TreacherCollins Syndrome

7/30/2019 TreacherCollins Syndrome

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TheNationalOrganization

forRareDisorders

NORD Guides for Physicians #12

The Physicians Guide toTreacher Collins Syndrome


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For more inormation about NORDs programs and services, contact:

National Organization or Rare Disorders (NORD)

PO Box 1968

Danbury, CT 06813-1968

Phone: (203) 744-0100

Toll ree: (800) 999-NORD

Fax: (203) 798-2291

Website: www.rarediseases.org Email: [email protected]

NORDs Rare Disease Database and Organizational Database may be

accessed at www.rarediseases.org.

Contents 2012 National Organization or Rare Disorders


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1

What is Treacher Collins syndrome?

Treacher Collins syndrome (TCS) is a rare genetic disorder characterized

primarily by abnormalities in the development o the head and ace.

Underdevelopment(hypoplasia)ofthecheekbonesandrelatedstructures(zygomatic bones) as well as the jawbone are common ndings.

Consequently, patients generally have a distinctive acial appearance. The

jaws, ears and eyes are commonly aected, potentially causing respiratory,

hearingandvisioncomplications.TCSisahighlyvariabledisorder.Mild

cases can go unrecognized and undiagnosed, while severe cases can lead to

serious, lie-threatening respiratory complications.

TCSisestimatedtoaffectapproximately1in10,000-50,000individuals.The disorder is named ater Edward Treacher Collins, a London

ophthalmologist who rst described the disorder in the medical literature in

1900.TCSisalsoknownasmandibulofacialdysostosisorTreacherCollins-

Franceschetti syndrome.

This booklet is the twelth in a series o ree publications or physicians

and other medical proessionals. It is NORDs hope that patients and their

amilies will beneft rom this and other eorts to enhance awareness o

the almost 7,000 rare diseases aecting an estimated 30 million Americans.


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What causes Treacher Collins syndrome?

TCS is caused by mutation o the TCOF1, POLR1Cor POLR1D genes. In the

case o TCOF1 or POLR1D, the mode o inheritance is autosomal dominant,

while in the case o POLR1Cit is autosomal recessive.

Geneticdiseasesaredeterminedbythecombinationofgenesfora

particular trait that are contained within the chromosomes received rom

the ather and the mother. Dominant genetic disorders occur when only

a single copy o an abnormal gene is necessary or the appearance o the

disease. The abnormal gene can be inherited rom either parent, or occurs

asanewmutationintheaffectedindividual.In60%ofTSCcases,the

mutation is a new mutation without a positive amily history o the disorder.However, a parent may be mildly aected and unaware that they have the

disorder.Theriskofpassingtheabnormalgenefromaffectedparentto

offspringis50%foreachpregnancy.

Recessive genetic disorders occur when the same abnormal gene is

inheritedfrombothparents.Theriskfortwocarrierparentstobothpass

thedefectivegeneandhaveanaffectedchildis25%witheachpregnancy.

The TCOF1geneislocatedonthelongarm(q)ofchromosome5,aregion

whichisdesignated5q32.TCOF1encodesaproteinknownastreacle.

TheexactrolethattreacleplaysinthedevelopmentofTCSisnotfully

understood. Researchers have determined that treacle plays a role in the

creation o certain small structures ound within cells that assemble

proteins (ribosomes). Deects in ribosome biogenesis are termed

ribosomopathies. POLR1Cand POLR1Darelocatedonchromosomes6and

12respectivelyatpositions6q21.2and13q12.2.POLR1Cand POLR1D

encodesubunitsofRNApolymerasesIandIII,whicharealsoessentialfor

ribosomebiogenesis.ItseemslikelythatmutationsinPOLR1Cand POLR1D

also result in decient ribosome biogenesis which is insucient to meet the

prolieration and growth needs o cells during development o the embryo.

BecauseTCSishighlyvariable,researchersspeculatethatadditionalgenetic

and possibly environmental actors may also play a role in the variable

severity o the disorder.


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What symptoms are associated with

Treacher Collins syndrome?

The specic symptoms present in TCS can vary dramatically rom one

person to another, even among members o the same amily. TCS aectscertain bones o the ace, ears and around the eyes. These abnormalities

are symmetrical (almost identical on both sides o the ace). In some cases,

serious respiratory complications can develop. It is important to note that

aected individuals will not have all o the symptoms discussed below.

Underdevelopmentofthecheekbonesandnearbystructuresoftenresults

inasunkenappearanceofthefaceandisdescribedasmalarhypoplasia

withorwithoutnotchingofthezygomaticbones.Anabnormallysmalljaw may cause problems with swallowing or breathing. Children may be

described as having eatures o Robin Sequence which include severe

micrognathia,glossoptosis(atonguethatisdisplacedfartherbackinthe

mouth than normal) with or without clet palate. Other airway problems

suchasblockageornarrowingofthenasalpassages(choanalatresiaor

stenosis) or airway narrowing (pharyngeal hypoplasia) can compound the

breathing issues o a newborn. Obstructive breathing problems includingbut not limited to sleep apnea can be dangerous and potentially cause

neonatal death.

