Cartilage-hair hypoplasia

The RMRP gene provides instructions for the body to create a type of molecule called a "noncoding RNA." The job of this RNA is to attach to a few other proteins and form an enzyme called "mitochondrial RNA-processing endonuclease," or RNase MRP. Enzymes help the chemical reactions inside of our cells. Most enzymes in our body have more than one function. One of the jobs of the RNase MRP enzyme is to help copy the DNA within the energy-producing centers of cells known as mitochondria. This RNase MRP is also thought to help make sure that cells are replicated in an organized way by maintaining the cell cycle. A third role for this enzyme is to help make ribosomal RNA, another type of RNA that is needed to help turn amino acids into complete proteins. Because all of these functions are very important for the cell, a person with a genetic change or mutation in RMRP can have problems in many parts of their body and many body systems as seen with Cartilage-Hair Hypoplasia.

Cartilage-Hair Hypoplasia (CHH) is an autosomal recessive condition. This means that if a parent has a child with CHH, any future children would each have a 25% chance of having CHH as well. There is a 50% chance that children of the couple would be carriers, like the parents. There is a 25% chance that children of the couple would not have inherited any gene change from either parent.

While it is possible for any person to be a carrier of CHH, the disorder is exceptionally rare. However, genetic testing is available and anyone considering genetic testing should review all of the benefits and limitations of testing with a genetic counselor, medical geneticist or someone with expertise in skeletal dysplasias/dwarfism, meaning a disorder involving short stature.

Because the features of CHH are easily identified early in life, it is extraordinarily unlikely for someone to have CHH and not know it. However, genetic testing for an individual suspected of having CHH or another skeletal dysplasia can be useful for their family members or future children to understand the chances of also having CHH. If a person themselves has CHH, they can only pass on a single RMRP mutation to any child, therefore their partner would also have to be a carrier of an RMRP in order to have a child who also has CHH. Populations that could have a higher chance of having both parents be carriers are those of Old Amish or Finnish ancestries.

The Little People of America (LPA) has an extensive list of companies that sell products designed to help individuals with Cartilage-Hair Hypoplasia, and other forms of dwarfism have as normal a life as possible. Due to their short stature, it can be difficult for little people to find clothing and shoes, for example. Check the LPA website for updates on items to assist with daily life.

Cartilage-Hair Hypoplasia (CHH) is a condition that can be complicated to manage due to the wide-ranging health problems that individuals can develop and also because not everyone ever develops some problems, while others do. There are several different types of specialists that can be involved in the care of a person with CHH. Orthopedic specialists can help identify complications due to loose joints, bone growth issues like scoliosis and bowing of the legs. An immunologist is very important because some of the major health impacts of CHH can be on the immune system which increases the chances someone with CHH can develop life-threatening infections. Hematologist can become involved if the immunologist uncovers a problem since they are experts in blood disorders. People with CHH also have a risk for lung problems so a pulmonologist is often involved in their care. In early childhood or in the newborn phase, a baby with CHH may be treated by a gastroenterologist if they have megacolon, a problem when the colon is obstructed that can be dangerous. Finally, anyone with CHH will often work with a medical geneticist and/or genetic counselor to learn more about the genetic cause of their condition and whether other family members might benefit from testing. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Cartilage-Hair Hypoplasia (CHH) is a condition that affects everyone somewhat differently. Height along with other health problems can vary. Some individuals might not have some of the more serious medical issues and may wish to be involved in activities with their peers like sports, gym class and recess. In general, there are some activities that may pose a risk to individuals with dwarfism due to their unique physique. Some specific activities that may warrant caution include: tackle football or other full contact sports; trampoline jumping; using ankles or knees to hang from playgrounds; using one’s head to hit the ball in soccer; jumping from heights; and tumbling. These suggested limitations do not mean that individuals with CHH who are doing well should not be as active as possible. Exercise is good to help build muscle, keep normal weight and participating in activities often allows young people with CHH to interact with their peers. As with any condition, anyone with CHH should talk to their medical team before starting a new activity.

The usual abbreviation of Cartilage Hair Hypoplasia is CHH. No other common abbreviations are used by patients and doctors to describe this condition.

People with cartilage-hair hypoplasia can live a normal lifespan. While some of the complications of CHH, like severe immunodeficiency mean that people need to watch their health very closely, they can be effectively managed. The biggest danger to people with CHH are opportunistic infections, meaning infections that take advantage of a person’s weak immune system. These types of infections can be fatal, especially at young ages. Additionally, the increased risk of cancer, specifically lymphoma, which is most often diagnosed in people with severely weak immune systems, can also be life-threatening. With proper management, individuals with CHH should not have a shortened lifespan.

For more information on how to stay healthy with CHH, talk with your doctor to ensure you are doing everything to optimize your medical management.

