Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Non-pulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and ten deletions, we have identified an additional thirty eight novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, twenty missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic whereas four familial cases with three showing maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA binding domain, indicating its plausible role in gene regulation. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

OBJECTIVE. The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure. PATIENTS/METHODS. This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of ≤85%, ≤75%, ≤60%, and ≤40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium. RESULTS. Analysis of 41 infants showed that incidence of oxygen saturation ≤60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration ≤85%, 75%, and 40%; cumulative time ≥30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in ≤2 attempts significantly more often in the mivacurium group (35% vs 71%). CONCLUSIONS. Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.

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Advances in neonatal medicine have led to increased survival of infants born at the limits of viability, resulting in an increased incidence of bronchopulmonary dysplasia (BPD). BPD is a chronic lung disease of premature infants characterized by the arrest of alveolarization, fibroblast activation, and inflammation. BPD leads to significant morbidity and mortality in the neonatal period and is one of the leading causes of chronic lung disease in children. The past decade has brought a surge of trials investigating cellular therapies for the treatment of pulmonary diseases. Mesenchymal stem cells (MSCs) are of particular interest because of their ease of isolation, low immunogenicity, and antiinflammatory and reparative properties. Clinical trials of MSCs have demonstrated short-term safety and tolerability; however, studies have also shown populations of MSCs with adverse pro-inflammatory and myofibroblastic characteristics. Cell-based therapies may represent the next breakthrough therapy for the treatment of BPD, however, there remain barriers to implementation as well as gaps in knowledge of the role of endogenous MSCs in the pathogenesis of BPD. Concurrent high-quality basic science, translational, and clinical studies investigating the fundamental pathophysiology underlying BPD, therapeutic mechanisms of exogenous MSCs, and logistics of translating cellular therapies will be important areas of future research.

Melnick-Needles syndrome (MNS) is a rare X-linked bone dysplasia characterised by facial dysmorphology and radiographic abnormalities [Melnick and Needles, 1966;97:39–48]. Previously, all published cases of MNS were associated with only 4 mutations [Robertson et al., 2003;33:487–491; Santos et al., 2010;152A:726–731], all localised within exon 22 of FLNA, the gene encoding the cytoskeletal protein filamin A. Here we report 3 new mutations in FLNA that are associated with MNS. One affected member of the first family with the mutation p.Y1229S presented with a stroke while this patient’s daughter, previously known to be affected from a young age, developed multiple sclerosis. A second unrelated patient with a typical phenotype is shown to have the mutation c.1054G>T (p.G352W) within exon 7 of FLNA. A third individual with an atypical presentation but radiological findings very similar to those seen in classic MNS has a deletion likely to affect residues within repeat domain 14. These findings indicate that the mutational spectrum for MNS is wider than previously appreciated and has implications for genetic testing strategies employed to confirm a diagnosis of this rare disorder.