Approximately5%ofindividualswithTCSdisplaydevelopmentaldecits

or neurological problems such as psychomotor delay. However, intelligence

is generally unaected with normal language development. Nonetheless,

issues with speech development can occur because o hearing loss, clet

palate or diculties producing sounds because o structural distortion.

Otological fndings

Some people with TCS may have ears that appear normal. In others, the

externalearsmaybeabnormallysmallorcompletelyabsent.Otological

ndings potentially associated with TCS include;

Absent,abnormallysmallorunderdevelopedexternalears

Malformedexternalears

Atresiaorstenosisoftheexternalauditorycanals

Conductivehearingloss(rangingfrommildtosevere)usuallydueto

malormations o structures within the middle ear


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Ophthalmic fndings

Eye abnormalities associated with TCS can give aected individuals a

saddened acial appearance. Lower eyelid abnormalities can cause the

eyestodryout,whichincreasestheriskofeyeinfection.Specicocular

abnormalities associated with TCS include;

Notching(coloboma)ofthelowereyelid

Downwardangleoftheupperandlowereyelids(downwardslanting

palpebral ssures)

Partialorcompleteabsenceofthelowereyelashes

Droopingeyelids

Visionloss

Narrowedtearducts(dacrostenosis)

Dental fndings

Approximately60%ofindividualswithTCSmaydevelopdental

abnormalities including;

Missingteeth(toothagenesis) Discolorationoftheteeth(enamelopacities)

Widely-spacedteeth

Abnormaleruptionofcertainteeth(ectopiceruptionofmaxillary

rst molars)

Malocclusion(improperpositioningoftheteethandjaw)

AdditionalsymptomsandphysicalfeaturesmaybeassociatedwithTCS.

These ndings occur less requently and can include;

Ahighlyarchedroofofthemouth(palate)

Cleftpalate

Nasaldeformity

Widelyspacedeyes

Notchingoftheuppereyelid

Anabnormallywidemouth(macrostomia)

Abnormalscalphairpattern(frontoftheearsandextendingtoward

thecheeks)

Congenitalheartdefect


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How is Treacher Collins syndrome diagnosed?

Adiagnosisismadebaseduponathoroughclinicalevaluation,adetailed

patient history, and identication o characteristic ndings. Specialized

imagingtechniquessuchasx-raysorcomputedtomographymaybe

performedtoassesstheextentofcertaincraniofacialabnormalitiessuchas

middle and inner ear structures.

Moleculargenetictestingtoconrmadiagnosisisavailablethrough

commercial and academic research laboratories to detect mutations in the

TCOF1, POLR1Cand POLR1Dgenes.Approximately90-95%ofindividuals

have an identiable mutation o the TCOF1 gene.

Prenataldiagnosisispossiblethroughchorionicvillussamplingoramniocentesis i a TCOF1, POLR1Cor POLR1D gene mutation has been

identiedinanaffectedfamilymember.Prenatalscreeningviaultrasound

during mid-to-late gestation may detect cases with severe cranioacial

abnormalities.

Relatives, especially parents and siblings, o an individual diagnosed with

TCSshouldbecarefullyexaminedbecausemildcasesoftengounnoticed

and undiagnosed.


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How is Treacher Collins syndrome treated?

There is no cure or TCS. Treatment is aimed at the specic needs o each

individual.Manychildrenrequireamultidisciplinaryapproachinvolvinga

qualied cranioacial team, which can include a pediatric otolaryngologist,

audiologist, pediatric dentist, pediatric nurse, plastic surgeon, geneticist,

psychologistandotherhealthcareprofessionals.Geneticcounselingis

recommended or aected individuals and their amilies.

Specic therapies and surgeries depend upon several actors including age,

extentorseverityofthedisorder,overallhealthandpersonalpreference.

Forexample,differentabnormalitiesmaybetreatedatdifferentages.

Cleftpalatearound1-2yearsofage Zygomaticandorbitalreconstructionaround5-7yearsofage

Externalandinnerearreconstructionaround6yearsofage

Jawbonelengtheningorreconstructionrangefromnewbornto

teenagedependingupontheextentandseverityofthecondition.

Cranioacial

Surgery or individuals with TCS is best perormed at a cranioacial research

center. Surgery may be perormed to repair clet palate, reconstruct or

lengthenthejawortorepairotherbonesintheskull(e.g.,cheekbones,

zygomaticcomplex).Surgicalreconstructionmayalsoincludesmallimplants

orfatinjectionstomasktheseverityofacraniofacialmalformation.