Limb-lengthening surgery is a procedure that was initially developed in Russia in the 1950’s. Since then, it has been used to straighten or lengthen bones that have not grown properly, or to replace bones affected by trauma or disease. The first limb lengthening surgery in the United States was in 1988. While some individuals who have dwarfism have undergone limb lengthening, it is not currently considered a routine treatment for Cartilage Hair Hypoplasia (CHH) or other forms of dwarfism. Limb lengthening is somewhat controversial. In 2006, the Little People of America (LPA) the oldest and largest support organization for individuals with dwarfism, put out a position statement on this topic. The LPA is not publicly for or against limb-lengthening, however they do warn that there have been no strong clinical studies on this procedure. Additionally, there are significant risks of complication and the lengthening of limbs does not change any of the other health problems that can come with a condition like CHH. The LPA recommends that anyone considering limb-lengthening surgery should be evaluated by all the various specialists that are involved in their care and should work with an institution that has experience in this very unique procedure.

To learn more about the limb lengthening procedure visit this website.

Cartilage-Hair Hypoplasia (CHH) is a genetic condition that causes short stature with short arms and legs, small amounts of thin hair, an increased risk for cancer, and a weak immune system. CHH is part of a larger group of conditions called skeletal dysplasias, commonly referred to as dwarfism. Other symptoms of CHH include a lack of healthy red blood cells (anemia), and problems with the colon that can be present at birth. CHH gets its name due to poorly developed cartilage in long bones, such as the arms and legs. Cartilage is the type of tissue that helps connect our bones and hypoplasia means underdevelopment. Problems with cartilage can also cause extra flexibility in some joints, also known as hypermobility. Some people with CHH may not be able to fully extend their elbows due to problems with their cartilage. Up to 40% of people with CHH develop cancer, often before they turn 40 years old. The most common type of cancers diagnosed in people with CHH are lymphoma, a cancer of the cells in the immune system, and basal cell carcinomas which is a type of skin cancer. Other medical issues include problems with the colon (Hirschprung’s disease and megacolon).

Every person with CHH does not necessarily have the same symptoms or features. There can be people who are more mildly affected and others who have more severe health problems from CHH. It is not well-understood why this is, so it is hard to predict what issues a person will have once they are diagnosed, even if they have other family members who also have the condition.

CHH is an autosomal recessive disorder meaning that in order for a person to have CHH, they have to inherit two changed copies, or two mutations, of a specific gene called RMRP. There are no treatments that prevent the main symptoms of CHH like short stature, immune issues, and anemia. However, these symptoms can be managed effectively, which is why most people with CHH have a team of doctors including experts in genetics, immunology, hematology and orthopedics.

There is a useful factsheet about CHH for people and families living with CHH at the NORD Rare Disease site
http://rarediseases.org/rare-diseases/mckusick-type-metaphyseal-chondrodysplasia

For more information about the management of CHH, doctors can reference a recent article: Clinical Features and Management of Cartilage-Hair Hypoplasia

Because people with Cartilage-Hair Hypoplasia (CHH) have many different parts of their body and body systems affected, their doctor should be monitoring for several important issues. First, bone growth should be monitored by regular doctors visits, but also by imaging techniques such as x-rays to follow growth, joint problems and the spine. Children should be followed closely, but adults can still be followed as needed if specific issues arise.

A second very important part of CHH management is surveillance for infections. Children should be followed closely until at least age 2, even if they haven’t shown signs of a compromised immune system. The chickenpox is an especially threatening infection and any vaccines given to children with CHH should be attenuated (killed) vaccines, not live vaccines.

Children should be closely monitored for a bowel obstruction due to a specific condition called Hirschsprung disease that impacts the nerves in the intestine. Individuals with CHH should also be monitored for anemia. Anemia occurs when the body doesn’t have enough red blood cells. Doctors will look for signs of anemia which can include fatigue and dizziness.

Finally, individuals with CHH have an increased risk for certain types of cancer including lymphomas and basal cell carcinomas. There aren’t specific recommendations, however individuals should have regular examinations for any signs or symptoms of cancer with their doctor.

For more information about the management of CHH, doctors can reference a recent article: Clinical Features and Management of Cartilage-Hair Hypoplasia

In a study from Finland and Sweden of 19 women, the occurrence of human papillomavirus (HPV) was found in 44% of women with cartilage-hair hypoplasia. For this reason, it is important for a woman with cartilage-hair hypoplasia to be followed closely by her gynecologist (female doctor). For more information regarding HPV, see the Centers for Disease Control website.

Cartilage-hair hypoplasia (CHH) is caused by mutations in the RMRP gene. This gene is located on chromosome 9. Everyone has two copies of this gene, one inherited from each parent. With most conditions caused by mutations in genes, the mutation causes an important protein to not be made by the body, or causes a less useful version of a protein to be made. But, the RMRP gene is different. This gene does not have instructions for making a protein but actually creates a different type of molecule called a "noncoding RNA." The job of this RNA is to attach to a few other proteins and form an enzyme called "mitochondrial RNA-processing endonuclease," or RNase MRP. The name of this enzyme is where the gene gets its name. When a person has a mutation in RMRP, then this important enzyme canot be made.

There are some features of Cartilage-Hair Hypoplasia that every patient has, and others that only impact a small percentage. The major features that everyone with CHH has are disproportionate short stature (dwarfism) and short limbs. In approximately three out of four patients, these skeletal changes are able to be seen prenatally during ultrasounds. Almost 90% of individuals with CHH also have hypermobile joints meaning their joints have an unusually large range of movement. However, due to the way their bones are formed, these individuals most often cannot completely extend their elbows.

