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BackgroundThe clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype–phenotype correlations to improve genetic counselling and patients’ medical care.MethodsWe retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents.ResultsClinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype–phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype.ConclusionOur study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.

The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable '2q37-deletion syndrome' or Albright's hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype-phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1.

Background The clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype–phenotype correlations to improve genetic counselling and patients’ medical care.Methods We retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents.Results Clinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype–phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype.Conclusion Our study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.

Background Alimentary tract duplications (ATD) are a rare cause of intestinal obstruction in childhood. There are many case reports but few series about laparoscopy or thoracoscopy for ATD. The aim of our study was to report the outcome of minimally invasive surgery (MIS) for ATD. Methods This was a retrospective multicenter study from the GECI (Groupe d’Etude en Coeliochirurgie Infantile). We reviewed the charts of 114 patients operated on by MIS for ATD from 1994 to 2009. Results Sixty-two patients (54 %) had a prenatal diagnosis. Forty-nine patients (43 %) were symptomatic before surgery: 33 of those patients (63 %) with postnatal diagnosis compared to 16 (25 %) with prenatal diagnosis ( P  < 0.01). In this last group, the median age at onset of symptoms was 16 days (range = 0–972). One hundred and two patients had laparoscopy (esophageal to rectal duplications) and 12 patients had thoracoscopy for esophageal duplications. The mean operative time was 90 min (range = 82–98). There were 32 (28 %) resection anastomoses, 55 (48 %) enucleations, and 27 (24 %) unroofings. The conversion rate was 32 %, and in a multivariate analysis, it was significantly higher, up to 41 % for patients weighing <10 kg ( P  < 0.01). Ten patients (8 %) had unintentional perioperative opening of the digestive tract during the dissection. Eight patients had nine postoperative complications, including six small bowel obstructions. The median length of hospital stay was 4 days (range = 1–21) without conversion and 6 days (range = 1–27) with conversion ( P  = 0.01). The median follow-up was 3 months (range = 1–120). Eighteen of the 27 patients who underwent partial surgery had an ultrasound examination during follow-up. Five (18 %) of them had macroscopic residue. Conclusion This study showed that MIS for ATD is feasible with a low rate of complications. Patients with prenatal diagnosis should have prompt surgery to prevent symptoms, despite a high rate of conversion in small infants.

To compare the perception of global cardiovascular risk (GCVR) in hypertensive patients when followed by a male GP (MGP) or a female GP (FGP). This is cross-sectional study carried out in 2003 on 2 979 MGPs and 562 FGPs spread throughout France. The patients included were hypertensive patients either treated or untreated, uncontrolled (BP≥140/90 mmHg) with at least one other cardiovascular risk factor (CVRF) associated. GCVR of patients was both calculated according to European Society Hypertension (ESH) guidelines and subjectively estimated by the GP as “low”, “moderate”, “high” or “very high”. We included in this study 11 770 patients, mean age was : 63.7 ±11.2 and 54.1 % were men. Mean BP was 157±13/90±9 mmHg, hypertension was treated in 92 % of cases. Main other risk factors were dyslipidaemia (58 %), diabetes (25 %) and tobacco use (24 %). A target organ damage was reported among 38 % of patients and a cardiovascular disease among 29 %. According to ESH guidelines, the calculated GCVR was respectively “moderate” in 23.7 % of patients, “high” in 47.5 % and “very high” in 28.8 %. MGPs were following more patients at “very high risk” (29.2 % vs 26.7 % for FGPs). Basically the GCVR was underestimated since, according to the GP's “subjective estimation”, there was only 11.2 % of patients at “very high risk”, 38.1 % at “high risk”, 40.7 % at “moderate risk” and 9.1 % at “low risk”(GCVR was not estimated for 0.9 % of patients). The overall agreement rate between the GP's estimation of GCVR and its calculation was of 43.5 % (45 % for FGPs and 43.2 % for MGPs). The GCVR in uncontrolled hypertensive patients remains underestimated by GPs, without any significant difference between MGPs and FGPs although ESH guidelines have been extensively diffused.

P-202 Key Words: Angiotensin Receptor Blocker, Hypertension, Fixed Combination

The study objective was to assess by means of automated home blood pressure recordings the effect of HCTZ 25 mg in combination with valsartan 160 mg in hypertensive patients who were inadequately controlled with a fixed combination of ARB at a high dose and HCTZ 12,5 mg. Multicentre, open study, including 171 hypertensives, treated for at least 6 weeks with HCTZ 12,5 mg in combination with irbesartan 300 mg or candesartan 16 mg and whose mean teletransmitted home automated systolic/diastolic blood pressure (SBP/DBP) was greater than 135/85. Following a 6-week treatment period with the fixed combination valsartan/HCTZ 160/25 mg, a second home BP recording was performed prior to the visit to the clinic. Hypertension had been known for longer than 5 years; mean age was 64 ± 11 years, mean body mass index 29 ± 5 kg/m2 and mean home SBP/DBP (TensioPhone®, Tensiomed, Budapest) was 152 ± 14/87 ± 10 mmHg at inclusion. BP data were automatically transmitted by phone to a data management center. Associated risk factors were frequent such as hypercholesterolemia in 39%, a family history of CVD in 21 % and diabetes in 15%. At the end of the treatment period with valsartan/HCTZ 160/25 mg, a further decrease of −6/−4 mmHg (p<0.001) was observed associated with a strict DBP control (<85 mmHg) in 58% and for SBP (<135 mmHg) in 26%. BP lowering was more important for SBP (−13;−5) and DBP (−10;−3) when baseline BP was >155/92 mmHg in comparison with the SBP lowering (−7;0) and DBP lowering (−4;0) observed when baseline values were <144/83 mmHg. Conversely, the intensity in BP lowering was comparable in men and women, in obese and lean patients, and in patients with or without metabolic syndrome. In addition, no significant metabolic disturbances were reported, in particular in potassium, glucose or creatinine. In hypertensive patients, not adequately controlled with a fixed combination of an ARB at a high dose and HCTZ 12,5 mg, the doubling of the HCTZ dose in combination with valsartan 160 mg led to a significant improvement in BP control without metabolic disturbances. The higher the baseline BP values were the greater the lowering effect was. Am J Hypertens (2004) 17, 107A–108A; doi: 10.1016/j.amjhyper.2004.03.277