BACKGROUND: Costello syndrome (CS) is due to mutations in HRAS, with the most common mutation being c.34G>A (p.G12S), found in most patients in all the published series. 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 CS. A HRAS mutation was found in 27 patients, 15 of whom have been previously reported. 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 CS may be difficult in the newborn period, and should be considered in the differential diagnosis of the sick newborn infant with multisystem disease. Study of more cases will be required to establish if there is a definite association between severe disease and less common mutations.
BACKGROUND:Costello syndrome (CS) is due to mutations in HRAS, with the most common mutation being c.34G>A (p.G12S), found in most patients in all the published series. 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 CS. A HRAS mutation was found in 27 patients, 15 of whom have been previously reported. 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 CS may be difficult in the newborn period, and should be considered in the differential diagnosis of the sick newborn infant with multisystem disease. Study of more cases will be required to establish if there is a definite association between severe disease and less common mutations.
Authors: Karen W Gripp; Lindsey A Morse; Marni Axelrad; Kathryn C Chatfield; Aaron Chidekel; William Dobyns; Daniel Doyle; Bronwyn Kerr; Angela E Lin; David D Schwartz; Barbara J Sibbles; Dawn Siegel; Suma P Shankar; David A Stevenson; Mihir M Thacker; K Nicole Weaver; Sue M White; Katherine A Rauen Journal: Am J Med Genet A Date: 2019-06-20 Impact factor: 2.802
Authors: Angela E Lin; Barbara O'Brien; Laurie A Demmer; Kristina K Almeda; Cynthia L Blanco; Patrick F Glasow; Charles I Berul; Robert Hamilton; A Micheil Innes; Julie L Lauzon; Katia Sol-Church; Karen W Gripp Journal: Prenat Diagn Date: 2009-07 Impact factor: 3.050
Authors: Natalia Gomez-Ospina; Christin Kuo; Amitha Lakshmi Ananth; Angela Myers; Marie-Luise Brennan; David A Stevenson; Jonathan A Bernstein; Louanne Hudgins Journal: Am J Med Genet A Date: 2016-04-22 Impact factor: 2.802
Authors: Karen W Gripp; Eugenia Bifeld; Deborah L Stabley; Elizabeth Hopkins; Stefanie Meien; Kathy Vinette; Katia Sol-Church; Georg Rosenberger Journal: Am J Med Genet A Date: 2012-07-20 Impact factor: 2.802
Authors: K Nicole Weaver; Dehua Wang; James Cnota; Nicholas Gardner; Deborah Stabley; Katia Sol-Church; Karen W Gripp; David P Witte; Kevin E Bove; Robert J Hopkin Journal: Pediatr Dev Pathol Date: 2014-08-18
Authors: Karen W Gripp; Katia Sol-Church; Patroula Smpokou; Gail E Graham; David A Stevenson; Heather Hanson; David H Viskochil; Laura C Baker; Bridget Russo; Nick Gardner; Deborah L Stabley; Verena Kolbe; Georg Rosenberger Journal: Am J Med Genet A Date: 2015-04-25 Impact factor: 2.802