Meier-Gorlin syndrome

Women with Meier-Gorlin Syndrome are recommended to have gynecological examinations due to increased risk for polycystic ovaries, irregular periods and smaller uterus.

If someone receives a diagnosis of Meier-Gorlin syndrome other family members might want to consider genetic testing. Genetic counselors help to determine who could benefit from genetic testing by taking a family history and explaining the inheritance pattern for Meier-Gorlin syndrome. Since the majority of Meier-Gorlin syndrome cases are inherited in a recessive manner, if an individual is found to have changes in both copies of a Meier-Gorlin gene then both parents can speak with a genetic counselor regarding genetic testing. Parental testing allows for an assessment of possible other children or future children at risk for also having the condition. A genetic counselor can help to determine other family members who might also be at risk for being carriers for Meier-Gorlin syndrome.
Visit [link url="findageneticcounselor.com” target=”_blank”>Find a genetic counselor to learn more about testing other family members for Meier-Gorlin syndrome in the United States.

Typically, a salvia or blood sample is sufficient for genetic testing. The type of sample depends on the genetic test and the laboratory used for testing. Before a sample is taken, a physical examination is performed by a medical geneticist and a discussion about genetic testing by a genetic counselor.

A medical geneticist or genetic counselor can help provide direction of what specialist doctor need to be seen for Meier-Gorlin syndrome. Such specialists could include: ear nose and throat specialist, endocrinologist, cardiologist, pulmonologist, speech therapist, and orthopedic specialists.
Talk with your doctor or genetic counselor in finding these specialists in your area. Visit [link url="www.findageneticcounselor.com” target=”_blank”>Find a genetic counselor to find a genetic counselor in your area in the United States.

Meier-Gorlin syndrome can be abbreviated to MGS.

Meier-Gorlin syndrome is a rare genetic condition that is largely characterized by three main features; microtia (small or absent outer ear), patellar aplasia or hypoplasia (small or absent kneecap), and proportionate short stature. Meier-Gorlin syndrome is a type of dwarfism. A clinical diagnosis of Meier-Gorlin can be made if an individual displays two of the three main features. These individuals are classified as having dwarfism meaning that they are much shorter than the average individual. Additional features of individuals with Meier-Gorlin syndrome can include congenital pulmonary emphysema, feeding problems, mammary hypoplasia in females (underdeveloped breast tissue), and urogenital anomalies such as undescended testes in males and underdevelopment of labia in females. Small head size is typically noted but does not affect affect intellect.

Individuals with Meier-Gorlin syndrome typically have short stature. The medical community typically defines short stature as two standard deviations below the average height in a specific population. The Little People of America organization defines dwarfism as anyone who is under 4 feet 10 inches as an adult.

Congenital pulmonary emphysema, also known as congenital lobar emphysema, is a respiratory condition where air enters through the lungs but cannot escape. This can lead to breathing difficulties or in severe cases respiratory distress. Some cases may be mild where the individual might have trouble breathing during infancy but goes unnoticed. In severe cases, congenital pulmonary emphysema can also lead to hyperinflation of the lungs leading to compression of surrounding organs. About half of individuals with Meier-Gorlin syndrome have congenital pulmonary emphysema. Typically, congenital pulmonary emphysema presents during the neonatal period, but some individuals present with this symptom during late childhood.

Individuals with Meier-Gorlin syndrome will be much shorter than the average individual. These individuals will usually have proportionate short stature. Head size is typically smaller. Individuals with Meier-Gorlin syndrome may have hearing loss or narrow ear canals due to the small or absent outer ear. These individuals will usually have recurrent respiratory infections during childhood and about half of individuals with this condition will have congenital pulmonary emphysema which can lead to difficulty breathing and in severe cases, can lead to heart complications. Individuals with a underdeveloped or absent knee cap can experience knee joint instability, pain and early arthritis in the knee.
Read more about health problems for individuals with Meier-Gorlin syndrome under "Symptoms" tab.

Find a genetic counselor to learn more at www.findageneticcounselor.comwww.findageneticcounselor.com.

The genes that are known to cause Meier-Gorlin syndrome: ORC1, ORC4, ORC6,CDC45L, MCM5, GMNN, CDT1, and CDC6. These genes each contain instructions to make a protein. The proteins from each of these genes combine to make a complex important for DNA replication. Patients with mutations in the ORC1 and ORC4 have a more severe presentation of short stature and small head size. Meier-Gorlin Syndrome is a recessive disorder which means that both copies of the gene have been mutated or changed, the one inherited from the mother and the one inherited from the father.
For more information about the genes causing Meier-Gorlin Syndrome visit Genetics Home Reference .

