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Disease Profile

Treacher Collins 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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

Q75.4

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)

Treacher Collins-Franceschetti syndrome; Mandibulofacial dysostosis; TCOF;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

Treacher Collins syndrome (TCS) is a condition that affects the development of bones and other tissues of the face. The signs and symptoms vary greatly, ranging from almost unnoticeable to severe. Most affected people have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Other features may include cleft palate, eye abnormalities, and hearing loss.[1] TCS may be caused by mutations in the TCOF1, POLR1C, or POLR1D genes.[2] When the TCOF1 or POLR1D gene is responsible, it is inherited in an autosomal dominant manner.[2] However, about 60% of autosomal dominant cases are due to a new mutation in the gene and are not inherited from a parent.[1] When the POLR1C gene is responsible, it is inherited in an autosomal recessive manner.[2] In some cases, the genetic cause of the condition is unknown.[1]

Symptoms

The signs and symptoms of Treacher Collins syndrome vary greatly, ranging from almost unnoticeable to severe. Most affected people have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems.[3]

People with Treacher Collins syndrome often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called a coloboma. Some people have additional eye abnormalities that can lead to vision loss. The condition is also characterized by absent, small, or unusually formed ears. Defects in the middle ear (which contains three small bones that transmit sound) cause hearing loss in about half of affected people. People with Treacher Collins syndrome usually have normal intelligence.[3] 

You can read additional information about the features of Treacher Collins syndrome through MedlinePlus and GeneReviews.

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 bone mineral density
0004348
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
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
Hypoplasia of the zygomatic bone
Cheekbone underdevelopment
Decreased size of cheekbone
Underdevelopment of cheekbone

[ more ]

0010669
Malar flattening
Zygomatic flattening
0000272
Micrognathia
Small lower jaw
Small jaw
Little lower jaw

[ more ]

0000347
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Open bite
Absence of overlap of upper and lower teeth
Open bite between upper and lower teeth

[ more ]

0010807
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Short face
Decreased height of face
Decreased length of face
Vertical shortening of face

[ more ]

0011219
Skeletal dysplasia
0002652
30%-79% of people have these symptoms
Absent eyelashes
Failure of development of eyelashes
0000561
Conductive hearing impairment
Conductive hearing loss
Conductive deafness

[ more ]

0000405
Eyelid coloboma
Cleft eyelid
Notched eyelid

[ more ]

0000625
Frontal bossing
0002007
Iris coloboma
Cat eye
0000612
Low anterior hairline
Low frontal hairline
Low-set frontal hairline

[ more ]

0000294
Microtia
Underdeveloped ears
Small ears

[ more ]

0008551
Narrow internal auditory canal
0011386
Reduced number of teeth
Decreased tooth count
0009804
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth

[ more ]

0006482
Abnormality of the adrenal glands
Adrenal abnormalities
0000834
Abnormality of the vertebral column
Abnormal spine
Abnormal vertebral column
Abnormality of the spine

[ more ]

0000925
Blepharospasm
Eyelid spasm
Eyelid twitching
Involuntary closure of eyelid
Spontaneous closure of eyelid

[ more ]

0000643
Brachycephaly
Short and broad skull
0000248
Branchial fistula
0009795
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Choanal atresia
Obstruction of the rear opening of the nasal cavity
Blockage of the rear opening of the nasal cavity

[ more ]

0000453
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Dysphasia
0002357
Encephalocele
0002084
Facial cleft
Cleft of the face
0002006
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Global developmental delay
0001263
Glossoptosis
Retraction of the tongue
0000162
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of penis
Underdeveloped penis
0008736
Hypoplasia of the thymus
Small thymus
0000778
Microphthalmia
Abnormally small eyeball
0000568
Multiple enchondromatosis
0005701
Narrow mouth
Small mouth
0000160
Patent ductus arteriosus
0001643
Preauricular skin tag
0000384

Cause

Treacher Collins syndrome (TCS) is caused by changes (mutations) in any of several genes: TCOF1 (in over 80% of cases), POLR1C, or POLR1D. In a few cases, the genetic cause of the condition is unknown.

These genes appear to play important roles in the early development of bones and other tissues of the face. They are involved in making proteins that help make ribosomal RNA (rRNA). rRNA is a chemical needed to make new proteins that are necessary for normal function and survival of cells. Mutations in these genes can reduce the production of rRNA, which may cause cells involved in the development of facial bones and tissues to die early. This premature cell death may lead to the signs and symptoms of TCS. It is still unclear why the effects of these mutations are generally limited to facial development.[1]

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.

    Treatment

    There is currently no cure for Treacher Collins syndrome (TCS).[4] Treatment is tailored to the specific needs of each affected person. Ideally, treatment is managed by a multidisciplinary team of craniofacial specialists.

    Newborns may need special positioning or tracheostomy to manage the airway. Hearing loss may be treated with bone conduction amplification, speech therapy, and/or educational intervention.[5]

    In many cases, craniofacial reconstruction is needed. Surgery may be performed to repair cleft palate, to reconstruct the jaw, or to repair other bones in the skull. The specific surgical procedures used and the age when surgery is performed depends on the severity of the abnormalities, overall health and personal preference.[4]

    There are some possible treatments that are being investigated. Researchers are looking for ways to inhibit a protein called p53, which helps the body to kill off unwanted cells.[4][5] In people with TCS, p53 is abnormally activated, leading to the loss of specific cells and ultimately causing features of TCS. It has been proposed that inhibiting the production of p53 (or blocking its activation) may help to treat affected people. However, more research is needed to determine if this type of treatment is effective and safe.[4]

    Researchers are also studying the use of stems cells found in fat tissue to be used alongside surgery in people with TCS and other craniofacial disorders. Early studies have shown that surgical outcomes may be improved using these stem cells to help stimulate the regrowth of affected areas. However, this therapy is still experimental and controversial.[4][5]

    Management Guidelines

    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      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

            • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
            • Genetics Home Reference (GHR) contains information on Treacher Collins 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.
              • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
              • 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 Treacher Collins syndrome. Click on the link to view a sample search on this topic.

                References

                1. Treacher Collins syndrome. Genetics Home Reference. June, 2012; https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome. Accessed 10/27/2014.
                2. Marie-Paule Vazquez. Treacher Collins syndrome. Orphanet. January, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=861. Accessed 10/27/2014.
                3. Treacher Collins syndrome. Genetics Home Reference (GHR). 2006; https://ghr.nlm.nih.gov/condition/treacher-collins-syndrome. Accessed 2/28/2011.
                4. Treacher Collins Syndrome. NORD. May 24, 2013; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/647/viewAbstract. Accessed 10/27/2014.
                5. Sara Huston Katsanis and Ethylin Wang Jabs. Treacher Collins Syndrome. GeneReviews. August 30, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1532/. Accessed 10/27/2014.
                6. Treacher-Collins syndrome. MedlinePlus. September 8, 2013; https://www.nlm.nih.gov/medlineplus/ency/article/001659.htm. Accessed 10/27/2014.
                7. J Dixon, P Trainor and MJ Dixon. Treacher Collins syndrome. Orthodontics & Craniofacial Research. May, 2007; 10(2):88-95. Accessed 10/27/2014.

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