Two novel variants in CNTNAP1 in two siblings presenting with congenital hypotonia and hypomyelinating neuropathy.

Homozygous frameshift variants in CNTNAP1 have recently been reported in patients with arthrogryposis and abnormal axon myelination. In two brothers with severe congenital hypotonia and foot deformities, we identified compound heterozygous variants in CNTNAP1, reporting the first causative missense variant, p.(Cys323Arg). Motor nerve conductions were markedly decreased. Nerve microscopical lesions confirmed a severe hypomyelinating process and showed loss of attachment sites of the myelin loops on the axons, which could be a characteristic of Caspr loss-of-function. We discuss the pathophysiology of the myelination process and we propose to consider this disorder as a congenital hypomyelinating neuropathy.

Impact of rapid influenza diagnostic test on physician estimation of viral infection probability in paediatric emergency department during epidemic period.

BACKGROUND: The clinical diagnosis of influenza is difficult in the younger children. OBJECTIVES: Evaluate the impact of rapid influenza diagnostic test (RIDT) on clinicians' estimation of the clinical probability of influenza in children. STUDY DESIGN: This prospective study included children aged from 1 month to 5 years who were admitted in a university paediatric emergency department during an influenza epidemic period and presented with fever without source. The RIDT Quickvue(®) was performed on nasopharyngeal aspiration and results were confirmed with immunofluorescence and/or PCR. The clinical probability of influenza and serious bacterial infection (SBI) was evaluated for each child before and after the physician(s) was informed of the RIDT results. RESULTS: 170 children were included from January 15th through March 18th, 2013. After the only clinical examination, the overall clinical probability of influenza was 66.0% [CI 95%: 63.04-68.4], and was significantly increased at 92.4% [CI 95%: 89.5-95.3] in case of positive RIDT and significantly decreased at 30.8% [CI 95%: 29.0-32.5] in case of negative RIDT without knowing the results of laboratory tests. Whereas the initial clinical probability of influenza were appropriate regarding the prevalence (66.0% vs. 57.0%), the probability of SBI was overestimated (30.2% vs. 8.8%). The RIDT result positive enabled a significant decrease in orders for chest X-rays (64,4% vs. 45.8%, p<0,05) and laboratory tests (71,1% vs. 41.1%, p<0,05). CONCLUSIONS: The RIDT seems to be a useful diagnostic tool for ED clinicians in epidemic conditions. Improving clinician estimation of flu probability would reduce orders for imaging and testing.

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

BACKGROUND: Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. METHODS: A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. RESULTS: Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. CONCLUSIONS: Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.