Genetic tests have three different types of results; positive, negative, or variants of uncertain significance (VUS). A positive result means that there was a genetic change found that can cause a gene to not work properly. Negative result means that there was no genetic changes found that would cause the gene to not work properly. A variant of uncertain significance means that a genetic change was detected but it is uncertain whether this genetic change is causing the gene to not work properly.
Visit [link url="findageneticcounselor.com” target=”_blank”>Find a genetic counselor to discuss a variant of uncertain result from a genetic test with a genetic counselor in the United States.

Individual s with Meier-Gorlin Syndrome will be smaller than the typical adult, but this height difference can vary. There are reports of individuals being much shorter and some individuals who are average height. Adults with this condition will usually have sparse or absent underarm arm, but normal pubic hair. Females with this condition have less breast density, and some have a smaller uterus. Currently there is little information regarding reproduction for woman with Meier Gorlin Syndrome, but there is a possible increased risk for preterm labor. Males born with undescended testes may be at an increased risk for fertility problems.
For more information or questions about Meier-Gorlin Syndrome symptoms, visit [link url="www.findageneticcounselor.com” target=”_blank”>Find A Genetic Counselorto find a genetic counselor in the United States.

Several features of Meier-Gorlin syndrome might be detected prior to birth and also during the first few years of life. The majority of individuals with this condition will be very small during pregnancy which is called intrauterine growth restriction (IUGR). Typically, individuals with Meier-Gorlin will continue to have delayed growth during their first year of life. This will continue into childhood as having "delayed bone age" meaning their bones are growing at a much slower rate than typical for children their age. In general, growth hormones are not successful for individuals with Meier-Gorlin syndrome. However, there have been reports of growth hormone being effective if the individual has delayed growth during the first year of life due to a lack in a hormone called Insulin Growth Factor 1 (IGF1).

The majority of individuals with this condition will have knee hyperextension due to the underdeveloped or absent kneecap. A small portion of babies with this condition will be born with one or both feet that are twisted inward and downward called club foot.

About half of individuals with this syndrome will have a much smaller head than a typical baby. Some individuals will have hearing loss due to underdeveloped or absent outer ear. For the majority of individuals with Meier-Gorlin syndrome intellect is normal. There have been reported cases of individuals with delayed motor development, and speech delays.

Feeding problems are common during infancy and even into childhood. These problems can vary from having a very small appetite to severe reflux that can sometimes require a feeding tube. Half of individuals with this condition will have congenital pulmonary emphysema which will present during infancy or early childhood. Some individuals with Meier-Gorlin will have a "soft" or a weak breathing tube which can lead to breathing problems. Respiratory tract infections are common for children with Meier-Gorlin, but typically not during adulthood.
Congenital heart defects (structural defect with heart) is not common for individuals with this condition, but a small percentage of individuals have reported a heart defect. Over half of males with this condition will have undescended testes and some females will be born with an underdeveloped labia.

For more information or questions about Meier-Gorlin syndrome symptoms, visit [link url="www.findageneticcounselor.com” target=”_blank”>Find A Genetic Counselor to find a genetic counselor in the United States.

After an initial diagnosis of Meier-Gorlin syndrome it is important to be evaluated by several different specialists. The presentation of this syndrome can be variable which means that it is important that all individuals with a Meier-Gorlin syndrome diagnosis gets evaluated for all possible symptoms at the time of diagnosis. The following evaluations/specialists might be useful after a Meier-Gorlin syndrome diagnosis:
Ear nose and throat specialist for a hearing examination
Orthopedic examination and knee imaging
Growth evaluation and endocrine workup
Physical examination and CAT scan by a pulmonary specialist for respiratory tract infections and congenital pulmonary emphysema
Cardiac ECG and ultrasound for congenital heart defects

To learn more about the first steps after an initial diagnosis of Meier-Gorlin syndrome discuss with your doctor a referral to a medical geneticist. Also visit [link url="findageneticcounselor.com” target=”_blank”>Find a genetic counselor to find a genetic counselor in your area in the United States.

All types of Meier-Gorlin syndrome except Meier-Gorlin syndrome Type 6 is inherited in an autosomal recessive manner. This means that if both parents are found to be carriers for genetic changes in one of the Meier-Gorlin genes then there is a 25% chance of having another child with Meier-Gorlin syndrome. There is a 50% chance with each pregnancy of a child being a carrier for Meier-Gorlin Syndrome just like each parent. There is a 25% chance of the child not inheriting either genetic change from either parent.

