare diseases, but on a much more personal level.

There are ongoing obstacles and delays regarding the amount of information, expertise, research, diagnosis and treatment options for patients, all of which contribute to additional suffering for entire families.

Most patients with a rare disease will require longer and more frequent visits with their primary care physician.

However, they often come more prepared for visits because they have become self-appointed experts about their disease.

This is generally due to the lack of studies, evidence-based research, and treatment information for most rare diseases.

Although some patients have a high level of understanding, others may need advice on how to interpret the information they have found.

Because of the lack of general understanding around their condition, patients with rare diseases are extra vigilant to any potential signs of enhanced symptoms or deterioration.

Often times, it makes sense for a general practitioner to refer a patient to genetic counseling and testing.

This can be revealing and rewarding, especially in those cases where there is a family history of the disease.

It is also important to try and maintain a continuity of care for a patient. Building a strong medical file and a personal relationship with a provider is critical to receiving optimal care.

A long-term, trusting, and supportive therapeutic relationship can make the rare disease a little bit less overwhelming.

Because rare diseases are so challenging, it’s common for primary care doctors to coordinate and consult often with other treating specialists and healthcare providers.

A multisystem involvement can require complex care by a number of providers, anchored by the primary physician.

Sharing experiences can be empowering.

This means that support groups are vital in helping a patient with a rare disease have a more positive experience as they work through their disease and their issues.

Those dealing with a rare disease often encounter major financial burdens as well. Parents are often forced to reduce work hours or quit working altogether to care for a child with a rare disease.

Significant out-of-pocket expenses may be required for medical equipment or home accessibility modifications.

The following resources may help patients find both emotional and financial support:

Why Is Rare Disease Fundraising So Important?

Finding money to pay for all of the issues associated with rare diseases is critical. There are several challenges that are more difficult to address than with other more common diseases.

For example, because the patient population for each rare disease is relatively small, getting attention for funding can be problematic.

It’s easier to fundraise for cancer or heart disease than it is for Gaucher Disease or Sanfilippo Syndrome.

Offsetting costs is also critical because costs for patients with rare diseases tend to be on the high side.

Patients often require many doctor visits and extensive testing before they even get a diagnosis.

Prescription drugs, if they are available, are more costly because they are not manufactured in high quantities.

Pharmaceutical companies do develop and research drugs but those companies also need to appease their stakeholders.

That means they spend most of their time and resources on making drugs that will contribute positively to their bottom line.

A recent study showed that orphan drugs that treat only one rare disease account for only 7.9% of money spent on developing and manufacturing drugs.

Because rare diseases are so often debilitating and life threatening, as a patient’s disease progresses, treatment becomes even more expensive.

Many times, patients require caretakers to help manage their health. They must often schedule their lives around doctors’ visits and other appointments, including seeing expensive specialists.

Lack of funding also means few patients are available to participate in studies and trials of different treatments.

This can produce limited results which makes it harder for doctors to develop effective treatment plans for those who have been diagnosed.

Despite these challenges, there are several organizations that can help parents with the financial issues related to rare diseases.

What to Do If Your Child Is Diagnosed with A Rare Disorder

There are a number of rare diseases that specifically afflict children. Some of the more common ones include:

  • Acute Lymphocytic Leukemia
  • Angelman Syndrome
  • Apert Syndrome
  • Aase-Smith Syndrome
  • Batten Disease
  • Carpenter Syndrome
  • Coarctation of the Aort
  • Chronic Myelogenous Leukemia (CML)
  • Crouzon Syndrome
  • Cystic Fibrosis
  • Duchenne Muscular Dystrophy
  • Ewing’s Sarcoma
  • Eisenmenger Syndrome
  • Fabry Disease
  • Fragile X
  • Epidermolysis Bullosa
  • Gastroschisis
  • Gaucher Disease
  • Hirschsprung’s Disease
  • Hurler Syndrome
  • Krabbe Disease
  • Legg-Calve-Perthes Disease
  • Marfan’s Disease
  • Microcephaly
  • Niemann Pick Disease
  • Neuroblastoma
  • Neurofibromatosis
  • Patent Ductus Arteriosus
  • Pompe Disease
  • Prune Belly (Eagle-Barrett) Syndrome
  • Sanfilippo Syndrome
  • Spina Bifida
  • Sickle Cell Anemia
  • Tay-Sach
  • Tetralogy of Fallot
  • Tourette’s syndrome
  • Williams Syndrome

Any time a child is affected with a medical issue, it can be a tough issue to deal with for an entire family.

But when the diagnosis involves a rare disease, the complications and challenges multiply exponentially.

Parents of children with rare disorders will need family and medical support, just like other parents of children with special needs, but that support may not be as easy to find.

Better informed parents are able to become better informed advocates for their children.

For a variety of reasons, newborn screening is critical. The test is easily administered with a simple heel prick blood test.

An initial screening may indicate the need for further screening or testing.

