SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V

Sánchez‐Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual‐Pascual SI, López de Munaín A, Garcia‐Barcina MJ, Alvarez V on behalf of the Genetics of Spastic Paraplegia study group. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.     

A puzzle over several decades: eye anomalies with FRAS1 and STRA6 mutations in the same family

Ng WY, Pasutto F, Bardakjian TM, Wilson MJ, Watson G, Schneider A, Mackey DA, Grigg JR, Zenker M, Jamieson RV. A puzzle over several decades: eye anomalies with FRAS1 and STRA6 mutations in the same family. Fraser syndrome (FS) and microphthalmia syndromic 9 (MCOPS9) are autosomal recessive conditions with distinct, and some overlapping features affecting the ocular, respiratory and cardiac systems. Mutations in FRAS1 and FREM2 occur in FS, and mutations in STRA6 occur in MCOPS9. We report two sibships, in the same family, where four deceased offspring had ocular, respiratory and cardiac abnormalities. Two sibs with microphthalmia had syndactyly and laryngeal stenosis, suggesting a clinical diagnosis of FS. Our results indicate that they were compound heterozygotes for novel FRAS1 mutations, p.Cys729Phe and p.Leu3813Pro. The other two sibs, first cousins to the first sib pair, had anophthalmia, lung hypoplasia and cardiac anomalies, suggesting a retrospective diagnosis of MCOPS9. Our results indicate compound heterozygous STRA6 mutations, a novel frameshift leading to p.Tyr18* and a p.Thr644Met mutation. The one surviving individual from these sibships is heterozygous for the p.Tyr18*STRA6 mutation and has bilateral ocular colobomata and microphthalmia. This work emphasises the need for careful phenotypic characterisation to determine genes for assessment in ocular syndromic conditions. It also indicates that heterozygous STRA6 mutations may rarely contribute to microphthalmia and coloboma.     

The value of C-reactive protein and lactate in the acute abdomen in the emergency department

ABSTRACT: CASE PRESENTATION: This report describes the presentation of three critically ill patients with non-traumatic acute abdominal pain and increased concentrations of the biomarkers C-reactive protein (CRP) and lactate. In these three patients an exploratory laparotomy was carried out. Remarkably, the laparotomy showed no intra-abdominal abnormalities. We discuss the usefulness of these biomarkers in practice and their influence on establishing a diagnose and making a decision to perform an intervention. CONCLUSION: We conclude that biomarkers lactate and CRP in patients with acute abdominal pain should only be used in adjunct to the history and clinical findings, as they are not specific and can be misleading in establishing a diagnosis. In addition, relying on these biomarkers may contribute to more diagnostic examinations and/or unnecessary invasive interventions (for example laparotomy).     

Simplified treatment of acute staphylococcal osteomyelitis of childhood. The Finnish Study Group

OBJECTIVE: Recommendations on treatment of acute staphylococcal osteomyelitis of children, based mostly on retrospective analyses, comprise surgical drainage, up to 6 weeks fo antimicrobials guided by the erythrocyte sedimentation rate, and the possibility of switching to the oral route only if monitoring of serum bactericidal titer is guaranteed. A prospective study was conducted to test whether the treatment could be simplified. DESIGN: Fifty pediatric cases of acute Staphylococcus aureus osteomyelitis were randomized to receive 150 mg/kg/day of cephradine divided in four doses, or 40 mg/kg/day in four doses of clindamycin. The treatment was initiated intravenously, but switched to oral administration mostly within 4 days, using the same doses. The peak antimicrobial serum inhibitory titer or bactericidal titer was not measured. The course of illness was monitored by blood leukocytes, erythrocyte sedimentation rate, and serum C-reactive protein. The follow-up was extended to 1 year posthospitalization. SETTING: Eight tertiary pediatric-orthopedic hospitals in Finland. MAIN OUTCOME MEASURE: Full recovery and remaining healthy at least 12 months from hospital discharge. RESULTS: The lower and upper extremities were affected in 72% and 8% of patients, respectively. No surgery at all or needle aspiration only was performed in 62% and drilling in 38%. C-reactive protein and the sedimentation rate normalized within 9 days and 29 days, respectively. X-ray changes developed in 68% but had no prognostic significance. The mean hospitalization time was 11 days, and the total duration of antimicrobials was 23 days. No failure has occurred nor have long-term sequelae been observed in any patient. CONCLUSIONS: Treatment of pediatric acute staphylococcal osteomyelitis can be simplified and costs reduced by keeping surgery at a minimum, shortening hospitalization and the course of antimicrobials, switching quickly to the oral route, and not monitoring serum bactericidal activity.     

Metastatic malignant melanoma presenting with hypercalcaemia and bone marrow involvement

We report a 75-year-old female patient with a background of malignant melanoma who presented with hypercalcaemia to our institution. She was aggressively treated but declined clinically. Computed tomography head and X-ray studies were suggestive of multiple myeloma, but bone marrow examination was significant for metastatic malignant melanoma. Very few patients with melanoma present with these features, and it further exemplifies the importance of close follow-up and the aggressive nature of this disease process.     

The influence of some perinatal variables on neonatal blood pressure

Adult hypertension has been linked to fetal growth. This study investigates whether this link is evident in the newborn. We measured blood pressure by oscillometry in 248 healthy neonates on day 3/4 of life. Antenatal data and neonatal measurements were obtained from hospital records. Elevated neonatal blood pressure correlated with higher birthweight. There was no correlation between placental weight and blood pressure. Babies born by caesarean section had lower systolic blood pressure. Babies of maternal smokers had higher diastolic blood pressure, but their mothers (45% of this study) had lower blood pressure than non-smokers. Thus, smoking was associated with a significant change in both maternal and neonatal blood pressure, and may be an important influence on the developing cardiovascular system.     

Psoriasis: pathophysiology and oral manifestations

Psoriasis is a chronic, remitting and relapsing inflammatory skin disorder with a strong genetic predisposition. Psoriasis affects 1–3% of the world's population in their early lives representing a disabling condition with significant social and economic impact. Despite a great deal of research on the etiology and tissue destruction mechanisms, the disease is not well understood. The purpose of this paper is to provide current information from the literature with a special focus on oral manifestations. The major signs and symptoms presented in the oral environment of a psoriasis patient may include geographic tongue, fissure tongue, gingival and/or mucosal lesions. Inflammatory temporomandibular joint lesions have been reported in less than 5% of psoriasis patients. Multiple treatment strategies, be they topical or systemic, have been applied to these patients for symptom relief but not for cure.