Implication of the SH3TC2 gene in Charcot-Marie-Tooth disease associated with deafness and/or scoliosis: Illustration with four new pathogenic variants.

The autosomal recessive demyelinating form of Charcot-Marie-Tooth can be due to SH3TC2 gene pathogenic variants (CMT4C, AR-CMTde-SH3TC2). We report on a series of 13 patients with AR-CMTde-SH3TC2 among a French cohort of 350 patients suffering from all type of inheritance peripheral neuropathy. The SH3TC2 gene appeared to be the most frequently mutated gene for demyelinating neuropathy in this series by NGS. Four new pathogenic variants have been identified: two nonsense variants (p.(Tyr970*), p.(Trp1199*)) and two missense variants (p.(Leu1126Pro), p.(Ala1206Asp)). The recurrent variant p.Arg954* was present in 62%, and seems to be a founder mutation. The phenotype is fairly homogeneous, as all these patients, except the youngest ones, presented scoliosis and/or hearing loss.

[Transverse reductional anomaly and atypical fibrodysplasia ossificans progressiva: A case diagnosed late]. / Anomalie réductionnelle transverse et fibrodysplasie ossifiante progressive atypique, à propos d'un cas de diagnostic tardif.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by the association of congenital bone abnormalities and extraskeletal ossification flare-ups occurring in muscles and fasciae. Early diagnosis is important to prevent ossification flare-ups, but some atypical presentations can lead to errors in diagnosis and therefore delay. Here, we report on a case of an atypical presentation of FOP in a girl, in whom prominent transverse reductional abnormalities delayed diagnosis. The patient developed extraskeletal ossifications and progressive fibrosis that led to motor restrictions. Since early diagnosis is important, we discuss the clinical presentations of FOP and the differential diagnoses.

[Clinical signs of Marfan syndrome in children under 10 years of age]. / Signes cliniques évocateurs d'un syndrome de Marfan chez l'enfant de moins de 10ans.

Diagnosing Marfan syndrome in young children is difficult because of the great variability of expression of the disease and because the phenotype evolves over the life course. The goal of this retrospective study was to describe the first clinical symptoms in children under 10 years of age with Marfan syndrome and to evaluate the pertinence of the new 2010 Ghent criteria in comparison with the 1996 criteria. Seventeen patients under 10 by the time of the first medical examination were included. All children had an FBN1 gene mutation that was secondarily demonstrated. Clinical data including ophthalmological, cardiac, and orthopaedic examinations obtained during the first medical examination were analyzed. The most frequent abnormalities encountered were high arched palate (82%), arachnodactyly (71%), and flatfoot (59%). Aortic aneurysm (47%) and ectopic lens (35%) were also seen at the time of diagnosis. According to the 2010 Ghent criteria, the diagnosis of Marfan syndrome could be obtained in 71% of patients after identification of the mutation of the FBN1 gene, whereas only 59% of patients were diagnosed using the older criteria. All organs can be affected during childhood. An early diagnosis is essential in order to set up specific management.

[Deadly nightshade (Atropa belladonna) intoxication in a 2-year-old child]. / Un cas d'intoxication aiguë par la belladone (Atropa belladona) chez une enfant de 2ans.

Plant intoxications account for 5% of all intoxication cases according to French anti-poison centers. We report an uncommon case of intoxication with deadly nightshade (Atropa belladonna) in a 2-year-old child. The child presented at the ER with an atropinic syndrome, both central and peripheral, after ingestion of wild berries a few hours before. The fruit and leaves brought in by the mother allowed the anti-poison center to identify belladonna, in agreement with clinical findings. The child was kept in the intensive care unit for 48 h and progression was favorable with symptomatic treatment.

[Lumpectomy vs oncoplastic surgery for breast-conserving therapy of cancer. A prospective study about 99 patients]. / Traitement conservateur des cancers du sein: zonectomie vs oncoplastie. Etude prospective à propos de 99 patientes.

