Crisponi syndrome: a new mutation in CRLF1 gene associated with moderate outcome.

SUMMARY: Crisponi syndrome (CS) is a rare, autosomal recessive disorder, characterized by hyperthermia, extensive muscular contractions in the face after even minimal stimuli or crying, hypertonia, opisthotonus, camptodactyly, and typical facial features. Recently, it has been demonstrated that CRLF1 (cytokine receptor-like factor 1) gene mutation is associated with CS. Here we report a case of CS with a new mutation in the CRLF1 gene associated with moderate clinical phenotype.

The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome.

In type I blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), eyelid abnormalities are associated with ovarian failure. Type II BPES shows only the eyelid defects, but both types map to chromosome 3q23. We have positionally cloned a novel, putative winged helix/forkhead transcription factor gene, FOXL2, that is mutated to produce truncated proteins in type I families and larger proteins in type II. Consistent with an involvement in those tissues, FOXL2 is selectively expressed in the mesenchyme of developing mouse eyelids and in adult ovarian follicles; in adult humans, it appears predominantly in the ovary. FOXL2 represents a candidate gene for the polled/intersex syndrome XX sex-reversal goat.

Role of rHuEpo on blood transfusions in preterm infants after the fifteenth day of life.

The specific aim of the study was to assess the safety and efficacy of recombinant human erythropoietin (rHuEpo) in reducing the need for blood transfusions in preterm infants after the 15th day of life. Between 1 October 1994 and 1 October 1995, 107 preterm infants, gestational age < or = 34 weeks, were admitted to the Neonatal Intensive Care Unit and received rHuEpo subcutaneously, 900 U/kg week-1, 3 times weekly, supplemented with iron and vitamin E. Treatment was started at 8 days of life and lasted from a minimum of 6 weeks to a maximum of 3 months. A total of 116 preterm infants of the same gestational age, admitted to the Neonatal Intensive Care Unit from 1 January 1992 to 31 December 1992, served as controls. Entry criteria were gestational age < or = 34 weeks and no major congenital malformation. There were no differences in routine care between the two groups. Hematological measurements and transfusion requirements were followed during therapy. The infants were divided into two groups according to birth weight (< 1500 g and > or = 1500 g), and for each group the number of patients who received blood transfusions and when blood transfusions occurred, before or after the 15th day of life, was recorded. There was a statistically significant difference only for transfusions carried out after the 15th day of life (p < 0.002). No adverse effects attributable to rHuEpo during the treatment were noted. The results indicate that early rHuEpo treatment, in combination with iron supplements, is effective in reducing the need for blood transfusions in preterm infants after the 15th day of life.

Italian multicentre study on very low-birth-weight babies. Neonatal mortality and two-year outcome.

The Italian multicentre study on very low-birth-weight babies is the first collaborative project in Italy on the health status of newborns weighing 500-1499 g at birth: 634 such babies were admitted in 1987-88 to eight Italian NICUs; 424 infants survived and were followed until two years of age, corrected for prematurity. Logistic regression analysis of pre-admission risk factors of in-hospital mortality identified eight statistically significant variables: birth weight, gestational age, sex, antepartum steroids, 1-min Apgar score and, on admission to the NICU, body temperature, pH and absence of spontaneous respiration. Using the equation derived from the logistic model, a theoretical mortality rate was calculated for each centre, predicted on the basis of the local incidence of preadmission risk factors. In no case was the predicted mortality significantly different from the observed one. At two years of age, 8 children were blind and 48 had motor disability. Of these, 46 had cerebral palsy: based on a functional evaluation score 14 had severe (degree 4), 20 intermediate (degree 3) and 12 mild cerebral palsy (degree 2). Among 25 variables entered in a logistic regression as risk factors for cerebral palsy, only periventricular leukomalacia and acidosis were significantly associated with the outcome.

Italian Multicenter Study on Very Low Birth Weight Babies.

The Italian Multicenter Study on Very Low Birth Weight babies (IMS-VLBW) is the first collaborative investigation performed in Italy on the health status of newborns weighing less than 1500 g at birth. Eight Neonatal Intensive Care Units (NICUs) participated in the study: Cagliari, Napoli, Padova, Palermo, Roma, Sassari, Trieste, Udine. Data were analyzed in the Laboratorio di Epidemiologia e Biostatistica of the Istituto Superiore di Sanità. The objectives of the study were established in the following: a) to collect accurate descriptive data on neonatal morbidity, mortality and long term outcome of VLBW babies admitted to NICUs; b) to analyze the risk factors of unfavourable outcome (death or handicap) and to analyze, with respect to outcome, the relationships between risk factors, neonatal diseases and therapeutical procedures; c) to test the feasibility of a multicenter follow-up programme based on the use in all participating Centers of the same diagnostic criteria (the results of follow-up will be presented in a forthcoming paper). In the years 1987 and 1988, 634 newborns weighing 500-1499 g at birth were enrolled in the study. In-hospital mortality for the whole group was 33.1% (65.1% in the 500-999 g birth weight class and 19.2% in the 1000-1499 g class). Mortality was not different for inborn vs outborn babies. A high incidence of unfavourable perinatal conditions was observed in these babies, namely birth asphyxia, sub-optimal care during transport, poor clinical conditions on arrival to the NICU. Neonatal diseases, like respiratory distress syndrome and peri-intra ventricular hemorrhage were also frequent and severe. A logistic regression analysis of pre-admission risk factors of in-hospital death identified eight statistically significant variables: birth weight; gestational age; sex; antenatal steroid stimulation of lung maturity; first minute Apgar score; absence of spontaneous respiration, body temperature and pH on arrival to the NICU. Using the equation derived from the logistic regression analysis a theoretical mortality rate, predicted on the basis of the local incidence of pre-admission risk factors, was calculated for each Center. In no case the predicted mortality was statistically different from the observed one, suggesting that in our study differences in observed mortality rates from one Center to another are largely influenced by pre-admission risk factors.