What can we learn from old microdeletion syndromes using array-CGH screening?

Most microdeletion syndromes identified before the implementation of array-comparative genomic hybridization (array-CGH) were presumed to be well-defined clinical entities. However, the introduction of whole-genome screening led not only to the description of new syndromes but also to the recognition of a broader spectrum of features for well-known syndromes. Here, we report on 10 patients presenting with mental retardation associated with atypical features not suggestive of a known microdeletion and a normal standard karyotype. Array-CGH analyses revealed five microdeletions in the DiGeorge region, three microdeletions in the Williams-Beuren region and two microdeletions in the Smith-Magenis region. Reevaluation in these patients confirmed that the diagnosis remained difficult on clinical grounds and emphasized that well-known genomic disorders can have a phenotype that is heterogeneous and more variable than originally thought. The widespread use of array-CGH shows that such patients may be more readily achieved on the basis of genotype rather than phenotype.

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

[A rare cause of neonatal occlusion by a palpable abdominal mass: Meckel's diverticulum]. / Une cause exceptionnelle d'occlusion néo-natale avec masse abdominale palpable: le diverticule de Meckel.

The authors report an unusual case of newborn obstruction by Meckel's diverticulum. Symptoms were repeated vomiting and a rounded mass was palpated in right lower quadrant. This mass looked like a fecalith on X Rays which also showed dilated gas filled loops of intestine. A barium enema showed no trouble of rotation, a good filling of last loops of small bowel, then a large kind of pocket, filled from the bowel. Operation discovered a huge (6 x 5 cm) Meckel's diverticulum compressing small intestine and pushing the cecum towards the upper quadrant. Treatment was ileal resection followed by end to end anastomosis. A very few newborn obstructions by Meckel's diverticulum were published; mechanisms are intussusception, volvulus, herniation. No similar case as reported was found in literature.

[A spectacular and benign syndrome of neonatal convulsions: deep sleep myoclonus]. / Un syndrome spectaculaire et bénin de "convulsions néonatales": les myoclonies du sommeil profond.

Four case reports concerning neonates presenting, without any predisposing factors, severe and lasting myoclonus, occurring exclusively during sleep. These began between 1 and 4 days of age and stopped between 3 weeks and 5 months. Electro-encephalogram was normal, even during episodes of clonus which occurred during deep sleep. A predisposing genetic factor is likely. A better knowledge of this syndrome should avoid hospitalizations and misuse of anticonvulsive treatments.

Voluntary total fasting: a challenge for the medical community.

A movement opposing the nuclear arms race asked for medical surveillance of four people intending to go without food for an unlimited period. The course of fasting was uneventful until day 28-35, when weight loss reached 18%. In one subject fasting was ended on day 38 owing to development of Wernicke's encephalopathy; the others agreed to suspend their fast by day 40. The presence of physicians, offered under defined conditions, may have contributed to the timely cessation of this protest.

KIE: Medical attendance on fasting members of a French anti-nuclear group, part of the international Fast for Life movement, is described. Four physicians agreed to authenticate the fast, release health bulletins, provide medical surveillance, advise on lifestyle and hygiene, and warn of impending permanent damage. Conditions set by the doctors for their involvement included arrangements for proxy decision making, awareness of risks on the part of the fasters, daily medical examinations, and withdrawal of surveillance if medical decisions were not implemented. The circumstances and course of the 40-day fast are related, and the role of the physicians in this episode is discussed.

Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. I. Virus shedding.

From September 1979 to July 1980 inclusive, rotaviruses were prospectively detected by electron microscopy (EM) and ELISA in 82 (29%) of 283 children under two years of age who were admitted to a general pediatric ward in Paris. Rotavirus was found in 43 (36%) of 119 children with diarrhea and in 40 (24%) of 164 children without diarrhea; thus of 83 children shedding rotavirus, 40 (48%) were not diarrheic. Virus shedding that was not associated with diarrhea was observed in 71% of neonates, in 50% of one- to six-month-old children, and in 26% of 7-24-month-old children. Rotavirus shedding was statistically correlated (P less than .01) only with those cases of diarrhea with fever and vomiting ( DFV syndrome). Consequently, relative risk (RR) for the DFV syndrome in patients who were shedding virus was 2.07 (P less than .001) vs. 0.95 for other types of diarrhea. These observations show that asymptomatic rotaviral infection is not an infrequent occurrence; that the association between rotavirus and diarrhea is not necessarily an etiologic one; and that the DFV syndrome appears as a major clinical expression of rotaviral disease. Consequently, recovery of rotavirus from feces is of little diagnostic significance since it does not give a differentiation between rotavirus-induced and rotavirus-associated diarrhea.

Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. II. Serological response.

Serological response to rotavirus and virus shedding were prospectively studied in 179 children (neonatal to 24-month-old) upon admission to a hospital during an 11-month period. Analysis of the evolution of IgG and IgM ELISA titers revealed 24 cases of rotaviral disease (serological response and diarrhea), 13 cases of asymptomatic infection (serological response and no diarrhea), 36 cases of virus carriage (absence of a serological response), three cases of past infection, and six possible cases of nosocomial infection. Rotaviral disease was encountered two out of three times and was characterized by diarrhea associated with fever and vomiting. Asymptomatic rotaviral infection and disease, observed from the neonatal period onwards, affected 2% of neonates, 20% of one- to six-month-old children, and 37% of 7-24-month-old children. In contrast, virus carriage occurred in 27%, 19%, and 14% of those children respectively. Altogether these results indicate that during the period 1-24 months of age, when asymptomatic rotaviral infection and disease were prevalent, approximately two of 10 children had rotaviral disease, one of 10 had asymptomatic infection, two of 10 were virus carriers, and five of 10 were not infected with rotavirus.

[Purulent pleurisy, esophagopleural fistula and presence of Torulopsis glabrata in the pleura]. / Pleurésie purulente, fistule oesopleurale et présence dans la plèvre de Torulopsis glabrata.

The authors report the simultaneous discovery of a septic pleural effusion and an esophagopleural fistula in a 4 year-old patient. The yeast Torulopsis glabrata found in the pleural effusion does not seem to behave as a pathogen but more likely as a witness of a fistula between the gastrointestinal tract and the pleura.

[Mediastinal emphysema in diabetic ketoacidosis. 2 cases]. / Emphysème médiastinal au cours d'une acido-cétose diabétique. Deux observations.

The authors report 2 cases of spontaneous pneumomediastinum observed in 2 male children aged 11 and 9 years respectively, during a bout of diabetic ketoacidosis. This association is probably not uncommon. The course of the pneumomediastinum is usually rapidly favorable. Its pathogenesis is discussed.