Another major feature of CHH, and partially where it gets its name, is the blonde, sparse fine hair that most people with CHH have on their heads. Finally, CHH is associated with several different problems affecting blood cells, especially red blood cells and special immune cells called T-cells. Almost 80% of people with CHH may have enlarged red blood cells that don’t carry enough hemoglobin, which is called macrocytic hypoplastic anemia. This most often affects children with CHH. Also, the special immune cells called T-cells don’t work correctly in people with CHH which increases their chances of getting infections, in particular chickenpox (varicella). Finally, individuals with CHH have an increased risk for certain types of cancer including lymphomas (cancer of immune system cells) and basal cell carcinomas (skin cancer).

To learn more about the symptoms of cartilage hair hypoplasia, talk with your doctor or consult with a medical geneticist or genetic counselor. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

There is no routine testing for newborns to diagnose Cartilage-Hair Hypoplasia (CHH). If there is a specific concern for CHH, a targeted test must be ordered.

Many states have adopted newborn screening for severe combined immunodeficiency (SCID) using a specialized test that looks at T-cells. These calls are one type of cell affected in CHH and another conditions that cause weakened immunity. In the United States, almost all babies undergo newborn screening for a variety of disorders before they leave the hospital. Newborn screening can diagnose conditions that might not have obvious symptoms at first, but can cause severe and life-threatening problems if not diagnosed early. An abnormal newborn screening result does not diagnose CHH, but would lead doctors to evaluate a child for SCID along with other syndromes like DiGeorge, CHARGE, Jacobsen, Trisomy 21, RAC2, DOCK8 deficient hyper-IgE and CHH.

Right now, most states include SCID on their newborn screening. These states are: Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Idaho, Illinois, Iowa, Maine, Massachusetts, Michigan, Minnesota, Mississippi, Montana, Nebraska, New Hampshire, New Jersey, New Mexico, New York, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin, and Wyoming. SCID screening is also occurring in the District of Columbia, Navajo Nation, and Puerto Rico. In 2016, additional states planning to add SCID to the newborn screen including Alaska, Georgia, Kentucky, Maryland, North Carolina, and North Dakota. Five states are not currently screening newborns for SCID: Alabama, Arizona, Kansas, Missouri, and Indiana. States can update their newborn screen disease list. For the most up to date information about diseases screened for in your state, visit Baby’s First Test. People interested in advocacy efforts to add SCID to additional states can learn more through the Immune Deficiency Foundation.

If a person is suspected to have Cartilage-Hair Hypoplasia (CHH), their doctor may run a series of tests to narrow down the diagnosis. The most specific test that can be done is a genetic test to look for mutations, or changes, in the RMRP gene. All known cases of CHH are caused by mutations in this gene. However, there are two other conditions that are similar to CHH that can also be caused by mutations in RMRP, so doctors may also take bone x-rays or run blood tests to specify the diagnosis after a genetic change is found. In other cases, a physical examination along with genetic testing could lead doctors to diagnose CHH because of the specific physical features like light, sparse hair. Because the condition can have a wide range of features in different individuals, the process of receiving a diagnosis might be different for each patient.

To learn more about genetic testing, talk with your doctor or contact a genetic counselor. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

For the most up to date information on clinical trials, contact the following resources.

Since there is only one gene that has ever been identified as causing Cartilage-Hair Hypoplasia (CHH), there is only one genetic test for CHH. This test looks for gene changes (mutations) the RMRP gene. However, because there are several similar disorders that can also be caused by mutations in RMRP, the best way to clarify a CHH diagnosis is to meet with an expert in skeletal dysplasias (conditions that result in short stature) so they can order other tests like bone x-rays and blood work to look for other symptoms that are very specific to CHH. Images showing short and thick bones, with abnormally wide ends can diagnose CHH by the time a child is 6-9 months old. That is because these bone abnormalities are present in everyone with CHH, while other features like weakened immune system and cancer does not affect all individuals.

To learn more about a diagnosis of CHH, talk with your doctor or contact a physician with expertise in skeletal dysplasias.

Cartilage-Hair Hypoplasia (CHH) is very rare. Because it is so uncommon, and because of the way CHH is inherited, most people who have CHH are often the only person in their family to have this diagnosis. In order to have CHH, a person has to be born with two RMRP mutations (changes), with one mutation inherited from each parent. In the general population it is very rare for an individual to carry a mutation in RMRP. Even if two people who each carry one single RMRP mutation were to have children together, there is a 1 in 4 chance (25%) with each pregnancy that the child will have CHH. So, it is possible for a couple who both carry single RMRP mutations to have no children with CHH, or multiple children with CHH. However, because it is so uncommon to be an RMRP mutation carrier, most people with CHH do not have another members of their family, like aunts, uncles, grandparents or cousins with the same condition.

