Greig cephalopolysyndactyly syndrome

Title

Other Names:

GCPS; Greig syndrome; Polysyndactyly with peculiar skull shape

Categories:

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary Summary

Greig cephalopolysyndactyly syndrome (GCPS) is a congenital disorder that affects development of the limbs, head, and face. Findings might include an extra finger or toe (polydactyly), fusion of the skin between the fingers or toes (syndactyly), widely spaced eyes (ocular hypertelorism), and an abnormally large head size (macrocephaly).^[1]The features of this syndrome are highly variable, ranging from polydactyly and syndactyly of the upper and/or lower limbs to seizure, hydrocephalus , and intellectual disability. Progression of GCPS is dependent on severity. Greig cephalopolysyndactyly syndrome is caused by mutations in the GLI3 gene. This condition is inherited in an autosomal dominant pattern. Treatment is symptomatic.^[2]

Last updated: 12/10/2015

Symptoms Symptoms

The symptoms of Greig cephalopolysyndactyly syndrome (GCPS) are highly variable, ranging from mild to severe. People with this condition typically have limb anomalies, which may include one or more extra fingers or toes (polydactyly), an abnormally wide thumb or big toe (hallux), and the skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, developmental delay, and intellectual disability.^[1]

Last updated: 12/15/2015

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Macrocephaly	Large head circumference Large head Increased size of skull [ more ]	0000256
Postaxial hand polydactyly	Extra pinkie finger Extra pinky finger Extra little finger [ more ]	0001162
Preaxial foot polydactyly		0001841
30%-79% of people have these symptoms
3-4 finger syndactyly	Webbed 3rd-4th fingers	0006097
Accelerated skeletal maturation	Advanced bone age Early bone maturation [ more ]	0005616
Broad hallux phalanx	Broad bone of big toe Wide bone of big toe [ more ]	0010059
Broad thumb	Broad thumbs Wide/broad thumb [ more ]	0011304
Finger syndactyly		0006101
Frontal bossing		0002007
High forehead		0000348
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Telecanthus	Corners of eye widely separated	0000506
Toe syndactyly	Fused toes Webbed toes [ more ]	0001770
Wide nasal bridge	Broadened nasal bridge Broad nasal root Broad nasal bridge Wide bridge of nose Nasal bridge broad Increased width of nasal bridge Increased width of bridge of nose Increased breadth of nasal bridge Increased breadth of bridge of nose Widened nasal bridge [ more ]	0000431
5%-29% of people have these symptoms
Abnormal heart morphology	Abnormality of the heart Abnormally shaped heart [ more ]	0001627
Abnormality of muscle fibers		0004303
Agenesis of corpus callosum		0001274
Camptodactyly of toe		0001836
Congenital diaphragmatic hernia		0000776
Craniosynostosis		0001363
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Delayed cranial suture closure		0000270
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Hirsutism	Excessive hairiness	0001007
Hydrocephalus	Too much cerebrospinal fluid in the brain	0000238
Hyperglycemia	High blood sugar	0003074
Hypospadias		0000047
Inguinal hernia		0000023
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Joint contracture of the hand		0009473
Metopic synostosis		0011330
Postaxial foot polydactyly	Extra toe attached near the little toe	0001830
Preaxial hand polydactyly	Extra thumb	0001177
Seizures	Seizure	0001250
Umbilical hernia		0001537
1%-4% of people have these symptoms
1-3 toe syndactyly	Webbed 1st-3rd toes	0001459
Broad hallux	Broad big toe Wide big toe [ more ]	0010055
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Scaphocephaly		0030799
Trigonocephaly	Triangular skull shape Wedge shaped skull [ more ]	0000243
Variable expressivity		0003828

Showing of 41 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2018

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome (GCPS). The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.^[1]

Different genetic changes involving the GLI3 gene can cause GCPS. In some cases, the condition results from a chromosome abnormality—such as a large deletion or rearrangement of genetic material—in the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of GCPS.^[1]

Last updated: 12/15/2015

Inheritance Inheritance

Greig cephalopolysyndactyly syndrome (GCPS) is often inherited in an autosomal dominant pattern. This means that to be affected, a person only needs a change (mutation) in one copy of the GLI3 gene in each cell. In some cases, an affected person inherits a gene mutation or chromosomal abnormality from one affected parent. Other cases occur in people with no history of the condition in their family. A person with GCPS syndrome has a 50% chance with each pregnancy of passing the altered gene to his or her child.^[1]

