Novel de novo SCN2A mutation in a child with migrating focal seizures of infancy.

BACKGROUND: Migrating focal seizures of infancy are characterized by seizure onset within 7 months of age, migrating focal motor seizures with multifocal ictal electroencephalography discharges intractable to conventional antiepileptic drugs, and poor prognosis. Reported genetic etiologies include SCN1A and KCNT1 mutations and homozygous deletion of the PLCB1 gene. Here we report a novel SCN2A mutation in a child with this syndrome. PATIENT: A 7-week-old girl was admitted to our hospital for management of status epilepticus. She was the product of a full-term unremarkable pregnancy. Seizures started around 5 weeks of age and remained medically refractory. Electroencephalography showed multifocal epileptiform discharges as well as seizures arising from multifocal regions in both cerebral hemispheres. Based on her phenotype, a diagnosis of migrating focal seizures of infancy was made. RESULT: A novel de novo missense mutation was identified in the SCN2A gene, exon 22 (coding for voltage-gated sodium channel type II): c.3977T>A (p.V1326D). This mutation affects a highly evolutionarily conserved area of the gene and replaces hydrophobic nonpolar valine with polar aspartic acid; thus, it is predicted to affect protein function and is presumed pathogenic. DISCUSSION: This report expands our knowledge of the genetic basis of migrating focal seizures of infancy to include mutations in SCN2A gene.

Strict glycemic targets need not be so strict: a more permissive glycemic range for critically ill children.

OBJECTIVE: The goal was to determine whether a more permissive glycemic target would be associated with a decreased incidence of hypoglycemia but not increased mortality rates in critically ill pediatric patients. METHODS: This retrospective study evaluated clinical and laboratory data for 177 patients who underwent 211 consecutive surgical procedures for repair or palliation of congenital heart defects at Driscoll Children's Hospital. To establish the relationship between postoperative glycemia and subsequent morbidity and mortality rates, patients were stratified into 4 groups according to their median glucose levels, that is, euglycemia (60-125 mg/dL, 3.3-6.9 mmol/L), mild hyperglycemia (126-139 mg/dL, 6.9-7.7 mmol/L), moderate hyperglycemia (140-179 mg/dL, 7.7-9.9 mmol/L), or severe hyperglycemia (>or=180 mg/dL, >or=9.9 mmol/L). Postoperative outcomes for those groups also were compared with outcomes for a more permissive glycemic target group (90-140 mg/dL, 5-7.7 mmol/L). RESULTS: The peak and mean blood glucose measurements and duration of hyperglycemia were not different for survivors and nonsurvivors in the first 24 hours after surgery. Nonsurvivors had higher peak glucose levels (389.3 +/- 162 mg/dL vs 274.4 +/- 106.3 mg/dL, 21.4 +/- 8.9 mmol/L vs 15.1 +/- 5.9 mmol/L) and longer duration of hyperglycemia (3.06 +/- 1.67 days vs 2.11 +/- 0.92 days) during the first 5 postoperative days, compared with survivors. Mortality rates were significantly higher for the moderate (38.8%) and severe (58.3%) hyperglycemia groups, compared with the euglycemia (6.02%) and permissive target (4.69%) groups. The incidence of hypoglycemia was significantly higher in the euglycemia group (31.8%), compared with the permissive target group (17.18%). CONCLUSIONS: Postoperative hyperglycemia is associated with increased morbidity and mortality rates in children after surgical repair of congenital heart defects. A more permissive glycemic target is associated with a lower incidence of hypoglycemia but not increased mortality rates in these patients.

Impact of postoperative hyperglycemia following surgical repair of congenital cardiac defects.

The objective of this study was to determine the prevalence of postoperative hyperglycemia in pediatric patients following surgery for congenital cardiac defects and its impact on morbidity and mortality. It was designed as a retrospective cohort study in a pediatric intensive care unit of a university-affiliated free-standing children's hospital. A cohort of 213 patients who underwent 237 surgical procedures for repair or palliation of congenital cardiac defects comprised the study. Postoperative blood glucose measurements and all clinical and laboratory data were compiled for the first 10 days after surgery. The intensity and duration of hyperglycemia were analyzed for association with hospital morbidities and mortality. Mild and severe hyperglycemia were highly prevalent in our cohort (97% and 78%, respectively). Survivors had significantly lower peak (289.7 +/- 180.77 mg/dl vs. 386 +/- 147.95 mg/dl), mean (110.13 +/- 36.22 mg/dl vs. 146.75 +/- 57.12 mg/dl), and duration (2.59 +/- 2.3 days vs. 5.35 +/- 2.8 days) of hyperglycemia compared to nonsurvivors. Duration of hyperglycemia was independently associated with morbidity [odds ratio (OR): 1.95; p < 0.001] and mortality (OR: 1.41; p = 0.03) by multivariate logistic regression. Hyperglycemia is common in children following surgical repair or palliation of congenital cardiac defects. Postoperative hyperglycemia is associated with increased morbidity and mortality in these patients.