To learn more about Cartilage-Hair Hypoplasia and family history, talk with your doctor or contact a genetic counselor. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Without genetic testing, diagnosing Cartilage-Hair hypoplasia (CHH) can be more difficult because of the wide range of features and severity in different people with the condition. In young children, the bone abnormalities are not always easy to identify until a child is 9 to 12 months old. X-rays of the bones can uncover specific abnormalities seen in CHH like abnormal increase in hardening of bone (irregular sclerosis) and widened and dysplastic metaphyses (widened parts at the end of long bones like arms and legs). If these skeletal findings are present, laboratory studies looking for abnormalities in blood and immune cells (B and T cell immunodeficiency and anemia) could help narrow down a diagnosis to CHH. Most people with CHH, although not all of them, also have the hair hypoplasia leading to the light color, sparse hair that is part of the condition’s name. There are many other features that aren’t as common as short stature, blood and immune system problems and sparse hair that can be seen in CHH, which is why meeting with an expert in genetics and skeletal dysplasias can help confirm a diagnosis through imaging of the bones, laboratory findings and physical examination, and/or genetic testing.

To learn more about a diagnosis of CHH, talk with your doctor or contact a physician with expertise in skeletal dysplasias.

Both males and females are diagnosed with Cartilage-Hair Hypoplasia (CHH) at equal rates. There is no link to gender with this condition. The gene associated with CHH, called the RMRP gene, is found on chromosome 9. Men and women all have two copies of this chromosome, so they have an equal chance of carrying a gene change on RMRP.

Cartilage Hair-Hypoplasia (CHH) is a specific disorder with specific features. However, CCH is part of a spectrum of disorders that are all due to mutations, or changes, in the same gene, RMRP. People with RMRP mutations will always show features of Cartilage-Hypoplasia (CHH) or of one of the CHH spectrum disorders: Metaphyseal dysplasia without hypotrichosis (MDWH), CHH, or the rare Anauxetic Dysplasia.

The reason that people with mutations in the same gene, or even people in the same family with the same genetic mutation develop different features of CHH or CHH spectrum disorders is still not well understood. However, everyone with a mutation in RMRP does show features of at least one of these disorders. This is why genetic testing alone isn’t enough to diagnose CHH. Anyone who thinks they, or their family member may have CHH should meet with a medical genetics expert in conditions involving short stature (skeletal dysplasias) so the right diagnosis can be made.

A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website .

If an individual has Cartilage-Hair Hypoplasia (CHH) that means they were born with a mutation, or change, in both copies of a specific gene called RMRP. This is called a recessive condition. Whenever a person has a child, they pass on half of their genes to their child, and the other parent does the same. This means that if one parent has CHH, they will automatically pass on one RMRP mutation to each child. Because it takes two RMRP mutations to have CHH, the other parent would also have to pass on a mutated copy of the RMRP gene in order for the child to be affected. In the general population, it is very, very rare to have an RMRP mutation. Therefore, the chances of this happening are very low. Therefore, most people with CHH who decide to have children have a very low chance of having a child with CHH. It is possible for the partner of a person with CHH to undergo genetic testing prior to conception of any children so these risks can be clarified. If the partner without CHH is not a carrier, then the couple will not have a child with CHH. Populations that could have a higher chance of having both parents be carriers are those of Old Amish or Finnish ancestries.

To discuss your reproductive risks and options, contact a genetic counselor. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Cartilage-Hair Hypoplasia (CHH) is an autosomal recessive condition. This means that in order to have CHH, a person must be born with a mutation, or change, in both copies of the RMRP gene. Genes carry instructions for many different functions and traits. We have over 20,000 genes, and for each of these genes we have two versions, one we inherit from our mother and one we inherit from our father. If each parent is a carrier, or has one normal copy of the gene and one copy with a mutation, they could have a child with CHH. Each time a child is conceived, each parent must pass on one of their copies: the normal copy, or the copy of the mutation. If the child inherits the copy with the mutation from its mother, and the copy of the mutation from its father, the child will be affected with CHH.

It is not unusual for a person with CHH, or other recessive conditions to have no family history of the condition. This is because the condition is rare, so the vast majority of the population does not carry a mutation in the RMRP gene. Even the parents of a person with CHH would not have any features of CHH because they would only be carriers of one single RMRP mutation, which isn’t enough to cause any health problems.

If a parent has a child with CHH, any future children would each have a 25% chance of having CHH as well. There is a 50% chance they would have a child who is a carrier for a single mutation in the RMRP gene that causes CHH, however the other parent of any future children would also need to be a carrier in order for that couple to have a child with CHH. There is a 25% chance they would have a child with no mutations in either copy of their RMRP gene.

While it is possible for any person to be a carrier of CHH, the disorder is exceptionally rare. Genetic testing is available. Anyone considering genetic testing should review all of the benefits and limitations of testing with a genetic counselor, medical geneticist or someone with expertise in skeletal dysplasias/dwarfism, meaning a disorder involving short stature. Because the features of CHH are easily identified early in life, it is extraordinarily unlikely for someone to have CHH and not know it. However, genetic testing for an individual suspected of having CHH or another skeletal dysplasia can be useful for their family members or future children to understand the chances of also having CHH. If a person themselves has CHH, they will pass on a single RMRP mutation to any child. In other words, if a person has CHH, all of their children will be carriers of CHH. When these children go on to have their own children, their partner would also have to be a carrier of an RMRP mutation in order to have a child who also has CHH. Populations that could have a higher chance of having both parents be carriers are those of Old Amish or Finnish ancestries.

