Beckwith-Wiedemann syndrome: Clinical, histopathological and molecular study of two Tunisian patients and review of literature.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a rare overgrowth syndrome characterized by congenital malformations and predisposition to embryonic tumors. Loss of methylation of imprinting center 2 (IC2) is the most frequent alteration and rarely associated with tumors compared to paternal uniparental disomy of chromosome 11 (UPD(11)pat) and gain of methylation of imprinting center 1. METHODS: Our study aimed to describe the clinical, histopathological and genetic characteristics of two patients and establish genotype-phenotype correlations. The clinical diagnosis was based on the criteria defined by the international expert consensus of BWS. Molecular study of 11p15.5 methylation status was assessed using methylation-specific-multiplex ligation probe amplification (MS-MLPA). RESULTS: Patients were aged 12 months and 3 months and fulfilled the clinical score of BWS. MS-MLPA showed molecular alterations consisting of loss of methylation in IC2 (IC2-LOM) at the maternal allele for one patient and a mosaic UPD(11)pat for the second patient in whom follow-up at 6months revealed adrenocortical carcinoma (ACC) with low grade of malignancy. Molecular subtypes guide the follow-up and tumor surveillance, our major concern. CONCLUSION: We have to take into account the psychological impact of a possible tumor whatever the underlying mechanism is. Nevertheless, the tumor risk remains high for UPD(11)pat. Our study extended the phenotype of BWS with absence of macrosomia in Tunisian patients, contrasting with literature, and added a supplementary case of ACC in the tumor spectrum of BWS patients with UPD(11)pat.

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.

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).