Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases.

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.

Prevalence of peripheral arterial disease in high-risk patients using ankle-brachial index in general practice: a cross-sectional study.

AIMS: The deleterious nature of peripheral arterial disease (PAD) is compounded by a status of underdiagnosed and undertreated disease. We evaluated the prevalence and predictive factors of PAD in high-risk patients using the ankle-brachial index (ABI). METHODS: The ABI was measured by general practitioners in France (May 2005-February 2006) in 5679 adults aged 55 years or older and considered at high risk. The primary outcome was prevalence of PAD (ABI strictly below 0.90). RESULTS: In all, 21.3% patients had signs or symptoms suggestive of PAD, 42.1% had previous history of atherothrombotic disease and 36.6% had two or more cardiovascular risk factors. Prevalence of PAD was 27.8% overall, ranging from 10.4% in patients with cardiovascular risk factors only to approximately 38% in each other subgroup. Prevalence differed depending on the localization of atherothrombotic events: it was 57.1-75.0% in patients with past history of symptomatic PAD; 24.6-31.1% in those who had experienced cerebrovascular and/or coronary events. Regarding the classical cardiovascular risk factors, PAD was more frequent when smoking and hypercholesterolemia history were reported. PAD prevalence was also higher in patients with history of abdominal aortic aneurysm, renal hypertension or atherothrombotic event. Intermittent claudication, lack of one pulse in the lower limbs, smoking, diabetes and renovascular hypertension were the main factors predictive of low ABI. CONCLUSIONS: Given the elevated prevalence of PAD in high-risk patients and easiness of diagnosis using ABI in primary care, undoubtedly better awareness would help preserve individual cardiovascular health and achieve public health goals.

Progressive symmetrical erythrokeratoderma: report of a Turkish family and evaluation for loricrin and connexin gene mutations.

We report here the first Turkish patient with progressive symmetric erythrokeratoderma. The patient's skin lesions appeared in the axillae at 3 months of age, and gradually spread to other flexural areas and to the trunk. Dermatological examination of the boy at 3.5 years of age revealed symmetric, hyperkeratotic plaques with erythematous outlines on the neck, wrists, armpits, trunk and posterior knees. The histopathological changes were nonspecific, including marked hyperkeratosis, irregular acanthosis, focal papillomatosis and perivascular lymphocytic infiltrates. Molecular studies of the loricrin (LOR), connexin 31 (GJB3) and connexin 30.3 (GJB4) genes did not identify a disease-causing mutation. These results further underline the genetic heterogeneity of the erythrokeratodermas.

[Influence of percutaneous coronary intervention in non ST-elevation acute coronary syndromes on prescription of secondary prevention medications. Data from the S-Témoin Registry]. / Prevention secondaire après syndrome coronaire aigu sans sus-décalage de ST en fonction de l'utilisation de l'angioplastie coronaire: l'étude S-Témoin.

BACKGROUND: The interaction between the use of percutaneous coronary intervention (PCI) for non-ST-elevation acute coronary syndromes and the use of secondary prevention medications was analysed in the French S-Témoin Registry. METHODS: The population consisted of 2433 patients seen by their cardiologists at an outpatient clinic 2-12 months after non ST-elevation ACS; the survey was carried out from September 2004 to April 2005. RESULTS: Overall, patients undergoing PCI (75% of the population) had higher levels of prescription of recommended secondary prevention medications. Multivariate logistic regression analysis showed that the use and type of coronary intervention (drug eluting versus bare metal stents) was an independent correlate of the use of dual antiplatelet therapy. In addition, time from the acute episode was also a strong correlate of dual antiplatelet therapy. Statins were also more often used in patients with PCI. CONCLUSION: Patients not treated with PCI are less likely to receive appropriate secondary prevention medications after non ST-elevation acute coronary syndromes. Specific efforts should be directed towards these patients, in particular as regards the prescription of dual antiplatelet therapy.

Persistent hyperinsulinaemic hypoglycaemia of infancy: case report.

Hyperinsulinism, although rare, is the most common cause of persistent hyperinsulinaemic hypoglycaemia in infancy. Because of persistent hypoglycaemia, serious difficulties are encountered in the long term management of this condition. A male neonate, after an uncomplicated full-term pregnancy, had been admitted to another hospital with convulsions on the third post-natal day. Meningitis had been suspected at that time and treated with phenobarbital and he had been discharged from the hospital. At three-months old he was referred to our department for persistent convulsions and lethargy. His parents were of 1st degree consanguinity. His blood glucose level was found to be 24 mg/dl (1.33 mmol/L). Because of the dangerously high insulin level during hypoglycaemia (insulin/glucose > 0.3), the absence of ketonuria, and the need for a high dose of glucose infusion (> 15 mg/kg/min) to achieve normoglycaemia and a glycaemic response to glucagon despite the hypoglycaemia, a diagnosis of persistent hyperinsulinaemic hypoglycaemia of infancy was made. Since maximal doses of prednisone, glucagon, diazoxide, octreotide and high infusion of glucose were ineffective in achieving normoglycaemia, a subtotal (80%) pancreatectomy was done. Postoperatively intermittent hypoglycaemic episodes continued. These were controlled with low doses of octreotide. Histology revealed diffuse adenomatous hyperplasia (nesidoblastosis). The boy is now in the sixth post-operative month and developing normally.