Real-world utility of overnight oximetry for the screening of obstructive sleep apnea in children.

BACKGROUND: Obstructive sleep apnea (OSA) is a common problem in children and can result in developmental and cognitive complications if untreated. The gold-standard tool for diagnosis is polysomnography (PSG); however, it is an expensive and time-consuming test to undertake. Overnight oximetry has been suggested as a faster and cheaper initial test in comparison to PSG as it can be performed at home using limited, reusable equipment. AIM: This retrospective case control study aims to evaluate the effectiveness of a home oximetry service (implemented in response to extended waiting times for routine PSG) in reducing the time between patient referral and treatment. METHODS: Patients undergoing diagnostic sleep evaluation for suspected OSA who utilized the Queensland Children's Hospital screening home oximetry service in the first year since its inception in 2021 (n = 163) were compared to a historical group of patients who underwent PSG in 2018 (n = 311). Parameters compared between the two groups included time from sleep physician review to sleep test, ENT review, and definitive treatment in the form of adenotonsillectomy surgery (or CPAP initiation for those who had already undergone surgery). RESULTS: The time from sleep physician review and request of the sleep-related study to ENT surgical treatment was significantly reduced (187 days for the HITH oximetry group vs 359 days for the comparable PSG group; p-value <0.05), and time from sleep study request to the report of results was significantly lower for patients in the oximetry group compared to those in the PSG group (11 days vs 105 days; p-value <0.05). CONCLUSION: These results suggest that for children referred to a tertiary sleep center for possible obstructive sleep disordered breathing, a home oximetry service can be effective in assisting sleep evaluation and reducing the time to OSA treatment.

Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth, pulmonary hypertension, microcephaly, and spasticity.

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.

Diffuse lung disease in infants less than 1 year of age: Histopathological diagnoses and clinical outcome.

INTRODUCTION: Interstitial lung disease (ILD) in infants is rare. Clinical and radiological features are often non-specific, and overlap with growth disorders and infection. In infants with severe respiratory compromise, lung biopsy is often necessary to guide acute management, but the risk and diagnostic yield of this procedure is incompletely understood. AIMS: To retrospectively review infants undergoing open lung biopsy for suspected ILD at a large referral center; to determine morbidity and mortality related to the procedure; and to describe subsequent diagnosis and outcome. METHODS: Lung biopsies performed in infants (aged <1 year) between January 1, 2005 and March 31, 2012 were identified and clinical data were collected. Biopsies were reclassified using the ChILD classification for diffuse lung disorders in infants. RESULTS: Twenty-seven infants were identified, with the number of biopsies performed increasing each year over the study period. There was no mortality and negligible morbidity associated with biopsy. Diagnoses seen were similar to those reported by the ChILD network. Histopathological diagnosis was not compatible with life in the absence of lung transplant in 6/27 (22%) of infants. Of the 14 children longitudinally followed up (median 0.5 (0.4 - 5.81) years), only four continued to require supplemental oxygen. CONCLUSION: Lung biopsy in infants with suspected ILD is safe, and histopathological diagnosis frequently assists treatment decisions, particularly with regard to withdrawal of care.

High tracheal bifurcation: an unusual cause of left bronchial obstruction.

Congenitally short trachea is an uncommon abnormality. It is characterized by a reduced number of tracheal cartilage rings. As a result, the carina is situated at a higher level than usual. That causes the left main bronchus to course abnormally behind the arch of the aorta, rendering it prone to compression. We report the case of an infant who underwent successful aortopexy of the aortic arch for this condition.

Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome.

BACKGROUND: Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, ß 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. RESULTS: We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. CONCLUSIONS: These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.