A Novel Noonan Syndrome RAF1 Mutation: Lethal Course in a Preterm Infant.
Bottom Line: A novel mutation in the RAF1 gene was identified: c.782C>G (p.Pro261Arg) in heterozygosity, not described previously in the literature.Consequently, the common clinical course in this mutation and its respective contribution to the early fatal outcome is unknown.No conclusion can be established regarding genotype/phenotype correlation.
Affiliation: Neonatal Intensive Care Unit , Portugal.
Noonan syndrome is a relatively common and heterogeneous genetic disorder, associated with congenital heart defect in about 50% of the cases. If the defect is not severe, life expectancy is normal. We report a case of Noonan syndrome in a preterm infant with hypertrophic cardiomyopathy and lethal outcome associated to acute respiratory distress syndrome caused by Adenovirus pneumonia. A novel mutation in the RAF1 gene was identified: c.782C>G (p.Pro261Arg) in heterozygosity, not described previously in the literature. Consequently, the common clinical course in this mutation and its respective contribution to the early fatal outcome is unknown. No conclusion can be established regarding genotype/phenotype correlation.
No MeSH data available.
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Mentions: This male infant was born to healthy non-consanguineous parents. It was the mother’s first pregnancy, complicated at 28 weeks of gestation by polyhydramnios. The fetal ultrasounds revealed bilateral hydronephrosis (right 14 mm, left 10 mm), bladder wall thickening and shortened long bones. He was delivered at the 30th week of gestation by cesarean section due to fetal distress by placental abruption. Apgar scores were 3/3/4 at one, five and ten minutes respectively, with sustained bradycardia. The bodyweight was 1840 g (P75-90), height 38 cm (P10) and head circumference 32 cm (P90). The newborn was intubated and ventilated in the first minutes and one dose of exogenous surfactant was given due to respiratory distress syndrome. Physical examination revealed marked hypotonia, generalized edema and shortened limbs. The echocardiogram showed poor contractility, low cardiac output, myocardial hypertrophy and mild pericardial effusion. Hence, the newborn was submitted to invasive ventilation, fluid replacement, albumin and inotropic support. He developed metabolic acidosis requiring correction and antibiotic therapy was performed due to sepsis. In the first days of life, cerebral ultrasound was normal. In the second day, a weight loss of 7.6% was confirmed, along with redundant skin, course facies, hepatomegaly and palpable kidneys. The echocardiogram showed improved function and vascular filling, left myocardial hypertrophy and signs of pulmonary hypertension. Clinical and electric seizures were observed, requiring treatment with phenobarbital. On day four, dopamine was suspended but invasive ventilation and dobutamine were maintained. Five days later ventilatory and hemodynamic status were stable on non-invasive ventilation. At this time a significant reduction of edema (weight loss of 400 g: –22% of weight birth) was observed. On day ten, dobutamine was suspended and the echocardiogram confirmed hypertrophic cardiomyopathy with left ventricular outflow tract obstruction (Figure 1). Propranolol was initiated (maximum dose of 4 mg/kg/day) with the heart rate around 150 bpm. Seizures were controlled and cerebral ultrasound on day 15 revealed a grade II intraperiventricular hemorrhage. Investigation included karyotype (46,XY), plasma amino acids, serum lactate, ammonia, total and esterified carnitine, urine metabolic screen and renal ultrasound, all with normal results. TORCH screen was negative.
No MeSH data available.