Genetics of congenital heart diseases in syndromic and non-syndromic patients: new advances and clinical implications

Piacentini, Gerardo; Digilio, María Cristina; Sárközy, Anna; Placidi, Silvia; Dallapiccola, Bruno; Marino, Bruno

doi:10.2459/01.jcm.0000247428.51828.51

Cited by 11 publications

(8 citation statements)

References 72 publications

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“…Unlike malformation syndromes in which a specific and distinctive morphologic feature of the CHD itself may lead to the diagnosis (e.g., the morphology of the aortic root of Williams–Beuren syndrome or the dysplastic pulmonary valve leaflets of Noonan syndrome) [Piacentini et al, 2007], it is not the cardiac phenotype which leads to the diagnosis of BDLS. In our series however pulmonary stenosis appears to be the most common congenital defect, representing 39% of all cardiac defects and being present in 11.4% of our population as an isolated defects and overall in 12.6% of our CDLS patients.…”

Section: Discussionmentioning

confidence: 99%

Analysis of congenital heart defects in 87 consecutive patients with Brachmann‐de Lange syndrome

Selicorni

Colli

Passarini

et al. 2009

American J of Med Genetics Pt A

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Congenital heart defects (CHDs) have been estimated to occur in approximately 20% of patients with Brachmann-de Lange syndrome (BDLS, also known as Cornelia de Lange syndrome, OMIM 122470). We report on the results of a prospective echocardiographic evaluation of a cohort of 87 Italian BDLS patients with longitudinal follow-up from 5 to 12 years. A cardiac anomaly was identified in 29/87 (33.3%) including 28 (32.2%) patients with a structural CHD, and an additional patient (1.2%) with isolated non-obstructive hypertrophic cardiomyopathy (HCM). Of the 28 patients with a CHD, 12 (42.9%) had an isolated obstructive CHD, 10 of which were pulmonary stenosis (36%), 8 (28.6%) had an isolated left to right shunt, and the remainder showed a combination of structural anomalies. Overall incidence of pulmonary stenosis was 39% (11/28). Isolated late-onset mitral or tricuspid valve dysplasia, albeit hemodynamically insignificant, was detected at follow-up examination in 4 (14.3%) patients older than 10 years, previously known to be normal. In contrast to previous studies, only two patients required surgery, one for closure of a large perimembranous ventricular septal defect (VSD) and associated ASD closure (1), and another for VSD closure and relief of pulmonary valve stenosis (1). The remainder are receiving medical follow-up. We believe that the overall frequency (33.3%) and evidence of 4 late onset dysplastic valves anomalies justifies both echocardiographic assessment in all BDLS patients at the first diagnostic assessment, and later on during medical follow-up.

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Section: Discussionmentioning

confidence: 99%

Analysis of congenital heart defects in 87 consecutive patients with Brachmann‐de Lange syndrome

Selicorni

Colli

Passarini

et al. 2009

American J of Med Genetics Pt A

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“…25 Other organ systems, beyond the skeleton, can be involved, although not commonly. Congenital cardiac defects are seen in chondroectodermal dysplasia, 26 the short-rib polydactyly disorders (complex outlet defects including isolated ventricular septal defects), 27 and in Larsen syndrome. 28 Gastrointestinal anomalies are rare among the skeletal disorders, but congenital megacolon can be seen in cartilage hair hypoplasia, 29 malabsorption syndrome in Schwachmann-Diamond syndrome, 30 and omphaloceles in otopalatodigital syndrome, 31 and atelosteogenesis I/Boomerang dysplasia.…”

