A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation.

Noonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a de novo mutation in exon 7 of the RAF1 gene: c.776C > A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C > A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of RAF1 mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a RAF1 p.Ser259Tyr mutation.

Extremely preterm infants in Tunisia: Where are we now?

BACKGROUND: Extremely preterm infants are newborns born before 28 weeks of gestation. Survival of these immature newborns depends on resuscitation and the quality of care during hospitalization. OBJECTIVE: To determine survival and neurologic outcomes at2 years after extremely preterm birth. METHODS: It is a retrospective multicentric study in 5 neonatal intensive care units (NICU) in 2012-2013.All live births less than 28 weeks gestation were included. RESULTS: A total of 109 births were recorded. Prenatal corticosteroids were given in 47% of cases. Mean weight was 989g and mean age was 26 weeks gestation. Ninety percent of patients had respiratory distress syndrome and 67% of them needed respiratory support. Surfactant was given to 29% of newborns. The mortality rate atdischarge was 76%.The first cause of mortality was nosocomial infections. At thecorrected age of 2 years, 27% of survivors had abnormal neurologic outcome. CONCLUSION: In our study, survival and neurologic outcomes ofextremely preterm infants were poor.In this high-risk population, improving perinatal care remains a challenge to improve long-term outcome in Tunisia.

Premature Birth, low Birth Weight and Birth Defects after assisted reproductive therapies. a 18-year comparative study.

BACKGROUND: As assisted reproductive therapies (ART) become more common in Tunisia, it was relevant to define the associated perinatal risks. The risk of multiple births and its correlate after ART were well admitted. We aimed to disclose whether ART were associated with increased perinatal risks in singletons and twins from ART comparatively with spontaneous conception. METHODS: A retrospective descriptive and comparative study including all newborns conceived by ART and admitted between 1998 and 2015 and spontaneous newborns selected randomly. We compared separately singletons and twins from ART and natural conception for premature birth (PB) and low birth weight (LBW). For birth defects (BD), we compared the two groups condensed. RESULTS: We identified 425 ART newborns and 322 controls. The risk of PB was statistically higher, in both ART singletons and twins than in controls. Among singletons, the use of ART was associated with statistically significant increased rates of LBW and VLBW. Among twins, this result was valuable only for VLBW. Newborns conceived with ART had a risk of BD that was three times higher than in controls. BD risk was statistically higher with ICSI (Intra Cytoplasm Sperm Injection), ovulation inductor and in vitro fertilization. BD risks were 2.4 times higher with ICSI than with all others therapies condensed. CONCLUSIONS: This study highlighted the increased perinatal risks even in singleton from ART comparatively with natural conception. The exact mechanisms underlying all these risks remain unclear. Further studies are required to prove the part of ART underlying parental factors, and sterility itself.

Congenital diaphragmatic eventration complicated with neonatal gastric perforation.

Congenital diaphragm eventration is a rare and usually asymptomatic developmental defect. Neonatal gastric perforation is also a rare but lifethreatening condition. In our knowledge, the association of these two pathologies has been, exceptionally reported. We report a case who illustrates clinical and radiological features of this possible co-morbidity. A full-term male neonate was born from uneventful pregnancy and delivery. The antenatal scan was reported as normal. At birth, clinical exam was normal, no special resuscitation was necessary. The newborn was examined and admitted the 4th day of life for fever, tachypnea, cyanosis, hemodynamic shock and refusing feeds. Clinical examination suggested peritonitis. Chest radiography and ultrasonography suggested congenital hernia. A laparotomy was performed after a brief resuscitation and confirmed the presence of diaphragm eventration with gastric perforation. Suturing of gastric perforation with a diaphragmatic plication was performed with favorable evolution.

Inherited ADMATS13 deficiency: When to evoke the in the newborn?

Inherited ADMATS13 or Upshaw-Schulman syndrome (USS) is caused by the deficiency of the Von Willebrand factor-cleaving protease. It is characterized by recurrent episodes of thrombocytopenia reversible by fresh frozen plasma (FFP) infusions, microangiopathic hemolytic anemia, and microvascular thrombosis leading to ischemic damage of multiple organs with end stage renal failure, or neurological sequelae in the absence of appropriate treatment. The typically reported features of USS in neonates are severe jaundice with hyperbilirubinemia, thrombocytopenia and /or combs negative hemolytic anemia, and an increased creatinine.We presented a clinical case of USS with unusual features, which delayed the diagnosis.USS was declared at sixth hours of life with diffuse hemorrhage related to an early neonatal infection. Analysis of the plasma, at the age of 20 months, revealed low ADAMTS13 activity in the patient (<1%).Inherited ADMATS13 deficiency manifestations may overlap with other conditions, which may delay diagnosis and lead to visceral and neurological damage. The diagnosis should be, early considered in some clinical conditions: discrepancy between the severity of a hemorrhagic syndrome and thrombocytopenia, recurrence, resistance to symptomatic treatment. The diagnosis can be suggested by the normalization of platelet count after FFP transfusions.

Povidone Iodine Pleurodesis for Refractory Congenital Chylothorax: A Review of Literature.

BACKGROUND: Povidone iodine (PVI) pleurodesis is commonly used in adult. However, this procedure is still nonconsensual in newborns. AIMS: This article aimed to report a new case of refractory congenital chylothorax (CCT) managed with PVI pleurodesis with a review of previousreported cases. METHODS: a systematic review of similar cases published in PubMed. Clinical patterns, therapeutic modalities and outcome variables werereported. RESULT: In a full term neonate presenting refractory CCT, PVI pleurodesis was performed at day 16 of life by one intrapleural instillation of PVI4% with rapid success and no side effects. Renal function and thyroid tests stilled normal before and after instillation. The analysis of 18 casesreported in Medeline and our observation provided the following data: this procedure was successful without side effects in 11/19 cases. Severeside effects were reported in four patients with high risks before procedure. CONCLUSION: PVI pleurodesis seems to be effective and inoffensive in the management of refractory CCT. It may be a good alternative tosurgery. Nevertheless, randomized studies on large neonatal population are required to precise: the risks and benefits of this procedure, thetiming and the modalities of its realization (duration of intervention, dilution and dosage of PVI) according to the patient`s field (gestational age,weight and associated morbidity).

Transported neonates in Tunisia.

AIMS: To describe the transport of sick neonates to a tertiary care hospital and evaluate their condition at arrival and outcome. METHODS: A multicenter, prospective cohort study was performed in 7 NICUs in Tunisia from 1st april to 31 July 2015.Demographic parameters, transport details and clinical features at arrival were recorded. All neonates were followed up till discharge or death. RESULTS: A total of 239 consecutive neonates were enrolled in the study representing 5.7% of all admitted infants. Maternal risk factors were present in 26% of neonates admitted. Sex-ratio was 1.46. Preterm infants represented 24% of transported babies. Seventeen percent of neonates had severe respiratory distress and 10% had hemodynamic troubles. Referred hospital was not informed in 24% of cases. Regarding the transport mode, 113 newborns (47.5%) were transported in ambulance accompanied by a nurse. Documentation during transfert was present in 14% of cases. Five babies expired on arrival despite resuscitation.  Rate mortality was 8.4%. CONCLUSION: Transporting neonates in developing countries is a challenge. Organized transport services in Tunisia are not always available. So, in cases of at-risk pregnancy, it is safer to transport the mother prior to delivery than to transfer the sick baby after birth.