Pneumothorax from subpleural blebs-a new association of sotos syndrome?

We describe two unrelated patients with molecularly confirmed Sotos syndrome with multiple subpleural blebs and pneumothorax. We propose this as a new association. Patient 1 is a 3-year-old boy with a 1.9 Mb interstitial deletion of the long arm of chromosome 5, with breakpoints at q35.2 and q35.3, encompassing NSD1 and Patient 2 is a 9-year-old girl with a de novo truncating mutation within NSD1. Both patients presented with sudden onset dyspnea due to a unilateral pneumothorax: Patient 1 at the age of 18 months and Patient 2 at 9 years. In both, the pneumothorax recurred following removal of the chest drain and, on further investigations, multiple subpleural blebs were identified necessitating a pleurodesis and tissue resection. This is the first report of multiple subpleural blebs leading to pneumothorax in association with Sotos syndrome. Given the similar and unusual presentation in the two affected patients, we suggest that this may be a real association, albeit a rare one. While screening would not be advocated for such a rare association, we recommend that clinicians consider pneumothorax in patients with Sotos syndrome and sudden onset of dyspnea and are aware that it may be refractory to first line treatment.

Subpleural pulmonary cysts in children: Associations beyond Trisomy 21.

BACKGROUND: Small air-filled peripheral subpleural cysts are a well-described feature of pulmonary anatomy at computerized tomographic (CT) scan in children with Trisomy 21, yet only anecdotally described in association with other pathologies. The significance of these cysts is unknown. OBJECTIVE: To investigate and explore the pathogenesis of these subpleural cysts in children. MATERIALS AND METHODS: A retrospective review of 16 cases with subpleural cysts diagnosed on CT chest was performed. The distribution, location, and ancillary CT findings were recorded. Hospital charts were reviewed for clinical details, especially cardiac abnormalities, pulmonary artery hypertension (PAH) and genetic associations. Histopathological and clinical correlative data were recorded. RESULTS: Eleven of the 16 children (69%) were found to have an underlying chromosomal or genetic abnormality, six of whom had Trisomy 21. The remaining 5 of the 16 cases (21%) had miscellaneous disorders without an identifiable genetic basis. The most common co-morbidities were cardiac abnormalities (81%) and PAH (62.5%). Regardless of their underlying etiologies, the cysts were present bilaterally in most cases (14/16, 88%). We observed both the postnatal development and the progression of cysts in our cohort. On long-term follow-up, there were five deaths (31%) and six cases (38%) requiring maintenance oxygen therapy due to chronic hypoxia. Two cases (12.5%) became completely asymptomatic after correction of their underlying abnormalities. CONCLUSION: Subpleural cysts are not exclusive to Trisomy 21 and may be seen in other inherited or acquired causes, likely due to altered alveolar growth. We suspect these cysts are a sign of an underlying developmental disorder with variable clinical effect, especially in children with congenital cardiac disease.