Anyone considering genetic testing for Cartilage-Hair Hypoplasia (CHH) should meet with an expert in medical genetics or with a physician who has experience in identifying skeletal dysplasias. There are many specialty clinics around the country that focus on individuals and families with disorders involving short stature. The Little People Association of America has an long list of these clinics on their website.

Additionally, there are doctors with special training in genetics called medical geneticists. They often work with health care providers called genetic counselors. A genetics team can help coordinate genetic testing and also connect patients to other specialists that can help with the long-term follow-up for someone with CHH. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Without genetic testing, diagnosing CHH can be difficult because of the wide range of features and severity in different people with the condition. In young children, the bone abnormalities are not always easy to identify until 9 to 12 months old. X-rays of the bones can uncover specific abnormalities seen in CHH like abnormal increase in hardening of bone (irregular sclerosis) and widened and dysplastic metaphyses (widened parts at the end of long bones like arms and legs). If these skeletal findings are present, laboratory studies looking for abnormalities in blood and immune cells (B and T cell immunodeficiency and anemia) could help narrow down a diagnosis to CHH. Most people with CHH, although not all of them, also have the hair hypoplasia which leads to the light color, sparse hair that is part of the condition’s name. There are other less common features that can be seen in CHH, which is why meeting with an expert in genetics and skeletal dysplasias can help confirm a diagnosis through imaging of the bones, laboratory findings and physical examination, and/or genetic testing.

Contact a medical geneticist or genetic counselor for more information about genetic testing.

The best way to find any new developments is to visit www.clinicaltrials.gov and search for "cartilage hair hypoplasia". This website is free and open to the public. The website shows whether a study is still recruiting patients or whether it is closed. You can also speak with your doctor about helping you find research options available. The Little People of America, which is the oldest and largest support network for individuals with conditions causing short stature, has a Medical Resource Center on their website .

Cartilage-Hair Hypoplasia (CHH) is a rare condition. However, CHH is one of a larger group of disorders affecting bone growth and causing short stature called skeletal dysplasias. In the United States, there are Skeletal Dysplasia Clinics located throughout the country. These clinics specialize in diagnosing and treating individuals with conditions causing short stature, and other complications that may be due to their condition. The following list includes these clinics along with their contact information:

Alfred I. duPont Hospital for Children
Skeletal Dysplasia Program
1600 Rockland Road
Wilmington, Delaware
302-651-5916
[link url="www.Nemours.org/skeletaldysplasia” target=”_blank”>www.Nemours.org/skeletaldysplasia

Akron Children’s Hospital
Regional Skeletal Dysplasia Center
300 Locust Street
Suite 160
Akron, Ohio 44302
Contact: Shannon Leslie, RN, BSN
Coordinator Pediatric Orthopaedic Specialty Clinic
330-543-6633 or 330-543-0735

University of Missouri
Department of Pediatric Orthopaedics
For more information or to make an appointment call 573-884-2522 or
http://medicine.missouri.edu/ortho/pediatrics/

Katheryn O. and Alan C. Greenberg Center for Skeletal Dysplasias
Hospital for Special Surgery
535 East 70th Street
New York, NY 10021
212-774-7332
Email: [email protected]
http://www.hss.edu/skeletal-dysplasias.asp

Greenberg Center for Skeletal Dysplasias
Johns Hopkins University
Institute of Genetic Medicine
600 North Wolfe Street
Blalock 1008
Baltimore, MD 21287
Appointments: 410-995-3071
Program Coordinator: 410-614-0977
http://www.hopkinsmedicine.org/geneticmedicine/Clinical_Resources/Skeletal_Dysplasia/index.html

Seattle Children’s Hospital
Skeletal Health and Genetics Program
206-987-2109
http://www.seattlechildrens.org/clinics-programs/orthopedics/

Cedars-Sinai Medical Center
Skeletal Dysplasia Clinic
8700 Beverly Blvd.
PACT Bldg, 4th Floor
Los Angeles, CA. 90048
Appointments: 310-423-9914.
Genetic Counselor/Study Coordinator: 310-423-4495
http://www.csmc.edu/3992.html

Bone Dysplasia Clinic
Indianapolis, Indiana
Genetic Consultation and Counseling Contact: [email protected]

Ann & Robert H. Lurie Children’s Hospital of Chicago
Skeletal Dysplasia Program
Chicago, IL
312.227.6120

Cincinnati Children’s Hospital
Connective Tissue / Skeletal Dysplasias Clinic
Cincinnati, Ohio
Genetic counselor and clinic coordinator: 513-636-4351

Midwest Regional Bone Dysplasia Clinic
Clinical Genetics Center
University of Wisconsin-Madison
1500 Highland Ave.
Madison, WI 53705
Phone: 608-262-6228
E-mail: [email protected]

Children’s Hospital Colorado
Skeletal Dysplasia Clinic
13123 E. 16th Avenue
Aurora, CO 80045
303-724-2370

Northern California Skeletal Dysplasia Clinic
Oakland, California
The clinic is a collaboration between the two hospitals/health systems — Kaiser Permanente Northern California and Children’s Hospital and Research Center at Oakland.

