Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures.

Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay.

[Diagnosis of streptococcal tonsillitis in the pediatric department with the help of antigen detection test]. / Diagnostik af streptokoktonsillitis på børneafdeling ved hjaelp af antigendetektionstest.

INTRODUCTION: The aim was to examine the validity in the paediatric hospital department of an antigen detection test (ADT) for the diagnosis of streptococcal tonsillitis. MATERIAL AND METHODS: A prospective multicenter study including three Danish paediatric hospital departments was performed from May 1, 1998 to April 30, 1999. In 353 children aged 0-14 years the result of the ADT, Clearview Strep A, was compared with the result obtained with cultivation in an aerobic culture and the clinical parameters: hyperaemia, swelling, coating, adenitis and a temperature > or = 38.5 degrees C. In 126 patients the results of the ADT were also compared with white blood cell count (WBC), neutrofil count (NC) and C-reactive protein (CRP). RESULTS: The prevalence of Group A Streptococci (GAS) from culture was 15%. Sensitivity, specificity, positive and negative predictive value of ADT were 67%, 95%, 72% and 94%, respectively. The positive predictive value of the ADT was significantly lower in patients aged 0-4 years than in patients aged > or = 5 years (p = 0.02). The prevalence of positive ADT was significantly higher in patients with heavy growth of GAS than in patients with moderate or sparse growth (p = 0.01). The prevalence of adenitis (p = 0.003) and coating (p = 0.003) was significantly raised in ADT-positive patients. In patients with growth of Group A Streptococci in cultivation in an aerobic culture the prevalence of adenitis (p = 0.006) and elevated CRP (p = 0.03) was significantly raised. DISCUSSION: The sensitivity of 67% for the ADT is not satisfactory. However, in our opinion, this is not a sufficient argument against using ADT. It was a problem that the result of the ADT was sometimes difficult to read. Adjustment of the test procedure and the use of easy readable and high-sensitive optical immunoassay tests would probably improve the results significantly. Until the results of such studies exist, we suggest that the method of cultivation in an aerobic culture is used in the case of negative ADT, at least in patients with pronounced symptoms and/or clinical signs of streptococcal tonsilitis (adenitis and coating).