Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Single centre experience of the application of self navigated 3D whole heart cardiovascular magnetic resonance for the assessment of cardiac anatomy in congenital heart disease.

BACKGROUND: For free-breathing cardiovascular magnetic resonance (CMR), the self-navigation technique recently emerged, which is expected to deliver high-quality data with a high success rate. The purpose of this study was to test the hypothesis that self-navigated 3D-CMR enables the reliable assessment of cardiovascular anatomy in patients with congenital heart disease (CHD) and to define factors that affect image quality. METHODS: CHD patients ≥2 years-old and referred for CMR for initial assessment or for a follow-up study were included to undergo a free-breathing self-navigated 3D CMR at 1.5T. Performance criteria were: correct description of cardiac segmental anatomy, overall image quality, coronary artery visibility, and reproducibility of great vessels diameter measurements. Factors associated with insufficient image quality were identified using multivariate logistic regression. RESULTS: Self-navigated CMR was performed in 105 patients (55% male, 23 ± 12y). Correct segmental description was achieved in 93% and 96% for observer 1 and 2, respectively. Diagnostic quality was obtained in 90% of examinations, and it increased to 94% if contrast-enhanced. Left anterior descending, circumflex, and right coronary arteries were visualized in 93%, 87% and 98%, respectively. Younger age, higher heart rate, lower ejection fraction, and lack of contrast medium were independently associated with reduced image quality. However, a similar rate of diagnostic image quality was obtained in children and adults. CONCLUSION: In patients with CHD, self-navigated free-breathing CMR provides high-resolution 3D visualization of the heart and great vessels with excellent robustness.

Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising the two. METHODS: We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions and/or functional assays. RESULTS: We identified eight probands with CHH with (n = 3; Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%) harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause loss of function. Probands with FGFR1 mutations have severe gonadotropin-releasing hormone deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was observed only in the patient with the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor receptor substrate 2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of fibroblast growth factor receptor substrate 2α to FGFR1, thereby resulting in reduced mitogen-activated protein kinase signaling. CONCLUSION: FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM because the likelihood of a mutation increases from 10% in the general CHH population to 88% in these patients.Genet Med 17 8, 651-659.

Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.

Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity.

Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease. VIDEO ABSTRACT.

Congenital lobar emphysema presenting as an airway foreign body.

We report here the case of a 15 months old girl presenting with clinical signs and radiological exams highly suggestive of a foreign body (FB) aspiration. Diagnostic endoscopy revealed an overlooked bronchial malformation responsible for a congenital lobar emphysema (CLE). CLE presenting after one year of age is rare and can easily be misdiagnosed. Therefore, the possibility of an overlooked CLE needs to be known and evoked as an alternative diagnosis when dealing with children presenting with suspected FB aspirations. We report on this unexpected, yet misleading presentation of CLE and review the available literature on the subject.

Sonographic evaluation of children with congenital hypothyroidism

AbstractObjective:To establish benchmarks and study some sonographic characteristics of the thyroid gland in a group of euthyroid children aged up to 5 years as compared with age-matched children with congenital hypothyroidism.Materials and Methods:Thirty-six children (17 female and 19 male) aged between 2 months and 5 years were divided into two groups – 23 euthyroid children and 13 children with congenital hypothyroidism – and were called to undergo ultrasonography.Results:In the group of euthyroid children (n = 23), mean total volume of the thyroid gland was 1.12 mL (minimum, 0.39 mL; maximum, 2.72 mL); a homogeneous gland was found in 17 children (73.91%) and 6 children (26.08%) had a heterogeneous gland. In the group of children with congenital hypothyroidism (n = 13), mean total volume of the thyroid gland was 2.73 mL (minimum, 0.20 mL; maximum, 11.00 mL). As regards thyroid location, 3 patients (23.07%) had ectopic thyroid, and 10 (69.23%) had topic thyroid, and out of the latter, 5 had a homogeneous gland (50%) and 5, a heterogeneous gland (50%). In the group with congenital hypothyroidism, 6 (46.15%) children had etiological diagnosis of dyshormoniogenesis, 3 (23.07%), of ectopic thyroid, and 4 (30.76%), of thyroid hypoplasia.Conclusion:Thyroid ultrasonography is a noninvasive imaging method, widely available, easy to perform and for these reasons could, and should, be performed at any time, including at birth, with no preparation or treatment discontinuation, to aid in the early etiological definition of congenital hypothyroidism.

Coronary anomalies: what the radiologist should know

AbstractCoronary anomalies comprise a diverse group of malformations, some of them asymptomatic with a benign course, and the others related to symptoms as chest pain and sudden death. Such anomalies may be classified as follows: 1) anomalies of origination and course; 2) anomalies of intrinsic coronary arterial anatomy; 3) anomalies of coronary termination. The origin and the proximal course of anomalous coronary arteries are the main prognostic factors, and interarterial course or a coronary artery is considered to be malignant due its association with increased risk of sudden death. Coronary computed tomography angiography has become the reference method for such an assessment as it detects not only anomalies in origination of these arteries, but also its course in relation to other mediastinal structures, which plays a relevant role in the definition of the therapeutic management. Finally, it is essential for radiologists to recognize and characterize such anomalies.

Mixed subtype of congenital mesoblastic nephroma with poor evolution: a case report and literature review

Abstract A male child born at 27 weeks, weighting 1305 g and presenting with a right-sided abdominal tumor. Computed tomography scan demonstrated the presence of a solid mass compressing the right kidney. Puncture biopsy revealed congenital mesoblastic nephroma. The patient underwent total right nephroureterectomy, and died on the second day after surgery.