UNLABELLED: The integration of oncoplastic techniques with a concomitant contralateral symmetrization procedure is a novel surgical approach that allows wide excisions and prevents breast deformities. AIM OF THE STUDY: This prospective study was undertaken to compare the accuracy of breast resection, between standard narrow lumpectomy and oncoplastic surgery. PATIENTS AND METHODS: Ninety-nine consecutive women undergoing breast cancer resection were enrolled in a prospective study comparing oncoplastic surgery (42 women) and standard lumpectomy (57 women). The size of the glandular resection, the width of the nearest margins, the ratio of clear margins and the need for further surgery were recorded. RESULTS: The oncoplastic approach resulted in significantly greater glandular resection and wider free histological margins than did standard lumpectomy. The need for re-exicsional surgery was significantly lower in the oncoplastic group than in the lumpectomy group. Furthermore, a trend towards fewer secondary mastectomies was seen for the oncoplastic approach versus standard lumpectomy. CONCLUSIONS: The use of oncoplastic techniques and concomitant symmetrization of the contralateral breast allows extensive resections for conservative treatment of breast carcinoma achieves accurate tumour resection and reduces the need for further surgery.

[Ovarian cancer: incidence and mortality in France]. / Les cancers de l'ovaire: incidence et mortalité en France.

OBJECTIVES: To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000. MATERIALS AND METHODS: Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates. RESULTS: With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers. CONCLUSION: The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

Pre-operative arterial embolisation of a uterine rhabdomyosarcoma in a 14-year-old girl.

We report a young patient suffering from a uterine rhabdomyosarcoma. Particular features of the present case are: accuracy of the tumour spread evaluation performed by MRI of the pelvis; and the use of pre-operative arterial embolisation. The present multimodal management highlights the usefulness of cooperation between surgeons and radiologists in lowering operative bleeding and finally permitting uterine conservation.

[Surrogate mothers and ovarian transposition: two attitudes to be considered in young women with cervical carcinoma. A case report]. / Mère porteuse et transposition ovarienne: deux attitudes à considérer dans le cancer du col utérin de la femme jeune. A propos d'un cas.

In cases of cervical cancer, there are 2 major advantages to preserving the ovaries, with or without transposition: hormone function is maintained during subsequent cancer treatment and patient quality of life is improved. We report the first case of pregnancy in a surrogate mother following stimulation of a transposed ovary before irradiation and chemotherapy for a squamous cell carcinoma of the uterine cervix. Because of the wide dissemination of information on the technical progress in this area, patients are now in a position to make therapeutic choices that are no longer guided by strictly medical considerations.

[Evaluation and treatment of endometrial cancer]. / Evaluation et traitement des cancers de l'endomètre.

Endometrial cancer is the most common gynaecologic cancer and its incidence increases with age. Prognosis is good because in over 80% of cases the cancer is discovered early. Preoperative work-up should include definition of the operability of such patients, who are often elderly with frequent co-morbidity. Preoperative evaluation and operative findings allow guiding the treatment and evaluating the prognosis. Main determinants are local extension, penetration into the myometrium, histologic stage of the tumour and involvement of lymph modes or peritoneum. Surgery is the first approach since it establishes the evaluation and comprises the first step of treatment. When necessary, subsequent treatment uses irradiation. Treatment with hormones or antimitotic drugs is less effective and is used for forms that are locally advanced, metastatic or recurrent after initial treatment.

Successful in vitro fertilization-surrogate pregnancy in a patient with ovarian transposition who had undergone chemotherapy and pelvic irradiation.

OBJECTIVE: To present a case of IVF-surrogate pregnancy in a patient with ovarian transposition who had undergone chemotherapy and total pelvic irradiation. DESIGN: Case report. SETTING: Teaching hospital. PATIENT(S): A 29-year-old woman who had undergone Wertheim's hysterectomy for a bulky carcinoma of the uterine cervix. INTERVENTION(S): Ovarian transposition before chemotherapy and total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to the surrogate mother. MAIN OUTCOME MEASURE(S): Results of the IVF cycle. RESULT(S): A twin pregnancy at the first cycle and two live newborns. CONCLUSION(S): This is the first reported case of ovulation induction and oocyte retrieval performed on a transposed ovary.