By identifying a condition as early as possible, a condition can be treated earlier and often times with better results.

Genetic counseling can also play an important role by helping families understand if more than one family member is predisposed to certain rare diseases.

Again, knowing this early on allows for proactive treatment and to lay out available options for all those who may require monitoring.

When parents know what to expect, they can take better care of their child, resulting in better health outcomes.

Information and Resources About Rare Diseases

There are a number of organizations and resources that can provide a wealth of information regarding diagnosis, treatment and research of rare diseases:

Rare Disease database, diagnosis, drug and treatment information

The National Organization for Rare Disorders (NORD) is a federation of nonprofit voluntary health organizations serving people with rare disorders.

NORD also shares information about opportunities to participate in clinical trials and other studies so that patients and their physicians can decide whether specific studies are appropriate for them.

Orphanet is a reference portal for rare diseases and orphan drugs. It has general information about diseases and international treatment centers and research opportunities.

Orphanet’s aim is to help improve the diagnosis, care, and treatment of patients with rare diseases.

The National Institutes of Health has comprehensive information on rare diseases.

The National Center for Biotechnology Information (NCBI) has a database, MedGen, that organizes information related to human genetic conditions.

The National Institutes of Health has published a Genetics Home Reference: Your Guide to Understanding Genetic Conditions

The Genetic and Rare Diseases website guide How to Get Involved in Research has information about clinical research trials and patient registries. Clinical research trials can be a good way to find cutting-edge treatments for rare conditions.

Rare Best Practices is a European resource with clinical practice guidelines for rare diseases.

The Rare Diseases Clinical Research Network (RDCRN) aims to develop new treatments, deepen knowledge, raise awareness, and direct patients to appropriate services.

It is assisted by the efforts of researchers, doctors, and patient groups. The RDCRN has a Contact Registry for patients who are interested in learning about clinical research trials.

Sites that focus on genetics and genetic rare disease information

National Society of Genetic Counselors

The American College of Medical Genetics has a searchable database of US genetics clinics

The American Society of Human Genetics maintains a database of its members, which includes individuals who live outside of the United States, some of whom may be researchers that do not provide medical care.

Genes in Life

Genetic Alliance

Baby’s First Test

Family and Children Friendly information

The Developmental Genome Anatomy Project (DGAP) identifies chromosomal rearrangements in patients with multiple congenital anomalies and then to uses that information to map and identify genes that are disrupted or dysregulated in critical stages of human development.

To find individuals with the same chromosome disorder

Chromosome Disorder Outreach (CDO) provides information on chromosomal conditions and family matching.

Chromosome Disorder Outreach
PO Box 724
Boca Raton, FL 33429
Family Helpline: 561-395-4252
E-mail: [email protected]
Web site: www.chromodisorder.org

Unique is a source of information and support for families and individuals affected by rare chromosome disorders.

This organization is based in the United Kingdom but welcomes members worldwide. Unique also has a list of Registered Chromosome Disorders.

Unique - Rare Chromosome Disorder Support Group
PO Box 2189
Caterham
Surrey CR3 5GN
United Kingdom
Telephone: 440 1883 330766
E-mail: [email protected]
Web site: www.rarechromo.org 

Unique is also a charity supporting, informing and networking website that brings together families with a rare chromosome disorder or some autosomal single gene disorders.

The following online resources can help you find a genetics professional in your community:

Research of Genetics and Rare Diseases through the NIH

The National Institutes of Health (NIH) supports research to improve the health of people with rare diseases.

Many of the 27 Institutes and Centers at the NIH fund medical research for rare diseases.

One of these Centers, the National Center for Advancing Translational Sciences (NCATS), focuses on getting new cures and treatments to all patients more quickly.

The NCATS Office of Rare Diseases Research (ORDR) guides and coordinates NIH-wide activities involving research for rare diseases. Some of the NCATS programs for rare diseases include:

Efforts to improve and bring to market treatments for rare diseases are coordinated by the Food and Drug Administration (FDA).

The Office of Orphan Products Development (OOPD) provides incentives for drug companies to develop treatments for rare diseases.

Since 1983, the OOPD program has helped develop and bring to market more than 400 drugs and biologic products for rare diseases.

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Referenced Sources

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    Eurordis.org. Retrieved online, July 2019.
  2. Rare Disease Facts and Figures: 1 in 10 Americans is Living With a Rare Disease.
    Global Genes. February 27, 2009.
  3. What is a Rare Disease?
    Rare Disease Day. Retrieved online, July 2019.
  4. What Is a Rare Disease?
    Eurodis. 17/04/07.
  5. About Rare Diseases.
    Orpha.net. 25/10/12.
  6. A Look at Some Key Statistics on Rare Diseases in the U.S.
    The Associated Press. Rdmag.com. 03/25/2015.
  7. Ring chromosome 14 syndrome.
    Genetics Home Reference. Retrieved online, July 2019.