Contact information:
Kaiser Permanente
Ericka Okenfuss, MS
Skeletal Dysplasia Clinic
Kaiser Permanente Genetics
280 W. MacArthur Blvd.
Oakland, CA 94611
Phone: 510-752-6839

Children’s Hospital Oakland
Emily Rettner, MS Genetics Dept.
Children’s Hospital and Research Center at Oakland
747 52nd St.
Oakland, CA 94609
Phone: 510-428-3550

Skeletal Dysplasia Clinic for Children
Children’s National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
Administrative Office: 202-884-2187

St. Louis Children’s Hospital, MO.
Skeletal Dysplasia Clinic
Appointments: 314.454.KIDS (5437) or 800.678.KIDS (5437)
http://www.stlouischildrens.org/content/medservices/skeletaldysplasiaclinic.htm

Texas Children’s Hospital/Baylor University
Skeletal Dysplasia Center
Houston, Texas
Phone: 832-822-4298
E-mail: [email protected]
http://imgen.bcm.tmc.edu/molgen/cg/clinics/sd_index.html

Genetic Skeletal Disorders Clinic
Children’s Healthcare of Atlanta
Judson Hawk Clinic
5455 Meridian Mark Rd. NE, Suite 200
Atlanta, GA 30342
http://www.choa.org/Childrens-Hospital-Services/Genetics/Genetic-Conditions/Skeletal-Disorders-Clinic
Phone: 404-785-2239
Fax: 404-785-9111

Cartilage-Hair Hypoplasia (CHH) is a very rare disorder. There are believed to be less than 700 people currently living with CHH. Individuals have been reported in populations throughout the world, but in the Old Order Amish population between 1 in 500 to 1 in 1,000 people are thought to have CHH. That means that 1 in 10 people with Old Order Amish ancestry are carriers of a single RMRP mutation. If two carriers have a child together, there is a 25% that the child will have CHH. Carriers of a single mutation often do not know they are carriers, unless they decide to have genetic testing, because carriers of one mutation don’t have any symptoms or features of the condition. People with Finnish ancestry also havea higher rate of CHH. In the Finnish population, about 1 in 23,000 people have CHH, and about 1 in 76 are carriers.

People and families living with CHH who wish to learn more about the risk to be a carrier of CHH or have an affected child should work with a genetic counselor who can give them an individual assessment. A genetic counselors in a particular area can be found on the [link url=" http://nsgc.org/p/cm/ld/fid=164″ target=”_blank”>National Society of Genetic Counselors website.

Research about individuals with Cartilage-Hair Hypoplasia (CHH) has shown that by age 65, the chances of a person with CHH to develop cancer is about 41%. This means that most people with CHH do not develop cancer. However, the lifetime risk is greatly increased above that of the general population. One study of people with CHH found that most of the cancers were diagnosed between ages 15 and 45.

The types of cancer seen in people with CHH are non-Hodgkin lymphoma (cancer of immune system cells), squamous cell carcinoma (skin cancer), leukemia (cancer of blood-forming cells), and Hodgkin lymphoma (another cancer of immune cells). There also seems to be much higher rates of basal cell carcinoma, a skin cancer, although those are easily treated. While uncommon, people with CHH can develop more than one type of cancer in their lifetime, although this is possible for individuals without CHH as well.

It is important that individuals with CHH are monitored for these cancer risks by a medical professional. For more information about cancer risks and CHH, talk with your doctor or contact a genetic counselor.

Individuals with Cartilage-Hair Hypoplasia (CHH) typically have normal intelligence and can learn and go to school with other children their age. Because of some of the physical differences in children with CHH, they could benefit from Early Intervention services that might involve physical therapy or occupational therapy. These types of therapies could provide a benefit throughout life so these individuals can remain as active as possible, as this actually provides a benefit to their overall health, just like it does for individuals without CHH.

A mutation, or change, in the same gene that causes CHH, the RMRP gene, causes another similar disorder called Anauxetic dysplasia. Some individuals with Anauxetic dysplasia have mild intellectual disabilities and will require extra help in school.

Because of the immune problems of some people with CHH, it is recommended that they avoid live vaccines which is a common recommendation for people with compromised immune systems. Not all vaccines have live virus in them, so those vaccines that use inactivated agents are thought to be safe.

It is recommended that individuals with CHH do get all possible vaccinations because it will help protect them from particular diseases. This is especially important because of their compromised immune system.

Cartilage-Hair Hypoplasia (CHH) is a highly variable condition. Not everyone with CHH is going to have the same symptoms or the same severity of symptoms. Therefore, before considering pregnancy, a woman with CHH should discuss all of the health risks that might be unique to her situation due to her size and any other health problems. However, it is possible for women with various forms of dwarfism, including CHH, to successfully carry a pregnancy. Often a Cesarean section is recommended due to the small size of the pelvis however women are able to deliver healthy babies, including average sized babies.

To learn more about CHH and carrying a pregnancy, talk with your OBGYN.

