Genetics of Primary Ciliary Dyskinesia

The investigators have established a Consortium of 9 geographically-dispersed clinical research sites to study rare disease of the airways, including Primary Ciliary Dyskinesia (PCD). PCD is a genetic disorder with defective mucociliary clearance (MCC), sinus and pulmonary disease with chronic infection, and organs located on the wrong side of the body in about 50% of patients (Kartagener Syndrome). Lung disease occurs early in children with PCD, but establishing a diagnosis remains a major challenge, based on the traditional approaches of using electron microscopy and/or ciliary waveform analysis to define abnormalities of ciliary ultrastructure and/or function.

For this study, blood or buccal samples for DNA will be collected and genetic testing in patients with known or suspected PCD will be performed. This study can include term neonates with respiratory distress of unknown etiology and features of PCD, particular laterality defects (situs inversus or heterotaxy). The key hypothesis for this study is that a genetic test panel of 32 genes will confirm a diagnosis in most patients with PCD.

Inclusion criteria

• Any patient who has ≥ 2 clinical features (+/- lab) characteristic of PCD, including:

• Neonatal respiratory distress after term (or near-term) birth
• and/or laterality defect ( situs inversus or heterotaxy)
• and/or daily wet cough before 6 months of age
• and/or middle ear disease
• and/or chronic nasal congestion before 6 months of age
• and/or bronchiectasis
• and/or male infertility due to sperm tail dysfunction
• and/or low nasal nitric oxide levels (<77 nanoliters/minute)
• and/or defective ciliary ultrastructure

Exclusion criteria

• Known diagnosis of cystic fibrosis with classic clinical presentation and elevated sweat chloride levels and/or two known disease-causing Cystic Fibrosis transmembrane conductance regulator (CFTR) mutations, or documented primary or acquired immunodeficiency.
• Known explanation for bronchiectasis (and other clinical features), such as α1-antitrypsin deficiency (ZZ or ZS), inflammatory bowel disease or rheumatoid arthritis.
• Any patient who is unwilling or unable to provide consent or to comply with the testing required in this protocol

A participant should not be in the study if they have not had a standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease.