Alessandra Schiavino

Respiratory insufficiency in a newborn with congenital hypothyroidism due to a new mutation of TTF-1/NKX2.1 gene

NK2 homeobox‐1 (NKX2.1) gene encoding the thyroid transcription factor‐1 (TTF‐1) plays a critical role in lung, thyroid, and central nervous system morphogenesis and function; mutations cause a rare form of progressive respiratory failure associated with alterations of surfactant synthesis, composition, and homeostasis. Molecular mechanisms are heterogeneous and poorly explored. A 28 days old male, soon after birth, presented respiratory failure requiring oxygen treatment at FiO2 27%, prolonged for 2 weeks. Routine neonatal screenings detected a high thyroid stimulating hormone concentration. On day 27 congenital hypothyroidism was confirmed and substitutive treatment was begun. Since the persistence of respiratory symptoms sweat test, CFTR mutation, lymphocyte subpopulations, and sputum cultures were tested, resulting negative. Brain and cardiac defects were also ruled out. Bronchoscopy and BAL analysis were normal. Computed tomography showed bilateral multiple ground glass attenuation, consolidative areas and diffuse bronchial wall thickening. Based on the severity of symptoms, the exclusion of other causes of respiratory disease and the CT findings of interstitial lung disease, we investigated genes affecting the surfactant homeostasis. Sequencing analysis of the three exons of the TTF1 revealed a heterozygous mutation c.334G > T that results in the replacement of glycine in position 112 with a stop codon, generating a nonsense protein that lacks the correct transactivation domain in the C‐terminal region. Genetic analysis of the family showed that the father, who was asymptomatic, carried the mutation. Screening for TTF‐1 deletions or mutations should always be considered in children with congenital hypothyroidism and an unexplained neonatal respiratory distress or neurodevelopmental deficits. Pediatr Pulmonol. 2014; 49:E42–E44.

Pleural effusion from intrathoracic migration of a ventriculo-peritoneal shunt catheter: pediatric case report and review of the literature

BackgroundPleural effusion is a rare complication of ventriculo-peritoneal (VP) cerebrospinal fluid (CSF) shunting and its diagnosis is difficult in patients with neurological and consciousness impairment.Case reportHerein we report the case of a child affected by Pfeiffer syndrome and hydrocephalus, shunted at the age of 3 months, who developed acute respiratory failure due to a right-sided pleural effusion 2 years later. Plain chest radiographs and computed tomography (CT) showed the intrathoracic migration of the right VP shunt abdominal tip. Beta-2 transferrin, a marker for CSF, was found in the pleural fluid and the hypothesis of a CSF hydrothorax was confirmed. Effusion was treated with a thoracentesis. Seven days after, the right VP shunt was revised; a ventriculo-atrial (VA) shunt was also placed on the left side to serve as the main CSF shunt and to prevent the recurrence of hydrothorax. We review the pediatric cases of CSF hydrothorax reported in the literature and discuss the mechanisms underlying this complication together with the possible treatments.ConclusionPleural effusion due to VP shunt insertion is a rare and potentially life-threatening condition that should be suspected in any patient with a VP shunt and respiratory failure. Signs of hydrothorax may moreover represent the only clinical evidence of a shunt-related complication in case of neurologically severely compromised patients in which neurologic examination cannot help to make a diagnosis.

SP-C deficiency: Three different phenotypes for the same mutation

SP-C dysfunction is one of the most frequent causes of Interstitial Lung Disease (ILD). We describe three pts with the same SP-C mutation but different phenotypes. Case 1: TD, 3 yrs, persistent cough, dyspnoea, ground glass opacities and subpleural micronodules at CT. SP-C gene analysis positive for the mutation I73T. Hydroxychloroquine was started, 3 months later TD was asymptomatic, CT improved and normalised after 6 months. Case 2: UM, 4 yrs, healthy up to 6 months, when a RSV caused severe respiratory insufficiency. Normal bronchoscopy, CT with ILD. Referred at one yr, O2 and steroid dependent, CT with wide ground glass opacities and “honeycomb”. Despite systemic steroids CT worsened. Lung biopsy showed desquamative interstitial pneumonia (DIP), ultrastructure was consistent with surfactant deficiency. Genetical analysis showed the I73T mutation. After the 6th iv bolus of high dose steroids CT worsened, hydroxychloroquine was started with a reduction of O2 and steroid needs. The last CT is stable, O2 discontinued. Case 3: CR, recurrent pneumonia in the first year, admitted at 15 months (Naples) for acute respiratory distress. Chest Xray with wide opacities and interstitial thickening, CT scan increased parenchymal density and multiple consolidation. Because of prolonged VM tracheostomy was performed. A lung biopsy, examinated in our Hospital, showed ILD with DIP/alveolar proteinosis. Ultrastructurel was consistent with congenital abnormalities of surfactant proteins. Molecular analysis showed the presence of the mutation I73T. Hydroxychloroquine started after the biopsy, the patient died after 2 weeks Conclusion: This study confrims the eterogeneity of SP-C deficiency despite same genetic mutations.