Obstructive airways can be a serious problem not always obvious to parents

orclinicians.Asleepornapstudymaybeusedtohelpdeterminetheseverity o the obstruction and may infuence the treatment plan. In severe

cases, newborn inants may require intubation, an immediate tracheotomy

or early mandibular distraction. Insertion o a gastrostomy tube may be

necessarytoensurepropernutritionalintakewhileprotectingtheairway.

Multiplesurgeriesmayberequiredtotreatthevariouscraniofacial

abnormalities that are potentially associated with TCS. Despite the number

o surgeries, results vary rom one person to another and the end result is

rarely ully corrective.


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Otological

Assessmentofaninfantshearingiscritical.Afullassessmentshouldbe

done early during lie, even beore one year o age and then yearly, in order

to ensure proper speech development.

Surgery to the middle ear may be an option to restore hearing in some

cases. However, surgery is not required or benecial in all cases. Some

individuals may benet rom bone-anchored hearing aids that augment or

restore hearing. Some individuals may benet rom surgical implantation o

this type o hearing aid. Speech therapy and educational intervention may

also be used to help individuals with hearing loss.

Reconstructionoftheexternalear,externalauditorycanalandthemiddleear may be necessary in some cases or unctional or cosmetic purposes.

Generally,reconstructionoftheexternalearshouldbeperformedrst.

Ophthalmologic

Ocular abnormalities may be treated with corrective lenses, contact lenses

and other supportive techniques. Eye ointments may be used, especially at

night, to prevent the eyes rom drying out during sleep.

Surgery may be necessary to correct a lower lip coloboma or to help with

vision problems because o misaligned eyes (strabismus). In some cases,

individuals may undergo surgery to correct drooping eyelids, which can

helppreventtheeyesfromdryingoutandlowertheriskofinfection.Eyelid

surgerymayalsohelptoimprovethefacialexpression.Obstructedtear

ducts may also require surgery in some cases.

Dental

Articialteeth,bracesanddentalimplantsmaybenecessarytotreatdental

anomalies such as misaligned teeth. Dental surgery may also be required in

some cases.

Anesthesia Considerations

StructuralairwayproblemsassociatedwithTCScanmakeitdifcult

or anesthesiologists to manage and maintain an airway during surgery.

Properevaluationincludingacomprehensivepreoperativeassessment

and complete clinical history should be perormed to best plan an

anesthetic strategy.


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8

Patient Support and Resources

National Organization for Rare Disorders (NORD)

55KenosiaAvenue

POBox1968

Danbury,CT06813-1968

Phone:(203)744-0100


Fax:(203)798-2291

www.rarediseases.org

[email protected]


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NORD gratefully acknowledges the

assistance of the following medical

experts in the preparation of this

booklet:

Dr. Paul Trainor

StowersInstituteforMedicalResearch,

KansasCity,MO64110,USA

Dr. Pedro A. Sanchez-Lara

ChildrensHospitalLosAngeles

University o Southern Caliornia

LosAngeles,CA90027,USA

Dr. Michael Dixon

UniversityofManchester,

Manchester,M139PT,UK


12/12

NORD Guides for Physicians #12

#1 The Pediatricians Guide toTyrosinemia Type 1

#2 The Pediatricians Guide to OrnithineTranscarbamylase Defciency...andother Urea Cycle Disorders

#3 The Physicians Guide toPrimary Lateral Sclerosis

#4 The Physicians Guide to

Pompe Disease

#5 The Physicians Guide toMultiple System Atrophy

#6 The Physicians Guide toHereditary Ataxia

#7 The Physicians Guide to GiantHypertrophic Gastritis andMenetriers Disease

#8 The Physicians Guide to Amyloidosis

#9 The Physicians Guide toMedullary Thyroid Cancer

#10 The Physicians Guide toHereditary Angioedema (HAE)

#11 The Physicians Guide toThe Homocystinurias

#12 The Physicians Guide toTreacher Collins Syndrome

These booklets are available ree o charge.

To obtain copies, call or write to NORD or

download the text rom www.rarediseases.org.

This booklet was made possible through a

bequest from the estate of Joanne P. Robinson.

For inormation on rare disorders

and the voluntary health organi-

zations that help people aected

by them, visit NORDs web site at

www.rarediseases.org or call

(800) 999-NORD or

(203) 744-0100.

NORD helps patients and amilies

aected by rare disorders by

providing:

Physician-reviewedinformation

in understandable language

Referralstosupportgroupsand

other sources o help

Networkingwithotherpatients

and amilies

Medicationassistanceprograms Grantsandfellowshipsto

encourage research on rare

diseases

Advocacyforhealth-related

causes that aect the rare-

disease community

Publicationsforphysiciansandother medical proessionals

Contact NORD at

[email protected].

National Organization or

Rare Disorders (NORD)POBox1968

Danbury,CT06813-1968

Phone:(203)744-0100


Fax:(203)798-2291

Documents

TreacherCollins Syndrome