Aicardi-Goutières-Syndrom

Aicardi-Goutières syndrome (AGS) is a rare severe progressive encephalopathy which starts in early infancy. Hallmarks include calcifications of the basal ganglia, chronic lymphopleocytosis and abnormal interferon-α elevations in cerebrospinal fluid (CSF). The disorder mimicks intrauterine infections, but is a genetic disorder, mostly inherited by an autosomal recessive trait with a variable genetic and clinical spectrum. In clinical and laboratory presentation, there is an overlap to infantile systemic lupus erythematosus. Four different genes have been identified to date, others are assumed. They code for nucleases, which are involved in cellular repair mechanisms by cleaving RNA-DNA particles. Mutations cause, via enzyme inactivation, a chronic overstimulation of the innate immune system, leading to increased CSF interferon-α production. Prenatal diagnosis is available for known mutations.     

Papillon-Lefèvre syndrome

Papillon- Lefèvre syndrome (PLS) is a rare autosomal recessive disorder of keratinization characterized by palmoplantar hyperkeratosis, periodontopathy and precocious loss of dentition. The exact pathomechanism of these clinical events mainly remains speculative. This paper describes two cases of PLS with classic clinical features and briefly review the relevant literature.     

Aicardi-Goutières综合征

Aicardi-Goutières综合征(AGS)是一组罕见的以神经系统及皮肤受累为主的遗传性疾病,主要临床特征包括颅内多发钙化灶、脑白质病变、脑脊液(CSF)慢性淋巴细胞增多症和冻疮样皮损。至今已发现7个AGS致病基因,包括TREX1、RNASEH2B、RNASEH2C、RNASEH2A、SAMHD1、ADAR1和IFIH1基因。文章全面论述了AGS的发病机制、临床表现、辅助检查、诊断及鉴别诊断、治疗进展及预后。     

Special Time in a crèche

The paper describes Special Time carried out in a crèche with a boy with developmental delay and autistic features. Special Time is a form of therapeutic intervention that consists of weekly sessions during which a child is given individual attention by a teacher, an educator or a specific professional. A key aspect of the methodology is that there is a Work Discussion seminar where the professional can be helped to develop the specific stance required by the work and give meaning to the child’s communication. In this case, the Work Discussion seminar was tailor-made and included the Special Time professional and the head of the crèche who presented her work with the child's parents and with the educators, which took place in parallel with the Special Time sessions. The developments achieved by the child in the area of language, his capacity to relate to people, the symbolic use of toys and play, and the reduction of autistic states of mind and behaviour is illustrated through excerpts from the sessions.     

The neuropathology of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome is an autosomal recessive neurodegenerative disorder with unique characteristics which include cerebrospinal fluid lymphocytosis, cytokine involvement (interferon-alpha in plasma and in cerebrospinal fluid), a unique distribution of cerebral calcifications, and early loss of myelin. Surprisingly only a very small number of detailed neuropathological studies are available. This paper summarizes the findings. Calcifications are both present as concretions and as perivascular cuffs of calcium surrounding small vessels. Small vessel involvement (microangiopathy) is apparent from a typical distribution of microinfarctions in at least one case studied. Together with signs of extracerebral vascular involvement known from earlier reports this finding points to microangiopathy as an important pathogenic mechanism in Aicardi-Goutières syndrome.     

Aicardi-Goutières syndrome (AGS).

In 1984, Jean Aicardi and Fran?oise Goutières described 8 children showing both severe brain atrophy and chronic cerebrospinal fluid lymphocytosis, with basal ganglia calcification in at least one member of each affected family. The course was rapid to death or a vegetative outcome. Aicardi and Goutières correctly predicted that the disorder would be genetic, but emphasised that "some features, especially the pleocytosis, may erroneously suggest an inflammatory condition". The increased interferon-alpha in affected children (Pierre Lebon, Paris) mimicked congenital viral infection, but the associated chilblains (pernio) pointed to lupus erythematosus and an autoimmune mechanism. Genetic research led by Yanick Crow has clarified these puzzling relationships in Aicardi-Goutières syndrome, a syndrome that now includes conditions previously known as microcephaly-intracranial calcification syndrome, pseudo-TORCH and Cree encephalitis. At the time of writing, Crow's team has discovered that over 80% of families with Aicardi-Goutières syndrome have mutations in one of four nuclease genes, the exonuclease TREX1 and the genes for all three subunits of the ribonuclease H2 enzyme complex. Aicardi-Goutières syndrome is both genetically and phenotypically heterogeneous, with a range of severity from life-threatening perinatal illness to mild late infancy onset. All infants of whatever genotype have increased interferon-alpha in the first year of life and this appears to be the final common pathway that links Aicardi-Goutières syndrome, congenital virus infection and systemic lupus erythematosus.     

Corneal involvement in Papillon-Lefèvre syndrome

We describe a 7-year-old boy with classic dental and dermatologic findings of Papillon-Lefère syndrome. In addition to these manifestations, he had bilateral, almost symmetric, hypertrophic-looking corneal leukoma. This case demonstrates that patients with Papillon-Lefèvre syndrome should undergo ophthalmologic examination in addition to frequent dental examination.