Ettore Piro

The world of twins: an update.

In last years, owing to the widespread availability of assisted-reproduction technology, multiple pregnancy rates in Western countries have increased. In twin pregnancies, an increased rate of gestational complications, intrauterine growth restriction (IUGR), preterm birth and severe perinatal conditions is present. These complications are more frequent in monozygotic twins compared to dizygotic twins as well as an increased relative risk of chromosomal abnormalities and congenital malformation. Monochorionic twins are at higher risk for complications, since they share a common placenta where an imbalance in unidirectional arteriovenous anastomoses can lead to twin–twin transfusion syndrome. This extremely dangerous condition, if not early identified, can determine severe fetal complications with mortality rates that, in case of no treatment, reaches 90%. Laser photocoagulation is the treatment of choice in severe twin-to-twin transfusion syndrome with high survival rate. IUGR occurs more frequently in MC twins and along with prematurity and perinatal pathology is considered an important determinant of developmental delay.

Prematurity and twinning

Aim of the study: Newborns from multiple pregnancies are increasing in number and demonstrate a higher perinatal morbidity and mortality compared to singletons. Prematurity is the main reason for most neonatal diseases in twins, but other variables may play a role and their prenatal evaluation may improve the overall outcome. Main findings: Prematurity is six times more frequent in twins and therefore birth weight is significantly lower compared to singletons. Thus, twins are more exposed to prematurity related diseases (respiratory, cardiovascular, infectious, etc.) and to long-term complications (especially neurological disabilities). Results: It is very difficult to estimate the increased risk of neonatal morbidity related to twinning independently to the increased risk of prematurity and therefore to interpret data on morbidity rates, in particular regarding the neurodevelopmental outcome. Conclusion: Prevention of preterm birth is a primary goal in managing multiple pregnancies, together with prophylaxis with corticosteroids in order to improve foetal lung maturity. Accurate risk assessment strategies and adequate obstetrical-neonatological management of multiple pregnancies may reduce the increasing need for neonatal intensive care and for health resources in the long-term follow-up that has been observed over the last decades.

Predictive factors of abdominal compartment syndrome in neonatal age.

In the pediatric population, abdominal compartment syndrome (ACS) is a known complication of abdominal wall defect repair. However, there are only few reports on ACS in newborns and only a proposal of critical intra-abdominal pressure value (IAP) in term newborns, absent in preterm newborns. Although the prevalent clinical sign is tense abdominal distension, it may be difficult to distinguish ACS from pathologies that will not require decompression. The purpose of this study was to identify predictors for ACS and therefore morbidity or mortality indicators. We reviewed newborns presenting with tense abdominal distension and end organ failure. Anamnestic, clinical, laboratory, and instrumental investigations were analyzed to extrapolate predictors. Outcomes were compared with a control group. The incidence of ACS in our neonatal intensive care unit was 5% in the overall population of babies, 16% in tracheal-ventilated newborns, and 57% in infants with abdominal wall defects. We found that, with onset of acidosis or high gastric residuals, the lactate values will be predictive for mortality. We can also suggest paying particular attention to high lactate values just at the onset of distension, in infants with more advanced gestational age, with previously surgical repair, to determine early surgical intervention independently of a specific IAP measurement.

Perlman syndrome: clinical report and nine-year follow-up.

We present the clinical and follow‐up data of a female infant with Perlman syndrome from birth to the age of 9 years. Main features of Perlman syndrome include polyhydramnios, fetal overgrowth, neonatal macrosomia, macrocephaly, dysmorphic facial features, visceromegaly, nephroblastomatosis, and a predisposition for Wilms tumor. In our patient, the nephromegaly with nephroblastomatosis was not present at birth or during the neonatal period; it became evident in the first months of postnatal life. A Wilms tumor was diagnosed when she was about 1 year old. Long term follow‐up documents the natural history of Perlman syndrome and allows us to establish the long‐term prognosis of the affected individuals.