Last updated: 12/16/2015

Diagnosis Diagnosis

Yes. GLI3 is the only gene known to be associated with Greig cephalopolysyndactyly syndrome (GCPS). Genetic testing is available to analyze the GLI3 gene for mutations. Mutations involving GLI3 can be identified in greater than 75% of people with GCPS.^[2]

Last updated: 12/16/2015

Greig cephalopolysyndactyly syndrome (GCPS) is diagnosed based on clinical findings and family history. Major findings of GCPS include:

an abnormally large head size (macrocephaly) greater than the 97th percentile

widely spaced eyes (ocular hypertelorism)

limb anomalies including extra fingers or toes (polydactyly)

fused skin between the fingers and toes (cutaneous syndactyly)

A diagnosis is established in a first degree relative of a known affected individual if that person has polydactyly with or without syndactyly or craniofacial features (macrocephaly, widely spaced eyes). A diagnosis is additionally established in a person who has features of GCPS and a mutation in the GLI3 gene.^[2]

Last updated: 12/16/2015

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.

Treatment Treatment

Treatment for Greig cephalopolysyndactyly syndrome (GCPS) is symptomatic. Treatment might include elective surgical repair of polydactyly. Evaluation and treatment of hydrocephalus might additionally occur if hydrocephalus is present.^[2]

Hydrocephalus is a condition characterized by excessive accumulation of fluid in the brain. This fluid is cerebrospinal fluid (CSF) - a clear fluid that surrounds the brain and spinal cord. Excess CSF builds up when it cannot drain from the brain due to a blockage in a passage through which the fluid normally flows. This excess fluid causes an abnormal widening of spaces in the brain called ventricles; this can create harmful pressure on brain tissue.^[3]

Treatment of hydrocephalus often includes surgical insertion of a shunt system-in which a catheters (tubes) are surgically placed behind both ears. A valve (fluid pump) is placed underneath the skin behind the ear and is connected to both catheters. When extra pressure builds up around the brain, the valve opens, and excess fluid drains through the catheter. This helps lower pressure within the skull (intracranial pressure).^[4]

Last updated: 12/16/2015

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome (see these terms). The disorder is allelic to Pallister-Hall syndrome and one form of the acrocallosal syndrome. Visit the Orphanet disease page for more information.

Organizations 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

Children's Craniofacial Association
13140 Coit Road Suite 517
Dallas, TX 75240
Toll-free: 800-535-3643
Telephone: 214-570-9099
Fax: 214-570-8811
E-mail: contactCCA@ccakids.com
Website: http://www.ccakids.com/
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: faces@faces-cranio.org
Website: http://www.faces-cranio.org/
Let's Face It
University of Michigan School of Dentistry Dentistry Library
1011 North University
Ann Arbor, MI 48109-1078
E-mail: faceit@umich.edu
Website: http://media.dent.umich.edu/faceit/info/
This website does not appear to be actively updated any longer. However the information and resources may be helpful.
World Craniofacial Foundation
P.O. Box 515838
Dallas, TX 75251-5838
Toll-free: 800-533-3315
Telephone: 972-566-6669
Fax: 972-566-3850
E-mail: info@worldcf.org
Website: http://www.worldcf.org/

Do you know of an organization? We want to hear from you.

Learn More 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 Greig cephalopolysyndactyly 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

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
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 Greig cephalopolysyndactyly syndrome. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I am researching the link between Greig cephalopolysyndactyly syndrome, hydrocephalus, and seizures. I am curious about the reason for the hydrocephalus: is it a blockage issue or a slow draining issue? See answer

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References References

Greig cephalopolysyndactyly syndrome. Genetics Home Reference (GHR). 2006; http://ghr.nlm.nih.gov/condition/greig-cephalopolysyndactyly-syndrome. Accessed 12/10/2015.
Leslie G Biesecker, MD. Greig Cephalopolysyndactyly Syndrome. GeneReviews. 6/19/2014; http://www.ncbi.nlm.nih.gov/books/NBK1446/. Accessed 12/10/2015.
Hydrocephalus Fact Sheet. NINDS. July 27, 2015; http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm. Accessed 12/16/2015.
Ventriculoperitoneal shunting. MedlinePlus. 10/29/2013; https://www.nlm.nih.gov/medlineplus/ency/article/003019.htm. Accessed 12/16/2015.