Clinical Phenotype in an Early-Onset French Pediatric Population: Charcot-Marie-Tooth's Disease Type 2A.

Charcot-Marie-Tooth's disease type 2A (MCT2A), induced by mutation of the mitofusin 2 (MFN2) gene represents the main cause of MCT2. The aim of this study is to provide details of the clinical and electromyographic phenotype of MCT2A in a pediatric population. We conducted a French multicenter retrospective study, including all children with a genetic diagnosis of MCT2A. Thirteen MCT2A children were included with a beginning of symptoms before the age of 10 years ("early-onset group"). We report two new mutations: c.1070 A → T (p.Lys357.Met) and c.280 C → G (p.Arg94Gly). The evolution of the disease is marked by a fast worsening for three patients with loss of motor autonomy, while the evolution is relatively stable for eight patients. The group of early-onset MCT2A seems more heterogeneous than previously described, with a nonconstant severe phenotype.

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.

[Airbag-related death in a toddler. A poorly known danger?]. / Conséquences fatales de l'ouverture d'un « airbag ¼ chez un nourrisson. Un danger méconnu ?

We report the case of an 8-month-old baby killed by the deployment of an airbag. He was correctly positioned, in a safety seat designed for his age class, on the passenger side, and rear-facing. The accident occurred at low speed, on the left front of the car, without provoking any harm to the mother who was driving the vehicle, but the impact led to airbag deployment. A CT scan showed an occipital fracture, hemorrhagic parenchymal contusions, subarachnoid hemorrhage and edema, which quickly led to fatal intracranial hypertension. Severe retinal hemorrhages were also noted. Brain death was declared 24h later. Both direct impact and violent projection of the head are involved in the severity of brain lesions. Retinal hemorrhages are similar to what is observed in shaken-baby syndrome. To our knowledge, this is the first French publication on this topic in childhood. In France, children are allowed to be positioned on the passenger side seat, but the airbag, if present, is supposed to be deactivated, which is not always possible. In recent cars, depowering the airbag is easy, with on/off switches, but these systems are not uniform between models. Moreover, it is very likely that this possibility is ignored by numerous parents. A widespread communication on this topic should be initiated in France to prevent such events. Banning infants from front passenger seats completely does not seem possible. Nevertheless, greater attention on the part of police departments and better information to drivers appear necessary.

[Extrarespiratory manifestations of Mycoplasma pneumoniae: a case report]. / Atteintes extra-respiratoires dues à Mycoplasma pneumoniae : à propos d'un cas.

Extrapulmonary manifestations of Mycoplasma pneumoniae are sometimes severe and may even be life-threatening. A 10-year-old patient was hospitalized due to a flu-like illness lasting 48 h with impaired general condition, after an extended stay in Africa. There was an inflammatory syndrome associated with hyponatremia, but malaria was negative. A triple antibiotic therapy with ceftriaxone, amikacin, and josamycin was started. The progression was marked by the appearance of hypoxemia pneumoniae associated with extrarespiratory manifestations. He initially presented with acute polyradiculoneuropathy, followed by thrombotic events associated with polyserositis, polyarthritis, a maculopapular rash, and then a hemophagocytic syndrome. Bacteriological samples isolated M. pneumoniae in nasopharyngeal secretions with a positive serology. The appropriate antibiotic therapy associated with corticosteroids and immunoglobulins led to clinical improvement and the patient progressed toward complete recovery. The pathogenesis of M. pneumoniae infection remains largely unknown. However, two main categories have been proposed. The lung injury is caused by the invasion of the respiratory epithelium, whereas the extrarespiratory manifestations are probably due to immunological disorders. The knowledge of extrarespiratory manifestations and their pathomechanisms allows further adjustments to therapeutic management.

[Multicentric study of medical care and practices in spinal muscular atrophy type 1 over two 10-year periods]. / Amyotrophie spinale type 1 : enquête multicentrique des pratiques de soins et d'accompagnement palliatif sur deux périodes successives de 10ans.