Intrauterine growth restriction and congenital malformations: a retrospective epidemiological study

BackgroundIntrauterine growth restriction (IUGR) and small for gestational age (SGA) birth have been considered possible indicators of the presence of malformations. The aim of this study is to evaluate such relationships in a population of newborns, along with other epidemiological and auxological parameters, in particular the ponderal index (PI).MethodsWe analyzed the birth data of 1093 infants, classified according to weight for gestational age as SGA, appropriate for gestational age (AGA) or large for gestational age (LGA). The prevalence of malformations was analyzed in relation to weight percentile at birth and SGA birth, maternal smoking, pregnancy diseases and PI.ResultsOur analysis showed no significant relationship between the prevalence of malformations and SGA birth. Maternal smoking and pregnancy diseases were strongly related to SGA birth, but not to a higher prevalence of malformations. PI, however, had a significant relationship with a higher prevalence of malformations, if analyzed as either a continuous variable or a categorical variable (cutoff: < 2.4).ConclusionsThe association between congenital malformations and birth weight for gestational age seems to be weak. As part of diagnostic screening for malformations in the neonatal period, PI could be considered a better predictor of risk than weight percentile.

Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly and hypoplastic left middle cerebral artery

Prenatal ultrasonographic detection of unilateral cerebral ventriculomegaly arises suspicion of pathological condition related to cerebrospinal fluid flow obstruction or cerebral parenchimal pathology. Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures. Congenital and acquired types are recognized and have been described, mainly in late childhood, adolescence and adult ages. We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome. Prenatal imaging, cerebral vascular anomaly responsible for the cerebral hemiatrophy and the early clinical evolution have never been described before in such a young child and complete the acquired clinical descriptions in older children. Differential diagnosis, genetic investigations, neurophysiologic assessments, short term clinical and developmental follow up are described. Dyke-Davidoff-Masson syndrome must be ruled out in differential diagnosis of fetal unilateral ventriculomegaly. Early clinical assessment, differential diagnosis and cerebral imaging including cerebral MRI angiography allow the clinicians to diagnose also in early infancy this rare condition.

A premature infant with Costello syndrome due to a rare G13C HRAS mutation

Costello syndrome is caused by mutations in the HRAS proto‐oncogene whose clinical features in the first year of life include fetal and neonatal macrosomia with subsequent growth impairment due to severe feeding difficulties. We report on a premature male with Costello syndrome due to a rare G13C HRAS mutation and describe his clinical features and evolution during the first year of life. The diagnosis of Costello syndrome may be difficult at birth, especially in very preterm infants in whom feeding difficulties, reduced subcutaneous adipose tissue and failure to thrive are also part of their typical presentation.

Intrauterine growth pattern and birthweight discordance in twin pregnancies: a retrospective study.

BackgroundTwins, compared to singletons, have an increased risk of perinatal mortality and morbidity, due mainly to a higher prevalence of preterm birth and low birthweight. Intrauterine growth restriction (IUGR) is also common and can affect one or both fetuses. In some cases, however, one twin is much smaller than the other (growth discordance). Usually, high birthweight discordance is associated with increased perinatal morbidity. The aim of this study is to describe the epidemiological features of a population of twins at birth, with particular reference to the interpretation and clinical effects of birthweight discordance.MethodsWe evaluated retrospectively the clinical features of 70 infants born from twin pregnancies and assessed birthweight discordance in 31 pregnancies where both twins were followed at our institution. Discordance was treated both as a continuous and a categorical variable, using a cutoff of 18%. Possible relationships between birthweight discordance and other variables, such as maternal age, gestational age, birthweight percentile, number of SGA newborns in the pair, Hematocrit (Ht) discordance and neonatal anemia, prevalence of malformations, neonatal morbidity and death, were analyzed.ResultsIn our cohort birthweight percentile decreased slightly with increasing gestational age. Birthweight discordance, on the contrary, increased slightly with the increase of gestational age.A high discordance is associated to the presence of one SGA twin, with the other AGA or LGA. In our population, all 6 pregnancies in which discordance exceeded 18% belonged to this category (one SGA twin).Ht discordance at birth is associated to the presence of neonatal anemia in a twin, but it is not significantly related to weight discordance.Finally, in our case history, weight discordance is not associated in any way with the prevalence of malformations, morbidity and mortality.ConclusionsBirthweight discordance is an important indicator of complications that act asymmetrically on the two fetuses, affecting intrauterine growth in one of them, and usually determining the birth of a SGA infant.Our case history shows a significant statistical association between pair discordance and IUGR in one of the twins, but we could not demonstrate any relationship between discordance and the prevalence of malformations, morbidity and mortality.

