Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

Prospective survey of indoor fungal contamination in hospital during a period of building construction.

An 18-month survey of indoor fungal contamination was conducted in one haematology unit during a period of construction work. Air was sampled with a portable Air System Impactor and surfaces with contact Sabouraud plates. During this survey the mean concentration of viable fungi in air was 4.2 cfu/m(3) and that for surfaces was 1.7 cfu/plate. At the beginning of construction work, there were increases in airborne fungal spores (from 3.0 to 9.8 cfu/m(3)) in the unit, but concentrations did not exceed 10 cfu/m(3) during the 18-month period. The most frequently recovered airborne fungi were Penicillium spp. (27-38%), Aspergillus spp. (25%) and Bjerkandera adusta, a basidiomycete identified with molecular tools (7-12%). Blastomycetes accounted for more than 50% of the fungal flora on surfaces. Investigating the impact of a new air-treatment system (mobile Plasmair units), there were significant reductions in fungal contamination for the Plasmer -treated rooms, and in these rooms we observed the same level of fungal load whether construction work was in progress or not.

Reduced fungal contamination of the indoor environment with the Plasmair system (Airinspace).

Aspergillus spp. and other moulds cause life-threatening opportunistic infections in immunocompromised patients. Indoor contamination and construction work that liberate fungal spores are a major source of nosocomial aspergillosis. Dijon hospital is a tertiary care institution in northeast France undergoing construction work beside high-risk clinical units. To determine the impact of this activity, a surveillance programme was implemented one year before building work began in order to establish baseline levels of contamination. Air and surface fungal contamination in adult and paediatric haematology units were prospectively examined following use, or not, of a new air-treatment system with mobile Plasmair units (Airinspace). There were significant reductions in overall fungal contamination for the Plasmair treated rooms for air and surface samples in both clinical units. Plasmair treatment also significantly reduced A. fumigatus in the air. These data suggest that Plasmair units may provide an efficient method of reducing indoor fungal contamination in hospitals.

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children.

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.

Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia.

PURPOSE: In patients with neutropenia, thoracic computed tomography (CT) halo and air-crescent signs are recognized as major indicators of invasive pulmonary aspergillosis (IPA). Nevertheless, the exact timing of CT images is not well known. PATIENTS AND METHODS: Seventy-one thoracic CT scans were analyzed in 25 patients with neutropenia with surgically proven IPA. RESULTS: On the first day of IPA diagnosis with early CT scan (d0), a typical CT halo sign was observed in 24 of 25 patients. At that time, the median number of thoracic lesions was two (range, one to six), and pulmonary involvement was bilateral in 12 cases. The halo sign was present in 68%, 22%, and 19% of cases on d3, d7, and d14, respectively. Similarly, the air-crescent sign was seen in 8%, 28%, and 63% of cases on the same days. Otherwise, a nonspecific air-space consolidation aspect was seen in 31%, 50%, and 18% of cases on the same days. The analysis of calculated aspergillary volumes on CT showed that, despite antifungal treatment, the median volume of lesions increased four-fold from d0 to d7, whereas it remained stable from d7 to d14. Overall, 21 patients (84%) were cured by the medical-surgical approach. CONCLUSION: In patients with neutropenia, CT halo sign is a highly effective modality for IPA diagnosis. The duration of the halo sign is short, and it demonstrates the value of early CT. The increase of the aspergillosis size on CT in the first days after IPA diagnosis is not correlated with a pejorative immediate outcome when using a combined medical-surgical approach.

Adverse outcome of infants with metastatic neuroblastoma, MYCN amplification and/or bone lesions: results of the French society of pediatric oncology.

To assess the relevance of MYCN amplification and bone lesions in stage 4 neuroblastoma (NB) in infants aged <1 year, 51 infants with stage 4 NB were enrolled. Three groups of patients were defined according to the type of metastases and the resectability of the primary tumour. Group I comprised 21 infants with radiologically detectable bone lesions, Group II 22 patients with an unresectable primary tumour and Group III eight patients with only metaiodobenzylguanidine (MIBG) skeletal uptake. MYCN oncogene content was assayed in 47/51 tumours and found to be amplified in 17 (37%). The 5-year event-free survival (EFS) rate of these 51 infants was 64.1% (+/- 7.1%). In a univariate analysis, bone lesions, MYCN amplification, urinary vanillylmandelic/homovanillic acid ratio and serum ferritin levels adversely influenced outcome. In the multivariate analysis, radiologically detectable bone lesions were the most powerful unfavourable prognostic indicator: the EFS rate was 27.2% for these infants compared to 90% for infants without bone lesions (P<0.0001). Our data emphasize the poor prognosis of infants affected by stage 4 NB with bone lesions, especially when associated with MYCN amplification. Given the poor results in this group whatever the treatment, new therapeutic approaches need to be investigated in the future.

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.

PURPOSE: The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients. PATIENTS AND METHODS: Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively. RESULTS: The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value < 9 g/L were associated with better outcome. CONCLUSION: In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.

[Dopa-sensitive muscular dystonia. Segawa's syndrome. A case report]. / Dystonie musculaire dopa-sensible. Syndrome de Segawa. A propos d'un cas.