There is not a specific newborn test used for Meier-Gorlin syndrome. If a doctor is suspicious for Meier-Gorlin syndrome, but does not meet the clinical features for the syndrome, genetic testing might be considered to look for changes in the Meier-Gorlin genes.

As of January 3, 2019, we are not aware of any specific clinical trials for Meier-Gorlin syndrome at this time. However, there are many clinical trials for individuals with primordial dwarfism. If interested in a particular clinical trial discuss with your doctor if it would be appropriate for you. Check https://clinicaltrials.gov/ to look for any clinical trials for Meier-Gorlin syndrome.

Treatments for Meier-Gorlin syndrome is dependent upon the individual’s symptoms. The following are all different treatment options and medical management tools for different symptoms present in individuals with Meier-Gorlin syndrome:
Hearing aids for hearing loss
Rehabilitation advice, arch supports, and orthopedic surgery for small/absent kneecaps, knee complaints, and flat feet
Growth hormone treatment for impaired growth and low levels of a growth hormone called IGF1
Speech therapy due to delayed motor and speech development early in life
Nasal tube feeding due to poor growth or feeding difficulties during early life
Antibiotics or surgery due to respiratory tract infections
Orchioplexy surgery due to undescended testes in males
Cardiac surgery due to congenital heart defects
Estrogen treatment and breast augmentation surgery due to small breast size in females

At this time there is no increased prevalence in any particular country. There have been reports of Meier-Gorlin syndrome worldwide. This condition is more likely to occur if parents are closely related.

The majority of individuals with Meier-Gorlin syndrome do not have an intellectual disability. There is one case report of an individual with Meier-Gorlin syndrome having an intellectual disability, but in general intellectual disability is not associated with Meier-Gorlin syndrome.

There is limited information regarding women with Meier-Gorlin syndrome and pregnancies. It is encouraged to have a gynecological examination prior to pregnancies since there seems to be a higher risk for having a smaller uterus and polycystic ovaries. Women with this condition might be at a higher risk for preterm labor and should discuss with doctor regarding proper care during pregnancy.

Some individuals with Meier-Gorlin syndrome do not report any difficulty with physical activities. Since premature arthritis in the knees is a common symptom with individuals with this condition, it would be important to have this discussion with your doctor regarding the appropriate level of physical activities.

According to the United States Department of Justice in the American Disability Act, dwarfism, like in individuals with Meier-Gorlin syndrome, is a recognized condition under the Americans with Disability Act (ADA). Opinions regarding whether dwarfism is a disability can vary within the community.

In addition to your primary care provider, a medical geneticist can assist in coordinating proper medical care for individuals with Meier-Gorlin syndrome. A medical geneticist can be helpful to make sure that the proper specialists are seen throughout the individual’s lifetime. While some specialists are only needed to be seen during initial diagnosis other specialist must been seen on an annual basis such as an ear nose and throat specialist. Your medical geneticist will be able to coordinate proper medical care alongside your primary care provider.

It is fairly common for individuals with Meier-Gorlin syndrome to have knee pain and early arthritis. These individuals could benefit from a multidisciplinary approach involving orthopedic specialist and a rehabilitation specialist. These specialists might recommend using specialized shoes, or strength enhancing exercises and sports to help with these symptoms.

In order for your children to also have Meier-Gorlin syndrome means that your partner would need to be a carrier for the condition or have the condition. If you have Meier Gorlin syndrome and your partner is a carrier than there is a 50% chance with each pregnancy to have a child with the condition. Since you have the condition, if your partner is not a carrier for Meier Gorlin syndrome all of your children will be carriers for the condition.
The only different inheritance pattern is Meier Gorlin Type 6, which is due to one genetic change in one Meier Gorlin gene. In this case there is a 50% chance of with each pregnancy of a child having this condition.

A genetic counselor is a healthcare professional with a Masters degree trained in medical genetics and counseling techniques. If you were referred to a genetic counselor regarding a recent diagnosis with Meier-Gorlin syndrome, a genetic counselor might ask you questions regarding your medical history, ask questions about your family history, discuss Meier-Gorlin syndrome and its inheritance. A genetic counselor might also offer you genetic testing and provide you information to decide if whether genetic testing is a good option for you. If you have already had genetic testing performed, the genetic counselor can go over the results and explain what this result means for you and your family.

