title: Fatal congenital hypertrophic cardiomyopathy and a pancreatic nodule morphologically identical to focal lesion of congenital hyperinsulinism in an infant with costello syndrome: case report and review of the literature.
abstract: Costello syndrome is characterized by constitutional mutations in the proto-oncogene HRAS, causing dysmorphic features, multiple cardiac problems, intellectual disability, and an increased risk of neoplasia. We report a male infant with dysmorphic features, born prematurely at 32 weeks, who, during his 3-month life span, had an unusually severe and ultimately fatal manifestation of hypertrophic cardiomyopathy and hyperinsulinemic hypoglycemia. Molecular studies in this patient demonstrated the uncommon Q22K mutation in the HRAS gene, diagnostic of Costello syndrome. The major autopsy findings revealed hypertrophic cardiomyopathy, congenital myopathy, and a 1.4-cm pancreatic nodule that was positive for insulin expression and morphologically identical to a focal lesion of congenital hyperinsulinism. Sequencing of KCNJ11 and ABCC8, the 2 most commonly mutated genes in focal lesion of congenital hyperinsulinism, revealed no mutations. While hyperinsulinism is a recognized feature of RASopathies, a focal proliferation of endocrine cells similar to a focal lesion of hyperinsulinism is a novel pathologic finding in Costello syndrome.
authors: Brandon S
authors: BS
authors: Sheffield
authors: Stephen
authors: S
authors: Yip
authors: Eduardo D
authors: ED
authors: Ruchelli
authors: Christopher P
authors: CP
authors: Dunham
authors: Elizabeth
authors: E
authors: Sherwin
authors: Paul A
authors: PA
authors: Brooks
authors: Amitava
authors: A
authors: Sur
authors: Avash
authors: A
authors: Singh
authors: Derek G
authors: DG
authors: Human
authors: Millan S
authors: MS
authors: Patel
authors: Anna F
authors: AF
authors: Lee
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000151:congenital* / Q000473:pathology; D044903:Congenital Hyperinsulinism / Q000209:etiology* / Q000473:pathology; D056685:Costello Syndrome / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000473:pathology; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Costello syndrome; HRAS; RASopathy; congenital myopathy; focal lesion of congenital hyperinsulinism; hypertrophic cardiomyopathy