Inverted duplication with deletion: first interstitial case suggesting a novel undescribed mechanism of formation.

Inverted duplications with terminal deletions are a well-defined family of complex rearrangements already observed for most of chromosome extremities. Several mechanisms have been suggested which could lead to their occurrence, either through non-homologous end joining, non-allelic homologous recombination, or more recently through an intrastrand fold-back mechanism. We describe here a patient with intellectual disability and pharmacoresistant epilepsy, for which array CGH analysis showed the first interstitial case of inverted duplication with deletion on chromosome 1p. Furthermore, SNP array analysis revealed an associated segmental isodisomy for the distal part of 1p, which led us to consider a replicative mechanism to explain this abnormality. This observation extends the range of this once telomeric rearrangement.

Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations.

GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid beta-galactosidase (GLB1). In addition, allelic variants of this gene can result in Morquio B disease (MBD), a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1 gene have been identified so far, but only few could be proven to be predictive for one of the GM1 gangliosidosis subtypes or MBD. We performed genotype analyses in 16 GM1 gangliosidosis patients of all phenotypes and detected 28 different genetic lesions. Among these, p.I55FfsX16, p.W65X, p.F107L, p.H112P, p.C127Y, p.W161X, p.I181K, p.C230R, p.W273X, p.R299VfsX5, p.A301V, p.F357L, p.K359KfsX23, p.L389P, p.D448V, p.D448GfsX8, and the intronic mutation IVS6-8A>G have not been published so far. Due to their occurrence in homozygous patients, four mutations could be correlated to a distinct GM1 gangliosidosis phenotype. Furthermore, the missense mutations from heteroallelic patients and three artificial nonsense mutations were characterized by overexpression in COS-1 cells, and the subcellular localization of the mutant proteins in fibroblasts was assessed. The phenotype specificity of 10 alleles can be proposed on the basis of our results and previous data.

Recessive hereditary methaemoglobinaemia, type II: delineation of the clinical spectrum.

Type II recessive hereditary methaemoglobinaemia (RHM) is a rare disease due to generalized NADH-cytochrome b5 reductase (cytb5r) deficiency. It results in mild cyanosis and severe neurological impairment. The clinical features and long-term outcome are poorly documented, and there are no systematic reviews. We examined six cases of type II RHM, four of which were new, together with 45 previously published cases, in order to establish the range of phenotypic expression. The clinical picture was very similar in most cases, with severe encephalopathy, microcephaly, generalized dystonia, movement disorders and mild cyanosis. The neurological prognosis was poor; in particular, none of the patients walked or spoke. In addition, the possibility of an atypical and milder phenotype was considered. We concluded that children with unexplained severe encephalopathy associated with generalized dystonia should be examined for cyanosis and have a methaemoglobinaemia assay performed. The diagnosis can be confirmed by very low cytb5r activity in both red and white blood cells. Here we report three novel mutations in the NADH-cytochrome b5 reductase gene. Prenatal diagnosis of this extremely severe disease should be proposed to affected families.

[Management of acute visual loss in children]. / Conduite à tenir devant une baisse aiguë de l'acuité visuelle chez l'enfant.

Acute or rapidly progressive visual loss in children needs urgent attention and treatment. It may be unilateral orbilateral. Etiology depends upon the involved areas: eye ball, optic nerve, retro-chiasmatic pathways. Psychogenic origin is quite common in school-age children, however, it has to be considered last. Unilateral visual loss may be overlooked. Acute total transitory visual loss may be due to epilepsy or to migraine. Rapidly progressive visual loss may be due to retinal disease, optic neuritis or cortical blindness. Management of visual loss depends on clinical features, associated symptoms, and aspect of the optic disc. It needs collaboration between ophthalmologist,pediatrician and neuropediatrician. Retinal hemorrhages first call to mind a traumatic origin. Swelling of the optic disc may be due to increased intracranial pressure or due to optic neuritis. When the optic disc is normal it is necessary to rule out organic diseases before establishing the diagnosis of a psychogenic vision disturbance. In emergency, brain neuroimaging is the best way to diagnose intracranial mass and visualize optic pathways.

[Mental retardation and environment: contribution of growth curves to etiological diagnosis]. / Déficience intellectuelle et environnement: contribution des courbes de croissance au diagnostic étiologique.

Although deprived environment is known for more than 50 years to be one of the etiology of mental retardation in infancy, this remains unrecognized by many paediatricians and family practitioners. Yet if appropriate therapeutic measures are instituted early enough, future development of the child is good. A study of the growth curves in relation with the environmental changes, can help to diagnose environmental mental retardation. As an illustration, we present the cases of 5 children first addressed for developmental delay, and secondly removed from their usual environment for psychosocial reasons. Mean duration of follow-up was 10 years, including at least 5 years after the removal. All 5 children had non-organic failure to thrive which was displayed only on the retrospective study of their records. Four recovered from their developmental retardation.

