Rare Rheumatology News

Disease Profile

Meier-Gorlin syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Ear, patella, short stature syndrome; Microtia, absent patellae, micrognathia syndrome

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

Meier-Gorlin syndrome (MGS) is a very rare inherited condition characterized by very small ears and ear canals, short stature, and absent or very small kneecaps (patellae).[1][2][3] Other signs and symptoms can include hearing loss, feeding problems, respiratory tract abnormalities, small chin, and small head size. People with MGS may also have characteristic facial features including a small mouth, full lips and a narrow nose. Females with MGS may have underdeveloped breasts. Most people with this syndrome have normal intelligence.

There are many forms of MGS and it can be caused by mutations in any of eight different genes: ORC1, ORC4, ORC6, CDT1, CDC6, CDC45L, MCM5 and GMNN.[4] Most forms of MGS are inherited in an autosomal recessive pattern. The form caused by the GMNN gene is inherited in an autosomal dominant pattern. MGS is diagnosed based on the clinical signs and symptoms. Genetic testing can aid in the diagnosis. Treatment is based on the symptoms. Most people with this syndrome have normal lifespans. The exact prevalence of MGS has not been determined, but is estimated to be less than 1-9/1,000,000.[2]

Symptoms

Most people with Meier-Gorlin syndrome have all three characteristic features of this condition, including small ears, absent or underdeveloped kneecaps (patellae), and short stature.[5] Additional features may include small head size, low-set ears, small mouth, full lips, cleft palate, small chin, and abnormalities of the genitalia or urinary tract. Affected individuals may experience feeding and breathing problems in early infancy.[5] The OMIM database provides a full list of the signs and symptoms of Meier-Gorlin syndrome.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Anotia
0009892
Atresia of the external auditory canal
Absent ear canal
0000413
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Mandibular aplasia
Failure of development of lower jaw
Missing lower jaw

[ more ]

0009939
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Microtia, third degree
0011267
Narrow mouth
Small mouth
0000160
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Slender long bone
Long bones slender
Thin long bones

[ more ]

0003100
30%-79% of people have these symptoms
Abnormality of the ribs
Rib abnormalities
0000772
Aplastic clavicle
Absent collarbone
0006660
Camptodactyly of finger
Permanent flexion of the finger
0100490
Clitoral hypertrophy
Enlarged clitoris
0008665
Clitoral hypoplasia
Small clitoris
Underdeveloped clit

[ more ]

0000060
Craniosynostosis
0001363
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Hypoplastic labia majora
Small labia majora
Underdeveloped vaginal lips

[ more ]

0000059
Hypoplastic labia minora
Underdeveloped inner lips
0000064
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Patellar aplasia
Absent kneecap
0006443
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Respiratory failure
0002878
5%-29% of people have these symptoms
Bifid uvula
0000193
Breast aplasia
Absent breast
0100783
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
Epispadias
0000039
Global developmental delay
0001263
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias
0000047
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Specific learning disability
0001328
Submucous cleft hard palate
0000176
Thick vermilion border
Full lips
Increased volume of lip
Plump lips
Prominent lips
Thick lips

[ more ]

0012471
Percent of people who have these symptoms is not available through HPO
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
0002644
Absent glenoid fossa
0006591
Absent sternal ossification
0006628
Aplasia/Hypoplasia of the patella
Absent/small kneecap
Absent/underdeveloped kneecap

[ more ]

0006498
Autosomal recessive inheritance
0000007
Birth length less than 3rd percentile
0003561
Blepharophimosis
Narrow opening between the eyelids
0000581
Breast hypoplasia
Underdeveloped breasts
0003187
Breech presentation
Feet or buttocks of fetus positioned near opening of uterus
0001623

Cause

Meier-Gorlin syndrome (MGS) is caused by genetic changes (mutations) in one of eight different genes. MGS, type 1 is caused by mutations in the ORC1 gene on chromosome 1p32. MGS type 2 is caused by mutations in the ORC4 gene on chromosome 2q22-q23. MGS type 3 is caused by mutations in the ORC6 gene on chromosome 16q12. MGS type 4 is caused by mutations in the CDT1 gene on chromosome 16q24. MGS, type 5 is caused by mutations in the CDC6 gene on chromosome 17q21.[4] MGS, type 6 is caused by mutations in the GMNN gene. MGS, type 7 is caused by mutations in the CDC45L gene and MGS, type 8 is caused by mutations in the MCM5 gene.[4]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Meier-Gorlin syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Meier-Gorlin syndrome. Click on the link to view a sample search on this topic.

            Selected Full-Text Journal Articles

              References

              1. Ear, patella, short stature syndrome. National Organization of Rare Disorders (NORD). 2007; https://rarediseases.org/rare-diseases/ear-patella-short-stature-syndrome/.
              2. De Munnik SA, Hoefsloot EH, Roukema J, Schoots J, Knoers NVAM, Brunner HG, Jackson AP, Bongers EMHF. Meier-Gorlin Syndrome. Orphanet J of Rare Dis. 2015; 10(114):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574002/pdf/.
              3. Meier-Gorlin Syndrome. Genetics Home Reference (GHR). Feb 2014; https://ghr.nlm.nih.gov/condition/meier-gorlin-syndrome.
              4. Meier-Gorlin Syndrome 1. Online Mendelian Inheritance in Man (OMIM). Updated 7/10/2017; https://www.omim.org/entry/224690. Accessed 5/14/2012.
              5. Bongers EM et al. Meier-Gorlin syndrome: report of eight additional cases and review. American Journal of Medical Genetics. 2001; 102:115-124. https://www.ncbi.nlm.nih.gov/pubmed/11477602. Accessed 5/14/2012.
              6. Fryns JP. Clinical Dysmorphology. 1998; https://www.ncbi.nlm.nih.gov/pubmed/9690002. Accessed 3/23/2010.

              Rare Rheumatology News