In most cases of Cartilage-Hair Hypoplasia (CHH), it is possible to determine that a fetus is affected with some form of bone growth disorder during pregnancy due to the measurements of the arms and legs in proportion to the body. This is usually seen on ultrasound by 16 to 18 weeks. However, due to the many different types of conditions affecting bone growth and height, called skeletal dysplasias, it is not always possible to diagnose the specific type of condition until the baby is born. In families where someone has already been diagnosed with CHH, or where the parents already know that they carry a mutation in RMRP , the gene that causes CHH, it may be possible to test the DNA of the fetus to confirm this diagnosis. This can be done by a procedure called an amniocentesis where a small amount amniotic fluid, which contains the cells of the fetus, is sampled and tested. If there is not already a known diagnosis or positive genetic test result in a family, it is usually not possible to provide a diagnosis until after birth.

To learn more about testing options during pregnancy, talk with a genetic counselor. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

In newborns with Cartilage-Hair Hypoplasia, a type of blood problem called hypoplastic anemia, might lead to the baby needing blood transfusions. Children can also be born with gastrointestinal issues that can cause obstructions including megacolon and another disorder called Hirschsprung disease. These colon issues can sometimes require surgery to fix. Babies should also have their immune system checked, especially their lymphocytes and T-cells in order to find out if they could have a high chance of developing infections. Not every child born with CHH will have all of these problems, but because each of them has a special treatment available it is important that newborns who are known or suspected to have CHH be followed closely.

If you are concerned that your newborn has CHH, talk with your child’s doctor.

When Cartilage-Hair Hypoplasia (CHH) was first discovered in the 1960’s, it was called McKusick type metaphyseal chondrodysplasia, after the famous geneticist Victor McKusick who first studied this condition in the Amish population. The metaphysis is the wide part near the end of a bone. The prefix "chondro" means cartilage and dysplasia refers to abnormal growth. It has also be described as Immunodeficiency with Short-Limbed Dwarfism. Currently, CHH is the most commonly used name for this condition.

CHH is part of a group of disorders called skeletal dysplasias. Skeletal dysplasias are conditions that affect the bones of an individual and lead to short stature and shorter arms and legs. There are hundreds of different types of skeletal dysplasias and they all have different causes and different features. These types of conditions are also referred to as dwarfism, which is an older term but still used.

Cartilage-Hair Hypoplasia (CHH) is the most common name for this condition used by doctors. The other names like McKusick type metaphyseal chrondodysplasia are not used very much these days; however, these names may be referenced in older medical articles so they are still useful to know.

The height of individuals with Cartilage-Hair Hypoplasia (CHH) is the most apparent feature. Final adult height ranges from about 2 ¾ feet to about 5 feet. Additionally, the highly characteristic appearance of the hair of an individual with CHH, which is very light in color, sparse, and very fine, is also a very specific feature. While the short stature usually becomes apparent over time, it may not be identified in people that are mildly affected by CHH when they are first born.

Because it is so rare, there are no national support groups specific for Cartilage Hair Hypoplasia. However, there are support groups for short stature syndromes and immune deficiency syndromes.

Little People of America, commonly referred to as the LPA is an extraordinarily active organization that has been in existence for decades and provides support, information and networking opportunities for individuals and families with all forms of short stature, including CHH. Within LPA there are ways to connect with other individuals diagnosed with CHH including the annual meeting which is very well attended by members and a good place to network with other patients. LPA’s website is [link url="www.lpaonline.org” target=”_blank”>www.lpaonline.org and their contact information is:

Little People of America, Inc. (LPA)
250 El Camino Real
Suite 201
Tustin CA 92780
Phone: 888-572-2001 (toll-free); 714-368-3689
Fax: 714-368-3367
Email: [email protected]
[link url="www.lpaonline.org” target=”_blank”>www.lpaonline.org

Other resources include:

Human Growth Foundation
An organization devoted to supporting people with growth disorders and growth hormone deficiencies.
997 Glen Cove Avenue Suite 5
Glen Head NY 11545
Phone: (800) 451-6434
Secondary Phone: (516) 671-4041
[email protected]

Immune Deficiency Foundation
An organization devoted to improving the diagnosis and treatment of primary immune deficiencies such as cartilage-hair hypoplasia.
40 West Chesapeake Avenue Suite 308
Towson, MD 21204
Phone: (800) 296-4433
[email protected]

MAGIC Foundation for Children’s Growth
An organization that provides support services to families with children living with from disorders and diseases that affect growth.
6645 W. North Avenue
Oak Park IL 60302
Phone: (800) 362-4423
Secondary Phone: (708) 383-0808
[email protected]

Jeffrey Modell Foundation
The Jeffrey Modell Foundation is a resource for families and children with primary immunodeficiency disorders
747 3rd Avenue
New York, NY 10017
Tel: 1-800-JEFF-855
http://www.info4pi.org

All of the research that has been done on Cartilage-Hair Hypoplasia (CHH) as of Spring 2019, has found that this condition is always due to mutations, or changes, in a single gene, RMRP. There haven’t been any known cases of CHH that are not genetic or that are due to another genetic cause.

To learn more about the gene change that causes CHH, talk with your doctor or contact a genetic counselor. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Cartilage-Hair Hypoplasia is a specific disorder with specific features. However, CCH is part of a spectrum of disorders that are all due to mutations in the same gene, RMRP.