[Study of visual field and vigabatrin treatment in children]. / Etude du champ visuel et traitement par vigabatrin chez l'enfant.

INTRODUCTION: Concentric visual field defects have been described in association with vigabatrin, a GABA mimetic antiepileptic agent. Few cases have been reported in children. METHODS: A systematic ophthalmological examination was performed in 14 children treated with vigabatrin for seizures. A manual kinetic perimetry test (Goldmann) was done in 11 cases. The ERG was recorded in the 3 cases where perimetry could not be done. RESULTS: All children were asymptomatic. The mean age was 9.6 years. The mean duration of vigabatrin treatment was 41 months. The visual field was abnormal when central and peripheral fields were constricted. A visual field defect was discovered in 6 cases: 4 were severe, 2 were mild. When vigabatrin treatment was stopped, 1 case became worse, 1 case was slightly better, and 1 case remained stationary. A disturbed ERG was found in 3 children (depressed b-wave, raised a/b ratio). CONCLUSION: The visual field defects discovered in children treated with vigabatrin are similar to those described in adults. The incidence and progression of visual field constriction in children with and after vigabatrin treatment are not yet well known. Children treated with vigabatrin should therefore have systematic and regular ophthalmological perimetry, and ERG examinations.

[Management of abused children: at what cost? what for?]. / Prise en charge des enfants maltraités: à quel prix? pour quoi faire?

The prospective follow up of abused children after their hospitalization is illustrated by the report of a sibship. Dysfunction in management and therapy is often observed and is detrimental to the children. Many levels of our society are implicated. This means that there is still a lot to do to obtain adequate therapy for these children.

[Progressive bulbopontine paralysis in children]. / Paralysie bulbopontine progressive de l'enfant.

A case of pons-bulbar palsy in a 10 year-old girl is reported. The authors insist on the fact that motor cranial nerve nuclear dysfunction was isolated, without any pyramidal tract disorder. They also emphasize the slow course of the disease, which after one year of quick progression was stable for the next 5 years. Nineteen identical cases were found in the literature. From this nosographic group, one must exclude patients with associated lateral spinal tract dysfunction: these patients must be discussed with the juvenile or infantile amyotrophic lateral sclerosis group. The heterogeneity of the pons-bulbar paralysis group is also underlined: the course may be quickly fatal or, on the contrary, protracted for a long time; genetic transmission is also quite variable.

[Bobble-head doll syndrome]. / Syndrome de la poupée à tête ballotante. "Bobble-head doll syndrome".

A new case of Bobble-head doll syndrome with aqueductal stenosis is presented in a 14 year-old boy. Ventriculocisternostomy performed 8 years after the onset of the abnormal movement resulted in moderate reduction of the head bobbling. Twenty-two cases were found in a review of the literature. In all cases there was a chronic slowly progressive hydrocephalus with usually a cyst of the third ventricle; aqueductal stenosis was less frequent. When recorded, psychomotor development was impaired. Treatment is neurosurgical. Pathogenesis remains unknown.

[Sarcoidosis in a child disclosed by blindness with major hypercalcemia]. / Sarcoïdose de l'enfant révélée par une cécité avec hypercalcémie majeure.

We report here a case of sarcoidosis, observed in a 12 year-old algerian girl. When the child was examined, at an advanced stage of the disease, her clinical condition was very critical, associating blindness, cachexia, hepatic and splenic enlargement, and major hypercalcaemia. Though chest roentgenograms were normal, the results of both functional pulmonary tests and broncho-alveolar lavage were pathologic. The diagnosis of sarcoidosis was confirmed by the finding of an elevated level of Angiotensin-converting enzyme, and by histologic lesions observed in liver, kidney and conjunctiva biopsies. The corticosteroid treatment improved the general condition, but it failed to better the visual state.

[Acute pyogenic sacroiliac arthritis in children]. / Arthrites aiguës sacro-iliaques à pyogènes de l'enfant.

Three children with pyogenic arthritis of the sacroiliac joints are presented. A study of the literature shows that this condition, although not well known, is not uncommon in childhood. Clinical features and particularly physical examination of the sacroiliac joints are described. They should lead to suspect sacroiliac disease. Radioisotope bone scanning is of great help as it substantially reduces the delay in correct diagnosis. Antibiotic treatment is usually sufficient for adequate management of pyogenic sacroiliitis. The intravenous route for antibiotic administration is not mandatory.