Marshall syndrome: further evidence of a distinct phenotypic entity and report of new findings.

Marshall syndrome and type II Stickler syndrome are caused by mutations in COL11A1, which codes for the proα1chain of collagen XI. Collagen XI is a minor fibrillar collagen co-expressed with collagen II in cartilage and the vitreous of the eye. Characteristic features of Marshall syndrome include midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Deletions, insertions, splice site, and missense mutations in COL11A1 have been identified in Stickler syndrome and Marshall syndrome patients. In this study, we describe the clinical presentations of seven patients with Marshall syndrome from three unrelated Saudi families, inherited as autosomal dominant (two families) and autosomal recessive (one family). Cardinal clinical features of Marshall syndrome are manifested in all patients. One patient had ectodermal abnormalities. Mutations (c.2702G > A in exon 34,IVS50 + 1G > A, and IVS50 + lG > C) were identified in COL11A1 in affected members. Interestingly, the first report of autosomal recessive Marshall syndrome was from Saudi Arabia caused by the same mutation (c.2702G > A, p.Gly901Glu) as in one of our families. This study depicts detailed phenotypic and genetic description of dominant and recessive forms of Marshall syndrome due to COL11A1 mutations.

Novel homozygous mutation in DSP causing skin fragility-woolly hair syndrome: report of a large family and review of the desmoplakin-related phenotypes.

Desmoplakin is an important cytoskeletal linker for the function of the desmosomes. Linking desmoplakin to certain types of cardiocutaneous syndromes has been a hot topic recently. Skin fragility-woolly hair syndrome is a rare autosomal recessive disorder involving the desmosomes and is caused by mutation in the desmoplakin gene (DSP). We report five members from a large family with skin fragility-woolly hair syndrome. The index is a 14-year-old girl with palmoplantar keratoderma, woolly hair, variable alopecia, dystrophic nails, and excessive blistering to trivial mechanical trauma. No cardiac symptoms were reported. Although formal cardiac examination was not feasible, the echocardiographic evaluation of the other two affected younger siblings was normal. Homozygosity mapping and linkage analysis revealed a high LOD score region in the short arm of chromosome 6 that harbors the DSP. Full sequencing of the DSP showed a novel homozygous c.7097 G>A (p.R2366H) mutation in all affected members, and the parents were heterozygous. This is the report of the third case/family of the skin fragility-woolly hair syndrome in the literature. We also present a clinical and molecular review of various desmoplakin-related phenotypes, with emphasis on onset of cardiomyopathy. The complexity of the desmoplakin and its variable presentations warrant introducing the term 'desmoplakinopathies' to describe all the phenotypes related to defects in the desmoplakin.

Selection criteria for resuscitation and survivability rates for neonates at the limit of viability.

AIM: To evaluate outcomes of a cohort of infants born at 23 weeks' gestational age after introducing a new selection score for resuscitation in the delivery room (DR). METHODS: This was a retrospective charts review study using data from the maternal and newborn registry funded by the Qatar National Research Fund. Parents were consulted prenatally and their wishes were honored. The plan of resuscitation was based on the new selection score. The seven components of the score were four antenatal and three immediate postnatal in the DR. Each component received a score of zero, one, or two according to its presence, uncertainty or absence, respectively. Only a score of≥7 would receive active resuscitation unless specified otherwise during prenatal consultation. RESULTS: The study reviewed 60 infants that were delivered over a two year period. The DR death rate was 23 of 60 (38%). Thirty-seven infants (61%) were admitted to the NICU. The score was applied only on 37 infants where all score criteria were reported in their files. Twenty infants had score <7; of them 13 (65%) died in the DR and 7 were admitted to NICU of whom two (29%) survived to discharge. Seventeen babies with scores≥7 admitted to NICU of whom nine (51%) survived to discharge. The survival rate to discharge was 13 of 37(35%). A satisfaction survey included 33 neonatal physicians; 32 neonatologists stated the score was easy to comprehend, 26 voted for easy to implement, and 30 voted for ethical relief and moral comfort. CONCLUSIONS: Using a resuscitation score of seven was associated with improved survival until the discharge of those infants resuscitated. NICU physicians described the score as functional and convenient.

Establishing the change in antibiotic resistance of Enterococcus faecium strains isolated from Dutch broilers by logistic regression and survival analysis.

In this study, we investigated the change in the resistance of Enterococcus faecium strains isolated from Dutch broilers against erythromycin and virginiamycin in 1998, 1999 and 2001 by logistic regression analysis and survival analysis. The E. faecium strains were isolated from caecal samples that had been randomly collected from six slaughterhouses. Moreover, between the sample collection in 1998 and the sample collection in 1999, virginiamycin and the macrolide antibiotics (of which erythromycin is a member) have been banned in The Netherlands from use in broiler feeds as growth promoter. In the logistic regression analysis we used the internationally accepted cut-off values to determine whether bacteria were resistant or not. In the survival analysis, inhibition of bacterial growth was the event and time to event was replaced by concentration of antibiotic to event. As a consequence, changes in the growth of bacteria can be tested over an entire range of concentrations and no cut-off value for resistance has to be determined. We performed the survival analysis by use of a Cox logistic model with an odds ratio (OR) for the increase of the odds of the basic hazard rate as outcome. Both the logistic regression and the survival analyses showed that resistance to erythromycin and virginiamycin decreased during the study period. In the logistic regression model the ORs associated with the fraction of bacteria inhibited by the antibiotics in 2001 as compared to 1998 were 3.76 (2.57-5.49) for erythromycin and 11.65 (7.68-17.66) for virginiamycin. The corresponding ORs from the survival analysis were lower; 2.88 (2.21-3.76) and 2.11 (1.80-2.49), respectively. The reason for the differences between the ORs of the survival analysis and the logistic regression analysis is probably because most changes in resistance included the cut-off value and logistic regression specifically examines those changes.