Christine Reyes

Novel SCN1A Mutation in a Proband With Malignant Migrating Partial Seizures of Infancy

OBJECTIVE To characterize a novel SCN1A mutation in a proband with malignant migrating partial seizures of infancy. DESIGN Genomic DNA was isolated from blood and submitted for commercial testing. The identified missense mutation was confirmed in brain DNA obtained at autopsy. Genomic DNA from the brain of the proband was analyzed by comparative genome hybridization, and the coding exons of SCN9A were amplified. Quantitation studies of the mutant transcript were performed. SETTING Childrens National Medical Center and Yale University School of Medicine. PROBAND: A full-term female infant who experienced seizure onset at age 10 weeks, with progression of hemiclonic, apneic, and multifocal migrating partial seizures leading to recurrent status epilepticus and death at age 9 months. MAIN OUTCOME MEASURES Electroencephalographic and magnetic resonance imaging results, quantitative RNA expression, and secondary mutation test results. RESULTS The heterozygous missense mutation c.C5006C>A was identified by sequencing genomic DNA from blood and was confirmed in brain DNA. The resulting amino acid substitution p.A1669E alters an evolutionarily conserved residue in an intracellular linker of domain 4 of the SCN1A sodium channel protein Na(v)1.1. The mutant transcript is found to be expressed at levels comparable to the wild-type allele in brain RNA. No variation in copy number was detected in the chromosome region 2q24 containing SCN1A or elsewhere in the genome. No mutations were detected in the linked sodium channel gene SCN9A, which has been reported to act as a modifier of SCN1A mutations. CONCLUSION This report expands the spectrum of SCN1A epileptic channelopathies to include malignant migrating partial seizures of infancy.

Placental weight and neurologic outcome in the infant: a review

Objective: To review the agreement of published standards on placental weights (PW) and fetal–placental (F/P) ratios, examine factors contributing to PW and ask whether aberrant placental weight is associated with adverse neurologic outcome. Methods: We conducted a literature search for standards of PW, F/P ratio and the relationship of PW to perinatal death, neonatal encephalopathy or cerebral palsy. We reviewed 17 studies of normative PW and 10 of F/P ratios. Since 1990, seven studies compared mean and extreme percentile bounds between 35 and 42 weeks of gestation. Nine publications examined PW and neurologic outcome. Results: Untrimmed placentas were heavier by 131–193 g. F/P ratios differed by 0.2–2.34 between trimmed and untrimmed placentas. Fresh, frozen or fixed preparation prior to weighing had minimal effect on weight. Gender and race had negligible affect. Placentas from caesarean sections averaged 75 g heavier than vaginal deliveries. There were no consistent associations of aberrant PW and neurologic outcome. Conclusions: Reference standards of recent studies on trimmed placentas were largely in agreement. Current findings relating aberrant PW and adverse neurologic outcome are inconclusive. Further study of the relationship between placental weight and neonatal encephalopathy or cerebral palsy is warranted, in representative populations using within-study controls.

Multiple Papillary Fibroelastomas of the Heart

We report the case of a 41-year-old woman who presented with extensive papillary fibroelastomas of the heart after multiple previous surgical procedures for hypertrophic cardiomyopathy. This case is significant because of the locally aggressive nature of the cardiac papillary fibroelastoma.

Evaluation of the BiliChek Being Used on Hyperbilirubinemic Newborns Undergoing Home Phototherapy

CONTEXT Newborns are often screened prior to discharge for hyperbilirubinemia. Transcutaneous bilirubin analyzers, such as the BiliChek, are promoted as screening tools, but it is unclear whether they also function well as monitoring devices. Newborns on home phototherapy require frequent determinations of serum bilirubin levels to monitor therapy effects. A transcutaneous bilirubin analyzer would be helpful to limit blood draws and enhance staff efficiency. We evaluated the accuracy of the BiliChek analyzer in this setting. OBJECTIVE Is the BiliChek sufficiently accurate to monitor the effectiveness of home phototherapy and establish when to terminate therapy? DESIGN Paired serum bilirubin results and results from the BiliChek were obtained from newborns on home phototherapy during daily home health care visits. RESULTS The BiliChek demonstrates a negative bias (mean bias, -1.71 mg/dL; 95% confidence interval, -1.89 to -1.52 mg/dL) compared with serum bilirubin values. This bias worsens as the serum bilirubin level rises. If a value of 14 mg/dL or less obtained using the BiliChek had been used as the cutoff for termination of phototherapy, 45% of newborns would have had therapy terminated prematurely. If, knowing the negative bias of the BiliChek, the cutoff for termination of therapy was set at less than or equal to 11 mg/dL, then 29% of newborns would have had therapy terminated prematurely. CONCLUSIONS The values obtained using the BiliChek, compared to serum bilirubin values, have a negative bias that worsens at the higher bilirubin levels expected in newborns at home on phototherapy. The BiliChek does not provide sufficient accuracy to be utilized to monitor newborns on home phototherapy or to ascertain when to discontinue such therapy.

Benign sacrococcygeal neoplasm arising at birth from a giant congenital melanocytic nevus

Giant congenital melanocytic nevi (CMN) are considered to be premalignant with the highest risk for conversion to melanoma. Solid tumors within giant CMN presenting at birth are relatively unusual, and a variety of malignancies have been reported within these masses. However, the frequency of malignancy in these tumors is unknown. We report the unusual case of a female neonate who was born with 2 large, perianal masses within a giant CMN over her trunk. We resected the larger of the 2 masses because of discomfort and bleeding. The mass consisted of an outgrowth of melanocytes with benign characteristics. The smaller of the 2 masses was managed expectantly and has subsequently decreased in size. We propose that pathologically benign masses within giant CMNs may not require immediate resection. We will discuss the management and pathologic findings of this case and review the literature regarding management of CMN-associated neoplasms arising at birth.

Intracardiac tumor causing left-ventricular outflow-tract obstruction in a newborn

The following report describes the case of newborn girl with an asymptomatic systolic murmur, which on imaging revealed a nearly obstructive mass in the left-ventricular outflow tract. The mass was resected and found to be consistent with a rhabdomyoma. Here, we describe the pathologic and clinical characteristics of this tumor.