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Manju A Kurian,
Esther Meyer,
Grace Vassallo,
Neil V Morgan,
Nandhini Prakash,
Shanaz Pasha,
Nebula A Hai,
Salwati Shuib,
Fatima Rahman,
Evangeline Wassmer,
J Helen Cross, Finbar J O'Callaghan,
John P Osborne,
Ingrid E Scheffer,
Paul Gissen,
Eamonn R Maher
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ABSTRACT: The epileptic encephalopathies of infancy and childhood are a collection of epilepsy disorders characterized by refractory, severe seizures and poor neurological outcome, in which the mechanism of disease is poorly understood. We report the clinical presentation and evolution of epileptic encephalopathy in a patient, associated with a loss-of-function mutation in the phospholipase C-β 1 gene. We ascertained a consanguineous family containing a male infant who presented with early-onset epileptic encephalopathy for detailed clinical phenotyping and molecular genetic investigation. In addition, a cohort of 12 consanguineous families of children with infantile spasms were analysed for linkage to the phospholipase C-β 1 gene locus. The male infant presented with tonic seizures in early infancy and subsequently developed infantile spasms. Over time, he developed drug-resistant epilepsy associated with severe neurological regression and failure to thrive. Molecular genetic investigation revealed a homozygous loss-of-function 0.5-Mb deletion, encompassing the promoter element and exons 1, 2 and 3 of phospholipase C-β 1 in the index case. Linkage to the phospholipase C-β 1 locus was excluded in the 12 other consanguineous families, consistent with genetic heterogeneity in this disorder. Although phospholipase C-β 1 deficiency has not previously been reported in humans, the Plcb1 homozygote knockout mouse displays early-onset severe tonic seizures and growth retardation, thus recapitulating the human phenotype. Phospholipase C-β 1 has important functions in both hippocampal muscarinic acetylcholine receptor signalling and in cortical development. Thus, the discovery of a phospholipase C-β 1 mutation allows us to propose a novel potential underlying mechanism in early-onset epileptic encephalopathy.
Brain 10/2010; 133(10):2964-70. · 9.46 Impact Factor
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A A Mallick,
P M Sharples,
S E Calvert,
R W A Jones,
M Leary,
A L Lux, F J O'Callaghan,
J P Osborne,
J S Patel,
A T Prendiville,
S Renowden,
P E Jardine
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ABSTRACT: Cerebral venous sinus thrombosis (CVST) in children is associated with a high incidence of serious morbidity and mortality. The presenting features are variable. It can be diagnostically challenging and the optimal treatment is uncertain.
To describe the features of a series of children with CVST treated in a single paediatric neurology centre and to discuss the role of local thrombolysis.
Electronic databases were searched using diagnostic labels and International Classification of Diseases (ICD) codes to identify children aged 1 month to under 17 years with CVST. Their records were reviewed.
21 children were identified over a period of 8.25 years with a median age of 7.1 years. The presenting symptoms included headache (15 children), vomiting (14 children) and visual disturbance (eight children). Signs found included papilloedema (16 children), fever (six children) and sixth nerve palsy (six children). The most common underlying condition was middle ear infection (13 children). All cases received unfractionated heparin and four severe cases received local pharmacological thrombolysis. 48% of cases had an adverse outcome (death, chronic intracranial hypertension, residual hemiparesis or sixth nerve palsy).
CVST has non-specific presenting features and a high risk of significant morbidity. CVST is typically found in association with a predisposing condition. Although heparin is the mainstay of treatment, thrombolysis may reverse deterioration as seen in three cases in this series. However, there is insufficient evidence to recommend the routine use of thrombolysis at present.
Archives of Disease in Childhood 07/2009; 94(10):790-4. · 2.88 Impact Factor
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ABSTRACT: We investigated the effects of head growth prenatally, during infancy, and during later periods of development on cognitive function at the ages of 4 and 8 years.
We studied 633 term-born children from the Avon Longitudinal Study of Parents and Children cohort whose head circumference was measured at birth and at regular intervals thereafter. Their cognitive function was assessed with the Wechsler Preschool and Primary Scale of Intelligence at the age of 4 years and with the Wechsler Intelligence Scale for Children at the age of 8 years. Linear regression analysis was used to calculate postnatal head growth between successive time points, conditional on previous size, and to examine the relationship between head growth during different periods of development and later IQ.
