GERMLINE GAIN-OF-FUNCTION MUTATIONS of ALK DISRUPT CENTRAL NERVOUS SYSTEM DEVELOPMENT

International audienceNeuroblastoma (NB) is a frequent embryonal tumour of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK, MIM 105590) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harbouring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes

Etude rétrospective des hospitalisations des nourissons de moins d'un mois, examinés aux urgences pédiatriques de l'hôpital Jean Verdier (Bondy) entre mai 2003 et mai 2004

PARIS13-BU Serge Lebovici (930082101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Enregistrement et codage par le PMSI des mort-nés de 2010 à 2013 à l’hôpital Jean-Verdier, hôpitaux universitaires Paris Seine-Saint-Denis

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Follow-up of babies born to mothers with antiphospholipid syndrome: Preliminary data from the European neonatal registry.

In this review preliminary data on the follow-up of 141 babies born to mothers with antiphospholipid syndrome are reported. In spite of maternal treatment, the rate of both preterm delivery and low birth weight were 16 and 17%, respectively. At birth, no clinical evidence of perinatal thrombosis was observed. Placental transfer of antiphospholipid antibodies occurred in 20, 25 and 43% of cases for lupus anticoagulant, anticardiolipin and anti-\u3b22-glycoprotein I antibodies, respectively. At 24 months of follow-up, four children showed behaviour abnormalities suggesting the possible need for long-term neurological evaluation in this clinical setting

European registry of infants born to mothers with antiphospholipid syndrome: preliminary results.

The registry is an European, multicentre, prospective and longitudinal study which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). In this article we report preliminary results obtained from 138 mothers and 141 babies (three twin pregnancies). At birth, 16.3% of neonates were less than 37 weeks of gestation and 17% were low birth weight; in addition, 11.3% of neonates were small for gestational age. No cases of neonatal thrombosis were observed. During follow-up period five children showed behavioral abnormalities. A long term clinical follow-up will be necessary to evaluate the neuropsychological development of these children