While genetic testing is able to determine the gene changes that causes this condition in the majority of the time, some individuals with a clinical diagnosis do not receive a genetic diagnosis of Meier-Gorlin syndrome. Even with a negative genetic test result this does not mean you do not have Meier-Gorlin syndrome. It is possible that there are other genes that have not yet been discovered that causes Meier-Gorlin syndrome.

Meier-Gorlin syndrome is a rare condition. It is estimated that there are 1-9 individuals with this condition per 1,000,000 individuals. Researchers believe this might be an underestimation due to under reporting and possible misdiagnoses.

The majority of Meier-Gorlin cases are inherited in an autosomal recessive manner. Genetic material is condensed into packages called chromosomes which contain many genes. There are two copies of each gene from each parent. When a condition is inherited in an autosomal recessive manner this means that both copies of the gene are not working properly. If an individual has one working gene and a non-functional gene this means that the individual is a carrier for the condition. This means that if both parents are carriers for Meier-Gorlin syndrome then there is a 25% chance of having a child with the condition. Sometimes, these genetic changes occur sporadically and these individuals can be the first ones in their family to present with the condition. This is called a "de novo" change which means a genetic change occurred during the formation of the sperm or egg cell or early on during fetal development.
Meier-Gorlin syndrome type 6 is inherited in an autosomal dominant manner. This means that having one copy of the gene called GMNN not working properly will lead to the condition. This means that these individuals have a 50% chance of passing along the condition to a future child.

During a physical examination performed by a medical geneticist might look a little differently than a physical examination performed by a primary care doctor. A medical geneticist is trained to look for clues that might suggest that a child has a genetic condition. During the examination, the geneticist might look closely at the individual’s face to look for unique features that are specific to a genetic condition. For example, individuals with Meier-Gorlin syndrome are more likely to have unique facial features like a smaller mouth, full lips, high nose bridge, and a narrow nose. While any individual might have these features, if several of these features are present it is additional clues that an individual might have Meier-Gorlin syndrome.

Several organizations provide ways to donate to help with research with primordial dwarf conditions. One such organization is the Human Growth Foundation , which provides research grants to researchers investigating human growth and its conditions. They provide opportunities for individuals to donate money to help these researchers. While the organization Little People of America do not support or fund medical research as a part of its mission, they provide up to date research regarding dwarfism, as well as other organizations that fund medical research.

Medical geneticists can make a diagnosis of Meier-Gorlin syndrome. A diagnosis of Meier-Gorlin syndrome is given when an individual has the key features of small/absent ears, small/absent kneecap, and small stature. Some individuals with Meier-Gorlin syndrome will present with only 2 out of the three key features of this syndrome, and some individuals might only have one key feature such as short stature.
If an individual is suspected to have Meier-Gorlin syndrome after a physical examination, but it is still unclear, genetic testing might be performed to look for changes in any of the Meier-Gorlin genes.
To learn more about receiving a diagnosis of Meier-Gorlin syndrome, speak with your doctor and discuss a referral to a medical geneticist. To learn more information about Meier-Gorlin Syndrome, visit [link url="findageneticcounselor.com” target=”_blank”>Find a Genetic Counselor to find a genetic counselor in the United States.

https://clinicaltrials.gov/ is a useful resource to find clinical trials across the United States. The site allows user to search for a particular condition like Meier-Gorlin syndrome and find past, current and future clinical trials. If interested in a clinical trial, contact your doctor to discuss if it’s right for you. For more information regarding a particular study, you or your doctor can contact the particular research team on the clinical trial study page.

Little People of America provides a list of medical centers that provide focused care for individuals with dwarfism. Speak with your doctor or medical geneticist regarding experts for individuals with dwarfism.

Little People of America provide resources to connecting individuals with dwarfism, like Meier-Gorlin syndrome, with local groups. Little People America divides the US into various districts and provides contact information for each district to connect individuals to the appropriate local resources.

Some individuals might have a clinical diagnosis of Meier-Gorlin syndrome but not have a molecular diagnosis of the condition. A clinical diagnosis means that they have at least two of the three key features of Meier-Gorlin syndrome. However, some of these individuals will not have a disease-causing variant (genetic mutation) detected by genetic testing. These individuals would not have a molecular diagnosis of Meier-Gorlin syndrome.

Most men with Meier-Gorlin syndrome do not have any fertility problems. However, there is an increased chance for fertility problems when a male is born with undescended testes. While this is usually fixed with surgery during the first year of life a small portion of males will later have fertility problems.

