doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.      

Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases

Preimplantation genetic diagnosis was performed in 61 day 3 embryos obtained by in-vitro fertilization from seven patient carriers of haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa, and FG syndrome, which is characterized by mental retardation and hypotonia. After multiplex polymerase chain reaction, 16 embryos were diagnosed as being unaffected, and these were transferred to the uterus on the following day (day 4). Of these embryos, six (37.5%) implanted, resulting in the delivery of a singleton and a twin pregnancy, a late second trimester miscarriage (twins at week 20) and a first trimester miscarriage at week 8. All the diagnoses were confirmed by amniocentesis. We report for the first time a late day 4 transfer of biopsied human embryos undergoing preimplantation genetic diagnosis. This transfer schedule allows an extra day to perform genetic analyses on single blastomeres and to monitor any adverse effect of the biopsy procedure.      

Dietary fibre, exercise and serum lipids and lipoprotein cholesterols in 12 to 15 year olds

Serum lipid and lipoprotein cholesterol levels track from childhood and are associated with risk of coronary heart disease. There is some evidence that these are influenced by dietary intake and exercise. Serum lipid and lipoprotein cholesterols were measured in a cohort of 119 British children aged 12–15 y who completed a dietary assessment and exercise questionnaire. The ratio of total- to high-density lipoprotein cholesterol fell with increasing fibre intake, but after adjustment for age, body mass index, sex and other dietary factors, this was not statistically significant. Children exercising at least once a day had significantly lower serum total cholesterol and low density lipoprotein cholesterol levels than those exercising less frequently, even after adjustment for the above factors and dietary fibre intake. No dietary factor was significantly associated with any lipid measure after adjustment for the above factors. The challenge is how to optimize exercise level in adolescent children.     

Colchicine for recurrent pericarditis in children

The incidence of recurrence of acute pericarditis in children varies from 15% to 30% and is accompanied by a high morbidity. Various treatment modalities have been used with variable success rates and side effects. La Serna et al. (Lancet 1987; 26: 1517) were the first to treat adults with recurrent pericarditis with colchicine, and were followed by other authors. To our knowledge no studies in children have been reported. In this paper, we present three children who suffered from viral or idiopathic recurrent pericarditis, despite multiple courses of non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids. They responded remarkably well to colchicine, which was administered for 6 months with no adverse reactions. They continue to do well 18, 11 and 12 months after cessation of treatment, respectively.     

Patients’ preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer†

The palliative radiotherapeutic management of unresectable non‐small‐cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient’s choice of Fx schedule after involvement in a decision‐making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision‐making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients’ preferences. Of 92 patients enrolled, 55% chose the longer schedule. English‐speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2–7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision‐making process. The decision board was useful in aiding decision‐making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients’ preferences, there were significant alterations of preferred schedules because of RO’s own biases.