AIM: Questions about care practices and the role of palliative care in pediatric neurodegenerative diseases have led the Neuromuscular Committee of the French Society of Neurology to conduct a retrospective study in spinal muscular atrophy type 1, a genetic disease most often leading to death before the age of 1 year. MATERIAL AND METHODS: A retrospective multicenter study from pediatricians included in the reference centers of pediatric neuromuscular diseases was carried out on two 10-year periods (1989-1998 and 1999-2009). RESULTS: The 1989-1998 period included 12 centers with 106 patients, the 1999-2009 period 13 centers with 116 children. The mean age of onset of clinical signs was 2.1 months (range, 0-5.5 months), the median age at diagnosis was 4 months (range, 0-9 months) vs 3 months. The median age of death was 7.5 months (range, 0-24 months) vs 6 months. The care modalities included physiotherapy (90 %), motor support (61 % vs 26 % for the previous period), enteral nutrition by nasogastric tube (52 % vs 24 %), and 3.4 % of children had a gastrostomy (vs 1.8 %). At home, pharyngeal aspiration was used in 64 % (vs 41 %), oxygen therapy in 8 %, noninvasive ventilatory support in 7 %. The mean age at death was 8.1 months (range, 0-24 months) vs 7 months, the time from diagnosis to death was 4 months vs 3 months. Death occurred at home in 23 % vs 17 %, in a pediatric unit in 62 % vs 41 %. The use of analgesics and sedative drugs was reported in 60 % of cases: 40 % morphine (vs 18 %) and benzodiazepines in 48 % (vs 29 %). Respiratory support was limited mostly to oxygen by nasal tube (55 % vs 54 %), noninvasive ventilation in 9 % of the cases, and intubation and assisted mechanical ventilation (2 %). DISCUSSION AND CONCLUSION: These results confirm a change in practices and the development of palliative care in children with a French consensus of practices quite different from the standard care in North-America and closer to the thinking of English medical teams. A prospective study within the 2011 national hospital clinical research program (PHRC 2011) is beginning in order to evaluate practices and the role of families and caregivers.

[Acute immune epiduritis in a child]. / Epidurite aiguë d'origine immunologique chez un enfant.

Acute epiduritis is an uncommon disease especially in children. We report an unusual case of acute epiduritis in a child, revealed by characteristic clinical signs and Magnetic Resonance Imaging (MRI). Given the absence of identified infectious or tumoral cause, and the ineffectiveness of antimicrobial treatment, a therapeutic test with polyvalent immunoglobulins was implemented. Rapid clinical improvement led to the retrospective diagnosis of probable immunological acute epiduritis.

Bladder exstrophy: evaluation of factors leading to continence with spontaneous voiding after staged reconstruction.

PURPOSE: We performed a long-term retrospective review of patients with bladder exstrophy to evaluate the results of staged surgical reconstruction in regard to urinary continence, spontaneous voiding and preservation of the upper urinary tract. MATERIALS AND METHODS: We reviewed the charts of 42 boys and 15 girls treated at Hôpital St. Joseph for bladder exstrophy between 1965 and 1995. All patients underwent staged repair, including bladder augmentation in 7 (12%) and secondary urinary diversion in 13 (23%). Criteria for good outcome in terms of continence are defined and factors influencing outcomes are reviewed. RESULTS: A total of 38 patients (67%) achieved good or acceptable urinary continence (22 or 39% and 16 or 28%, respectively). Outcome was poor in 19 patients, including 13 (23%) who underwent secondary urinary diversion. Bladder stones, which developed in 13 patients (23%), were the most common long-term complication of bladder exstrophy reconstruction. Ten patients who underwent pelvic osteotomies ultimately had better continence and 9 are dry. Bladder neck reconstruction was performed at a later age overall (mean 10 years). Repeat bladder neck reconstruction was generally associated with poor results. The technique of bladder neck reconstruction did not appear to influence outcome. CONCLUSIONS: A carefully planned surgical reconstruction for bladder exstrophy can lead to satisfactory long-term urinary continence in most patients. Factors contributing to successful results include early bladder closure, pelvic osteotomy, adequate bladder neck reconstruction with bladder neck suspension in girls, and a motivated child and family. Alternatives to surgical reconstruction should be discussed. Ultimate predictors of outcome in bladder exstrophy repair are difficult to ascertain.