Lequin, M.H.

Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study (Article)

2011-08-01T00:00:00Z

An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. In a prospective cohort study among 1,072 children followed from early fetal life onward, we examined whether maternal smoking during pregnancy, as a significant adverse fetal exposure, is associated with fetal (third trimester of pregnancy, n = 1,031) and infant kidney volume (2 years of age, n = 538) measured by ultrasound. Analyses were adjusted for various potential confounders. Among mothers who continued smoking, we observed dose-dependent associations between the number of cigarettes smoked during pregnancy and kidney volume in fetal life. Smoking less than five cigarettes per day was associated with larger fetal combined kidney volume, while smoking more than ten cigarettes per day tended to be associated with smaller fetal combined kidney volume (p for trend: 0.002). This pattern was not significant for kidney volume at the age of 2 years. Our results suggest that smoking during pregnancy might affect kidney development in fetal life with a dose-dependent relationship. Further studies are needed to assess the underlying mechanisms and whether these differences in fetal kidney volume have postnatal consequences for kidney function and blood pressure.

Absence epilepsy and periventricular nodular heterotopia (Article)

2010-09-01T00:00:00Z

We report a case of a girl who presented with typical absence seizures at age of 4.5 years. EEG showed absence seizures of sudden onset with 3 Hz spike-and-waves that also correlated with the clinical absences. The seizure semiology included subtle deviation of the eyes which prompted MRI investigation of the brain. This showed a periventricular nodular heterotopia in the mid to anterior horn of the right lateral ventricle. Although possibly coincidental, periventricular heterotopia are considered to be epileptogenic and this association has been reported once before. Migration disorders, such as in the periventricular heterotopia of our patient, may influence the formation and excitability of the striato-thalamo-cortical network involved in the generation of 3 Hz spike-waves.

Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants (Article)

2010-08-01T00:00:00Z

Background: Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker. Objective: Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants. Materials and methods: As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions. Results: Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate. Conclusion: Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values.

Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: A new polyalanine disorder? (Article)

2010-05-01T00:00:00Z

Background: The VACTERL association is a non-random association of congenital defects with an unknown aetiology in the majority of patients. Methods: A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheooesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced. Results: In a patient with the VACTERL association a 6-nucleotide insertion was found in the GCC repeat of the ZIC3 gene, which is predicted to expand the aminoterminal polyalanine repeat from 10 to 12 polyalanines. The polyalanine expansion is a novel ZIC3 mutation which was not found in 336 chromosomes from 192 ethnically matched controls. The mutation was also not present in the mother, suggesting it occurred de novo in the patient and is therefore a pathogenetic mutation. Conclusion: It is hypothesized that this novel and de novo polyalanine expansion in ZIC3 contributes to the VACTERL association in this patient. A newborn male is described with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of the VACTERL association overlaps with X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced, and a 6-nucleotide insertion was found that is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. This novel mutation was not present in the mother, nor in 336 chromosomes from 192 ethnically matched controls. It is hypothesised that this novel and de novo polyalanine expansion in the ZIC3 gene contributes to the VACTERL association in this patient.

Combined cardiological and neurological abnormalities due to filamin A gene mutation (Article)

2010-01-01T00:00:00Z

Background: Cardiac defects can be the presenting symptom in patients with mutations in the X-linked gene FLNA. Dysfunction of this gene is associated with cardiac abnormalities, especially in the left ventricular outflow tract, but can also cause a congenital malformation of the cerebral cortex. We noticed that some patients diagnosed at the neurogenetics clinic had first presented to a cardiologist, suggesting that earlier recognition may be possible if the diagnosis is suspected. Methods and results: From the Erasmus MC cerebral malformations database 24 patients were identified with cerebral bilateral periventricular nodular heterotopia (PNH) without other cerebral cortical malformations. In six of these patients, a pathogenic mutation in FLNA was present. In five a cardiac defect was also found in the outflow tract. Four had presented to a cardiologist before the cerebral abnormalities were diagnosed. Conclusions: The cardiological phenotype typically consists of aortic or mitral regurgitation, coarctation of the aorta or other left-sided cardiac malformations. Most patients in this category will not have a FLNA mutation, but the presence of neurological complaints, hyperlaxity of the skin or joints and/or a family history with similar cardiac or neurological problems in a possibly X-linked pattern may alert the clinician to the possibility of a FLNA mutation.

Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems (Article)

2005-01-01T00:00:00Z

We identified, by homozygosity mapping, a novel locus on 10q21.3-q22.1 for Goldberg-Shprintzen syndrome (GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect. Furthermore, since bilateral generalized polymicogyria was diagnosed in all patients in this family, this feature might also be considered a key feature of the syndrome. We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development.

Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. (Article)

2004-05-01T00:00:00Z

PURPOSE: To retrospectively compare thin-section computed tomographic (CT) scores obtained with five scoring systems for assessment of pulmonary disease in children with cystic fibrosis and to determine additional value of bronchial and arterial dimension measurements. MATERIALS AND METHODS: Scores obtained with five thin-section CT scoring systems were compared. A score of 0 indicated the absence of abnormalities; a higher score meant that more structural abnormalities were seen. Three observers assigned scores and then reassigned scores after intervals varying from 1-2 weeks to 1-2 months at review of thin-section CT scans obtained in 25 children with cystic fibrosis. Interobserver and intraobserver reliability was calculated with intraclass correlation coefficients. Quantitative measurements of bronchial and arterial dimensions were obtained. Thin-section CT scores were correlated (Spearman correlation) with bronchial and arterial dimensions and with results of pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV(1)). RESULTS: Scores with all five scoring systems were reproducible, with intraclass correlation coefficients of 0.74 and higher (P <.05), and showed significant correlations with FEV(1) (R = -0.73 to -0.69, P <.01). Ratio of bronchial diameter to accompanying pulmonary arterial diameter was correlated with thin-section CT scores but not with FEV(1). Ratio of bronchial wall thickness to accompanying pulmonary arterial diameter was not correlated with thin-section CT scores or PFT results. CONCLUSION: Thin-section CT scores were reproducible and were correlated with PFT results. Measurements of bronchial dimensions were not significantly related to scores or PFT results.

Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis (Article)

2004-01-01T00:00:00Z

For effective clinical management of cystic fibrosis (CF) lung disease it is important to closely monitor the start and progression of lung damage. The aim of this study was to investigate the ability of high-resolution computed tomography (HRCT) scoring systems and pulmonary function tests (PFT) to detect changes in lung disease. CF children (n=48) had two HRCT scans in combination with two PFT 2 yrs apart. Their scans were scored using five scoring systems (Castile, Brody, Helbich, Santamaria and Bhalla). "Sensitivity" was defined as the ability to detect disease progression. In this group of children, HRCT scores worsened. PFT remained unchanged or improved. Of the HRCT parameters, mucous plugging and the severity, extent and peripheral extension of bronchiectasis worsened significantly. Relationships between changes in HRCT scores and PFT were weak. Substantial structural lung damage was evident in some children who had normal lung function. These data show that high-resolution computed tomography is more sensitive than pulmonary function tests in the detection of early and progressive lung disease, and suggest that high-resolution computed tomography may be useful in the follow up of cystic fibrosis children and as an outcome measure in studies that aim to reduce lung damage.

Estimation of lung growth using computed tomography (Article)

2003-01-01T00:00:00Z

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days-17.6 yrs. CT-measured lung weight was correlated with predicted post mortem values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL x g(-1) at 15 days, decreased to 0.79 mL x g(-1) by 2 yrs and then increased steadily to 5.07 mL x g(-1) at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume.

Changes in globus pallidus with (pre)term kernicterus (Article)