The effects of mifepristone on uterine sensitivity to oxytocin and on fetal heart rate patterns.

OBJECTIVE: To compare the incidences of tachysystole, hypertonia and fetal heart rate (FHR) abnormalities in women treated by mifepristone plus prostaglandins (PGs), mifepristone alone or PGs alone for an unfavourable cervix. STUDY DESIGN: In this retrospective study, all women between 37 and 42 weeks were eligible for the study if they had undergone cervical ripening prior to labour induction. In group 1, the women were treated with mifepristone plus PGs (n=103). Group 2 women were treated with mifepristone alone (n=96) and group 3 women with PGs alone (n=100). Incidences of tachysystole, hypertonia and FHR abnormalities were compared. RESULTS: During induction of labour, tachysystole and hypertonia occurred more frequently in women treated with mifepristone. Severe bradycardia and recurrent late decelerations were more frequent after the initiation of oxytocin in groups 1 and 2 than in group 3. CONCLUSIONS: In this study, mifepristone increased the incidences of tachysystole, hypertonia and FHR abnormality.

[Standards, options, and recommendations for the radiotherapy of patients with endometrial cancer. FNCLCC (National Federation of Cancer Campaign Centers) and CRLCC (Regional Cancer Campaign Centers)]. / Standards, Options et Recommandations pour la radiothérapie des patientes atteintes de cancer de l'endomètre.

OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

Dissociated overexpression of cathepsin D and estrogen receptor alpha in preinvasive mammary tumors.

The role of estrogen as a promoter agent of sporadic breast cancer has been considered by assaying, in benign breast disease (BBD) and in situ carcinomas (CIS), 2 markers, the estrogen receptor alpha (ERalpha) and cathepsin D (cath-D) involved in estrogen action on mammary tissue. ERalpha and cath-D were assayed by quantitative immunohistochemistry using an image analyzer in 170 lesions of varying histological risk (94 BBD and 76 CIS), and in "normal" glands close to these lesions. The ERalpha level increased significantly in proliferative BBD with atypia (P < .001), in non-high-grade CIS (P < .001), and in adjacent "normal" glands. ERalpha level was decreased in high-grade ductal CIS (DCIS) and also in adjacent "normal" glands. Cath-D level increased in ductal proliferative BBD (P < or = .01) and in high-grade DCIS (P < or = .003), but not in the other lesions. After menopause, ERalpha level was increased (P = .012) but not cath-D level. According to Mac Neman test, the high-grade DCIS were predominantly ERalpha negative and cath-D positive (P = .0017), and the other CIS were predominantly ERalpha positive and cath-D negative (P = .0002). The 2 markers are overexpressed early in premalignant lesions, but independently. This dissociation suggests a branched model of mammary carcinogenesis involving 1 estrogen-independent pathway with high cath-D and low ERalpha levels (including high-grade DCIS) and 1 estrogen-dependent pathway, with high ERalpha level (including proliferative BBD with atypia and low-grade DCIS). We propose that ERalpha-negative breast cancers may develop directly from high-grade DCIS and that ERalpha assay in preinvasive lesions should be considered in prevention trials with antiestrogens.

Rheological properties of fetal red cells with special reference to aggregability and disaggregability analyzed by light transmission and laser backscattering techniques.