Metaphyseal Dysplasia without Hypotrichosis: The mildest condition within this spectrum is called metaphyseal dysplasia without hypotrichosis (MDWH). Individuals with MDWH have short stature and have changes to their bones that are visible through x-rays (metaphyseal dysplasia) but don’t have abnormal hair growth (hypotrichosis).

Cartilage Hair Hypoplasia: In the middle of the spectrum is CHH. Individuals have short stature, abnormal hair (hypotrichosis) and metaphyseal dysplasia.

Anauxetic Dysplasia: The third disorder in the spectrum is anauxetic dysplasia (AD) which has the most severe short stature and differences with many different bones in the body. Individuals may have dislocated hips, a barrel shaped chest, and a curvature of their spine. Some also have mild intellectual disability.

The main way to tell these different disorders apart is to have an evaluation with an expert, such as a medical geneticist. There aren’t any specific criteria to define each of these three disorders because even with one condition, like CHH, people can have a wide range of features.

For further evaluation of a CHH spectrum disorder, talk with your doctor or seek care from a medical geneticist. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website .

Individuals with Cartilage-Hair Hypoplasia (CHH) are part of a larger community of individuals with short stature. The oldest and largest support organization for this population is called the Little People of America (LPA). The LPA has officially come out against the use of the term "midget" to describe people with short stature, including those with CHH. This term is considered hurtful and has a history of use in abusive and bullying situations. Therefore, this term should never be used in reference to an individual with CHH or anyone else. Some people with short stature prefer the term dwarf and others prefer the term little person. Importantly, like with everyone else, individuals with CHH and other conditions of short stature are all unique individuals who may have different preferences and perspectives on such language.

People with Cartilage-Hair Hypoplasia (CHH) could benefit from financial assistance programs offered through the national organization called Little People of America (LPA). Their website includes information on educational and vocational grants for individuals with dwarfism as well as travel assistance to attend the annual LPA meetings which can be a very valuable social event.

There are no special diet restrictions for an individual with Cartilage-Hair Hypoplasia. If a patient is experiencing gastrointestinal problems due to CHH their doctor may talk to them about their diet. But, for most people with CHH, there is no impact on their diet or nutrition.

Short stature, which is often the most identifiable feature of Cartilage-Hair Hypoplasia (CHH), is also the main feature of a group of conditions called skeletal dysplasias. There are over 200 different types of skeletal dysplasias. While all of these conditions feature short stature, they all have differences that make each condition distinct.

There are several conditions that have similar bone issues (metaphyseal dysplasia) that are seen in CHH. These conditions are called Schmid dysplasia, Jansen dysplasia, and Shwachman-Diamond syndrome.

CHH is caused by mutations, or changes, in the RMRP gene, and the other conditions are caused by mutations in different genes. Genetic testing is one way that the correct diagnosis can be made.

There are two other conditions called Schimke immunoosseous dysplasia and Omenn syndrome that can be confused with CHH because these conditions also have short stature and a weak immune system. However, these conditions are also caused by mutations in different genes.

A weakened immune system is a major feature of another group of disorders called combined immunodeficiency syndromes. CHH is different than these syndromes because the immunodeficiency syndromes do not have short stature or bone problems as a primary feature.

For more information about the correct diagnosis of CHH, talk with your doctor or contact a medical geneticist. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website .

While Little People of America (LPA) is a national advocacy organization in the United States, there is also an international registry for individuals with skeletal dysplasia (dwarfism). The European Skeletal Dysplasia Network (ESDN) was created to help to understand the underlying cause of disorders related to bone growth and to help find better ways to diagnosis skeletal dysplasias.

The information for ESDN is:
Institute of Genetic Medicine
Newcastle University, International Centre for Life
Central Parkway
Newcastle upon Tyne NE1 3BZ
United Kingdom
Email: [email protected]
[link url="www.esdn.org” target=”_blank”>www.esdn.org

There is no cure for Cartilage-Hair Hypoplasia (CHH). Because CHH affects many different parts of the body like the bones, blood cells, immune system, and gastrointestinal system, treatment is based on each person’s specific symptoms. Not everyone with CHH has the same symptoms or requires the same treatments.

For some people with CHH, surgery can help with the colon obstruction problems (megacolon and Hirschsprung disease) and surgery can also help fuse bones in the spine and back that are unstable. This type of skeletal surgery can stabilize the vertebrae to make it easier for someone to breathe because it takes pressure off the lungs. For people with CHH who have a weakened immune system, treatment might include routine antibiotics and replacement of immune proteins that aren’t produced properly to fend off infections. If a person develops an infection, then it should be treated appropriately. One specific infection that can be especially dangerous is varicella which is the virus that causes chickenpox. There are medications available to treat varicella infections in people with CHH. For people with CHH who have severely compromised immune systems (SCID) who have many dangerous infections, a bone marrow transplant might help restore immunity. People with CHH also have an increased risk for certain types of cancer including leukemia and lymphomas. If these cancers develop they are treated the same way as they would in a person without CHH who develops these cancers.

Because CHH affects bone growth and therefore height, there have been some studies looking at the benefit of patients with CHH taking human growth hormone. Results of these studies have been mixed so this is not a treatment that is recommended for everyone. Patients should talk to their doctors about the benefits and limitations of human growth hormone.