Paternal uniparental disomy chromosome 14-like syndrome due a maternal de novo 160 kb deletion at the 14q32.2 region not encompassing the IG- and the MEG3-DMRs: Patient report and genotype-phenotype correlation.

The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2‐imprinted region are regulated by two differentially methylated regions (DMRs): the IG‐DMR and the MEG3‐DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal deletion at the 14q32.2‐imprinted critical region have been reported so far. Here we report on the first patient with a maternal de novo deletion of 160 kb at the 14q32.2 chromosome that does not involves the IG‐DMR or the MEG3‐DMR but elicits a full upd(14)pat syndromes phenotype encompassing the three mentioned MEGs. By the analysis of this unique genotype–phenotype correlation, we further widen the spectrum of the congenital anomalies associated to this rare disorder and we propose that the paternally expressed imprinted RTL1 gene, as well as its maternally expressed RTL1as antisense transcript, may play a prominent causative role.

10qter deletion: A new case

Vertebrate telomeres consist of tandem repeats of the TTAGGG sequence that cap the ends of chromosomes, protecting them from degradation and fusion. Extensive evidence has shown that telomere shortening and erosion lead to chromosome end-to-end fusions and genomic instability, causing mental retardation and/or malformation syndromes. So far, over 19,000 patients with mental retardation have been tested and reported of whom 2.5% appeared to have a subtelomeric rearrangement [Ravnan et al., 2006; Ballif et al., 2007; Ledbetter and Martin, 2007]. Since the identification of submicroscopic subtelomeric rearrangements as a major cause of mental retardation [Flint et al., 1995], testing for subtelomeric abnormalities among patients with mental retardation has become an important diagnostic tool. Although widespread screening among patients with mental retardation might be desirable, the current cost of testing is considered too expensive to allow unselected testing. Therefore clinical preselection is important. So far, selection for subtelomere testing has often been based on the checklist proposedbyDeVries et al. [2001]. (1, Family history of mental retardation; 2, prenatal onset growth retardation; 3, postnatal growth abnormalities; 4,>2 facial dysmorphic features; 5, one or more non-facial dysmorphic features and/or congenital abnormality). Some of the submicroscopic subtelomeric deletions result in a specific phenotype which may direct the clinician towards the diagnosis; the common forms of subtelomeric deletions such as 1p, 4p, 5p, 9p, 22q are quite consistent and the mental retardation is a typical feature [De Vries et al., 2003]. Patients with 10q26-qter deletion seem to have a consistent phenotype including psychomotor delay, growth retardation (preand/or postnatal), microcephaly, triangular face, hypertelorism, strabismus, prominent nasal bridge, low-set/malformed/large/ posteriorly rotated ears, micrognathia, short neck, cryptorchidism, ano/genital defects, congenital heart malformation and urinary tract/renal anomalies [Waggoner et al., 1999; Lukusa and Fryns, 2000; Courtens et al., 2006]. In contrast to these findings, normal individuals (at least 1% of the population [Ledbetter and Martin, 2007]) can also carry subtelomeric aberration like 10qter deletion and do not have any disability or dysmorphic features [Ravnan et al., 2006; Balikova et al., 2007]. Several mechanisms may explain the presence of subtelomeric imbalance in these people: (1) some recurrent chromosomal deletions, such as VCFS syndrome, have variable expressivity [McDonald-McGinn et al., 2001]. (2) The presence of an unmasked recessive allele in the affected patients may determine the phenotypic difference with the normal individuals [Lesnik Oberstein et al., 2006]. (3) Somatic mosaicism, with normal cell lines in the unaffected individuals, may explain the difference. (4) Epigenetic modifications could induce a phenotypic difference between affected patients and normal people. Moreover at present the size of most reported deletions has not been well molecularly characterized, thus complicating accurate genotype–phenotype correlations for these patients [Ledbetter and Martin, 2007]. Here we report on a patient with a 10 q26-10qter deletion. Our patient is a male, the first-born child of healthy non-consanguineous parents, with no family history of mental retardation or birth defects. He was born by caesarean delivery at 38 weeks of gestation. Birth weight was 2,980 g (3rd–10th centile), length was 48 cm (3rd–10th centile), and occipitofrontal head circumference (OFC) was 34 cm (10th–25th