When the influence of head growth was distinguished for different periods, only prenatal growth and growth during infancy were associated with subsequent IQ. At 4 years, after adjustment for parental characteristics, full-scale IQ increased an average of 2.41 points for each 1-SD increase in head circumference at birth and 1.97 points for each 1-SD increase in head growth during infancy, conditional on head size at birth. At 8 years, head circumference at birth was no longer associated with IQ, but head growth during infancy remained a significant predictor, with full-scale IQ increasing an average of 1.56 points for each 1-SD increase in growth.
The brain volume a child achieves by the age of 1 year helps determine later intelligence. Growth in brain volume after infancy may not compensate for poorer earlier growth.
PEDIATRICS 11/2006; 118(4):1486-92. · 4.47 Impact Factor
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ABSTRACT: To investigate if fetal, head, and somatic postnatal growth are independent predictors of cognition and estimate their relative importance compared to the effect size of social factors on cognitive function at 10 years.
Longitudinal population-based data from the birth questionnaire and the 5- and 10-year sweeps of the 1970 British Birth Cohort Study were used, including 11,244 subjects. Multiple linear regression and structural equation modeling were used in the statistical analysis. Standardized coefficients were used to measure and compare effect sizes.
Fetal growth, head, and somatic postnatal growth were significant independent predictors of cognition at age 10. These associations remained even among children born within the normal birth-weight range and those who did not experience neonatal problems. Effect of head size on cognition was greater than the effect of birth weight. Weight at 10 had a small negative effect on cognition. Gestational age was not directly associated with cognitive function, but it had a weak indirect effect. Parent's socioeconomic status was strongly associated with child's cognitive function.
Although effect sizes of prenatal and postnatal growth on cognition are modest compared with the strong effect size of social factors, they might have greater impact at the population level, since most children are born without low birth weight.
Annals of Epidemiology 07/2006; 16(6):469-76. · 3.21 Impact Factor
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ABSTRACT: To report the frequency of renal symptoms and complications of patients with tuberous sclerosis complex (TSC), to describe the ultrasonographic appearance of the kidneys in a population-based sample, and to investigate the relationship between a history of renal haemorrhage and renal lesions identified by ultrasonography.
As part of an epidemiological study, 179 patients with TSC were identified as living in the Wessex Region in the South of England. Patients were interviewed and examined in their homes, to elicit the presence of renal symptoms or a history of renal complications. Renal ultrasonography was used in consenting patients in their homes.
There was a history of renal complications in 16 (9%) patients; 149 consented to interview and examination, and 19 gave a history of renal symptoms in the previous year; 124 had renal ultrasonography; 86 (69%) had renal angiomyolipomas and 37 (30%) had renal cysts. Large lesions (>3 cm in diameter) were strongly associated with a history of symptomatic bleeding, although significant haemorrhage occurred in a 6-year-old child with small angiomyolipomas.
The formation of angiomyolipoma in TSC is common. Polycystic kidney disease, renal carcinoma and renal failure, although rare, occur in TSC. Most patients with angiomyolipomas have neither complications nor symptoms. There was no appreciable difference between the sexes in the risk of developing these lesions. Although less commonly seen in the very young, there is no identifiable relationship after adolescence between age and the risk of having a renal angiomyolipoma. Bleeding tends to occur from large lesions (>3 cm) but most such patients have remained asymptomatic to date.
BJU International 11/2004; 94(6):853-7. · 2.84 Impact Factor
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ABSTRACT: There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We investigated the relationship between brain growth in different periods of pre- and postnatal life and cognitive function in 221 9-year-old children whose mothers had taken part in a study of nutrition in pregnancy and whose head circumference had been measured at 18 weeks gestation, birth and 9 months of age. Cognitive function of the children and their mothers was assessed with the Wechsler Abbreviated Scale of Intelligence. Full-scale IQ at age 9 years rose by 1.98 points [95% confidence interval (CI) 0.34 to 3.62] for each SD increase in head circumference at 9 months and by 2.87 points (95% CI 1.05 to 4.69) for each SD increase in head circumference at 9 years of age, after adjustment for sex, number of older siblings, maternal IQ, age, education, social class, duration of breastfeeding and history of low mood in the post-partum period. Postnatal head growth was significantly greater in children whose mothers were educated to degree level or of higher socio-economic status. There was no relation between IQ and measurements of head size at 18 weeks gestation or at birth. These results suggest that brain growth during infancy and early childhood is more important than growth during foetal life in determining cognitive function.
Brain 03/2004; 127(Pt 2):321-9. · 9.46 Impact Factor
