Lujan-Fryns syndrome (mental retardation, X-linked, marfanoid habitus)

The Lujan-Fryns syndrome or X-linked mental retardation with marfanoid habitus syndrome is a syndromal X-linked form of mental retardation, affecting predominantly males. The prevalence is not known for the general population. The syndrome is associated with mild to moderate mental retardation, distinct facial dysmorphism (long narrow face, maxillary hypoplasia, small mandible and prominent forehead), tall marfanoid stature and long slender extremities, and behavioural problems. The genetic defect is not known. The diagnosis is based on the presence of the clinical manifestations. Genetic counselling is according to X-linked recessive inheritance. Prenatal testing is not possible. There is no specific treatment for this condition. Patients need special education and psychological follow-up, and attention should be given to diagnose early psychiatric disorders

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Surveying the Down syndrome mouse model resource identifies critical regions responsible for chronic otitis media

Chronic otitis media (OM) is common in Down syndrome (DS), but underlying aetiology is unclear. We analysed the entire available mouse resource of partial trisomy models of DS looking for histological evidence of chronic middle-ear inflammation. We found a highly penetrant OM in the Dp(16)1Yey mouse, which carries a complete trisomy of MMU16. No OM was found in the Dp(17)1Yey mouse or the Dp(10)1Yey mouse, suggesting disease loci are located only on MMU16. The Ts1Cje, Ts1RhR, Ts2Yah, and Ts65Dn trisomies and the transchomosomic Tc1 mouse did not develop OM. On the basis of these findings, we propose a two-locus model for chronic middle-ear inflammation in DS, based upon epistasis of the regions of HSA21 not in trisomy in the Tc1 mouse. We also conclude that environmental factors likely play an important role in disease onset

Angelman syndrome (AS, MIM 105830)

Angelman syndrome (AS) is a distinct neurogenetic syndrome, first described in 1965. The phenotype is well known in infancy and adulthood, but the clinical features may change with age. The main clinical characteristics include severe mental retardation, epileptic seizures and EEG abnormalilties, neurological problems and distinct facial dysmorphic features. Behavioural problems such as hyperactivity and sleeping problems are reported, although these patients present mostly a happy personality with periods of inappropriate laughter. Different underlying genetic mechanisms may cause AS, with deletion of chromosome 15 as the most frequent cause. Other genetic mechanisms such as paternal uniparental disomy, imprinting defect and mutation in the UBE3A gene are present in smaller groups of patients with AS. As the recurrence risk can be up to 50%, the clinical diagnosis of AS should be confirmed by laboratory tesing, and genetic counselling should be provided. Treatment of seizures, physical therapy or other intervention strategies are helpful to ameliorate the symptoms