2003-01-01T00:00:00Z

OBJECTIVE: We report serial magnetic resonance (MR) and sonographic behavior of globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the clinical context in very low birth weight preterm infants. On the basis of this information, we suggest means of diagnosis and prevention. METHODS: Charts and MR and ultrasound images of 5 preterm infants and 3 term infants with suspected bilirubin-associated brain damage were reviewed. Included were preterm infants with severe hearing loss, quadriplegic hypertonia, and abnormal hypersignal of globus pallidus on T2-weighted MR imaging (MRI). In 1 infant who died on day 150, the diagnosis was confirmed during the neonatal period. The others were picked up as outpatients and scanned at 12 or 22 months' corrected age. Three instances of term kernicterus were included for comparison of serial MRI in the neonatal period and early infancy: they were caused by glucose-6-phosphate dehydrogenase deficiency, urosepsis, and dehydration plus fructose 1-6 biphosphatase deficiency. RESULTS: Five preterm infants of 25 to 29 weeks' gestational age presented with total serum bilirubin (TSB) levels below exchange transfusion thresholds commonly advised. Mixed acidosis was present in 3 infants around the TSB peak. The bilirubin/albumin molar ratio was >0.5 in all, in the absence of displacing drugs. All failed to pass bedside hearing screen tests and had severe hearing loss on auditory brain response testing. Symmetrical homogeneous hyperechogenicity of globus pallidus was the alerting feature in 1 infant. Globus pallidus was hyperintense on T1-weighted MR images in this child. The other infants presented with severe developmental delay as a result of dyskinetic quadriplegia and hearing loss. Globus pallidus was normal on T1- but hyperintense on T2-weighted MR images at 12 or 22 months' corrected age. Subthalamic involvement was documented in coronal fluid attenuated inversion recovery MRI in 2 infants. The term infants with classical clinical presentation in the neonatal period had MR behavior similar to the preterms, but pallidal injury was not recognized with targeted sonographic examination. Their neonatal MR images demonstrated pallidal T1 hyperintensity and mild T2 hyperintensity. CONCLUSION: Acidotic very low birth weight preterm infants with low serum albumin levels develop MR-confirmed pallidal injury and hearing loss facing "accepted" TSB levels. Serial MRI documents a shift from acute mainly T1 hypersignal to permanent T2 hypersignal in globus pallidus within the late neonatal period. Subthalamic and not thalamic involvement helps to differentiate from ischemic or metabolic disorder. As newborns, these infants are rigid and have severe apnea, before developing hypertonic quadriplegia in infancy.

Tibial ultrasonometry in children (Doctoral Thesis)

2000-10-04T00:00:00Z

Anterior joint capsule of the normal hip and in children with transient synovitis: US study with anatomic and histologic correlation (Article)

1999-01-01T00:00:00Z

PURPOSE: To study the anatomic components of the anterior joint capsule of the normal hip and in children with transient synovitis. MATERIALS AND METHODS: Six cadaveric specimens were imaged with ultrasonography (US) with special attention to the anterior joint capsule. Subsequently, two specimens were analyzed histologically. These anatomic findings were correlated with the US findings in 58 healthy children and 105 children with unilateral transient synovitis. RESULTS: The anterior joint capsule comprises an anterior and posterior layer, mainly composed of fibrous tissue, lined by only a minute synovial membrane. Both fibrous layers were identified separately at US in 98 of 116 (84%) hips of healthy subjects and in all hips with transient synovitis. Overall, the anterior layer was thicker than the posterior layer. In transient synovitis compared with normal hips, no significant thickening of both layers was present (P = .24 and .57 for the anterior and posterior layers, respectively). Normal variants include plicae, local thickening of the capsule, and pseudodiverticula. CONCLUSION: Increased thickness of the anterior joint capsule in transient synovitis is caused entirely by effusion. There is no US evidence for additional capsule swelling or synovial hypertrophy.

Tumour type and size are high risk factors for the syndrome of "cerebellar" mutism and subsequent dysarthria (Article)

1999-01-01T00:00:00Z

OBJECTIVE: "Cerebellar mutis" and subsequent dysarthria (MSD) is a documented complication of posterior fossa surgery in children. In this prospective study the following risk factors for MSD were assessed: type, size and site of the tumour; hydrocephalus at presentation and after surgery, cerebellar incision site, postoperative infection, and cerebellar swelling. METHODS: In a consecutive series of 42 children with a cerebellar tumour, speech and neuroradiological studies (CT and MRI) were systematically analysed preoperatively and postoperatively. Speech was assessed using the Mayo Clinic lists and the severity of dysarthria using the Michigan rating scale. RESULTS: Twelve children (29%) developed MSD postoperatively. The type of tumour, midline localisation, and vermal incision were significant single independent risk factors. In addition, an interdependency of possible risk factors (tumour>5 cm, medulloblastoma) was found. CONCLUSION: MSD often occurs after paediatric cerebellar tumour removal and is most likely after removal of a medulloblastoma with a maximum lesion diameter>5 cm.