The life span for most individuals with Meier-Gorlin syndrome is not shorter. There can be life-threatening complications early in life due to congenital pulmonary emphysema and cardiac defects, but if these are not present, the lifespan is expected to be within the normal range.

For most individuals with Meier-Gorlin syndrome, growth hormone treatments are not beneficial. In some cases, growth hormone treatments are beneficial if the individual’s growth rate continues to decrease after the first year of life and there are low levels of a specific growth hormone called IGF1.

There are not specific support groups for Meier-Gorlin Syndrome but there are several support groups for individuals and families with primordial dwarfism:
Little People of America: This national organization provides support for over 200+ forms of dwarfism. Their mission includes providing support to individuals and families with dwarfism including connections to local chapters/national conferences, and information regarding resources for medical support, employment and education. Visit Little People of America for more information.
Walking with Giants Foundation: This foundation aims to support individuals and families with primordial dwarfism. This site aims to provide information regarding different primordial dwarfism syndromes and facilitating opportunities to meet other families with primordial dwarfism. Visit Walking with Giants Foundation for more information.

Sometimes there are clues that an individual might have Meier-Gorlin Syndrome during pregnancy but usually these are not detected. The most common feature for this condition is small growth of the baby during pregnancy also known as severe intrauterine growth restriction (IUGR). Sometimes an ultrasound can detect other abnormalities associated with this condition such as a heart defect or smaller jaw. However, these features can be common in pregnancies and associated with several conditions and does not indicate that an individual has Meier-Gorlin Syndrome. Typically this condition is not detected during pregnancy.

Meier-Gorlin syndrome is also known as ear patella short-stature syndrome (EPS).

As of January 13 2019, the long-term risks associated with Meier-Gorlin syndrome and congenital pulmonary emphysema is still unknown. Surgical resection can be considered in older patients with Meier Gorlin syndrome when respiratory distress is considered to be severe.

Meier-Gorlin syndrome can be separated into different types based on the genetic mutation. There are eight reported types of Meier-Gorlin syndrome, however Meier-Gorlin 1 and Meier-Gorlin 2 appear to be more common.
Meier-Gorlin syndrome 1 is due to changes in the ORC1 gene. Individuals with this type are significantly shorter and have a much smaller head compared to the other types.
Meier-Gorlin syndrome 2 is due to changes in the ORC4 gene. Individuals with the type are significantly shorter and have a much smaller head compared to the other types.
Meier-Gorlin syndrome 3 is due to changes in the ORC6 gene.
Meier-Gorlin syndrome 4 is due to changes in the CDT1 gene. There have been reports that congenital pulmonary emphysema is more common for Meier-Gorlin syndrome 4.
Meier-Gorlin syndrome 5 is due to changes in the CDC6 gene.
Meier-Gorlin syndrome 6 is due to changes in the GMNN gene. This type is considered dominant which means that only one of the genes is not working leading to Meier-Gorlin syndrome.
Meier-Gorlin syndrome 7 is due to changes to the CDC45L gene.
Meier-Gorlin syndrome 8 is due to changes in the MCM5 gene.
For more information regarding the different types of Meier-Gorlin syndrome consider talking with your doctor for a referral to a medical geneticist or visit [link url="www.findageneticcounselor.com” target=”_blank”>Find A Genetic Counselor to find a genetic counselor in the United States.

Individuals with primordial dwarfism and Meier-Gorlin syndrome have more difficulties with airway management than an individual of typical height. Anesthetic management is necessary in order to assess any special considerations regarding surgery for individuals with this condition.

If you have Meier-Gorlin syndrome, it is likely you will have short stature. There have been reports of individuals with short stature being injured by airbags. Individuals of short stature can get an authorized ON-OFF switch for drivers side airbags according to the National Highway Transportation Safety Administration. Visit the National Highway Transportation Safety Administration website for more information regarding safety and airbags.

There are several different conditions that have overlapping features with Meier-Gorlin syndrome. Meier-Gorlin syndrome is classified as a primordial dwarfism spectrum disorder and other conditions on this spectrum have similar features including small stature and a small head. Two primordial dwarfism spectrum disorders that share features with Meier-Gorlin syndrome include Seckel syndrome and micocephalic osteodysplastic primordial dwarfism. However, while these syndromes share similar features to Meier-Gorlin syndrome, they are distinctly different syndromes.
If you have questions about other diseases that can look like Meier-Gorlin syndrome, you can discuss with your doctor, ask for a referral to a medical geneticist, or visit [link url="findageneticcouselor.com” target=”_blank”>Find a genetic counselor to find a genetic counselor in your area.