Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

News for the Practitioner

News for the Practitioner     

Organisational factors in relation to control of blood pressure: an observational study

BACKGROUND: Studies show that 60-75% of treated patients with hypertension in general practice, still do not reach the recommended blood pressure targets of <150/90 mmHg. AIM: To investigate aspects of hypertension management in relation to sociodemographic variables, antihypertensive drug treatment, and organisational factors in primary care. DESIGN OF STUDY: Observational study over 3 years. SETTING: Eight general practices in Tayside, UK. METHOD: Participants were 560 randomly selected patients aged 40-79 years receiving treatment for hypertension. The outcome measurement was blood pressure control, expressed in binary form based on the British Hypertension Society audit standard of <150/90 mmHg. RESULTS: Of 536 eligible patients, 261 (49%) were defined as having inadequate blood pressure control at the end of the study period. No significant associations were discovered with sex, age, deprivation score and comorbidity. In those patients with inadequate control, 30% had no modifications to their drug treatment during the study period. Blood pressure control at the end of the study period was not associated with number of antihypertensive drugs taken or number of antihypertensive drug modifications. The mean number of clinician contacts was 11 (standard deviation = 8), and mean continuity in primary care was high, although this was not associated with improved blood pressure control. A higher proportion of hypertension-related consultations were associated with increased odds of having inadequate blood pressure control. CONCLUSION: Achieving adequate blood pressure control continues to represent a substantial health problem in a significant proportion of the hypertensive population. Patient, physician and organisational elements play a role in ensuring effective delivery of hypertension care in the community.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

Long-term follow-up and the role of surgery in adolescents with morbid obesity

PURPOSE: Obesity has become a health-care crisis in the United States. Adolescent obesity is now one of the most common childhood disorders, with 4.7 million American adolescents having a body mass index (BMI) greater than the 95th percentile. Most patients do not respond to diet modification or exercise programs and attention is now turning toward surgery as a source of weight loss in adolescents. Few studies have looked at the overall morbidity and mortality of weight loss surgery in this patient population. METHODS: This is a retrospective study of medical charts of 15 bariatric surgical procedures performed on 14 adolescents without known genetic syndromes associated with severe childhood obesity from 1971 to 2001 at the University of Minnesota. Procedures performed on these patients included vertical banded gastroplasty (n = 7), Roux-en-Y gastric bypass (n = 5), and jejunoileal bypass (n = 3). Jejunoileal bypass procedures were performed from 1971 to 1977, after which time this procedure was abandoned. Patient age ranged from 13 to 17 years (mean, 15.7 years). Mean follow-up time was 6 years, with 9 patients available for long-term follow-up. RESULTS: All procedures were performed using an open technique by 1 surgeon. There were no perioperative deaths; complications included 1 case of wound infection, 2 episodes of dumping syndrome that resolved without revision, 1 episode of hypoglycemia, and 1 case of short-term electrolyte imbalance in a patient who underwent jejunoileal bypass. The average BMI dropped from 58.5 +/- 13.7 to 32.1 +/- 9.7 kg/m(2) (P < .01)--a 45% reduction. CONCLUSIONS: Surgery for morbid obesity is safe and results in significant weight loss in adolescents who fail medical therapy.