Background: Costello syndrome (CS) is due to mutations in HRAS, with the commonest mutation being c.34G>A (p.G12S), found in most patients in all the published series1,3-7. A small number of less common mutations have been reported. Population studied: HRAS mutation analysis has been undertaken in 74 predominantly British patients with a possible diagnosis of Costello syndrome. A HRAS mutation was found in 27 patients, 15 of whom have been previously reported3. Phenotype analysis: Four cases had an unusually severe phenotype, associated in three cases with two unusual mutations, c.35G>A, p.G12D in two cases and c.34G>T, p.G12C in the other. Hypoglycaemia, renal abnormalities, severe early cardiomyopathy, congenital lung and airway abnormalities, pleural and pericardial effusion, chylous ascites and pulmonary lymphangectasia are confirmed as part of the clinical spectrum seen in CS. A lung pathology resembling alveolar capillary dysplasia is reported in one case. Conclusion: These cases illustrate that the diagnosis of Costello syndrome may be difficult in the newborn period, and should be considered in the differential diagnosis of the sick newborn infant with multi-system disease. Study of more cases will be required to establish if there is a definite association between severe disease and less common mutations.
- Costello syndrome
- Neonatal multi-system disease
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