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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Macrocephaly	Very frequent (present in 80%-99% of cases)
Postaxial hand polydactyly	Very frequent (present in 80%-99% of cases)
Preaxial foot polydactyly	Very frequent (present in 80%-99% of cases)
3-4 finger syndactyly	Frequent (present in 30%-79% of cases)
Accelerated skeletal maturation	Frequent (present in 30%-79% of cases)
Broad hallux phalanx	Frequent (present in 30%-79% of cases)
Broad thumb	Frequent (present in 30%-79% of cases)
Finger syndactyly	Frequent (present in 30%-79% of cases)
Frontal bossing	Frequent (present in 30%-79% of cases)
High forehead	Frequent (present in 30%-79% of cases)
Hypertelorism	Frequent (present in 30%-79% of cases)
Telecanthus	Frequent (present in 30%-79% of cases)
Toe syndactyly	Frequent (present in 30%-79% of cases)
Wide nasal bridge	Frequent (present in 30%-79% of cases)
Abnormal heart morphology	Occasional (present in 5%-29% of cases)
Abnormality of calvarial morphology	Occasional (present in 5%-29% of cases)
Abnormality of muscle fibers	Occasional (present in 5%-29% of cases)
Agenesis of corpus callosum	Occasional (present in 5%-29% of cases)
Camptodactyly of toe	Occasional (present in 5%-29% of cases)
Congenital diaphragmatic hernia	Occasional (present in 5%-29% of cases)
Cryptorchidism	Occasional (present in 5%-29% of cases)
Delayed cranial suture closure	Occasional (present in 5%-29% of cases)
Downslanted palpebral fissures	Occasional (present in 5%-29% of cases)
Hirsutism	Occasional (present in 5%-29% of cases)
Hydrocephalus	Occasional (present in 5%-29% of cases)
Hyperglycemia	Occasional (present in 5%-29% of cases)
Hypospadias	Occasional (present in 5%-29% of cases)
Inguinal hernia	Occasional (present in 5%-29% of cases)
Intellectual disability, mild	Occasional (present in 5%-29% of cases)
Joint contracture of the hand	Occasional (present in 5%-29% of cases)
Metopic synostosis	Occasional (present in 5%-29% of cases)
Postaxial foot polydactyly	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Umbilical hernia	Occasional (present in 5%-29% of cases)
1-3 toe syndactyly	Very rare (present in 1%-4% of cases)
Broad hallux	Very rare (present in 1%-4% of cases)
Autosomal dominant inheritance	-
Dolichocephaly	-
Trigonocephaly	-
Variable expressivity	-

Last updated: 9/1/2017

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

Management Guidelines

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.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Genetic and Clinical Studies of Congenital Anomaly Syndromes (also known as Phenotype and Etiology of Pallister-Hall Syndrome) which may be of interest to you.

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? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

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.

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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.