This article describes a follow-up of 25 boys diagnosed as having specific expressive language delay (SELD) in the 24-to 31-month age period. At the time of diagnosis, all subjects had Bayley MDI scores above 85, Reynell Receptive Language Age scores within 4 months of their chronological age, and Reynell Expressive Language Age scores at least 5 months below chronological age; most had vocabularies of fewer than 50 words and few if any word combinations. At follow-up, 16 boys were 3 years old, 7 were 3'/2, and 2 were 4 years of age. When seen for follow-up, half the 25 boys still had very poor expressive language. These boys were speaking at best in short, telegraphic sentences, and many had moderately severe articulation disorders with quite poor intelligibility. The 12 boys with better outcome had a range of language skills. All spoke in sentences to some extent, and each displayed some mastery of early morphemes (prepositions, plurals, articles, progressive tense, and possessives). However, few if any of the children spoke in completely fluent, syntactically complex, and morphologically correct language. Problems with copula and auxiliary verbs, with past tense inflections, and with pronouns seemed especially common. This research suggests that children with SELD at 24 to 30 months are at considerable risk for continuing language problems.

Childhood absence epilepsy (CAE) accounts for 10% to 12% of epilepsy in children under 16 years of age. We screened for mutations in the GABA(A) receptor (GABAR) beta 3 subunit gene (GABRB3) in 48 probands and families with remitting CAE. We found that four out of 48 families (8%) had mutations in GABRB3. One heterozygous missense mutation (P11S) in exon 1a segregated with four CAE-affected persons in one multiplex, two-generation Mexican family. P11S was also found in a singleton from Mexico. Another heterozygous missense mutation (S15F) was present in a singleton from Honduras. An exon 2 heterozygous missense mutation (G32R) was present in two CAE-affected persons and two persons affected with EEG-recorded spike and/or sharp wave in a two-generation Honduran family. All mutations were absent in 630 controls. We studied functions and possible pathogenicity by expressing mutations in HeLa cells with the use of Western blots and an in vitro translation and translocation system. Expression levels did not differ from those of controls, but all mutations showed hyperglycosylation in the in vitro translation and translocation system with canine microsomes. Functional analysis of human GABA(A) receptors (alpha 1 beta 3-v2 gamma 2S, alpha 1 beta 3-v2[P11S]gamma 2S, alpha 1 beta 3-v2[S15F]gamma 2S, and alpha 1 beta 3-v2[G32R]gamma 2S) transiently expressed in HEK293T cells with the use of rapid agonist application showed that each amino acid transversion in the beta 3-v2 subunit (P11S, S15F, and G32R) reduced GABA-evoked current density from whole cells. Mutated beta 3 subunit protein could thus cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents.

In a double-blind study, we compared the postoperative (post-op) blood loss in 161 children undergoing open heart surgery with cardiopulmonary bypass whose immediate post-op transfusion requirements were met with either very fresh whole blood (VFWB), 24- to 48-hour-old whole blood or reconstituted whole blood (packed red blood cells, fresh frozen plasma [FFP], and platelets). Assignment to treatment groups was not strictly random but dependent, in part, on the ability of families to provide directed donors for fresh blood. The three patient groups were comparable with respect to patient age, pre-op coagulation profiles (bleeding time, prothrombin time, activated partial thromboplastin time, platelet count, fibrin split products, fibrinogen, and platelet aggregation tests) difficulty of operative procedures and time spent on CPB. Mean 24-hour post-op blood loss in milliliters per kilogram was 50.9 +/- 9.3 in the VFWB group, 44.8 +/- 6.0 in the 24- to 48-hour-old group, and 74.2 +/- 8.9 in the reconstituted group (p = .03). When blood loss was compared in the 93 children less than 2 years of age, mean blood loss was 52.3 +/- 10.8 in the VFWB group, 51.7 +/- 7.4 in the 24- to 48-hour-old group, and 96.2 +/- 10.7 in the reconstituted group (P = .001). For subjects who had received reconstituted blood, 30- minute and 3-hour post-op platelet aggregation responses to adenosine diphosphate (10 mumol/L) and 30-minute aggregation response to epinephrine (2.5 mumol/L) were more depressed than in the VFWB and 24- to 48-hour groups (P less than .001, P = .005, and P = .02). Comparison of other post-op coagulation tests could not explain the increased blood loss in the reconstituted group. We conclude that the transfusion of less than 48 hours old whole blood is associated with significantly less post-op blood loss than the transfusion of packed red blood cells, FFP, and platelets in children under 2 years old who underwent complex cardiac surgery. The blood losses associated with the transfusion of VFWB and 24- to 48-hour-old blood are comparable and may be, in part, due to better functioning platelets.

Mutations in the gene encoding the gamma2 subunit of the gamma-aminobutyric acid type A receptor (GABRG2) have been reported to cause childhood absence epilepsy (CAE), febrile seizures (FS), and generalized epilepsy with FS plus (GEFS+). The authors analyzed GABRG2 in 47 unrelated patients with CAE, FS, and GEFS+ and identified a novel mutation that cosegregated with FS. Electrophysiologic studies demonstrated altered current desensitization and reduced benzodiazepine enhancement in mutant receptors.

Hearing loss is a relatively common condition in children, occurring in approximately 2 out of every 1,000 births with approximately 50% of reported diagnoses having a primary genetic etiology. Given the prevalence and genetic component of hearing loss, coupled with a trend toward early diagnosis with the institution of universal newborn hearing screening, The Genetics of Hearing Loss Clinic was established at The Children's Hospital of Philadelphia to manage the diagnosis, testing, and genetic counseling for individuals and families. This paper described a cohort of 660 individuals with a diagnosis of hearing loss evaluated between July 2008 and July 2015 in the Genetics of Hearing Loss Clinic. To elucidate the cause of hearing loss in this cohort for better management and prognostication, testing included single nucleotide polymorphism chromosomal microarray, hearing loss next generation sequencing panel, and additional clinical tests inclusive of thyroid and renal function studies, temporal bone magnetic resonance imaging, and electrocardiogram. Of those evaluated, most had bilateral sensorineural hearing loss, occurring in 489/660 (74%). Additionally, 612/660 (93%) of patients presented with a nonsyndromic form of hearing loss (no other observed clinical findings at the time of exam), of which pathogenic mutations in GJB2 were most prevalent. Of the individuals with syndromic manifestations (48/660), Usher and Waardenburg syndrome were most commonly observed. A family history of hearing loss (first degree relative) was present in 12.6% of families with available information. Through molecular analyses, clinical examination, and laboratory testing, a definitive etiologic diagnosis was established in 157/660 (23.8%) of individuals. © 2016 Wiley Periodicals, Inc.

BACKGROUND AND PURPOSE:The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis.

Neonatal HSV-2 encephalitis has a variable imaging appearance. Diffusion-weighted MRI is an important adjunct in the imaging evaluation of this disease. Watershed distribution ischemia in areas remote from the primary herpetic lesions may be seen.

Covering: January 2013 to online publication December 2014This review summarizes recent research in the chemical ecology of marine pelagic ecosystems, and aims to provide a comprehensive overview of advances in the field in the time period covered. In order to highlight the role of chemical cues and toxins in plankton ecology this review has been organized by ecological interaction types starting with intraspecific interactions, then interspecific interactions (including facilitation and mutualism, host-parasite, allelopathy, and predator-prey), and finally community and ecosystem-wide interactions.