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Disease Profile

Greig cephalopolysyndactyly 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.

Unknown

Age of onset

Antenatal

ICD-10

Q87.0

Inheritance

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

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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

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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.

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

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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.

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Not applicable

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Other names (AKA)

GCPS; Greig syndrome; Polysyndactyly with peculiar skull shape

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

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]

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]

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
Macrocephaly
Increased size of skull
Large head circumference
Large head

[ more ]

0000256
Postaxial hand polydactyly
Extra pinky finger
Extra pinkie 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
Early bone maturation
Advanced bone age

[ 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
Broad nasal bridge
Increased breadth of nasal bridge
Increased breadth of bridge of nose
Broadened nasal bridge
Broad nasal root
Widened nasal bridge
Wide bridge of nose
Nasal bridge broad
Increased width of nasal bridge
Increased width of bridge of nose

[ more ]

0000431
5%-29% of people have these symptoms
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect

[ more ]

0001627
Abnormal muscle fiber morphology
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
Mild mental retardation
Mental retardation, borderline-mild
Mild and nonprogressive 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
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

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]

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]

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]

    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 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]

      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

        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.

            References

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

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