Genetic Determinants of Kawasaki Disease

Kawasaki disease (KD) is an acute self-limited vasculitis of infancy and early childhood. Most patients recover without sequelae although the inflammatory process causes permanent damage to the coronary arteries in 20-25% of untreated children. An infectious aetiology is suspected, but the causative agent has not been identified. The investigators aim to identify the genes underlying both susceptibility to Kawasaki disease, and the development of coronary artery aneurysms.

The problem to be addressed;

Kawasaki disease is now the most common cause of acquired heart disease in children in Japan and North America. Kawasaki disease arises when genetically predisposed children encounter an as yet unidentified infectious agent which may cause only mild illness or no illness at all in children without the genetic predisposition. Other children may suffer permanent damage to the coronary arteries. Identification of the genes involved will help to improve understanding of the disease, and the development of better treatments.

Objective

The investigators aim to identify the genes underlying both susceptibility to Kawasaki disease, and the development of coronary artery aneurysms.

Design

The study will recruit nuclear families (affected child and their biological parents) through participating NHS hospitals or through the records of the UK Kawasaki Support Group.

Study size

400 affected children and both biological parents (i.e. 1200 participants)

Procedures

Informed consent using age appropriate patient/parent/guardian information sheets will be taken from parents (or from children aged 16 and over), assent will be taken from the child under the age of 16 (if appropriate). Children recruited during the acute illness; routine clinical and laboratory data and research samples (blood, urine, throat swab). Children recruited retrospectively; study questionnaire (completed by parents), saliva samples.Saliva samples from parents

Eligibility Criteria:
Inclusion Criteria:

* Affected children will be recruited if the treating clinician has made a diagnosis of possible Kawasaki disease (even if they do not fulfil the criteria below for Kawasaki disease).

The current standard diagnostic criteria for KD (Circulation 2001 103 335-336 doi: 10.1161/01.CIR 103.2.335) are:

The presence of fever for at least five days plus four of the following criteria:

1. Changes in the peripheral extremities Acute: erythema and oedema of hands and feet Convalescent: membranous desquamation of fingertips
2. Polymorphous exanthema
3. Bilateral painless bulbar conjunctival injection without exudate
4. Changes in lips and oral cavity: erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
5. Cervical lymphadenopathy (\>1.5cm diameter), usually unilateral Patients meeting not all of these criteria may meet the criteria for atypical Kawasaki disease, ie. if they have fever and two or three of the above criteria and elevation of CRP or echocardiographic evidence of coronary artery dilatation.

Parents of affected child must be biological parents.

Exclusion Criteria:

* children who do not have a diagnosis of possible Kawasaki disease