An infant with Costelio syndrome complicated with fatal hypertrophic obstructive cardiomyopathy

Tomita, Hideshi; Fuse, Shigeto; Ikeda, Kazuo; Matsuda, Kazuko; Chiba, Shunzo

doi:10.1111/j.1442-200x.1998.tb02000.x

Cited by 25 publications

(22 citation statements)

References 5 publications

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“…Each of these defects occurs in about one third of patients, although the combination of two defects has been observed. HCM in CS is characterized by left ventricle hypertrophy consisting of asymmetric septal thickening, frequent systolic anterior motion of the mitral valve, and decreased left ventricular compliance [13,23,40,44]. The association with mitral anomalies, such as prolapsing, myxomatous, redundant, or thick valve leaflets, is common.…”

Section: Discussionmentioning

confidence: 99%

Costello syndrome: clinical diagnosis in the first year of life

et al. 2007

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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.

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Section: Discussionmentioning

confidence: 99%

Costello syndrome: clinical diagnosis in the first year of life

et al. 2007

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“…Disarray is reported on Table III in one clinically diagnosed [Tomita et al, 1998] and 7 mutation-positive patients with Costello syndrome, a single patient with a KRAS mutation, 13 (one genotyped, 12 clinically diagnosed) Noonan syndrome and two clinically diagnosed CFC syndrome patients. Although the histologic and gross phenotype of HCM in Costello syndrome (Fig.…”

Section: Hypertrophic Cardiomyopathymentioning

confidence: 99%

“…Table III lists 11 patients with postmortem (n ¼ 8) or biopsy (n ¼ 3) tissue available for pathologic review. In addition to the initial description of myocardial fiber disarray in a clinically described Costello syndrome patient [Tomita et al, 1998], we report 7 (four study patients, three from the literature review) genotyped patients with disarray (7/10, 70% of all genotyped pathologic specimens). Additional findings included mild conduction system fibrosis at the bundle of His [patient 1 in Hinek et al, 2005;Estep et al, 2006;patient 44 in Lin et al, 2008b], coronary artery fibromuscular dysplasia with nesidioblastosis [patient 11 in Kerr et al, 2006], and small fiber myopathy with excess muscle spindle [patient 1 in van der Burgt et al, 2007].…”

mentioning

confidence: 99%

Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

Lin

Alexander

Colan

et al. 2011

American J of Med Genetics Pt A

106

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Cardiovascular abnormalities are important features of Costello syndrome and other Ras/MAPK pathway syndromes (“RASopathies”). We conducted clinical, pathological and molecular analyses of 146 patients with an HRAS mutation including 61 enrolled in an ongoing longitudinal study and 85 from the literature. In our study, the most common (84%) HRAS mutation was p.G12S. A congenital heart defect (CHD) was present in 27 of 61 patients (44%), usually non‐progressive valvar pulmonary stenosis. Hypertrophic cardiomyopathy (HCM), typically subaortic septal hypertrophy, was noted in 37 (61%), and 5 also had a CHD (14% of those with HCM). HCM was chronic or progressive in 14 (37%), stabilized in 10 (27%), and resolved in 5 (15%) patients with HCM; follow‐up data was not available in 8 (22%). Atrial tachycardia occurred in 29 (48%). Valvar pulmonary stenosis rarely progressed and atrial septal defect was uncommon. Among those with HCM, the likelihood of progressing or remaining stable was similar (37%, 41% respectively). The observation of myocardial fiber disarray in 7 of 10 (70%) genotyped specimens with Costello syndrome is consistent with sarcomeric dysfunction. Multifocal atrial tachycardia may be distinctive for Costello syndrome. Potentially serious atrial tachycardia may present in the fetus, and may continue or worsen in about one‐fourth of those with arrhythmia, but is generally self‐limited in the remaining three‐fourths of patients. Physicians should be aware of the potential for rapid development of severe HCM in infants with Costello syndrome, and the need for cardiovascular surveillance into adulthood as the natural history continues to be delineated. © 2011 Wiley‐Liss, Inc.

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“…In this series, 44% of patients would fulfill this definition of HCM. The 1.5-year-old girl described by Tomita et al [1998] is the sole patient with severe obstructive HCM in whom moderate myocyte fiber disarray was reported, the hallmark histologic finding of HCM. However, the distribution of ventricular hypertrophy in Costello syndrome appears to be somewhat heterogeneous and may include concentric left and biventricular involvement.…”

Section: Cardiac Hypertrophymentioning

confidence: 99%

Further delineation of cardiac abnormalities in Costello syndrome

et al. 2002

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We review the cardiac abnormalities in 94 patients (27 new, 67 literature) with Costello syndrome, an increasingly recognized syndrome consisting of increased birth weight, postnatal growth retardation, and distinctive facial, skin, and musculoskeletal features (MIM 218040). A cardiac abnormality was found in 59 (63%) patients, with each of three categories occurring in approximately one-third of patients. A cardiovascular malformation (CVM) was noted in 30%, typically pulmonic stenosis (46% of those with a CVM). Cardiac hypertrophy was reported in 34%, which involved the left ventricle in 50% and was usually consistent with classic hypertrophic cardiomyopathy (HCM). A variety of rhythm disturbances were reported in 33%. Most (74%) were atrial tachycardia that was reported as supraventricular, chaotic, multifocal, or ectopic. Of 31 patients with a rhythm abnormality, 22 (68%) had an additional abnormality, i.e., CVM (4), cardiac hypertrophy (12), or both (6). Nine patients had isolated dysrhythmia, five (56%) of whom died. All of the 12 (13%) patients who died had a cardiac abnormality. One patient died of embryonal rhabdomyosarcoma, but in the remainder, a cardiac cause of death could not be disproved. All patients with Costello syndrome need a baseline cardiology evaluation with echocardiography and Holter monitoring. Additional prospective evaluations, even in patients without apparent cardiac abnormalities, would be prudent, although data are insufficient to propose a specific schedule.

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An infant with Costelio syndrome complicated with fatal hypertrophic obstructive cardiomyopathy

Cited by 25 publications

References 5 publications

Costello syndrome: clinical diagnosis in the first year of life

Costello syndrome: clinical diagnosis in the first year of life

Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

Further delineation of cardiac abnormalities in Costello syndrome

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