1p36 deletion syndrome: Review and mapping with further characterization of the phenotype,a new cohort of 86 patients

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.     

The role of pancreatic venous sampling in the localization of occult insulinomas

The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production.     

Differential mechanisms of impairment of remote memory in Alzheimer's and frontotemporal dementia

This paper describes retrograde memory performances of 12 Alzheimer's disease (AD) patients and 12 frontotemporal dementia (FTD) patients. First of all, we observed that FTD and AD patients did not differ for language tests (verbal fluency tests and oral denomination 80), for semantic memory tests, for logical memory test and Benton visual memory test and differed for anterograde verbal memory and frontal tests. Concerning retrograde memory, there was no difference between AD and FTD patients in retrograde memory scores (autobiographical memory interview, Crovitz's task, French public events interview battery) and both FTD and AD patients exhibited a retrieval deficit in their remote memory. We observed that the mechanisms of remote memory deficit was different in FTD and in AD patients. We observed no classical paradigm of Ribot for FTD patient's remote informations, and they appeared to have lost of access to memories and executive difficulties. In AD, the results indicated these patients' ability to learn new information and to search semantic memory failed.     

Le syndrome de Smith-Magenis

Smith-Magenis syndrome is caused by a 17p11.2 deletion. It associates mental retardation, facial dysmorphism and brachydactyly; aberrant behavior and major sleep problems are present in 70% of the cases. It is probably under-diagnosed because the facial abnormalities are mild and the behavioral problems with hyperactivity and self-injuries are dominant, leading to the diagnosis of psychiatric pathology. However these behavioral problems are sufficiently characterized to allow the diagnosis of the syndrome and look for a 17p11.2 microdeletion. Otorhinolaryngologic, ophtalmologic, cardiac and renal abnormalities can be associated and their evaluation is necessary. Smith-Magenis syndrome is considered as a contiguous gene syndrome. Genes have been mapped and isolated to the critical region, but their participation in the pathogenesis of the syndrome remains unclear.     

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Prenatal X-irradiation increases GFAP- and calbindin D28k-immunoreactivity in the medial subdivision of the nucleus of solitary tract in the rat

Glial fibrillary acidic protein- (GFAP) and calbindin D28k-immunoreactivity (IR) were investigated in the medial subdivision of the nucleus of the solitary tract (mNST) of prenatally X-irradiated rats. Pregnant rats were exposed to a single whole-body X-irradiation on day 11 or 16 of gestation at a dose of 1. 3 Gy. The offspring were killed at 7-14 days of age for the immunohistochemical observations. Rat pups showed strong GFAP-IR at the level rostral to the obex when receiving X-rays on day 11 of gestation, with hypertrophy of astrocyte cell bodies and cytoplasmic processes, but weak GFAP-IR when receiving X-rays on day 16 of gestation. Calbindin D28k-IR was stronger in the animals receiving X-rays on day 11 or 16 of gestation compared to that in the control animals. In the present study, the increase of GFAP- and calbindin D28k-IR cells in the mNST might indicate that adaptative mechanisms are taking place to preserve integrated nervous system function and possibly, to provide neuroprotection.     

Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.     

One‐year survival of demented stroke patients: data from the Dijon Stroke Registry,France (1985–2008)

Background and purpose: Dementia is a frequent condition after stroke that may affect the prognosis of patients. Our aim was to determine whether post‐stroke dementia was a predictor of 1‐year case‐fatality and to evaluate factors that could influence survival in demented stroke patients. Methods: From 1985 to 2008, all first‐ever strokes were recorded in the population‐based stroke registry of Dijon, France (150 000 inhabitants). Dementia was diagnosed during the first month following stroke, according to DSM‐III and DSM‐IV criteria. Survival was evaluated at 1 year and multivariate analyses were performed using Cox proportional hazards to identify independent predictive factors. Results: We recorded 3948 first‐ever strokes. Among these stroke patients, 3201 (81%) were testable, and of these, 653 (20.4%) had post‐stroke dementia (337 women and 316 men). Demented patients had lower 1‐year survival than patients without dementia (82.9% vs. 86.9%, P = 0.013). However, in multivariate analysis, dementia did not appear as an independent predictor of 1‐year death. In demented stroke patients, age >80 years old, severe handicap at discharge, recurrent stroke within the first year and subarachnoid haemorrhage were associated with a higher risk of 1‐year death, and the risk was lower in the study period 2003–2008. Conclusions: Dementia after stroke is not independently associated with an increased risk of death at 1 year. In recent years, 1‐year case‐fatality decreased in demented as well as in and non‐demented patients suggesting that improvements in the management of stroke also benefited the most fragile patients.