Title

National surveillance study of Aicardi-Goutieres syndrome and other congenital infection-like phenotypes

Description

There are three objectives for the study:

1. To determine incidence study of Aicardi-Goutieres Syndrome in the United Kingdom and Ireland.

2. To develop a phenotypic classification of congenital infection-like phenotypes.

3. To define the natural history and phenotypic spectrum of Aicardi-Goutieres Syndrome.

Anonymised cases will be notified to the investigator via the BPNSU. Referring clinicians will be sent a questionnaire. Clinical data and imaging data will be reviewed by an expert panel. A DNA sample may be requested for mutation analysis provided appropriate consent is obtained. Clinical +/- mutational data will be collated.

Lead Clinician

Dr Yanick Crow, Senior Lecturer in Medical Genetics and Dr John Livingston, Consultant Paediatric Neurologist.

Disease name

Aicardi-Goutieres Syndrome (AGS)

Case Definition

Paediatric Neurologists are asked to report cases in the following categories:

1. Any child with a clinical and/or molecular diagnosis of AGS/pseudo-TORCH syndrome.

2. Any child in whom congenital infection is strongly suspected but serology is negative.

3. Unexplained intracranial calcification with oneor more (other) features listed below.

4. Unexplained leukodystrophy with one or more (other) of the features listed below.

5. Child with provisional diagnosis of pontocerebellar hypoplasia type 2 with one or more of the features listed below.

6. Chill-blain like lesions with one or more of the features listed below.

7. Any child with an SLE-like phenotype with one or more of the features listed below.

Supporting Features:

1.Intracranial calcification (basal ganglia, periventricular or deep white matter)

2.White matter changes (especially frontal +/- temporal cysts)

3.Raised csf white count (>5 cells/mm)

4.Raised csf interferon alpha

5.Raised csf pterins

6.Chillblain-like lesions (particularly of the digits, elbows, ear helices and nose).

7.Significant and unexplained neonatal hepatic transaminitis +/- hepatosplenomegaly

8.Significant perinatal thrombocytopenia.

9. Neonatal cardiomegaly/cardiomyopathy/myocarditis.

10.Glaucoma.

11. Abnormal auto-antibody profile.

Inclusion Criteria

Any child under 18 years who meets the case definition.

Exclusion Criteria

1. Confirmed diagnosis of congenital infection.

2. Confirmed diagnosis of a leukodystrophy other than AGS.