Primary Ciliary Dyskinesia:

Missing a Beat: Primary Ciliary Dyskinesia Impaired Airway Clearance and

Respiratory Disease

www.pcdfoundation.org

What is Primary Ciliary Dyskinesia (PCD)?

Umbrella term for inherited disorders the structure and/or function of motile (moving) cilia. More than 32 genes are implicated in causing PCD.

PCD and cystic fibrosis are both genetic disorders of the mucociliary clearance system with similar features and outcomes.

Cilia look deceptively simple. Cilia look deceptively simple.

What are Cilia?

What are Cilia?

In fact, they are extraordinarily complex with 700-750 genes involved in ciliary structure

Motile cilia, the type of cilia impaired in Motile cilia, the type of cilia impaired in PCD, are found in the lungs, sinuses, ears, PCD, are found in the lungs, sinuses, ears, ventricles of the brain and the organs of ventricles of the brain and the organs of reproduction. reproduction.

What are Cilia?

The respiratory tract is richly ciliated with The respiratory tract is richly ciliated with about 200 cilia per cellabout 200 cilia per cell

What are Cilia?

Respiratory cilia beat in a coordinated fashion, creating a moving ‘carpet’ of cilia.

Courtesy of John C. Carson, PhD, University of North Carolina at Chapel Hill

How Do Motile Cilia Work?

How Do Motile Cilia Work?

Courtesy of John C. Carson, PhD, University of North Carolina at Chapel Hill

Normal Ciliary Activity(Real Time)

The beat of normal cilia is extremely vigorous

(Real Time)

Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill

How Do Motile Cilia Work?

Vigorously beating motile cilia, working together with airway mucus, provide a critical, first-line defense against unwanted particles (debris, pathogens, etc.) in the airways.

How Do Motile Cilia Work?

What Happens in PCD?

In PCD, inherited genetic mutations alter the structure or function of motile cilia, dramatically impairing normal ciliary clearance.

This is PCD Ciliary Activity

(Real Time)

Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill

What Happens in PCD?

And so is this…PCD Ciliary Activity

(Real Time)

Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill

What Happens in PCD?

Ciliary Activity: Side by Side Comparison

(Real Time)

Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill

What Happens in PCD?

The drastic functional impairment caused by PCD results in:

•Chronic lung disease leading to respiratory failure/need for transplant

•Chronic ear and sinus infection

•Hearing loss

•Infertility/subfertility

•Increased risk of hydrocephalus and retinitis pigmentosa (inherited blindness)

What are Cilia?

Motile cilia activity is also required for organ placement during embryonic development.

About 50% of people with PCD have organ ‘laterality defects,’ meaning their organs are not in the ‘normal’ place.

What are Cilia?

Sometimes the organs are in a complete mirror-image arrangement called ‘situs inversus.’

As unusual as it is to have backwards organs, situs inversus is not generally dangerous.

What are Cilia?

Sometimes in PCD the organs are neither completely reversed nor completely where they should be.

This condition, called heterotaxy or ‘situs ambiguus’ is potentially life threatening.

What are Cilia?

PCD: Clinical Consequences

PCD-associated organ development defects put infants with PCD at 200X greater risk for congenital heart defects than the general population

The PCD Foundation is committed to supporting research to find a cure for PCD.

Our expanding research network boasts some of the top academic medical research sites in the country.

We’ve come a long way, but there is still a long way to go!

The PCDF: Finding Solutions

U of WA

Children’s LA

U of CO

U of WI

North-western

Wash U

U of TN

CHOP

Miami

U of SC

UNC

NIAID MDRainbowBabiesIndiana

Harvard -Boston)

Last Update 9/14

Tampa

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Ottowa

Montreal

Nova Scotia

CURRENT CENTERS UNC Chapel Hill, NCNIAID Bethesda, MDWash U St. Louis, MOSick Kids Toronto, OntarioU of Colorado Denver, COStanford Palo Alto, CAU of WA Seattle, WAIndiana U Indianapolis, IN

NEW CENTERS

Harvard Boston, MA

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Northwestern Chicago, IL

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AFFILIATE CENTERS U of Florida (*) Miami, FLChildren's LA (*) Los Angeles, CAU of TN Multiple sitesU of FL Tampa, FLU of Wisc Milwaukee, WIU of SC Columbia, SCCHEO Ottawa, OntarioMcGill Montreal, Quebec

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The PCDF: Finding Solutions

PCD Clinical Centers Network

Thank you so much for joining us today and helping to support our mission of providing help,

hope and a cure for families with PCD!

The PCDF: Finding Solutions