Severe myocardial fibrosis caused by a deletion of the 5' end of the lamin A/C gene.

OBJECTIVES: The goal of this study was to identify the underlying gene defect in a family with inherited myocardial fibrosis. BACKGROUND: A large family with an autosomal dominantly inherited form of myocardial fibrosis with a highly malignant clinical outcome has been investigated. Because myocardial fibrosis preceded the clinical and echocardiographic signs, we consider the disease to be a hereditary form of cardiac fibrosis. METHODS: Twenty-five family members were clinically evaluated, and 5 unaffected and 8 affected family members were included in a genome-wide linkage study. RESULTS: The highest logarithm of the odds (LOD) score (LOD = 2.6) was found in the region of the lamin AC (LMNA) gene. The LMNA mutation analysis, both by denaturing gradient gel electrophoresis and sequencing, failed to show a mutation. Subsequent Southern blotting, complementary deoxyribonucleic acid sequencing, and multiplex ligation-dependent probe amplification analysis, however, revealed a deletion of the start codon-containing exon and an adjacent noncoding exon. In vitro studies demonstrated that the deletion results in the formation of nuclear aggregates of lamin, suggesting that the mutant allele is being transcribed. CONCLUSIONS: This novel LMNA deletion causes a distinct, highly malignant cardiomyopathy with early-onset primary cardiac fibrosis likely due to an effect of the shortened mutant protein, which secondarily leads to arrhythmias and end-stage cardiac failure.     

Refractive error in premature infants

PURPOSE: To determine the incidence and the degree of refractive error between the ages of 2 weeks and 6 months in premature infants without retinopathy of prematurity and to seek a correlation between refractive error and age at examination, birth weight, or gestational age. SUBJECTS AND METHODS: In this observational cross-sectional study, eye refraction in 390 premature infants, with no ocular pathology, was measured by cycloplegic retinoscopy at the age of 2 weeks to 6 months. A correlation was sought between refractive error and perinatal variables. RESULTS: Of the 390 infants reviewed, 347 (89%) had a refractive error and 43 (11%) were emmetropic in both eyes. Most of the infants were hyperopic (76.8%). Myopia was observed in only 11.9%. Astigmatism was found in 24.4% of the infants. The mean age at examination was 2.1 +/- 1 months; the mean birth weight was 1639 +/- 444 g, and the mean gestational age at birth was 32.2 +/- 2.4 weeks. The mean spherical equivalent of refraction was +1.56 +/- 1.82 diopters (D) in the right eye and +1.55 +/- 1.78 D in the left eye. Refractive error was positively correlated with age at examination ( R = 0.16, P = 0.001). The mean refractive error was +1.24 D in infants aged 1 month or less and reached +2.50 D at the age of 4 to 6 months. Refractive error was not correlated with birth weight or gestational age. CONCLUSIONS: The incidence of refractive error in premature infants without retinopathy of prematurity in the first 6 months of life may be as high as 89%. Most of these infants are hyperopic. Eye refraction is correlated with age at examination, but not with birth weight or gestational age.     

Congenital Dysgranulopoietic Neutropenia in Two Siblings: Clinical, Ultrastructural, and in Vitro Bone Marrow Culture Studies

Two siblings with congenital neutropenia are reported. The first patient, female, died after Pseudomonas sepsis. The second patient male, suffered from recurrent pyogenic infections, with a more benign course. Bone Marrow (BM) and Peripheral Blood (PB) analysis in the second patient revealed a reduced number of granules and myelin bodies in the PB neutrophils, suggesting a developmental defect of primary and secondary granules. BM promyelocytes were almost normal, but the myelocytes and metamyelocytes showed defective granulogenesis. The BM in vitro granulocyte-macrophage-colony-forming cell (GM-CFC) growth and the PB white blood cells (WBC) granulocyte-macrophage-colony-stimulating factor (GM-CSF) production, which were analyzed in the second patient, showed normal numbers of GM-CFC, with differentiation mostly toward monocytes and a defect in the GM-CSF production capacity. The second patient's PB mononuclear cells or serum did not inhibit normal GM-CFC when added to control BM cells. We suggest that in this specific form of congenital neutropenia, which is probably an autosomal recessive disorder, the abnormal neutrophil granule production and the defective provision of GM-CSF by PB WBC are unique pathognomonic characteristics, possibly associated with the overt neutropenia.     

The course of epiphora after failure of silicone intubation for congenital nasolacrimal duct obstruction

Background One of the indications for dacryocystorhinostomy (DCR) in children with congenital nasolacrimal duct obstruction (CNLDO) is failure of silicone intubation. We evaluated the course of epiphora after failure of silicone intubation for CNLDO when DCR was not performed.Methods In a comparative cohort study carried out at a tertiary referral center, ten eyes of seven consecutive children who had failure of silicone intubation manifested as persistent epiphora over 2 months and whose parents refused DCR were followed up for an average of 50.4 months (range 33–70 months). Three lacrimal drainage systems of three other children who had failure of silicone intubation underwent uneventful DCR.Results In eight (80%) of the ten consecutive eyes with congenital nasolacrimal duct obstruction (six of the seven children, 86%), there was spontaneous complete resolution of the epiphora and normal dye disappearance test (DDT) at the end of the follow-up period. One child with Downs syndrome, allergic rhinitis, asthma and multiple site obstructions had improvement of symptoms but abnormal DDT. The epiphora in all three children who underwent DCR had disappeared by 6 months after surgery when the silicone tube was removed. No complications were noted during the follow-up.Conclusions Epiphora can spontaneously resolve after failure of silicone intubation in CNLDO, and DCR should no longer considered be compulsory in such cases unless complications evolve.The authors have no financial or proprietary interest in any of the products mentioned in this paper.Presented in part at the 107th American Academy of Ophthalmology Annual Meeting, Anaheim, CA, November 2003.     

Blunt pancreatic trauma in children

Purpose

To report our experience with blunt pancreatic trauma in pediatric patients and evaluate several various management strategies.

Methods

Ten children admitted over the last 10 years with pancreatic blunt trauma were included in the present series.

Results

The average time from injury to hospital admission was 2.4 days. All injuries resulted from accidents: bicycle handlebar injuries (5), being kicked by a horse (2), falls from a height (2), and injury sustained during closure of an electric gate (1). Additional systemic and abdominal injuries were recorded in 7 patients. The amylase levels at the time of patient admission were normal in 3 patients, mildly raised in 4 patients, and elevated in 3 patients. Abdominal computed tomography was performed in 10 patients, ultrasonography in 5, and endoscopic retrograde cholangiopancreatography (ERCP) in 4. Pancreatic injuries comprised 4 grade I, 3 grade II, and 3 grade III injuries. Grade I and II injuries were successfully managed by conservative treatment. The 3 children with grade III trauma and pancreatic ductal injury in the neck (1), body (1), and tail (1) of the gland were surgically treated, having an uneventful postoperative stay of 8?C14 days and no complications during the 1-year follow-up period.

Conclusion

The present study supports early ERCP as an essential part of the initial patient evaluation when pancreatic transection is highly suspected.