Section: Clinical Evaluation and Features In The Chondrodysplasiasmentioning

confidence: 99%

The skeletal dysplasias

Krakow¹,

Rimoin

2010

Genetics in Medicine

203

167

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Abstract:The skeletal dysplasias (osteochondrodysplasias) are a heterogeneous group of more than 350 disorders frequently associated with orthopedic complications and varying degrees of dwarfism or short stature. These disorders are diagnosed based on radiographic, clinical, and molecular criteria. The molecular mechanisms have been elucidated in many of these disorders providing for improved clinical diagnosis and reproductive choices for affected individuals and their families. An increasing variety of medical and surgical treatment options can be offered to affected individuals to try to improve their quality of life and lifespan. Genet Med 2010:12(6):327-341. Generalized disorders of cartilage and bone have been referred to as skeletal dysplasias, whereas those that affect an individual bone or group of bones have been referred to as dysostoses; however, these distinctions are blurring as their basic defects are elucidated. The skeletal dysplasias are associated with abnormalities in the patterning, development, maintenance, and size of the appendicular and axial skeleton and frequently result in disproportionate short stature. Until the early 1960s, most individuals with short stature were considered to have pituitary dwarfism, achondroplasia (short-limb dwarfism), or Morquio disease (short-trunked dwarfism). Presently, there are more than 350 well-characterized skeletal dysplasias that are classified primarily on the basis of clinical, radiographic, and molecular criteria. 1 They result from mutations in various families of genes that encode extracellular matrix proteins, transcription factors, tumor suppressors, signal transducers (ligands, receptors, and channel proteins), enzymes, cellular transporters, chaperones, intracellular binding proteins, RNA processing molecules, cilia and cytoplasmic proteins, and a number of gene products of currently unknown function. The skeletal dysplasiasThe skeletal dysplasias are disorders associated with a generalized abnormality in the skeleton. Although each skeletal dysplasia is relatively rare, collectively the birth incidence of these disorders is almost 1/5000. 2 These disorders range in severity from precocious arthropathy in relatively average stature individuals to severe dwarfism with perinatal mortality. These disorders can be associated with a variety of orthopedic, neurologic, auditory, visual, pulmonary, cardiac, renal, and psychological complications. EmbryologyThe human skeleton (from the greek, skeletos, "dried up") is a complex organ consisting of 206 bones (126 appendicular, 74 axial, and 6 ossicles). The musculoskeletal system also includes tendons, ligaments, and muscles, and, in addition to cartilage and bone, is involved in linear growth, mechanical support, movement, a blood cell and mineral reservoir, and protection of vital organs. These tissues and adipocytes all derive from mesenchymal precursor cells.The patterning and architecture of the skeleton during fetal development determine the number, size, and the shape of the future skeletal elem...

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“…The progress in surgical techniques and post-surgical care allow an increasing number of children with complex congenital disease to have longer live expectancy and survive to adult age. This patient population has different mechanisms of arrhythmia and provides a *Address correspondence to this author at the Hospital Italiano Buenos Aires, Argentina; E-mail: gustavo.maid@hospitalitaliano.org.ar different challenge for management compared to patient with absence of heart disease [3].…”

Section: Introductionmentioning

confidence: 99%

Written Consent to Use the Drug in Children: The Problem of Off-Label Drugs

Maid

Guerchicoff²,

Falconi³

et al. 2008

CPD

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Cardiac arrhythmias in pediatric patients have different mechanisms and frequencies compared to adult patients. There are many physiological differences between children and adults that may affect the pharmacodynamic and pharmacokinetic of the antiarrhythmic drugs in pediatric population. Children, and specially breast feeding children, cannot be considered low weighted adults to select antiarrhythmic drug doses. Although radiofrequency ablation has experienced great technological advances, it is performed in selected pediatric patients. Therefore, the main therapeutic strategy is the use of antiarrhythmic drugs in children. The medical management of arrhythmias in pediatric patients is challenging and complex. There are few clinical guidelines. There is scarce and incomplete information about the efficacy and safety of antiarrhythmic drugs in pediatric population. Most of the doses and drug administration intervals are extrapolated from adult population and applied to children. Antiarrhythmic drug doses have been extensively studied in adult population. However, in pediatric population, there are very few clinical trials and the safety of these drugs is not well known. In general, dose regimens are based on small uncontrolled studies, extrapolation of drug doses from studies performed in the adult population or physician experience. As a consequence, there is a need for further studies to assess the most effective antiarrhythmic drug regimens in children reducing the risk of side effects. Evidence suggests that medical research in pediatric population is necessary and morally valuable. But investigators involved must take care of moral and ethical values, including the respect for the child-subject and his parents or legal representatives, and this respect compels them to consider the patient and family in the decision making process. The participation request and the informed consent must be obtained according to the competitions the patient exhibits, trying to anticipate information about benefits and possible damages derived from the investigation in an understandable language for him. In our opinion the pharmacologic clinical investigation of antiarrhythmic treatments in pediatrics is necessary. More clinical studies must be carried out under rigorous scientific rules that contemplate the particular ethical dilemmas this population faces.

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Genetics of congenital heart diseases in syndromic and non-syndromic patients: new advances and clinical implications

Cited by 11 publications

References 72 publications

Analysis of congenital heart defects in 87 consecutive patients with Brachmann‐de Lange syndrome

Analysis of congenital heart defects in 87 consecutive patients with Brachmann‐de Lange syndrome

The skeletal dysplasias

Written Consent to Use the Drug in Children: The Problem of Off-Label Drugs

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