title: Costello syndrome: clinical diagnosis in the first year of life.
abstract: We report on three patients with Costello syndrome (CS) diagnosed during the first year of life and try to outline the clinical characteristics facilitating early recognition of this syndrome, which can now be corroborated by testing the HRAS gene. Phenotypical overlap of CS with Noonan (NS) and cardiofaciocutaneous syndrome (CFCS), particularly in neonatal age, is well known. Diagnostic features useful for recognition of CS in the first year of life are the following: (1) fetal and neonatal macrosomia with subsequent slow growth due to severe feeding difficulties, (2) developmental delay, (3) particularly coarse facial dysmorphisms and gingival hyperplasia, (4) skeletal anomalies as osteoporosis and metaphyseal enlargement, (5) hypertrophic cardiomyopathy (HCM) with asymmetric septal thickening and systolic anterior motion of the mitral valve, and (6) specific atrial arrhythmias. Following a clinical suspect of CS based on specific features, molecular screening of HRAS gene mutations should precede analysis of the other genes in the Ras-MAPK pathway implicated in related disorders with overlapping phenotypes.
authors.affiliation: Medical Genetics, Pediatric Cardiology, Bronchopneumology, Bambino Gesù Hospital, Rome, Italy. digilio@opbg.net
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Anna
authors.initials: A
authors.lastname: Sarkozy
authors.forename: Rossella
authors.initials: R
authors.lastname: Capolino
authors.forename: M Beatrice
authors.initials: MB
authors.lastname: Chiarini Testa
authors.forename: Giorgia
authors.initials: G
authors.lastname: Esposito
authors.forename: Andrea
authors.initials: A
authors.lastname: de Zorzi
authors.forename: Renato
authors.initials: R
authors.lastname: Cutrera
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D003937:Diagnosis, Differential; D005145:Face / Q000002:abnormalities*; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009634:Noonan Syndrome / Q000175:diagnosis; D010641:Phenotype; D012868:Skin Abnormalities / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D013577:Syndrome
chemical_list: D020928:Mitogen-Activated Protein Kinases