Blood viscosity factors and fetal erythrocyte aggregability were investigated with light transmission (Myrenne device) during a cross-sectional study of blood drawn in utero by cord venepunctures in 119 normal fetuses between 18 and 39 weeks gestation. There was a progressive increased blood viscosity at native hematocrit (p < 0.01) explained by a gradual increase in both hematocrit (from 33% to 40%, p < 0.05) and Dintenfass' 'Tk' RBC rigidity index (p < 0.05), while plasma viscosity remained constant at 1.18 +/- 0.01 mPa x s as well as the h/eta ratio (188.4 +/- 2.7 mPa(-1) x s(-1)). The RBC aggregation index 'M' remained almost equal to zero (mean value: 0.04 +/- 0.01) before 32 wk gestation and then increased (p < 0.05) until delivery. The upper physiological limit for this parameter before 32 wk (mean +/- 2 SD) is 0.18. The RBC aggregation index 'M1' remained constant during pregnancy at 2.98 +/- 0.26, i.e., the upper physiological limit for this parameter during the intrauterine life (mean +/- 2 SD) is 7.85. Both fibrinogen (r = 0.479, p < 0.05) and albumin (r = 0.494, p < 0.01) correlated with time so that the albumin/fibrinogen ratio remained stable. We then studied with the laser retrodiffusion technique the venous blood of 20 women (18-43 yr, 37-40 wk gestation) and the cord blood of their newborns at birth, comparing RBC aggregation of: mothers (M), maternal RBCs resuspended on newborn plasma (MF), newborn RBCs resuspended on maternal plasma (FM), and newborns (F). Aggregability is higher in M (RBC aggregation time M < MF < FM < F; p < 0.01); RBC aggregation index at 10 s M > MF > FM > F; p < 0.01), with in turn the symmetric inverse picture for the partial disaggregation threshold (M > MF = FM > F). Thus RBC disaggregability is higher in newborns, and suspensions on maternal and newborn plasma suggest that half of this difference in aggregability (and disaggregability) between fetal and adult blood results from plasma factors and another half from erythrocytes.

Aggregability and disaggregability of erythrocytes in women suffering from ovarian cancer: evidence for an increased disaggregation threshold.

In order to further characterize the alterations of erythrocyte aggregation described in ovarian cancer, we measured it with laser backscattering in eleven women suffering from ovarian cancer (mean age: 44.7 +/- 3.6, extreme values: 28-61 yr) compared with thirteen matched control women. Blood rheology exhibited a wide variability in cancer patients, with some unusually high values of plasma viscosity and/or RBC aggregation in individual cases. The only significant differences were found for the RBC disaggregation threshold which was higher in patients than in controls (78.06 +/- 10.14 vs 52.6 +/- 3.15 s(-1), p < 0.05), while hematocrit was lower (34.45 +/- 1.42 vs 38.23 +/- 0.75, p < 0.05). A negative correlation between hematocrit and corrected blood viscosity on the whole sample of subjects (r = 0.454, p < 0.05) indicates that hematocrit is decreased in subjects prone to high viscosity, resulting in similar values of apparent blood viscosity in controls and patients. Thus, a lower disaggregability of RBCs is evidenced in women with ovarian cancer, as well as a tendency to blood hyperviscosity compensated by a reduction of hematocrit which suggests that there may be some degree of 'viscoregulation'.

100 mg acetylsalicylic acid acutely decreases red cell aggregation in women taking oral contraceptives.

Since oral contraceptives (OC) are known to impair blood fluidity and to increase the risk of venous and arterial thrombosis, while acetylsalicylic acid (ASA) decreases the thrombotic risk and modifies some rheologic parameters, we compared the hemorheologic effects of ASA on blood rheology between women treated by OC and women who never received this medication. 25 women under OC were compared to 25 matched women who had never used OC. Blood viscosity (MT90 viscometer) and RBC aggregation (Myrenne aggregometer and AFFIBIO erythroaggregometer) were measured before and 1 hr after women received per os 100 mg ASA, after an overnight fast. The only significant difference between women under OC and controls was an increased RBC aggregation ('M' index +28%, p < 0.04; Affibio aggregation time -21%, p < 0.03). On the whole sample of 50 women as well as in the subgroup of women under OC, ASA decreased RBC partial disaggregation threshold (-1.7%, p < 0.01). These results confirm that RBC aggregation is increased under OC and suggest that 100 mg ASA acutely induces a partial reversal of this RBC hyperaggregation.