A four-year-old girl developed difficulty in walking due to dystonia of the right then left foot, rest tremor in both hands, and rigidity. These symptoms worsened upon exertion and in the evening and were remarkably responsive to L. dopa, suggesting the diagnosis of fluctuating muscular dystonia or Segawa syndrome.

[Paraganglioma of the carotid body. Apropos of a case in a 14-year-old child]. / Paragangliome du corpuscule carotidien. A propos d'un cas chez un enfant de 14 ans.

Carotid body tumors are encountered infrequently. We report a case of a fourteen year old boy presenting an inflammatory biologic syndrome with a right neck mass. The diagnosis was first an Hodgkin disease but the surgical approach and histological examination of the neck mass conclude to a benign carotid body tumor. A subadventitial excision allowed a complete recovery with one year follow up. The diagnosis of these tumors is essentially made by arteriography. They are benign in most of the cases but sometimes need for a vascular reconstructive surgery in very extended forms.

[Advantages of a single daily dose of sodium valproate in the child]. / Avantages d'une dose quotidienne unique de valproate de sodium chez l'enfant.

This study was aimed at testing the efficacy and innocuousness of a single dose of sodium valproate (SV) for the treatment of epilepsy, as compared with 3 daily doses. It was tested on 35 children, 5 to 15 years of age, presenting with the idiopathic form of generalized epilepsy. At the end of one year of treatment with 20 mg/kg/day of SV in 3 daily doses, the children were given a single dose at 8 PM daily. Every 3 months for a period of one year, patients were examined in order to monitor the clinical efficacy and side effects, liver function tests and serum levels of SV at 9 AM and 6 PM. Twenty patients who were well controlled with 3 daily doses had no fits with the single dose treatment. Ten patients, who had had one fit every 6 months during the observation year had no convulsions during the year on a single dose: however, 5 others who had had one fit every 6 months with 3 doses, had fits with the same frequency with the single dose treatment. There were no side effects. SV plasma levels at 9 AM were always higher than those at 6 PM. The efficacy of a single dose may result from the action of SV which increases the intra-cerebral levels of GABA, which are delayed and prolonged.

[Epilepsy with rolandic paroxysms and migraine, a non-fortuitous association. Results of a controlled study]. / Epilepsie à paroxysmes rolandiques et migraine, une association non fortuite. Résultats d'une étude contrôlée.

The incidence of migraine was studied in 4 groups of patients: patients with centro-temporal epilepsy, patients with absence of epilepsy, patients with partial epilepsy, and non-epileptic patients with a history of cranial trauma. Migraines were present in 62% of the patients with centro-temporal epilepsy, 34% of the patients with absence of epilepsy, 8% of the patients with partial epilepsy and 6% of the patients with cranial trauma. These results suggest that the association of centro-temporal epilepsy and migraine is non-fortuitous as well as, to a lesser degree, absence of epilepsy and migraine. The authors discuss the role of serotonin in the association epilepsy-migraine and suggest that centro-temporal epilepsy might be a feature for the diagnosis of migraine.

[Collaboration between child psychiatry and medical genetics. Genetic diseases with an atypical beginning]. / Collaboration pédo-psychiatrie--génétique médicale. Maladies génétiques à début atypique.

When a children psychiatrist, faced to atypical psychological troubles, comes up against difficulties in establishing a precise diagnosis, he may consider a genetic etiology and ask for a genetic consultation. He may encounter many problems when he suggests this specialized consultation to the parents. These have often been prepared for a long time to the necessity of a psychiatric therapy in order to cure their child's troubles. The geneticist's diagnosis will induce the parents and the psychiatrist to have a different look on the child and mostly will set limits to the possibilities of treatment.

Coffin-Lowry syndrome: a multicenter study.

The Coffin-Lowry syndrome is an inherited syndrome of mental retardation, characteristic facies and skeletal anomalies. The occurrence of severe manifestations in males, with no instance of male-to-male transmission, suggests an X-linked inheritance. The paper describes seven families from five European Centers.

[Respiratory syncytial virus infections in newborn infants]. / Infections à virus respiratoire syncytial du nouveau-né.

Twenty-three of 23 neonates were contaminated in the course of an outbreak of respiratory syncytial virus (RSV) in a neonatal care unit. Symptoms among 22 infected symptomatic infants included rhinitis (n = 21), dyspnea (n = 19), cough (n = 17), apnea (n = 5), seizures (n = 3), fever (n = 3). Five patients presented with severe respiratory distress. The occurrence of non-obstructive apnea was significantly correlated with a history of respiratory disease, RSV infection during the first 15 days of life and the severity of lower respiratory tract RSV infection.

[Thrombopenia during treatment with heparin. Apropos of a case]. / Thrombopénie au cours d'un traitement par l'héparine. A propos d'une observation.

A heparin-induced case of thrombocytopenia occurring in an adolescent is reported. Its physiopathology and treatment are discussed. Complications are not only bleeding, but also arterial or venous thrombosis. Usually, stopping of heparin therapy is necessary, but sometimes the treatment should be followed with low molecular weight heparin.